身體組成與癌症生存率：系統性回顧

研究探討身體組成與癌症生存的關聯，指出傳統人體測量法的限制導致結果不一致。隨著放射學評估技術的應用，科學家可更準確測量脂肪與肌肉組成，進一步理解其對癌症生存的影響。然而，如何整合新舊測量方法仍是一大挑戰。本研究回顧生物學基礎與流行病學證據，並提醒研究者解讀新評估方法時應注意的問題。

Bradshaw, P.T. Body composition and cancer survival: a narrative review. Br J Cancer 130, 176–183 (2024).

摘要  Abstract

對於理解身體組成與癌症生存之間的關係的興趣已持續了幾十年，最近有多篇系統性回顧文章探討這一主題。然而，目前的證據狀態基於異質的暴露定義，這些定義基於人體測量學，導致關於這一關聯的發現不一致。最近，該領域採用了放射學評估來測量身體組成的特定方面，這是一個令人興奮的方向，但將這些現代評估工具的發現與歷史上使用的人體測量數據的結果進行調和卻面臨挑戰。在本文中，我簡要回顧了身體組成與癌症生存之間聯繫的生物學基礎，並總結了流行病學證據，考慮到特定的暴露測量。隨著對新型評估的熱情高漲，我最後討論了研究人員在解釋這些新方法的結果時應該注意的問題。
Interest in understanding the relationship between body composition and cancer survival has remained strong for decades, with a number of recent systematic reviews on the topic. However, the current state of evidence is based on heterogeneous exposure definitions based on anthropometry, yielding inconsistent findings with regard to this association. Recently the field has taken an exciting direction with the application of radiological assessments to measure specific aspects of body composition, yet reconciliation of findings from these modern assessment tools with those from the historic use of anthropometric data proves challenging. In this paper, I briefly review the biological basis for a link between body composition and cancer survival and summarize the epidemiological evidence with consideration to specific exposure measures. As enthusiasm is building around novel assessments, I conclude with a discussion of issues that researchers should be aware of when interpreting results from these new modalities.

引言  Introduction

身體組成與癌症生存之間的關係已被研究了幾十年，最近的一項綜述和元分析指出，這些結果的發表可追溯到 30 多年前[1]。這一領域的大多數先前研究集中在過量脂肪的特徵上，通常通過從人體測量中得出的指標來評估[1, 2, 3]。對生存結果與脂肪量之間關聯的特定興趣源於對過量脂肪是多種高負擔癌症的風險因素的理解[4]，以及可能將其與癌症生存聯繫起來的生物學機制[5, 6, 7, 8]，還有它與癌症患者所經歷的其他高負擔共病（如糖尿病和心血管疾病）之間的關係[9, 10]。考慮到癌症倖存者中肥胖率的迅速上升[11]，這些聯繫尤其令人擔憂，但也因為一些癌症倖存者在診斷前後會經歷顯著的體重增加[12, 13]。 儘管人體組成的測量方法被廣泛使用，但其已知的局限性[14]可能在人體組成文獻中顯示的明顯矛盾發現中起著作用[15]。作為回應，研究人員最近將重點轉向臨床評估中更直接的脂肪和肌肉組織測量，這些評估能夠同時捕捉各種組織的數量和特徵。雖然有合理的聯繫表明，脂肪過多與死亡風險增加有關，但同樣有強有力的證據表明，較高的瘦體重，特別是肌肉，與風險降低相關[16]。更好地理解人體組成與生存之間的多維關係將有助於解決該領域中一些持續的困惑[15, 17]。
The relationship between body composition and cancer survival has been investigated for decades, as noted by a recent review and meta-analysis that included results published over 30 years ago [1]. Most previous studies in this area have focused on the characteristic of excess adiposity, typically assessed with metrics derived from anthropometric measurements [1,2,3]. The specific interest in the association between survival outcomes and fat mass stems from the understanding that excess adiposity is a risk factor for a number of high-burden cancers [4], the plausible biological mechanisms that may link it to cancer survival [5,6,7,8], and its relationships with other high-burden comorbidities experienced by cancer patients such as diabetes and cardiovascular disease [9, 10]. These connections are especially concerning given the rapid increase in obesity prevalence among cancer survivors [11], but also because some cancer survivors experience significant weight gain around and immediately after diagnosis [12, 13]. Despite their prolific use, anthropometric measures of body composition have well-known limitations [14] which may play a role in apparently paradoxical findings noted in the body composition literature [15]. In response, researchers have recently shifted focus to more direct measures of both fat and muscle tissue from clinical assessments that are able to capture the amount and characteristics of the quality of various tissues simultaneously. While there are plausible links suggesting that elevated adiposity is linked to greater risk of death, there is similarly strong evidence suggesting greater lean mass, in particular muscle, is associated with a reduction in risk [16]. A better understanding of the multi-dimensional nature of the body composition-survival relationship would help resolve some of the ongoing confusion in the field [15, 17].

在本報告中，我將首先回顧與肥胖和肌肉組織與癌症生存之間的相關生物機制。我將總結流行病學證據，探討生存與幾種常見的體成分指標之間的關係，這些指標涵蓋不同的癌症部位。在整篇論文中，我將強調這些不同體成分指標在評估和解釋這些關聯時的重要考量。
In this report, I will begin by reviewing the relevant biological mechanisms thought to link adiposity and muscle tissue to cancer survival. I will then summarize the epidemiological evidence of the relationship between survival and several common measures of body composition across cancer sites. Throughout the paper I will highlight important considerations for these different body composition metrics regarding the assessment and interpretation of the associations.

潛在機制  Potential mechanisms

如圖 1 所示，脂肪組織，特別是內臟脂肪，具有代謝活性，並且有許多後果被認為會以複雜的相互作用影響幾種癌症的病因和預後[18]。過多的脂肪與幾種促進細胞增殖的生長因子（如胰島素和類胰島素生長因子）水平升高相關[19, 20]。脂肪量的增加與血清游離脂肪酸水平升高相關，這是通過幾種促進脂解的機制實現的。其中一種機制是內臟脂肪組織對胰島素的抗脂解作用不太敏感，而對兒茶酚胺的脂解作用更敏感[21]；這對癌症患者尤其重要，因為兒茶酚胺水平因心理社會壓力、手術和治療而增加[22]。脂肪細胞還被認為分泌多種細胞因子，包括促進脂解的腫瘤壞死因子α（TNF-α）[23]。 由脂肪細胞驅動的游離脂肪酸在皮下和內臟脂肪組織中的增加被認為會抑制胰島素對葡萄糖攝取和氧化的作用[ 24]，從而導致胰島素抵抗的狀態，隨後胰腺會補償性地增加胰島素分泌，以維持葡萄糖的穩態[ 25]。這種胰島素的增加促使胰島素樣生長因子結合蛋白（IGF-BPs）減少，並隨之增加生物可用的胰島素樣生長因子 I（IGF-I）[ 25]。胰島素和 IGF-I，以及 TNF-α，會結合到細胞膜上的受體，刺激細胞增殖並抑制細胞凋亡，從而提供腫瘤發展的機制[ 18, 26]。這一途徑對某些癌症特別相關，例如乳腺癌[ 27]，因為乳腺細胞癌通常表現出胰島素受體[ 28]和 IGF-I 受體[ 29]的過度表達，使其對這些激素的增殖效應非常敏感。 雖然內臟脂肪與肥胖相關的胰島素抵抗有關，但有證據表明皮下脂肪，特別是深層皮下脂肪組織，也可能起到一定的作用。腹部周圍的皮下脂肪由兩層淺層和深層組織組成，並由筋膜分隔 [30]。深層皮下脂肪組織與內臟脂肪組織有幾個相似之處，包括相似的脂肪酸組成 [31] 和與胰島素抵抗的強相關性 [32]。這表明上述機制對某些皮下脂肪分佈模式也可能是相關的。
As illustrated in Fig. 1, adipose tissue, especially visceral fat, is metabolically active and has a number of sequelae that are believed to influence the etiology and prognosis of several cancers in a complex interplay [18]. Excess adiposity is associated with higher levels of several mitogenic factors, such as insulin and insulin like growth factors [19, 20] which can encourage proliferation of cancerous cells. An increase in fat mass is associated with elevated levels of serum free fatty acids through several mechanisms that encourage lipolysis. One such mechanism is that visceral adipose tissue is less sensitive to the antilipolytic effect of insulin and more sensitive to the lipolytic effects of catecholamines [21]; this may be particularly important for cancer patients as catecholamine levels are increased by psychosocial stress, surgery, and treatment [22]. Adipocytes are also known to secrete a variety of cytokines including the lipolysis stimulating tumor necrosis factor alpha (TNF-α) [23]. The increase in free fatty acids driven by adipocytes in both subcutaneous and visceral adipose tissue is thought to inhibit insulin’s effect on glucose uptake and oxidation [24] thereby resulting in a state of insulin resistance, and a subsequent compensatory increase in insulin secretion by the pancreas in an effort to maintain glucose homeostasis [25]. This increase in insulin precipitates a decrease in insulin-like growth factor binding proteins (IGF-BPs) and a successive increase in bioavailable insulin-like growth factor I (IGF-I) [25]. Both insulin and IGF-I, as well as TNF-α, bind to membrane-bound receptors on cells that stimulate cellular proliferation and inhibit apoptosis, thereby providing a mechanism for tumor development [18, 26]. This pathway is especially relevant to certain cancers, such as breast [27], as mammary cell carcinomas typically exhibit an over-expression of insulin receptors [28] and IGF-I receptors [29] making them very susceptible to the proliferative effects of these hormones. Although visceral fat has been implicated in obesity-related insulin resistance, there is evidence that subcutaneous fat, specifically deep subcutaneous adipose tissue, may also play a role. Subcutaneous fat around the abdomen is comprised of two layers of superficial and deep tissue separated by fascia [30]. Deep subcutaneous adipose tissue shares several similarities with visceral adipose tissue including a comparable fatty acid composition [31] and a strong association with insulin resistance [32]. This suggests the mechanisms mentioned above may also be relevant for certain patterns of subcutaneous fat distribution.

與肥胖相關的炎症也可能提供一條途徑，通過該途徑，過多的脂肪影響致癌過程 [ 33, 34]。除了 TNF-α，對過多脂肪組織的反應所產生的炎症標記物包括 C 反應蛋白（CRP）和白介素-6（IL-6），這些都已被認為通過各種機制與致癌過程有關 [ 18]。肥胖還參與調節其他具有腫瘤促進潛力的脂肪因子 [ 35]。循環中的脂聯素水平，這是一種具有抗炎和增敏胰島素作用的脂肪細胞特異性蛋白 [ 36]，在肥胖個體中較低，而瘦素的水平，這種物質有潛力作為生長因子，則與脂肪量呈正相關 [ 35]。除了過高脂肪量的全身性炎症影響外，越來越多的證據表明，圍繞腫瘤的脂肪細胞可能對腫瘤微環境中的局部炎症有重要影響 [ 18, 34]。這種局部炎症對於發生在脂肪組織儲存區附近的惡性腫瘤，特別是乳腺癌 [ 34]，尤其相關。
Obesity-related inflammation may also provide a pathway through which excess adiposity influences carcinogenesis [33, 34]. In addition to TNF-α, inflammatory markers produced in response to excess adipose tissue include C-reactive protein (CRP) and interleukin-6 (IL-6), all of which have been implicated in carcinogenesis through various mechanisms [18]. Obesity is also involved in the regulation of other adipokines with the potential for tumor promotion [35]. Circulating levels of adiponectin, an adipocyte-specific protein with anti-inflammatory and insulin sensitizing effects [36], are lower in obese individuals while levels of leptin, which has potential to act as a growth factor, are positively related to adiposity [35]. In addition to the systemic inflammatory effects of elevated adiposity, mounting evidence suggests that fat cells surrounding the tumor may have important influences on local inflammation in the tumor microenvironment [18, 34]. This local inflammation is especially relevant for malignancies that occur in close proximity to adipose tissue depots, such as breast cancer [34].

性激素是強效的有絲分裂促進劑，能刺激細胞增殖，因此在細胞分裂過程中增加 DNA 突變的可能性，並促進異常細胞的複製[ 37, 38, 39]。雄激素在脂肪組織中的芳香化產生雌酮，隨後轉化為雌二醇，這是最具代謝活性的雌激素[ 40]。這一途徑對男性和絕經後女性來說是雌激素的重要來源，與絕經前女性相比，後者卵巢產生的雌二醇更為重要，掩蓋了脂肪介導的形成[ 21]。脂肪量與性激素及相關結合蛋白之間的關聯，特別是雌二醇和性激素結合球蛋白（SHBG），被認為在致癌過程中扮演重要角色[ 41]。雌二醇對靶組織的可用性主要取決於循環中的 SHBG 量。 大約一半的血液中的雌二醇與性荷爾蒙結合球蛋白（SHBG）結合，其餘則與白蛋白結合或自由循環[42]。與肥胖相關的高胰島素血症的常見後果是 SHBG 的減少，這導致生物可用雌激素的增加，使得更多的自由或與白蛋白結合的雌二醇能夠與雌激素受體結合[41]。未經調節的雌二醇暴露和 SHBG 減少的聯合效應已被證明在肥胖的絕經後女性中導致自由雌二醇的增加超過兩倍，與正常體重的女性相比[42]。過多的脂肪量，通過身體質量指數（BMI，公斤體重除以米高的平方）評估，已被證明與雌酮、雌二醇、自由雌二醇、自由睾酮和催乳素呈正相關，與 SHBG 呈負相關[21, 43]。除了其促細胞增殖的潛力外，還有證據表明雌激素代謝會產生自由基，這可能會造成 DNA 損傷，從而啟動致癌過程[44, 45]。肥胖驅動的荷爾蒙失調的影響對於治療具有荷爾蒙病因的癌症特別相關。 特別是，芳香化酶抑制劑療法在肥胖的女性乳腺癌患者中顯示出效果較差 [ 46]。此外，雖然脂肪過多與男性的睾酮水平較低有關 [ 47]，但增加對與肥胖相關的生長因子和脂肪因子的暴露與雄激素受體的激活有關，這可能影響前列腺癌的進展 [ 48]。
Sex hormones are powerful mitogens which stimulate cellular proliferation therefore increasing the likelihood of a DNA mutation during cell division and encouraging replication of aberrant cells [37,38,39]. Aromatization of androgens in adipose tissue yields estrone which is subsequently converted to estradiol, the most metabolically active estrogen [40]. This pathway represents a significant source of estrogen for males and postmenopausal females, in contrast to premenopausal women where ovarian production of estradiol overshadows adipose-mediated formation [21]. The association between fat mass and sex hormones and related binding proteins, especially estradiol and sex hormone binding globulin (SHBG), are thought to play a significant role in carcinogenesis [41]. The availability of estradiol to target tissues is primarily determined by the amount of circulating SHBG. Approximately half of the estradiol in the blood is bound to SHBG, the remainder bound to albumin or freely circulating [42] A common consequence of obesity-related hyperinsulinemia is a reduction in SHBG, resulting in an increase in bioavailable estrogen allowing more free or albumin-bound estradiol to bind with estrogen receptors [41]. The combined effect of unregulated estradiol exposure and reduction in SHBG has been shown to result in a greater than two-fold increase in free estradiol among obese postmenopausal women compared to women of normal weight [42]. Excess adiposity, assessed by body mass index (BMI, weight in kilograms divided by squared height in meters), has been shown to be positively associated with estrone, estradiol, free estradiol, free testosterone and prolactin and negatively associated with SHBG [21, 43]. Besides its mitogenic potential, there is also evidence that estrogen metabolism generates free radicals which may inflict DNA damage thereby initiating carcinogenesis [44, 45]. The influence of obesity-driven hormone dysregulation is particularly relevant for treatment of cancers with a hormonal etiology. In particular, aromatase inhibitor therapy has been shown to be less effective in female breast cancer patients with obesity [46]. In addition, while adiposity is associated with lower testosterone levels in males [47], increased exposure to obesity-related growth factors and adipokines is related to activation of androgen receptors which may influence prostate cancer progression [48].

與脂肪組織相比，肌肉質量與一般有利的代謝和炎症特徵相關。肌肉細胞產生一系列稱為肌肉激素的蛋白質，這些蛋白質具有抗炎和增敏胰島素的影響，與脂肪激素的作用相對立[49]。這些因素以及其他因素，可能部分源於肌肉與身體活動之間的關係[50]。身體活動與胰島素敏感性的增加相關，這是通過增加骨骼肌細胞膜中 GLUT-4 葡萄糖轉運蛋白的表達來實現的[51, 52, 53, 54, 55]，並通過降低與胰島素功能受損相關的游離脂肪酸水平來實現[56]。這種胰島素敏感性的增加促使胰島素分泌的減少，這可能是觀察到的 IGF-BPs 增加[57]和在身體活動者中觀察到的 IGF 減少[58]的機制之一。身體活動調節這些代謝激素和生長因子的能力，暗示了這種暴露所觀察到的保護作用的另一種潛在途徑[59, 60]。 這種 IGF 的減少可能會提供額外的癌症保護，因為它可能通過促進肝臟 SHBG 產量的增加來減少性激素的暴露[61]。身體活動對癌症結果的有益影響也可能包括改善免疫反應[62]。定期的身體活動與自然殺手細胞的數量和細胞毒性增加有關，並且在幾個炎症標記物（包括 IL-6、CRP 和 TNF-α）中也出現了有利的變化[63]。
In contrast to adipose tissue, muscle mass is associated with a generally favorable metabolic and inflammatory profile. Muscle cells produce a number of proteins called myokines that have anti-inflammatory and insulin-sensitizing influences in opposition to the effects of adipokines [49]. These, and other factors, may be due in part to the relationship between muscle and physical activity [50]. Physical activity is associated with an increase in insulin sensitivity by increasing expression of the GLUT-4 glucose transporter in the plasma membrane of skeletal muscle [51,52,53,54,55] and by reducing the level of free fatty acids, which have been linked to impaired insulin function [56]. This increase in insulin sensitivity precipitates a decrease in insulin secretion, which is a possible mechanism for the observed increase in IGF-BPs [57] and decrease in IGF observed among physically active individuals [58]. The ability of physical activity to mediate these metabolic hormones and growth factors suggests another potential pathway for the observed protective effect of this exposure [59, 60]. This reduction in IGF may yield additional cancer protection as it may reduce sex hormone exposure by encouraging an increase in SHBG production by the liver [61]. The beneficial effects of physical activity on cancer outcomes may also include improvement of the immune response [62]. Regular physical activity has been associated with increases in number and cytotoxicity of natural killer cells, as well as favorable shifts in several inflammatory markers including IL-6, CRP, and TNF-α [63].

掩蓋我們對肌肉與癌症存活關係理解的事實是，肌肉質量常常因惡性腫瘤的存在而改變。腫瘤驅動的炎症引發了一種稱為惡病質的分解代謝狀態[ 64]，這導致脂肪和肌肉組織的損失[ 16]。肌肉損失通常最終會導致一種稱為肌少症的狀態，值得注意的是，這種情況也可以在沒有惡病質的情況下出現，並且在老年人群中經常觀察到[ 65]。重要的是，癌症患者通常同時呈現出高比例的脂肪組織和低量的肌肉質量，這種情況被稱為“肌少性肥胖”[ 16, 66]。低肌肉和高脂肪的組合與更大的全身性炎症和代謝功能障礙相關[ 67, 68, 69]，這使得解釋存活與個別組織測量之間的關係變得複雜。重要的是，肌少性肥胖可以在任何 BMI 下發生，甚至在正常體重範圍內[ 16]，這使得人體測量評估成為分類與癌症存活相關的身體組成表型的特別不可靠工具。
Obscuring our understanding of the muscle and cancer survival relationship is the fact that muscle mass is often altered by the presence of malignancy. Tumor-driven inflammation precipitates a catabolic condition known as cachexia [64], which results in loss of both fat and muscle tissue [16]. Muscle loss often culminates in a state referred to as sarcopenia, which should be noted can also manifest in the absence of cachexia and is frequently observed in aging populations [65]. Importantly, cancer patients often present with a high proportion of adipose tissue and low amount of muscle mass together, a condition termed “sarcopenic obesity” [16, 66]. This combination of low muscle and high fat is associated with greater systemic inflammation and metabolic dysfunction [67,68,69], which complicates the interpretation of the relationship between survival and the individual tissue measures. Importantly, sarcopenic obesity can occur at any BMI, even within the normal weight range [16], making anthropometric assessments especially unreliable tools to classify body composition phenotypes relevant for cancer survival.

體重指數  Body mass index

人體測量指標如身高和體重易於收集，且可以相對準確地獲得，這使它們在大型流行病學研究中具有吸引力 [14]。BMI 是目前用於確定人群體重狀態的標準。個體可被分類為體重過輕（<18.5）、正常體重（18.5–<25）、超重（25–<30）和肥胖（≥30）類別；後者類別可能進一步細分為 1 級（30–<35）、2 級（35–<40）和 3 級肥胖（≥40） [70]。在沒有癌症的個體中，BMI 與直接測量的體脂百分比之間的相關性被注意到範圍從 0.58 到 0.75 [71]，使得 BMI 與脂肪狀態的關聯性僅為中等。值得注意的是，與直接測量的脂肪或與肥胖相關的生物標記相比，BMI 往往低估肥胖狀態 [72, 73]。研究還顯示，在 BMI 的不同水平中，體脂肪存在顯著變異，這在癌症患者中可能尤其真實。一項研究顯示，BMI 僅將 26%的癌症患者群體分類為肥胖，而 59%則通過直接測量顯示有過多的脂肪質量 [74]。 在這項研究中，31% 的正常範圍 BMI（18.5–<25）的人有客觀測量的肥胖、低肌肉量或兩者兼具，使得正常體重的參考類別在結果分析中成為一個非常異質的身體組成表型混合體。
Anthropometric measures such as height and weight are easily gathered and can be collected with reasonable accuracy, making them attractive for large epidemiological studies [14]. BMI is the current standard for the determination of weight status in populations. Individuals may be classified into underweight (<18.5), normal weight (18.5–<25), overweight (25–<30) and obese (≥30) categories; the latter category potentially broken further into Class 1 (30–<35), Class 2 (35–<40), and Class 3 obesity (≥40) [70]. Correlations between BMI and directly-measured percent body fat have been noted to range from 0.58 to 0.75 among individuals without cancer [71], making BMI only moderately associated with adiposity status. Notably, BMI tends to underestimate obesity status when compared to direct measures of adiposity or obesity-related biomarkers [72, 73]. Studies have also shown significant variations in body fat within levels of BMI, which may be particularly true among cancer patients. One study showed that BMI only classified 26% of a cohort of cancer patients as obese while 59% had excess fat mass by direct measure [74]. In this study 31% of those with BMI in the normal range (18.5–<25) had either objectively-measured obesity, low muscle mass, or both, making the normal weight referent category for outcomes analyses a very heterogeneous mix of body composition phenotypes.

多項系統性回顧已經總結了有關癌症存活率與診斷時的 BMI 之間的文獻。一項涉及 15 個癌症部位的重大綜合分析最近考慮了肥胖（BMI ≥ 30）患者與非肥胖患者之間的存活結果。對於所有癌症的綜合，作者報告了整體死亡風險的適度增加（合併危險比（HR）[95%置信區間]：1.14 [1.09, 1.19]），以及癌症特異性死亡（合併 HR：1.17 [1.12–1.23]）[1]。對個別癌症的分析顯示，乳腺癌、結直腸癌和子宮癌的整體死亡風險增加（所有 HR 約為 1.2），而肺癌、腎細胞癌和黑色素瘤癌症存活者的死亡風險降低（HR 範圍從 0.74 到 0.86）。
A number of systematic reviews have summarized the literature on cancer survival in relation to BMI around the time of diagnosis. A large meta-analysis that involved studies for 15 cancer sites recently considered survival outcomes among those with obesity (BMI ≥ 30) compared to those without obesity. For all cancers combined, authors reported a modestly increased risk of overall mortality (pooled hazard ratio (HR) [95% confidence interval]: 1.14 [1.09, 1.19]) was well as cancer specific death (pooled HR: 1.17 [1.12–1.23]) [1]. Analyses of individual cancers indicated an increased risk of overall mortality for breast, colorectal, and uterine cancer (all HRs around 1.2), while a decreased risk of death among lung, renal cell carcinoma, and melanoma cancer survivors (HRs ranging from 0.74 to 0.86).

最近，全球癌症更新計劃（CUP global）小組考慮了多項人體測量指標與乳腺癌結果之間的關係。較高的 BMI 與更高的全因死亡率相關（在 64 項研究中，每增加 5 kg/m ² 的合併相對風險（RR）：1.07 [1.05–1.10]），以及乳腺癌特異性生存率（39 項研究，RR：1.10 [1.06–1.14]）、復發率（63 項研究，RR：1.05 [1.03–1.08]）和第二原發癌的發生率（11 項研究，RR：1.14 [1.04–1.26]）[ 3]。作者發現 BMI 與生存之間存在非線性的“J 形”關係，最低風險出現在超重狀態的閾值附近（BMI 25 對比 20，RR：0.95 [0.91–0.99]），隨著 BMI 增加到 2 級肥胖範圍（BMI 35 對比 20，RR：1.21 [1.12–1.30]）時風險上升。乳腺癌特異性生存率也報告了類似但不那麼明顯的劑量反應模式。 總體而言，這些發現被評為提供「強」和「可能」證據，顯示 BMI 與乳腺癌結果之間的聯繫，而關於復發和非乳腺癌相關死亡（包括心血管疾病）的趨勢則被認為提供了暗示性證據。
Most recently, the Global Cancer Update Program (CUP global) group considered the relationship between a number of anthropometric measures of adiposity and breast cancer outcomes. Elevated BMI was associated with greater all-cause mortality (across 64 studies, pooled relative risk (RR) per 5 kg/m²: 1.07 [1.05–1.10]) as well as breast-cancer specific survival (39 studies, RR: 1.10 [1.06–1.14]), recurrence (63 studies, RR: 1.05 [1.03–1.08]), and incidence of second primary cancers (11 studies, RR: 1.14 [1.04–1.26]) [3]. The authors found evidence of a nonlinear “J-shaped” relationship between BMI and survival, with the lowest risk occurring around the threshold for overweight status (BMI 25 vs. 20, RR: 0.95 [0.91–0.99]) with an uptick as BMI increased into the Class 2 obese range (BMI 35 vs. 20, RR: 1.21 [1.12–1.30]). A similar but less pronounced dose-response pattern was also reported for breast cancer-specific survival. In total, these findings were graded as providing “strong” and “probable” evidence for a link between BMI and breast cancer outcomes, while trends regarding recurrence and non-breast cancer related death (including cardiovascular disease) were considered to provide suggestive evidence.

最近的一項針對結直腸癌倖存者的研究回顧報告了普遍一致的發現。在結直腸癌倖存者中，BMI 與多項生存結果之間存在類似的“J 形”關係[2]。在 BMI 範圍的極端情況下，任何原因的死亡風險均有所增加；與正常體重狀態相比，BMI < 18.5 或≥35 的人群面臨更高的任何原因死亡風險（總體 HR：1.26 [1.15–1.37]和 HR：1.12 [1.02–1.22]，分別）。然而，超重範圍內的人群顯示出最低的死亡風險（HR：0.92 [0.86–0.99]）[2]。對於無病生存和結直腸癌特異性死亡也觀察到了類似的模式。
Generally concordant findings have been reported in a recent review of studies focused on colorectal cancer survivors. A similar “J-shaped” relationship between BMI and a number of survival outcomes has been reported among colorectal cancer survivors [2]. Risk of death from any cause was elevated at the extremes of the BMI range; compared to normal weight status those with BMI < 18.5 or ≥35 were at greater risk of death from any cause (summary HR: 1.26 [1.15–1.37] and HR: 1.12 [1.02–1.22], respectively). However, those in the overweight range displayed the lowest risk of death (HR: 0.92 [0.86–0.99]) [2]. Similar patterns were observed for disease free survival and colorectal cancer-specific deaths.

在過去十年中，幾項其他的綜合分析報告了不同癌症部位之間 BMI 與癌症特異性生存率之間的類似意外關聯。在腎癌患者中，肥胖和超重狀態與正常體重狀態相比，癌症特異性生存的風險較低（HR：0.85 [0.79, 0.93]），但在體重過輕的個體中則注意到風險大幅增加（HR：2.16 [1.15, 4.04]）[75]。對頭頸癌倖存者研究的定性總結顯示了類似的關聯，將肥胖與正常體重進行比較的 HR 在大多數考慮的報告中約為 0.7[76]。值得注意的是，這些與最近 Petrelli 綜合分析中報告的頭頸癌倖存者的子分析中所報告的合併 HR（HR：0.59 [0.33–1.05]）的大小相似[1]。
Over the last decade, several other meta-analyses have reported similarly unexpected associations between BMI and cancer-specific survival across different cancer sites. Among individuals with kidney cancer, obesity and overweight status was associated with lower risk of cancer-specific survival compared to those with normal weight status (HR: 0.85 [0.79, 0.93]), but a large increase in risk was noted among underweight individuals (HR: 2.16 [1.15, 4.04]) [75]. A qualitative summary of studies of head and neck cancer survivors showed a similar association, with HRs comparing obesity to normal weight around 0.7 for most reports considered [76]. Notably, these are similar to the magnitude of the pooled HR reported in the sub-analysis of head and neck cancer survivors (HR: 0.59 [0.33–1.05]) in the recent Petrelli meta-analysis [1].

中央肥胖的圍度測量
Circumference measures of central adiposity

雖然腰圍（WC）不像身高和體重那樣容易測量，但它是中央脂肪的一個常見指標，較高的數值往往表示代謝活躍的內臟脂肪組織的儲存量較大[77]。根據腰圍進行風險分層的常見閾值為男性 102 厘米和女性 88 厘米[78]。儘管這些測量對捕捉區域脂肪分佈具有更高的特異性，但它們也存在重要的缺陷。雖然這些評估提供了更精細的身體組成測量，但它們並不總是實用，並且不同測量協議之間可能存在顯著的變異性。腰圍還往往與整體身體大小的測量（如 BMI）有很強的相關性[79]，因此將其作為中央脂肪的獨立測量的統計應用需要謹慎考慮[80]。此外，雖然 WC 受到內臟脂肪量的強烈驅動，但它無法區分腹部周圍的皮下脂肪組織和內臟脂肪組織。 腰臀比（WHR），作為簡單腰圍的流行替代指標，可能更具問題性，因為較大的數值可能是由於腹部脂肪增加、臀部肌肉量減少或臀部和臀部周圍的皮下脂肪沉積增加所致[14]。這些不同的組織儲存可能具有重要特徵[81, 82]，在單一比率指標中變得混淆。
Although not as straightforward to measure as height and weight, waist circumference (WC) is a common measure of central adiposity, with higher values tending to indicate a greater deposit of metabolically active visceral fat tissue [77]. Common thresholds for risk stratification by WC are 102 cm for males and 88 cm for females [78]. Despite their greater specificity for capturing regional fat distribution, these measures possess important shortcomings. Although these assessments offer a more refined measure of body composition, they are not always practical, and there can be significant variability across different measurement protocols. Waist circumference also tends to be strongly correlated with overall body size measures such as BMI [79], and so its statistical application as an independent measure of central adiposity requires careful consideration [80]. Furthermore, although WC is driven strongly by visceral fat mass, it cannot distinguish between subcutaneous and visceral adipose tissue around the abdomen. Waist-hip ratio (WHR), a popular alternative to simple WC, may be more problematic, as larger values can be due to greater abdominal adiposity, reduced gluteal muscle mass, or greater subcutaneous fat deposition around the hips and buttocks [14]. These different tissue depots may have important characteristics [81, 82] that become muddled in a single ratio metric.

在現有文獻中，將癌症結果與中央脂肪的身體測量評估相關聯的研究要少得多。在最近的一項綜合分析中，Cheng 等人報告了中央脂肪增加與全因死亡率（合併風險比：1.30 [1.15–1.46]）和乳腺癌特異性死亡（風險比：1.26 [1.03–1.55]）之間的中等強度總體關聯，這是基於 14 項乳腺癌倖存者的研究[83]。對於結直腸癌的生存，作者還注意到全因死亡率的風險增加（風險比：1.24 [1.04, 1.47]）和結直腸癌特異性死亡率（風險比：1.27 [1.08, 1.49]）[83]。重要的是要注意，這些合併估計包括了使用 WC 或 WHR 的研究結果。由於這些可能反映了中央脂肪的不同表型[14]，因此暴露定義的異質性使解釋變得模糊。 然而，CUP 全球小組之前提到的乳腺癌結果的元分析確實對 WC 和 WHR 進行了單獨分析，並報告了 WC（每增加 10 厘米，總體 RR：1.18 [1.07–1.31]）或 WHR（每增加 0.1 單位，RR：1.30 [1.20–1.40]）與全因死亡率之間的強烈關聯證據，對於乳腺癌特定死亡的發現也相似[3]。儘管這些證據的強度，CUP 全球研究中對這些指標的總結研究數量較少，範圍從 3（WC 和乳腺癌特定死亡率）到 8（WHR 和全因死亡率）。鄭等人還報告說，升高的內臟脂肪與結直腸癌患者的整體死亡率（總體 HR：1.24 [1.04, 1.47]）和癌症特定死亡（HR：1.27 [1.08, 1.49]）相關，但對於前列腺癌患者的發現則是適度到無效的[83]。
Studies relating cancer outcomes to anthropometric assessments of central adiposity are much less common in the extant literature. In a recent meta-analysis, Cheng et al. reported moderately strong summary associations between elevated central adiposity and all-cause mortality (pooled HR: 1.30 [1.15–1.46]) and breast cancer-specific death (HR: 1.26 [1.03–1.55]) across 14 studies of breast cancer survivors [83]. For colorectal cancer survival, the authors also noted an increased hazard of all-cause mortality (HR: 1.24 [1.04, 1.47]) and colorectal cancer-specific mortality (HR: 1.27 [1.08, 1.49]) [83]. It is important to note that these pooled estimates included results from studies that used either WC or WHR. As these likely reflect different phenotypes of central adiposity [14], the heterogeneity of the exposure definition obscures the interpretation. However, the previously mentioned meta-analysis of breast cancer outcomes by the CUP global group did conduct separate analyses for WC and WHR and also reported strong evidence for relationships between all-cause mortality and WC (per 10 cm, summary RR: 1.18 [1.07–1.31]) or WHR (per 0.1 unit, RR: 1.30 [1.20–1.40]), with comparable findings for breast cancer-specific deaths [3]. Despite the strength of this evidence, the number of studies summarized for each of these measures in the CUP global study was small, ranging from 3 (WC and breast cancer specific mortality) to 8 (WHR and all-cause mortality). Cheng et al. also report that elevated visceral adiposity is associated with greater overall mortality (summary HR: 1.24 [1.04, 1.47]) and cancer-specific death (HR: 1.27 [1.08, 1.49]) among colorectal cancer patients, but modest to null findings for prostate cancer patients [83].

體重變化  Weight change

體重變化是脂肪量的另一種人體測量指標，因為成年期間的體重增加反映了持續的正能量平衡狀態和脂肪組織的積累 [80]。相反，對於那些有過多脂肪的人，故意減重已被證明對上述由肥胖引起的炎症和胰島素抵抗的生物標記有益 [84, 85]。研究人員使用的體重變化指標有所不同，理解各種表達方式在解釋廣泛文獻中的發現時是必要的。體重變化可以從人體測量變數的表達中得出，例如體重（以磅或公斤計）或 BMI，表示隨時間的絕對或百分比變化 [86]。由於身高的縮放同樣影響 BMI 百分比變化計算中的分子和分母，因此如果身高在一段時間內保持不變，則在數學上等同於百分比體重變化。然而，這些變數的絕對變化並不具備這一特性。 這種差異的一個重要後果是，隨著時間的推移，體重變化百分比以及絕對 BMI 變化意味著對於較小的個體來說，絕對體重變化更大。考慮到測量誤差和液體平衡的正常波動，已提出<3%的閾值來定義體重維持[86]。在文獻中，更常見的是使用<5%的絕對體重變化來定義體重維持，超過 5%的損失被歸類為任何體重減輕，而增重通常分為 5–<10%（中度增重）和≥10%（大幅增重）。
Weight change is an alternative anthropometric measure of adiposity, as weight gain during adulthood reflects a state of sustained positive energy balance and the accumulation of adipose tissue [80]. Conversely, intentional weight loss among those with excess adiposity has been shown to have beneficial effects on the aforementioned biomarkers of obesity-driven inflammation and insulin resistance [84, 85]. Weight change metrics used by researchers have varied somewhat, and an understanding of the various expressions is required when interpreting findings across the broad literature. Weight change can be derived from expressions of anthropometric variables such as weight (in pounds or kilograms) or BMI, representing absolute or percentage changes over time [86]. Because height scaling equally affects both the numerator and denominator in the calculation of percent change of BMI, it is mathematically equivalent to percent weight change if height is constant over time. However, absolute changes in these variables do not share this property. An important consequence of this difference is that percent weight change over time, as well as absolute BMI change over time, implies larger absolute weight changes for smaller individuals. Taking into account measurement error and normal fluctuations in fluid balance, a threshold of <3% has been proposed for defining weight maintenance [86]. More commonly, an absolute weight change of <5% is used to define weight maintenance in the literature, with losses more than 5% classified as any weight loss, and gains frequently divided into 5– < 10% (moderate gain) and ≥10% (large gain).

儘管體重增加的影響相當明確，但在流行病學研究中解釋與體重減輕相關的發現卻具有挑戰性，因為通常不會評估其意圖。故意的體重減輕通常是由於有目的地採用飲食和身體活動的做法，而無意的體重減輕則被認為反映了疾病的進展。值得注意的是，體重穩定也可能不是理想體成分的可靠指標，因為在體重穩定的癌症患者中已報告診斷後出現肌肉減少症和肌肉脂肪變性[87]。因此，在癌症生存研究中將體重穩定的個體視為參考組，可能與正常體重 BMI 類別所指出的問題相似[74]。
Although the implications of weight gain are fairly clear, interpretation of findings related to weight loss in epidemiological studies is challenging, as intentionality is not typically assessed. Intentional weight loss is typically due to the purposeful adoption of dietary and physical activity practices, while unintentional weight loss is thought to reflect disease progression. Notably, weight stability may also not be a reliable measure of ideal body composition, as incident sarcopenia and myosteatosis after diagnosis has been reported among weight stable cancer patients [87]. Therefore, considering weight stable individuals as the reference group in cancer survival studies likely shares the problems noted for the normal weight BMI category [74].

在乳腺癌診斷後體重增加與生存率的關係已在流行病學文獻中廣泛研究。2015 年對 12 項乳腺癌診斷後體重增加與生存率的隊列研究進行的綜合分析報告指出，與維持體重的人相比，基線水平增加 5%或以上的體重與任何原因的死亡風險增加相關[88]。然而，作者所呈現的更細緻的分析顯示，這是由於極端的體重增加（增加≥10%，HR：1.23 [1.09, 1.39]）所驅動，而對於那些增加 5%至<10%基線體重的人，幾乎沒有影響。值得注意的是，CUP 全球小組最近的回顧得出結論，乳腺癌診斷後 BMI 或體重變化之間的聯繫證據尚不確定，並需要進一步研究[3]。
Survival in relation to weight gain after breast cancer diagnosis has been examined extensively in the epidemiological literature. A 2015 meta-analysis of 12 cohort studies of post-diagnosis weight gain and breast cancer survival reported that weight gain of 5% or more from baseline levels was associated with greater risk of mortality from any cause compared to those who maintained weight [88]. However, the more granular analyses presented by the authors showed that this was driven by extreme weight gain (gain of ≥10%, HR: 1.23 [1.09, 1.39]) with a near-null effect for those gaining 5– < 10% of their baseline weight. Notably, the more recent review by the CUP global group concluded that evidence for a link between postdiagnosis BMI or weight changes was inconclusive, and required further study [3].

在結直腸癌倖存者中，一項包含 3 項研究的綜合分析檢視了生存終點與體重變化之間的關聯[89]。綜合估計並未顯示任何體重增加與整體死亡率（綜合 HR：1.03 [0.86, 1.19]）或結直腸癌特異性生存（HR：1.02 [0.84, 1.20]）之間的關聯[89]。然而，在個別研究中，較大的體重增加（絕對變化約 5 公斤或更多）與結直腸癌特異性生存[90, 91]和整體死亡率[90]之間的關聯最為明顯，無論是從診斷前到診斷後的變化，還是診斷後的變化[92]。儘管在該綜合分析中未進行總結，但在個別研究中，體重減輕與更高的死亡結果風險相關。隨後，在一個大型健康系統的結直腸癌患者隊列中，Meyerhardt 等人發現，診斷後體重減輕者的癌症特異性死亡風險（≥10%減少，HR：3.20 [2.33, 4.39]）和整體死亡率（HR：3.27 [2.56, 4.18]）更高[93]。 體重增加與結直腸癌生存之間的關聯幾乎為零（≥10% 增加 HR: 0.93 [0.63, 1.37]），但對整體死亡率則有提示性（HR: 1.20 [0.91–1.58]）。體重變化與結直腸癌生存之間的關係似乎比乳腺癌更為複雜，但顯示出較不明顯的凸形模式。
Among colorectal cancer survivors, a meta-analysis included 3 studies that examined the association between survival endpoints and weight change [89]. The pooled estimates did not suggest an association between any weight gain and overall mortality (pooled HR: 1.03 [0.86, 1.19]) or colorectal cancer-specific survival (HR: 1.02 [0.84, 1.20]) [89]. However, in individual studies, associations were most pronounced between larger weight gain (absolute change of around 5 kg or more) and colorectal cancer-specific survival [90, 91] and overall mortality [90] for pre- to post-diagnosis change, as well as overall mortality for post-diagnosis changes [92]. Although not summarized in that meta-analysis, weight loss in the individual studies was associated with a greater risk of mortality outcomes. Subsequently, in a large health system cohort of colorectal cancer patients, Meyerhardt et al. found a greater risk of cancer-specific death (≥10% loss, HR: 3.20 [2.33, 4.39]) and overall mortality (HR: 3.27 [2.56, 4.18]) among those who lost weight after diagnosis [93]. The association between weight gain and colorectal cancer survival was near-null (≥10% gain HR: 0.93 [0.63, 1.37]), but suggestive for overall mortality (HR: 1.20 [0.91–1.58]). The relationship between weight change and colorectal cancer survival seems to be somewhat more complex than for breast cancer, but indicates a less pronounced convex pattern.

影像學基於的身體組成測量
Imaging based measures of body composition

基於常規臨床影像的身體組成評估方法的出現徹底改變了這一研究領域[ 94, 95]。這些工具相較於人體測量法提供了許多優勢，包括不需要涉及人體測量數據的測量協議和後勤，或依賴不準確的自我報告數值。此外，組建足夠規模的隊列對於這類研究來說是高效且可行的，因為它們使用來自醫療記錄的現有影像[ 94]，因此不需要前瞻性招募。雖然這類研究擁有許多吸引人的特徵，但它們在理解癌症結果與身體組成之間的關係方面的實用性可能僅限於在診斷和治療過程中相關解剖區域的影像檢查是標準的惡性腫瘤。這些技術允許準確且可靠地量化皮下、內臟和肌內脂肪組織的量，以及骨骼肌組織。這些通常是從圍繞 L3 椎骨的單一影像中測量的橫截面面積（cm ² ）[ 94]。 這些數量有時以指數測量的方式表達，通過將橫截面面積除以平方身高來類似於 BMI [ 94]。除了數量外，脂肪組織和肌肉組織的質量也可以通過組織放射密度（以 Hounsfield 單位計）來計算。較高的脂肪組織放射密度表示脂肪細胞的脂質含量較少，並且可能有更多的炎症，而較低的肌肉放射密度則反映出在一定量的肌肉組織中脂肪浸潤較多，且肌肉細胞較少。
The advent of methods for body composition assessment based on routine clinical imaging has revolutionized this area of research [94, 95]. These tools offer a number of advantages over anthropometry including not requiring protocols and logistics involved with measurement of anthropometric data, or relying on inaccurate self-reported values. In addition, assembling cohorts of sufficient size is efficient and feasible for such investigations as they use existing images from the medical record [94] and so do not require prospective recruitment. While such studies possess a number of attractive features, their utility in understanding the relationship between cancer outcomes and body composition may be limited to malignancies where imaging in relevant anatomical regions is standard in the course of diagnosis and treatment. These techniques allow for accurate and reliable quantification of the amounts of subcutaneous, visceral, and intra-muscular adipose tissue, as well as skeletal muscle tissue. These are typically measured as cross-sectional areas (cm²) from a single image around the L3 vertebra [94]. These quantities are sometimes expressed as index measures by dividing cross-sectional area by squared height to resemble BMI [94]. In addition to quantity, adipose tissue and muscle tissue quality may also be calculated by a measure of tissue radiodensity (in Hounsfield units). Greater adipose tissue radiodensity indicates fat cells with less lipid content and potentially more inflammation, while lower muscle radiodensity reflects more fatty infiltration into a given quantity of muscle tissue, and fewer myocytes.

鄭等人的評論最近考慮了 203 項研究，涵蓋 10 個癌症部位，以尋找影像學測量脂肪組織量與癌症進展和生存之間的聯繫。根據納入的 128 份報告，作者報告了大多數癌症部位在所有脂肪組織量的測量（總量、內臟和皮下組織的面積或指數測量）中，總體風險比（HR）從適度到接近零 [83]。不考慮統計顯著性，還報告了一些暗示性的關聯：在乳腺癌中，觀察到皮下脂肪的整體死亡風險增加（合併 HR：1.36 [0.9, 2.05]），以及內臟脂肪的無進展生存期（HR：1.20 [0.4, 3.57]） [83]。有趣的是，在某些卵巢和前列腺癌的生存結果中，觀察到內臟或皮下脂肪的 HR 點估計低於零，儘管這些測量的置信區間跨越了零。作者引用了研究異質性和一些方法學限制作為所述不一致的可能因素。
The review by Cheng et al. recently considered 203 studies across 10 cancer sites for evidence linking imaging-based measures of adipose tissue quantity to cancer progression and survival. With the 128 reports included in the meta-analysis, the authors reported modest to near-null summary HRs across all measures of adipose tissue quantity (area or index measures of total, visceral, and subcutaneous tissue) for most cancer sites [83]. Without regard to statistical significance, a few suggestive associations were also reported: in breast cancer, a greater hazard of overall mortality was observed for subcutaneous fat (pooled HR: 1.36 [0.9, 2.05]), and for progression free survival for visceral fat (HR: 1.20 [0.4, 3.57]) [83]. Interestingly, HR point estimates below the null were observed for visceral or subcutaneous fat for some ovarian and prostate cancer survival outcomes, although the CI crossed the null for these measures. The authors cited study heterogeneity and some methodological limitations as possible factors for the noted inconsistencies.

脂肪組織的質量似乎也與死亡率有關，甚至獨立於脂肪組織的數量。在最近的一項結直腸癌患者研究中，內臟脂肪組織密度（VATD）和皮下脂肪組織密度（SATD）與整體死亡率呈正相關（每 8 HU 的 VAT：HR：1.21 [1.11, 1.32]；每 9 HU 的 SAT，HR：1.18 [1.11, 1.26]），對於結直腸癌死亡率也有類似的關聯[96]。另一份報告發現，在一組乳腺癌患者中，SATD 與更高的死亡率相關（高 SATD 值與中等 SATD 值相比，HR：1.45 [1.15, 1.81]），而 VAT 的關聯則較為溫和（高 VATD 與中等 VATD 相比，HR：1.16 [0.90, 1.50]）[97]。
Adipose tissue quality also seems to be related to mortality, even independent of adipose tissue quantity. In a recent study of colorectal cancer patients, visceral adipose tissue density (VATD) and subcutaneous adipose tissue density (SATD) were positively associated with overall mortality (per 8 HU in VAT: HR: 1.21 [1.11, 1.32]; per 9 HU in SAT, HR: 1.18 [1.11, 1.26]) with similar associations for colorectal cancer mortality [96]. Another report found that that SATD was associated with greater mortality among a cohort of breast cancer patients (high vs. mid SATD values, HR: 1.45 [1.15, 1.81]), while the association with VAT was more modest (high vs. mid VATD, HR: 1.16 [0.90, 1.50]) [97].

最近的一項回顧研究檢視了肌肉與癌症存活之間的關聯，並報告了一致的證據顯示低肌肉量與較差的存活率有關[ 98]。不幸的是，研究人群、方法學和其他因素的差異阻礙了對這些關聯的正式統合分析。通過骨骼肌放射密度評估的肌肉質量也逐漸成為一個重要的預後因素，幾項研究指出肌肉密度與死亡率之間存在反向關聯，有時與肌肉量無關[ 9, 99, 100, 101, 102]。
A recent review examined the association between muscle and cancer survival, and reported consistent evidence that low muscle quantity was related to poor survival [98]. Unfortunately, differences in study population, methodology, and other factors prevented a formal meta-analysis of these associations. Muscle quality, assessed by skeletal muscle radiodensity is also emerging as an important prognostic factor, with several studies noting inverse associations between muscle density and mortality, sometimes independent of quantity [9, 99,100,101,102].

討論  Discussion

生物學的合理性和流行病學證據的體積表明，身體組成與癌症生存之間存在聯繫，但仍然存在幾個問題。專注於 BMI 的報告一直不一致，有時對於體重狀態的建議與公共衛生官員對一般健康的推廣相矛盾。發現最佳 BMI 位於慢性疾病患者正常體重範圍的上限之上，被稱為“肥胖悖論”或“超重悖論”，這引發了激烈的爭議。然而，應該注意的是，在這一悖論中，J 形 BMI-死亡率曲線的最低點通常向右移動，而不是表明隨著 BMI 的增加風險單調下降（儘管後者已被觀察到）。選擇偏差被認為是這一悖論的罪魁禍首，但這種偏差關係可能必須是不合理的，才能使其成立。新興證據反而將測量誤差指向作為根本問題，因為 BMI 是一個不良的身體組成指標。 已經具體顯示，觀察到的死亡率曲線變化可能與脂肪和瘦體重的組成表達之間的對立關係一致，因此這些觀察結果並不像最初看起來那樣與一般信息相悖。事實上，一些研究人員已經提出將這一現象重新命名為“BMI 悖論”，以強調這種混淆是由於 BMI 作為脂肪量和分佈的相關測量的固有限制所驅動。對於腹部脂肪的中心測量，如腰圍（WC）和診斷後的體重增加，這些更精確的脂肪測量似乎更為一致，但這些指標的證據基礎相對較小。
Biological plausibility and volumes of epidemiological evidence suggest a link between body composition and cancer survival, but several issues remain. Reports focused on BMI have been inconsistent and sometimes suggest a contradictory message regarding weight status to what public health officials endorse for general health. The finding that the optimal BMI lies above the upper limit of the normal-weight range in those with chronic disease has been termed the “obesity paradox” or “overweight paradox” which has fueled a robust controversy [17, 103]. However, it should be noted that in this paradox, the nadir of the J-shaped BMI-mortality curve is often shifted to the right rather than suggesting a monotonic decrease in risk with greater BMI (although the latter has been observed). Selection bias has been suggested as the culprit for this paradox [17], but the biasing relationships may have to be unreasonable for this to be the case [104]. Emerging evidence has instead implicated measurement error as the underlying issue, as BMI is a poor metric of the putative aspects of body composition. It has specifically been shown that the observed shifts in the mortality curve may be consistent with opposing relationships between constituent expressions of fat and lean mass [105], and so these observations are not as contrary to general messaging as they might initially appear. In fact, some researchers have proposed this phenomena be re-named the “BMI paradox” to emphasize that the confusion is driven by BMI’s inherent limitations as a relevant measure of adiposity quantity and distribution [106]. Findings for central measures of adiposity, such as WC, and weight gain after diagnosis, which are more precise measures of adiposity, seem to be somewhat more consistent, but the evidence base for these metrics is relatively small.

基於影像的身體組成評估為研究臨床人群中不同脂肪和肌肉組織的多種特徵提供了令人興奮的機會。為了理解這些組織數量和質量指標之間的相互作用，身體組成的分析理想上應該將所有這些變量一起考慮，而不是以串行方式分析個別因素。脂肪與生存之間的矛盾或無關係常常被假設是由於與較高脂肪量相關的潛在保護因素，這些因素與較大的肌肉量有關[98]。事實上，最近對基於影像的脂肪和癌症生存的回顧指出，在研究中包含的 128 項研究中，只有 11 項在其個別分析中調整了肌肉，作者得出結論認為這可能導致報告之間的異質性[83]。考慮所有組織的同時性也得到了生物學的支持，因為我們對脂肪和肌肉之間相互關係的理解[49]。
Imaging-based body composition assessment offers an exciting opportunity to study multiple characteristics of different fat and muscle tissues in clinical populations. To understand the interplay between this myriad of tissue quantity and quality metrics, the analysis of body composition would ideally consider all of these variables together rather than analyzing individual factors in serial fashion. Paradoxical or null relationships between adiposity and survival are often hypothesized to result from potentially protective factors related to the greater muscle mass that tends to occur with higher fat mass [98]. In fact, the recent review of imaging based adiposity and cancer survival pointed out that only 11 of the 128 studies included in the study adjusted for muscle in their individual analyses, with the authors concluding that this potentially contributed to the noted heterogeneity across reports [83]. Simultaneous consideration of all tissues is also suggested by biology, given our understanding of the interrelationships between fat and muscle [49].

儘管基於影像的身體組成測量在該領域代表了一項重要的進展，但有幾點關於其解釋值得提及。基於 CT 的身體組成測量提供了對影像區域內脂肪和肌肉分佈的洞察。儘管這些指標與這些組織的總體積有很強的相關性，但它們並未量化確切的數量[107]。在基於影像的身體組成研究中，另一個持續考慮的問題是如何適當表達以橫截面面積測量的組織數量。雖然這並非標準，但研究人員通常會將面積測量按平方身高進行縮放，這與從體重和身高計算 BMI 的做法相似。這導致了內臟和脂肪組織指數（VATI 和 SATI，分別）以及骨骼肌指數（SMI）的測量。這一轉換的目標是創建與身高無關的身體組成數量測量。然而，在 BMI 計算中使用平方身高的做法是為了使得最終的基於體重的測量與身高無關，這並非沒有爭議[108]。 有趣的是，基於體重的身體組成測量，例如總瘦體重和總脂肪量，確實可以通過平方身高進行 BMI 風格的標準化。由此產生的指標，脂肪量指數（FMI）和瘦體重指數（LMI）具有加總為 BMI 的吸引特性，從而代表了對其組成組織區域的分解[109]。尚不清楚對個別基於面積的測量應用相同的標準化是否能達到相同的目標，其他縮放因子可能更為合適[110]。最終，基於面積和身高調整指數測量的不同用途可能會對文獻中關於脂肪和生存的變異性有所貢獻[83]。
Although imaging-based measures of body composition represent an important advancement in the field, some points regarding their interpretation bear mentioning. CT-based body composition measures provide insight into the distribution of fat and muscle in the regions being imaged. Although these metrics correlate strongly with total body volume of these tissues, they do not quantify the exact amount [107]. Another ongoing consideration in imaging-based body composition research is the appropriate expression of tissue quantity that is measured in cross-sectional areas. It has become common, although not standard, for researchers to scale area measures by squared height as in the practice of calculating BMI from weight and height. This results in measures of visceral and adipose tissue index (VATI and SATI, respectively), and skeletal muscle index (SMI). The goal of this transformation is to create measures of body composition quantity that are independent of stature. However, the use of squared height in the calculation of BMI was derived to make the resulting weight-based measure independent of height, which is not without controversy [108]. Interestingly, weight-based measures of body composition, such as total lean mass and total fat mass, do lend themselves to BMI-style normalization by squared height. The resulting metrics, fat mass index (FMI) and lean mass index (LMI) have the appealing property of summing to BMI, thus representing a decomposition into its constituent tissue compartments [109]. It is not clear that applying the same normalization to individual area-based measures achieves the same goal, and other scaling factors may be more appropriate [110]. Ultimately, different uses of area-based and height-adjusted index measures may contribute to the variations noted in the literature on adiposity and survival [83].

基於影像學模式的研究對臨床和流行病學研究提出了挑戰，其中一些已在放射學文獻中得到承認。然而，與癌症生存相關的身體組成的機會性評估有幾個特別相關的挑戰。由於這些指標是從僅在癌症診斷過程中獲得的影像中得出的，因此無法用來描述這些身體組成特徵在整個癌症過程中的關係。檢查身體組成與新發疾病之間的關聯將澄清它們與癌症亞型的病因或與診斷時疾病嚴重性相關的其他因素之間的關係。作為另一個後果，如果在診斷前需要對身體組成進行調整，研究人員仍然只能使用人類測量變數，通常是 BMI，這與專注於特定脂肪和肌肉特徵的重點不一致。此外，接受重複掃描的患者相對較少，至少在準確描述身體組成的縱向變化方面。 因此，利用重複身體組成評估的研究規模遠小於專注於基線值的研究 [ 87, 112]。此外，進行重複放射學測量的患者可能比未進行者更不容易出現較低階段的疾病 [ 87]，因此這類分析的結果可能無法普遍適用於所有癌症患者。
Research based on imaging modalities presents challenges to clinical and epidemiological research, some of which have been acknowledged in the radiology literature [111]. However, there are several specifically relevant to opportunistic assessments of body composition in connection with cancer survival. As these metrics are derived from images that are only obtained in the course of the cancer diagnosis, they are unable to be used to characterize the relationship between these body composition features across the entire cancer continuum. Examination of the associations between body composition and incident disease would clarify their relationship to the etiology of cancer subtypes or other factors related to disease severity at diagnosis. As another consequence, if adjustment for body composition before diagnosis is required, researchers are still relegated to the use of anthropometric variables, frequently BMI, which is discordant with the focus on specific fat and muscle characteristics. Furthermore, relatively few patients receive repeated scans, at least to the degree to accurately characterize longitudinal trajectories of body composition. Thus, studies that have utilized repeated body composition assessments have been much smaller than those focused on baseline values [87, 112]. In addition, those with repeated radiological measurements may tend to be less likely to have lower stage disease than those who do not [87], and so results of such analyses may not be generalizable to all cancer patients.

身體組成與癌症生存的領域正在迅速發展，臨床人群中可獲得詳細的組織評估。在設計對癌症倖存者有意義的干預措施時，調和來自各種評估方法的觀察性研究中有關身體組成的證據是一個持續的挑戰[ 95, 113]。雖然向更直接的身體組成測量轉變以進行生存研究是一個明顯的進步，但研究人員和臨床醫生應努力確定與公共健康指導方針一致且有意義的臨床目標。
The field of body composition and cancer survival is rapidly evolving with the availability of detailed tissue assessments in clinical populations. Reconciling evidence on body composition from observational studies across a broad array of assessment methodologies is an ongoing challenge when designing meaningful interventions for cancer survivors [95, 113]. While the shift toward more direct measures of body composition for survival research is a clear step forward, researchers and clinicians should to work to identify consistent and meaningful clinical targets that align with general public health guidelines.

參考文獻  References

1. Petrelli F, Cortellini A, Indini A, Tomasello G, Ghidini M, Nigro O, et al. 肥胖與癌症患者生存結果的關聯：系統性回顧與荟萃分析。JAMA Netw Open. 2021;4:e213520.
   Petrelli F, Cortellini A, Indini A, Tomasello G, Ghidini M, Nigro O, et al. Association of Obesity With Survival Outcomes in Patients With Cancer: A Systematic Review and Meta-analysis. JAMA Netw Open. 2021;4:e213520.Article PubMed PubMed Central Google Scholar 
2. 李燕，李超，吳剛，楊偉，王旭，段麗，等。結直腸癌患者的肥胖悖論：系統評價和元分析。營養評論。2022；80：1755–68。
   Li Y, Li C, Wu G, Yang W, Wang X, Duan L, et al. The obesity paradox in patients with colorectal cancer: a systematic review and meta-analysis. Nutr Rev. 2022;80:1755–68.Article PubMed Google Scholar 
3. Chan DSM, Vieira R, Abar L, Aune D, Balducci K, Cariolou M, et al. 乳腺癌診斷後的體脂肪、體重變化與預後：全球癌症更新計劃（CUP global）系統文獻回顧與元分析。國際癌症雜誌。2023;152:572–99。
   Chan DSM, Vieira R, Abar L, Aune D, Balducci K, Cariolou M, et al. Postdiagnosis body fatness, weight change and breast cancer prognosis: Global Cancer Update Program (CUP global) systematic literature review and meta-analysis. Int J Cancer. 2023;152:572–99.Article CAS PubMed Google Scholar 
4. Renehan AG, Zwahlen M, Egger M. 脂肪過多與癌症風險：來自流行病學的新機制見解。Nat Rev Cancer. 2015;15:484–98.
   Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer. 2015;15:484–98.Article CAS PubMed Google Scholar 
5. Pollak M. 胰島素和胰島素樣生長因子在腫瘤中的信號傳遞。Nat Rev Cancer. 2008;8:915–28.
   Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008;8:915–28.Article CAS PubMed Google Scholar 
6. Demark-Wahnefried W, Platz EA, Ligibel JA, Blair CK, Courneya KS, Meyerhardt JA, 等。肥胖在癌症生存和復發中的作用。癌症流行病學、生物標記與預防。2012;21:1244–59。
   Demark-Wahnefried W, Platz EA, Ligibel JA, Blair CK, Courneya KS, Meyerhardt JA, et al. The role of obesity in cancer survival and recurrence. Cancer Epidemiol Biomark Prev. 2012;21:1244–59.Article Google Scholar 
7. Parekh N, Chandran U, Bandera EV. 肥胖與癌症生存。營養年鑑。2012;32:311–42。
   Parekh N, Chandran U, Bandera EV. Obesity in cancer survival. Annu Rev Nutr. 2012;32:311–42.Article CAS PubMed Google Scholar 
8. Vucenik I, Stains JP. 肥胖與癌症風險：證據、機制與建議。紐約科學院年報。2012;1271:37–43。
   Vucenik I, Stains JP. Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann N. Y Acad Sci. 2012;1271:37–43.Article CAS PubMed PubMed Central Google Scholar 
9. Brown JC, Caan BJ, Prado CM, Weltzien E, Xiao J, Cespedes Feliciano EM, et al. 直腸癌患者的身體組成與心血管事件：一項基於人群的回顧性隊列研究。JAMA Oncol. 2019;5:967–72.
   Brown JC, Caan BJ, Prado CM, Weltzien E, Xiao J, Cespedes Feliciano EM, et al. Body Composition and Cardiovascular Events in Patients With Colorectal Cancer: A Population-Based Retrospective Cohort Study. JAMA Oncol. 2019;5:967–72.Article PubMed PubMed Central Google Scholar 
10. Cespedes Feliciano EM, Chen WY, Bradshaw PT, Prado CM, Alexeeff S, Albers KB, 等。乳腺癌倖存者的脂肪組織分佈與心血管疾病風險。J Clin Oncol. 2019;37:2528–36。
    Cespedes Feliciano EM, Chen WY, Bradshaw PT, Prado CM, Alexeeff S, Albers KB, et al. Adipose Tissue Distribution and Cardiovascular Disease Risk Among Breast Cancer Survivors. J Clin Oncol. 2019;37:2528–36.Article PubMed PubMed Central Google Scholar 
11. Greenlee H, Shi Z, Sardo Molmenti CL, Rundle A, Tsai WY. 癌症病史成人的肥胖盛行趨勢：來自 1997 年至 2014 年美國國家健康訪談調查的結果。J Clin Oncol. 2016;34:3133–40.
    Greenlee H, Shi Z, Sardo Molmenti CL, Rundle A, Tsai WY. Trends in Obesity Prevalence in Adults With a History of Cancer: Results From the US National Health Interview Survey, 1997 to 2014. J Clin Oncol. 2016;34:3133–40.Article PubMed PubMed Central Google Scholar 
12. Winkels RM, Snetselaar T, Adriaans A, van Warmerdam LJC, Vreugdenhil A, Slooter GD, 等。接受手術和輔助化療的結直腸癌患者體重變化：一項觀察性研究。癌症治療研究通訊。2016;9:111–5。
    Winkels RM, Snetselaar T, Adriaans A, van Warmerdam LJC, Vreugdenhil A, Slooter GD, et al. Changes in body weight in patients with colorectal cancer treated with surgery and adjuvant chemotherapy: An observational study. Cancer Treat Res Commun. 2016;9:111–5.Article Google Scholar 
13. van den Berg MM, Winkels RM, de Kruif JT, van Laarhoven HW, Visser M, de Vries JH 等。乳腺癌患者在化療期間的體重變化：一項元分析。BMC 癌症。2017;17:259。
    van den Berg MM, Winkels RM, de Kruif JT, van Laarhoven HW, Visser M, de Vries JH, et al. Weight change during chemotherapy in breast cancer patients: a meta-analysis. BMC Cancer. 2017;17:259.Article PubMed PubMed Central Google Scholar 
14. Snijder MB, van Dam RM, Visser M, Seidell JC。哪些體脂肪的方面特別危險，我們如何測量它們？國際流行病學雜誌。2006;35:83–92。
    Snijder MB, van Dam RM, Visser M, Seidell JC. What aspects of body fat are particularly hazardous and how do we measure them? Int J Epidemiol. 2006;35:83–92.Article CAS PubMed Google Scholar 
15. Prado CM, Gonzalez MC, Heymsfield SB。身體組成表型與肥胖悖論。當前臨床營養與代謝護理意見。2015;18:535–51。
    Prado CM, Gonzalez MC, Heymsfield SB. Body composition phenotypes and obesity paradox. Curr Opin Clin Nutr Metab Care. 2015;18:535–51.Article CAS PubMed Google Scholar 
16. Prado CM, Cushen SJ, Orsso CE, Ryan AM. 肌肉減少症和惡病質在肥胖時代的臨床和營養影響。Proc Nutr Soc. 2016;75:188–98.
    Prado CM, Cushen SJ, Orsso CE, Ryan AM. Sarcopenia and cachexia in the era of obesity: clinical and nutritional impact. Proc Nutr Soc. 2016;75:188–98.Article CAS PubMed Google Scholar 
17. Lajous M, Banack HR, Kaufman JS, Hernan MA. 患有慢性疾病的患者是否應該被告知增重？肥胖悖論與選擇偏差。美國醫學雜誌。2015;128:334–6.
    Lajous M, Banack HR, Kaufman JS, Hernan MA. Should patients with chronic disease be told to gain weight? The obesity paradox and selection bias. Am J Med. 2015;128:334–6.Article PubMed Google Scholar 
18. Iyengar NM, Hudis CA, Dannenberg AJ. 肥胖與癌症：局部和全身機制。年刊醫學。2015;66:297–309.
    Iyengar NM, Hudis CA, Dannenberg AJ. Obesity and cancer: local and systemic mechanisms. Annu Rev Med. 2015;66:297–309.Article CAS PubMed Google Scholar 
19. Zimmet PZ. 高胰島素血症——多麼無辜的旁觀者？糖尿病護理。1993;16:56–70.
    Zimmet PZ. Hyperinsulinemia-how innocent a bystander? Diabetes Care. 1993;16:56–70.Article PubMed Google Scholar 
20. Yu H, Rohan T. 胰島素樣生長因子家族在癌症發展和進展中的作用。國家癌症研究所雜誌。2000;92:1472–89.
    Yu H, Rohan T. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst. 2000;92:1472–89.Article CAS PubMed Google Scholar 
21. Wajchenberg BL. 皮下和內臟脂肪組織：它們與代謝症候群的關係。內分泌評論。2000;21:697–738。
    Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev. 2000;21:697–738.Article CAS PubMed Google Scholar 
22. Wackerhage H, Christensen JF, Ilmer M, von Luettichau I, Renz BW, Schonfelder M. 癌症兒茶酚胺難題。癌症趨勢。2022;8:110–22。
    Wackerhage H, Christensen JF, Ilmer M, von Luettichau I, Renz BW, Schonfelder M. Cancer catecholamine conundrum. Trends Cancer. 2022;8:110–22.Article CAS PubMed Google Scholar 
23. Green A, Rumberger JM, Stuart CA, Ruhoff MS. 腫瘤壞死因子-alpha 在 3T3-L1 脂肪細胞中對脂解的刺激是葡萄糖依賴的：對脂解長期調控的影響。糖尿病。2004;53:74–81。
    Green A, Rumberger JM, Stuart CA, Ruhoff MS. Stimulation of lipolysis by tumor necrosis factor-alpha in 3T3-L1 adipocytes is glucose dependent: implications for long-term regulation of lipolysis. Diabetes. 2004;53:74–81.Article CAS PubMed Google Scholar 
24. Roden M, Price TB, Perseghin G, Petersen KF, Rothman DL, Cline GW 等。自由脂肪酸引起的人類胰島素抵抗機制。臨床研究雜誌。1996;97:2859–65。
    Roden M, Price TB, Perseghin G, Petersen KF, Rothman DL, Cline GW, et al. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Investig. 1996;97:2859–65.Article CAS PubMed PubMed Central Google Scholar 
25. Kaaks R, Lukanova A。能量平衡與癌症：胰島素和胰島素樣生長因子-I 的角色。營養學會會議紀要。2001;60:91–106。
    Kaaks R, Lukanova A. Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proc Nutr Soc. 2001;60:91–106.Article CAS PubMed Google Scholar 
26. Blackburn GL, Waltman B. 肥胖與胰島素抵抗。在：A. McTiernan（編輯）。通過運動和體重控制進行癌症預防和管理，佛羅里達州博卡拉頓；CRC 出版社：2006 年。第 20 章，第 301–316 頁。
    Blackburn GL, Waltman B. Obesity and Insulin Resistance. In: A. McTiernan (ed). Cancer Prevention and Management Through Exercise and Weight Control, Boca Raton, FL; CRC Press: 2006. Ch. 20, p. 301–316.
27. Bruning PF, Bonfrer JM, van Noord PA, Hart AA, de Jong-Bakker M, Nooijen WJ. 胰島素抵抗與乳腺癌風險。國際癌症雜誌。1992；52：511–6。
    Bruning PF, Bonfrer JM, van Noord PA, Hart AA, de Jong-Bakker M, Nooijen WJ. Insulin resistance and breast-cancer risk. Int J Cancer. 1992;52:511–6.Article CAS PubMed Google Scholar 
28. Papa V, Belfiore A. 乳腺癌中的胰島素受體：生物學和臨床作用。內分泌學調查雜誌。1996；19：324–33。
    Papa V, Belfiore A. Insulin receptors in breast cancer: biological and clinical role. J Endocrinol Investig. 1996;19:324–33.Article CAS Google Scholar 
29. Papa V, Gliozzo B, Clark GM, McGuire WL, Moore D, Fujita-Yamaguchi Y, 等。胰島素樣生長因子-I 受體過度表達並預測人類乳腺癌的低風險。癌症研究。1993；53：3736–40。
    Papa V, Gliozzo B, Clark GM, McGuire WL, Moore D, Fujita-Yamaguchi Y, et al. Insulin-like growth factor-I receptors are overexpressed and predict a low risk in human breast cancer. Cancer Res. 1993;53:3736–40.CAS PubMed Google Scholar 
30. Walker GE, Verti B, Marzullo P, Savia G, Mencarelli M, Zurleni F 等。深層皮下脂肪組織：一種獨特的腹部脂肪儲存區。肥胖症。2007;15:1933–43。
    Walker GE, Verti B, Marzullo P, Savia G, Mencarelli M, Zurleni F, et al. Deep Subcutaneous Adipose Tissue: A Distinct Abdominal Adipose Depot. Obesity. 2007;15:1933–43.Article CAS PubMed Google Scholar 
31. Lundbom J, Hakkarainen A, Lundbom N, Taskinen MR。深層皮下脂肪組織的飽和度高於表層皮下脂肪組織。國際肥胖期刊（倫敦）。2013;37:620–2。
    Lundbom J, Hakkarainen A, Lundbom N, Taskinen MR. Deep subcutaneous adipose tissue is more saturated than superficial subcutaneous adipose tissue. Int J Obes (Lond). 2013;37:620–2.Article CAS PubMed Google Scholar 
32. Kelley DE, Thaete FL, Troost F, Huwe T, Goodpaster BH. 腹部皮下脂肪組織的細分與胰島素抵抗。美國生理學雜誌內分泌與代謝。2000;278:E941–8.
    Kelley DE, Thaete FL, Troost F, Huwe T, Goodpaster BH. Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance. Am J Physiol Endocrinol Metab. 2000;278:E941–8.Article CAS PubMed Google Scholar 
33. Bullo M, Garcia-Lorda P, Megias I, Salas-Salvado J. 全身性炎症、脂肪組織腫瘤壞死因子和瘦素表達。肥胖研究。2003;11:525–31.
    Bullo M, Garcia-Lorda P, Megias I, Salas-Salvado J. Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression. Obes Res. 2003;11:525–31.Article CAS PubMed Google Scholar 
34. Iyengar NM, Gucalp A, Dannenberg AJ, Hudis CA. 肥胖與癌症機制：腫瘤微環境與炎症。臨床腫瘤學雜誌。2016;34:4270–6.
    Iyengar NM, Gucalp A, Dannenberg AJ, Hudis CA. Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation. J Clin Oncol. 2016;34:4270–6.Article CAS PubMed PubMed Central Google Scholar 
35. van Kruijsdijk RC, van der Wall E, Visseren FL. 肥胖與癌症：功能失調的脂肪組織的角色。癌症流行病學、生物標記與預防。2009;18:2569–78.
    van Kruijsdijk RC, van der Wall E, Visseren FL. Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomark Prev. 2009;18:2569–78.Article Google Scholar 
36. Kelesidis I, Kelesidis T, Mantzoros CS. 脂聯素與癌症：系統性回顧。英國癌症雜誌。2006;94:1221–5。
    Kelesidis I, Kelesidis T, Mantzoros CS. Adiponectin and cancer: a systematic review. Br J Cancer. 2006;94:1221–5.Article CAS PubMed PubMed Central Google Scholar 
37. Preston-Martin S, Pike MC, Ross RK, Jones PA, Henderson BE. 細胞分裂增加作為人類癌症的原因。癌症研究。1990;50:7415–21。
    Preston-Martin S, Pike MC, Ross RK, Jones PA, Henderson BE. Increased cell division as a cause of human cancer. Cancer Res. 1990;50:7415–21.CAS PubMed Google Scholar 
38. Dickson RB, Stancel GM. 第 8 章：雌激素受體介導的正常和癌細胞過程。國家癌症研究所專刊。2000;2000:135–45。
    Dickson RB, Stancel GM. Chapter 8: Estrogen receptor-mediated processes in normal and cancer cells. J Natl Cancer Inst Monogr. 2000;2000:135–45.
39. Flototto T, Djahansouzi S, Glaser M, Hanstein B, Niederacher D, Brumm C, 等。激素和激素拮抗劑：在子宮內膜癌和乳腺癌致癌過程中的作用機制。激素代謝研究。2001;33:451–7。
    Flototto T, Djahansouzi S, Glaser M, Hanstein B, Niederacher D, Brumm C, et al. Hormones and hormone antagonists: mechanisms of action in carcinogenesis of endometrial and breast cancer. Horm Metab Res. 2001;33:451–7.Article CAS PubMed Google Scholar 
40. Judd HL, Shamonki IM, Frumar AM, Lagasse LD. 更年期後女性血清雌二醇的來源。婦產科學。1982;59:680–6。
    Judd HL, Shamonki IM, Frumar AM, Lagasse LD. Origin of serum estradiol in postmenopausal women. Obstet Gynecol. 1982;59:680–6.CAS PubMed Google Scholar 
41. Kaaks R, McTiernan A. 肥胖與性激素。在：A. McTiernan（編輯）。通過運動和體重控制進行癌症預防和管理，佛羅里達州博卡拉頓；CRC 出版社：2006 年。第 19 章，第 289–300 頁。
    Kaaks R, McTiernan A. Obesity and Sex Hormones. In: A. McTiernan (ed). Cancer Prevention and Management Through Exercise and Weight Control, Boca Raton, FL; CRC Press: 2006. Ch. 19, p. 289–300.
42. Key TJ, Allen NE, Verkasalo PK, Banks E. 能量平衡與癌症：性激素的角色。Proc Nutr Soc. 2001;60:81–9。
    Key TJ, Allen NE, Verkasalo PK, Banks E. Energy balance and cancer: the role of sex hormones. Proc Nutr Soc. 2001;60:81–9.Article CAS PubMed Google Scholar 
43. McTiernan A, Rajan KB, Tworoger SS, Irwin M, Bernstein L, Baumgartner R, 等。絕經後乳腺癌倖存者的脂肪量與性激素。J Clin Oncol. 2003;21:1961–6。
    McTiernan A, Rajan KB, Tworoger SS, Irwin M, Bernstein L, Baumgartner R, et al. Adiposity and sex hormones in postmenopausal breast cancer survivors. J Clin Oncol. 2003;21:1961–6.Article CAS PubMed Google Scholar 
44. Roy D, Liehr JG. 雌激素、DNA 損傷和突變。Mutat Res. 1999;424:107–15。
    Roy D, Liehr JG. Estrogen, DNA damage and mutations. Mutat Res. 1999;424:107–15.Article CAS PubMed Google Scholar 
45. Liehr JG. 雌二醇是一種基因毒性突變致癌物嗎？內分泌評論。2000；21：40–54。
    Liehr JG. Is estradiol a genotoxic mutagenic carcinogen? Endocr Rev. 2000;21:40–54.CAS PubMed Google Scholar 
46. Lee K, Kruper L, Dieli-Conwright CM, Mortimer JE. 肥胖對乳腺癌診斷和治療的影響。當前腫瘤學報告。2019;21:41。
    Lee K, Kruper L, Dieli-Conwright CM, Mortimer JE. The Impact of Obesity on Breast Cancer Diagnosis and Treatment. Curr Oncol Rep. 2019;21:41.Article PubMed PubMed Central Google Scholar 
47. Kelly DM, Jones TH. 睪酮與肥胖。肥胖評論。2015;16:581–606。
    Kelly DM, Jones TH. Testosterone and obesity. Obes Rev. 2015;16:581–606.Article CAS PubMed Google Scholar 
48. Olivas A, Price RS. 肥胖、炎症與晚期前列腺癌。營養與癌症。2021;73:2232–48。
    Olivas A, Price RS. Obesity, Inflammation, and Advanced Prostate Cancer. Nutr Cancer. 2021;73:2232–48.Article CAS PubMed Google Scholar 
49. Kirk B, Feehan J, Lombardi G, Duque G. 肌肉、骨骼與脂肪的相互作用：肌肉因子、骨因子和脂肪因子的生物學角色。當前骨質疏鬆報告。2020;18:388–400。
    Kirk B, Feehan J, Lombardi G, Duque G. Muscle, Bone, and Fat Crosstalk: the Biological Role of Myokines, Osteokines, and Adipokines. Curr Osteoporos Rep. 2020;18:388–400.Article PubMed Google Scholar 
50. Eckel J. 肌肉因子在代謝穩態和糖尿病中的作用。糖尿病學。2019;62:1523–8。
    Eckel J. Myokines in metabolic homeostasis and diabetes. Diabetologia. 2019;62:1523–8.Article CAS PubMed Google Scholar 
51. Ivy JL. 運動訓練在預防和治療胰島素抵抗及非胰島素依賴型糖尿病中的作用。運動醫學。1997;24:321–36。
    Ivy JL. Role of exercise training in the prevention and treatment of insulin resistance and non-insulin-dependent diabetes mellitus. Sports Med. 1997;24:321–36.Article CAS PubMed Google Scholar 
52. Goodyear LJ, Kahn BB. 運動、葡萄糖運輸和胰島素敏感性。年刊醫學。1998;49:235–61。
    Goodyear LJ, Kahn BB. Exercise, glucose transport, and insulin sensitivity. Annu Rev Med. 1998;49:235–61.Article CAS PubMed Google Scholar 
53. Booth FW, Gordon SE, Carlson CJ, Hamilton MT. 對抗現代慢性疾病的戰爭：通過運動生物學進行的主要預防。應用生理學雜誌。2000;88:774–87。
    Booth FW, Gordon SE, Carlson CJ, Hamilton MT. Waging war on modern chronic diseases: primary prevention through exercise biology. J Appl Physiol. 2000;88:774–87.Article CAS PubMed Google Scholar 
54. Borghouts LB, Keizer HA。運動與胰島素敏感性：一篇綜述。國際運動醫學雜誌。2000；21：1–12。
    Borghouts LB, Keizer HA. Exercise and insulin sensitivity: a review. Int J Sports Med. 2000;21:1–12.Article CAS PubMed Google Scholar 
55. Perez-Martin A, Raynaud E, Mercier J。肌肉中的胰島素抵抗及相關的代謝異常：運動的影響。肥胖評論。2001；2：47–59。
    Perez-Martin A, Raynaud E, Mercier J. Insulin resistance and associated metabolic abnormalities in muscle: effects of exercise. Obes Rev. 2001;2:47–59.Article CAS PubMed Google Scholar 
56. Roden M。自由脂肪酸如何抑制人類骨骼肌中的葡萄糖利用。新生理科學。2004；19：92–96。
    Roden M. How free fatty acids inhibit glucose utilization in human skeletal muscle. N Physiol Sci. 2004;19:92–96.CAS Google Scholar 
57. McCarty MF。上調 IGF 結合蛋白-1 作為抗癌策略：與熱量限制、運動和胰島素敏感性的相關性。醫學假說。1997；48：297–308。
    McCarty MF. Up-regulation of IGF binding protein-1 as an anticarcinogenic strategy: relevance to caloric restriction, exercise, and insulin sensitivity. Med Hypotheses. 1997;48:297–308.Article CAS PubMed Google Scholar 
58. 艾倫 NE, 蘋果比 PN, 卡克斯 R, 瑞納爾迪 S, 戴維 GK, 基伊 TJ。英國女性血清胰島素樣生長因子-I (IGF-I)、C-肽和激素結合蛋白水平的生活方式決定因素。癌症原因與控制。2003;14:65–74。
    Allen NE, Appleby PN, Kaaks R, Rinaldi S, Davey GK, Key TJ. Lifestyle determinants of serum insulin-like growth-factor-I (IGF-I), C-peptide and hormone binding protein levels in British women. Cancer Causes Control. 2003;14:65–74.Article PubMed Google Scholar 
59. Yee D, Paik S, Lebovic GS, Marcus RR, Favoni RE, Cullen KJ 等人。對胰島素樣生長因子 I 基因表達在惡性腫瘤中的分析：在人體乳腺癌中證據顯示其具有旁分泌作用。分子內分泌學。1989;3:509–17。
    Yee D, Paik S, Lebovic GS, Marcus RR, Favoni RE, Cullen KJ, et al. Analysis of insulin-like growth factor I gene expression in malignancy: evidence for a paracrine role in human breast cancer. Mol Endocrinol. 1989;3:509–17.Article CAS PubMed Google Scholar 
60. Fair AM, Dai Q, Shu XO, Matthews CE, Yu H, Jin F 等人。能量平衡、胰島素抵抗生物標誌物與乳腺癌風險。癌症檢測與預防。2007;31:214–9。
    Fair AM, Dai Q, Shu XO, Matthews CE, Yu H, Jin F, et al. Energy balance, insulin resistance biomarkers, and breast cancer risk. Cancer Detect Prev. 2007;31:214–9.Article CAS PubMed PubMed Central Google Scholar 
61. McTiernan A, Ulrich C, Slate S, Potter J。身體活動與癌症病因：關聯與機制。癌症原因與控制。1998;9:487–509。
    McTiernan A, Ulrich C, Slate S, Potter J. Physical activity and cancer etiology: associations and mechanisms. Cancer Causes Control. 1998;9:487–509.Article CAS PubMed Google Scholar 
62. Wetmore CM, Ulrich CM。將身體活動與癌症發生率聯繫起來的機制：運動與免疫功能。在：A. McTiernan（編）。通過運動和體重控制進行癌症預防與管理，佛羅里達州博卡拉頓；CRC 出版社：2006 年。第 9 章，第 157–176 頁。
    Wetmore CM, Ulrich CM. Mechanisms Associating Physical Activity with Cancer Incidence: Exercise and Immune Function. In: A. McTiernan (ed). Cancer Prevention and Management Through Exercise and Weight Control, Boca Raton, FL; CRC Press: 2006. Ch. 9, p. 157–176.
63. Hojman P. 運動透過調節免疫功能和炎症來保護免受癌症的影響。生物化學學會轉譯。2017;45:905–11。
    Hojman P. Exercise protects from cancer through regulation of immune function and inflammation. Biochem Soc Trans. 2017;45:905–11.Article CAS PubMed Google Scholar 
64. Aversa Z, Costelli P, Muscaritoli M. 癌症引起的肌肉消耗：預防和治療的最新發現。醫學腫瘤學進展。2017;9:369–82。
    Aversa Z, Costelli P, Muscaritoli M. Cancer-induced muscle wasting: latest findings in prevention and treatment. Ther Adv Med Oncol. 2017;9:369–82.Article PubMed PubMed Central Google Scholar 
65. von Haehling S, Morley JE, Anker SD. 衰弱症概述：流行率和臨床影響的事實與數據。肌肉消耗衰弱症學報。2010;1:129–33。
    von Haehling S, Morley JE, Anker SD. An overview of sarcopenia: facts and numbers on prevalence and clinical impact. J Cachexia Sarcopenia Muscle. 2010;1:129–33.Article Google Scholar 
66. Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, 等。呼吸道和消化道實體腫瘤患者中肌少症肥胖的流行率及臨床意義：一項基於人群的研究。柳葉刀腫瘤學。2008;9:629–35。
    Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. lancet Oncol. 2008;9:629–35.Article PubMed Google Scholar 
67. Prado CM, Wells JC, Smith SR, Stephan BC, Siervo M. 骨骼肌減少性肥胖：對當前證據的批判性評估。Clin Nutr. 2012;31:583–601.
    Prado CM, Wells JC, Smith SR, Stephan BC, Siervo M. Sarcopenic obesity: A Critical appraisal of the current evidence. Clin Nutr. 2012;31:583–601.Article CAS PubMed Google Scholar 
68. Lu CW, Yang KC, Chang HH, Lee LT, Chen CY, Huang KC。肌肉減少性肥胖與代謝症候群密切相關。Obes Res Clin Pr. 2013;7:e301–7。
    Lu CW, Yang KC, Chang HH, Lee LT, Chen CY, Huang KC. Sarcopenic obesity is closely associated with metabolic syndrome. Obes Res Clin Pr. 2013;7:e301–7.Article Google Scholar 
69. Batsis JA, Villareal DT。老年人的肌肉減少性肥胖：病因、流行病學和治療策略。Nat Rev Endocrinol. 2018;14:513–37。
    Batsis JA, Villareal DT. Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies. Nat Rev Endocrinol. 2018;14:513–37.Article PubMed PubMed Central Google Scholar 
70. 世界衛生組織。肥胖：預防和管理全球流行病。世界衛生組織技術報告系列。2000;894:1–253。
    World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:1–253.Google Scholar 
71. Gallagher D, Visser M, Sepulveda D, Pierson RN, Harris T, Heymsfield SB。身體質量指數在不同年齡、性別和族群之間比較身體脂肪的實用性如何？Am J Epidemiol. 1996;143:228–39。
    Gallagher D, Visser M, Sepulveda D, Pierson RN, Harris T, Heymsfield SB. How useful is body mass index for comparison of body fatness across age, sex, and ethnic groups? Am J Epidemiol. 1996;143:228–39.Article CAS PubMed Google Scholar 
72. Okorodudu DO, Jumean MF, Montori VM, Romero-Corral A, Somers VK, Erwin PJ 等。體重指數在識別由身體脂肪定義的肥胖方面的診斷性能：系統評價和元分析。國際肥胖雜誌（倫敦）。2010；34：791–9。
    Okorodudu DO, Jumean MF, Montori VM, Romero-Corral A, Somers VK, Erwin PJ, et al. Diagnostic performance of body mass index to identify obesity as defined by body adiposity: a systematic review and meta-analysis. Int J Obes (Lond). 2010;34:791–9.Article CAS PubMed Google Scholar 
73. Shah NR, Braverman ER。測量患者的脂肪量：體重指數（BMI）、體脂百分比和瘦素的實用性。PloS ONE。2012；7：e33308。
    Shah NR, Braverman ER. Measuring adiposity in patients: the utility of body mass index (BMI), percent body fat, and leptin. PloS ONE. 2012;7:e33308.Article CAS PubMed PubMed Central Google Scholar 
74. Gonzalez MC, Pastore CA, Orlandi SP, Heymsfield SB。癌症中的肥胖悖論：身體組成提供的新見解。美國臨床營養學雜誌。2014；99：999–1005。
    Gonzalez MC, Pastore CA, Orlandi SP, Heymsfield SB. Obesity paradox in cancer: new insights provided by body composition. Am J Clin Nutr. 2014;99:999–1005.Article CAS PubMed Google Scholar 
75. Kim LH, Doan P, He Y, Lau HM, Pleass H, Patel MI。關於體重指數對腎癌結果影響的系統評價與元分析。J Urol。2021；205：346–55。
    Kim LH, Doan P, He Y, Lau HM, Pleass H, Patel MI. A Systematic Review and Meta-Analysis of the Significance of Body Mass Index on Kidney Cancer Outcomes. J Urol. 2021;205:346–55.Article PubMed Google Scholar 
76. Hollander D, Kampman E, van Herpen CM。治療前體重指數與頭頸癌結果的關係：文獻回顧。Crit Rev Oncol Hematol。2015；96：328–38。
    Hollander D, Kampman E, van Herpen CM. Pretreatment body mass index and head and neck cancer outcome: A review of the literature. Crit Rev Oncol Hematol. 2015;96:328–38.Article PubMed Google Scholar 
77. Molarius A, Seidell JC。腹部肥胖分類的人體測量指標選擇——一項批判性回顧。Int J Obes Relat Metab Disord。1998；22：719–27。
    Molarius A, Seidell JC. Selection of anthropometric indicators for classification of abdominal fatness-a critical review. Int J Obes Relat Metab Disord. 1998;22:719–27.Article CAS PubMed Google Scholar 
78. Lean ME, Han TS, Morrison CE。腰圍作為指示需要進行體重管理的衡量標準。BMJ。1995；311：158–61。
    Lean ME, Han TS, Morrison CE. Waist circumference as a measure for indicating need for weight management. BMJ. 1995;311:158–61.Article CAS PubMed PubMed Central Google Scholar 
79. Mahmoud I, Al-Wandi AS, Gharaibeh SS, Mohamed SA。肥胖的人體測量指標之間的一致性和相關性：系統性回顧。《公共衛生》。2021；198：301–6。
    Mahmoud I, Al-Wandi AS, Gharaibeh SS, Mohamed SA. Concordances and correlations between anthropometric indices of obesity: a systematic review. Public Health. 2021;198:301–6.Article CAS PubMed Google Scholar 
80. Hu FB。第 5 章：脂肪和身體組成的測量。在：Frank Hu 編輯。《肥胖流行病學》。https://doi.org/10.1093/acprof:oso/9780195312911.003.0005 0 紐約：牛津大學出版社；2008。
    Hu FB. Ch 5: Measurements of Adiposity and Body Composition. In: Frank Hu, editor. Obesity Epidemiology. https://doi.org/10.1093/acprof:oso/9780195312911.003.0005 0 New York: Oxford University Press; 2008.
81. Goodpaster BH, Thaete FL, Simoneau JA, Kelley DE。皮下腹部脂肪和大腿肌肉組成獨立於內臟脂肪預測胰島素敏感性。《糖尿病》。1997；46：1579–85。
    Goodpaster BH, Thaete FL, Simoneau JA, Kelley DE. Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes. 1997;46:1579–85.Article CAS PubMed Google Scholar 
82. Dulloo AG, Jacquet J, Solinas G, Montani JP, Schutz Y. 體組成表型在肥胖和代謝綜合症途徑中的作用。國際肥胖雜誌 (倫敦)。2010;34:S4–17。
    Dulloo AG, Jacquet J, Solinas G, Montani JP, Schutz Y. Body composition phenotypes in pathways to obesity and the metabolic syndrome. Int J Obes (Lond). 2010;34:S4–17.Article PubMed Google Scholar 
83. Cheng E, Kirley J, Cespedes Feliciano EM, Caan BJ. 脂肪量與癌症生存率：系統評價與荟萃分析。癌症成因與控制。2022;33:1219–46。
    Cheng E, Kirley J, Cespedes Feliciano EM, Caan BJ. Adiposity and cancer survival: a systematic review and meta-analysis. Cancer Causes Control. 2022;33:1219–46.Article PubMed PubMed Central Google Scholar 
84. Deng T, Lyon CJ, Bergin S, Caligiuri MA, Hsueh WA. 肥胖、炎症與癌症。病理年鑑。2016;11:421–49。
    Deng T, Lyon CJ, Bergin S, Caligiuri MA, Hsueh WA. Obesity, Inflammation, and Cancer. Annu Rev Pathol. 2016;11:421–49.Article CAS PubMed Google Scholar 
85. Tahrani AA, Morton J. 體重減輕 10%或更多對超重或肥胖患者的好處：一項回顧。肥胖 (銀泉)。2022;30:802–40。
    Tahrani AA, Morton J. Benefits of weight loss of 10% or more in patients with overweight or obesity: A review. Obes (Silver Spring). 2022;30:802–40.Article Google Scholar 
86. Stevens J, Truesdale KP, McClain JE, Cai J. 體重維持的定義。國際肥胖期刊（倫敦）。2006;30:391–9。
    Stevens J, Truesdale KP, McClain JE, Cai J. The definition of weight maintenance. Int J Obes (Lond). 2006;30:391–9.Article CAS PubMed Google Scholar 
87. Brown JC, Caan BJ, Cespedes Feliciano EM, Xiao J, Weltzien E, Prado CM, 等。體重穩定掩蓋結腸直腸癌中的身體組成變化：一項回顧性隊列研究。美國臨床營養學雜誌。2021;113:1482–9。
    Brown JC, Caan BJ, Cespedes Feliciano EM, Xiao J, Weltzien E, Prado CM, et al. Weight stability masks changes in body composition in colorectal cancer: a retrospective cohort study. Am J Clin Nutr. 2021;113:1482–9.Article CAS PubMed PubMed Central Google Scholar 
88. Playdon MC, Bracken MB, Sanft TB, Ligibel JA, Harrigan M, Irwin ML。乳腺癌診斷後的體重增加與全因死亡率：系統評價與荟萃分析。國家癌症研究所雜誌。2015;107:djv275。
    Playdon MC, Bracken MB, Sanft TB, Ligibel JA, Harrigan M, Irwin ML. Weight Gain After Breast Cancer Diagnosis and All-Cause Mortality: Systematic Review and Meta-Analysis. J Natl Cancer Inst. 2015;107:djv275.
89. Otto SJ, Korfage IJ, Polinder S, van der Heide A, de Vries E, Rietjens JA, 等。身體活動和體重變化與結腸直腸癌的生活質量和死亡率的關聯：系統評價與荟萃分析。支持性癌症護理。2015;23:1237–50。
    Otto SJ, Korfage IJ, Polinder S, van der Heide A, de Vries E, Rietjens JA, et al. Association of change in physical activity and body weight with quality of life and mortality in colorectal cancer: a systematic review and meta-analysis. Support Care Cancer. 2015;23:1237–50.Article CAS PubMed Google Scholar 
90. Baade PD, Meng X, Youl PH, Aitken JF, Dunn J, Chambers SK。身體質量指數和身體活動對澳大利亞昆士蘭州結直腸癌患者死亡率的影響。癌症流行病學、生物標記與預防。2011;20:1410–20。
    Baade PD, Meng X, Youl PH, Aitken JF, Dunn J, Chambers SK. The impact of body mass index and physical activity on mortality among patients with colorectal cancer in Queensland, Australia. Cancer Epidemiol Biomark Prev. 2011;20:1410–20.Article Google Scholar 
91. Campbell PT, Newton CC, Dehal AN, Jacobs EJ, Patel AV, Gapstur SM。身體質量指數對結直腸癌診斷後生存的影響：癌症預防研究-II 營養隊列。臨床腫瘤學雜誌。2012;30:42–52。
    Campbell PT, Newton CC, Dehal AN, Jacobs EJ, Patel AV, Gapstur SM. Impact of body mass index on survival after colorectal cancer diagnosis: the Cancer Prevention Study-II Nutrition Cohort. J Clin Oncol. 2012;30:42–52.Article PubMed Google Scholar 
92. Meyerhardt JA, Niedzwiecki D, Hollis D, Saltz LB, Mayer RJ, Nelson H 等。治療後身體質量指數和體重變化對 III 期結腸癌患者癌症復發和生存的影響：來自癌症和白血病小組 B 89803 的研究結果。臨床腫瘤學雜誌。2008;26:4109–15。
    Meyerhardt JA, Niedzwiecki D, Hollis D, Saltz LB, Mayer RJ, Nelson H, et al. Impact of body mass index and weight change after treatment on cancer recurrence and survival in patients with stage III colon cancer: findings from Cancer and Leukemia Group B 89803. J Clin Oncol. 2008;26:4109–15.Article PubMed PubMed Central Google Scholar 
93. Meyerhardt JA, Kroenke CH, Prado CM, Kwan ML, Castillo A, Weltzien E 等。結直腸癌診斷後體重變化與加州北部凱薩醫療保健人群結果的關聯。癌症流行病學、生物標記與預防。2017;26:30–7。
    Meyerhardt JA, Kroenke CH, Prado CM, Kwan ML, Castillo A, Weltzien E, et al. Association of Weight Change after Colorectal Cancer Diagnosis and Outcomes in the Kaiser Permanente Northern California Population. Cancer Epidemiol Biomark Prev. 2017;26:30–7.Article Google Scholar 
94. Mourtzakis M, Prado CM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE。使用在常規護理中獲得的計算機斷層掃描圖像對癌症患者的身體組成進行量化的一種實用而精確的方法。應用生理學、營養學與新陳代謝。2008;33:997–1006。
    Mourtzakis M, Prado CM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab. 2008;33:997–1006.Article PubMed Google Scholar 
95. Brown JC, Cespedes Feliciano EM, Caan BJ。腫瘤學中身體組成的演變——流行病學、臨床試驗及患者護理的未來：事實與數字。肌肉消耗與肌肉萎縮雜誌。2018;9:1200–8。
    Brown JC, Cespedes Feliciano EM, Caan BJ. The evolution of body composition in oncology-epidemiology, clinical trials, and the future of patient care: facts and numbers. J Cachexia Sarcopenia Muscle. 2018;9:1200–8.Article PubMed Google Scholar 
96. Feliciano EMC, Winkels RM, Meyerhardt JA, Prado CM, Afman LA, Caan BJ。腹部脂肪組織的放射密度與結直腸癌的生存率相關。美國臨床營養學雜誌。2021;114:1917–24。
    Feliciano EMC, Winkels RM, Meyerhardt JA, Prado CM, Afman LA, Caan BJ. Abdominal adipose tissue radiodensity is associated with survival after colorectal cancer. Am J Clin Nutr. 2021;114:1917–24.Article PubMed PubMed Central Google Scholar 
97. Cheng E, Caan BJ, Chen WY, Irwin ML, Prado CM, Cespedes Feliciano EM. 脂肪組織放射密度與非轉移性乳腺癌患者的死亡率。臨床營養學。2022;41:2607–13。
    Cheng E, Caan BJ, Chen WY, Irwin ML, Prado CM, Cespedes Feliciano EM. Adipose tissue radiodensity and mortality among patients with nonmetastatic breast cancer. Clin Nutr. 2022;41:2607–13.Article CAS PubMed PubMed Central Google Scholar 
98. Cespedes Feliciano EM, Kroenke CH, Caan BJ. 癌症中的肥胖悖論：肌肉有多重要？營養年鑑。2018;38:357–79。
    Cespedes Feliciano EM, Kroenke CH, Caan BJ. The Obesity Paradox in Cancer: How Important Is Muscle? Annu Rev Nutr. 2018;38:357–79.Article CAS PubMed Google Scholar 
99. Sjoblom B, Gronberg BH, Wentzel-Larsen T, Baracos VE, Hjermstad MJ, Aass N, 等。骨骼肌放射密度對晚期非小細胞肺癌患者的生存預後具有預測性。臨床營養學。2016;35:1386–93。
    Sjoblom B, Gronberg BH, Wentzel-Larsen T, Baracos VE, Hjermstad MJ, Aass N, et al. Skeletal muscle radiodensity is prognostic for survival in patients with advanced non-small cell lung cancer. Clin Nutr. 2016;35:1386–93.Article PubMed Google Scholar 
100. Kroenke CH, Prado CM, Meyerhardt JA, Weltzien EK, Xiao J, Cespedes Feliciano EM, 等。肌肉放射密度與結直腸癌患者的死亡率。癌症。2018;124:3008–15。
     Kroenke CH, Prado CM, Meyerhardt JA, Weltzien EK, Xiao J, Cespedes Feliciano EM, et al. Muscle radiodensity and mortality in patients with colorectal cancer. Cancer. 2018;124:3008–15.Article PubMed Google Scholar 
101. Vrieling A, Kampman E, Knijnenburg NC, Mulders PF, Sedelaar JPM, Baracos VE 等。身體組成與腎細胞癌臨床結果的關係：系統評價與荟萃分析。歐洲泌尿學焦點。2018;4:420–34。
     Vrieling A, Kampman E, Knijnenburg NC, Mulders PF, Sedelaar JPM, Baracos VE, et al. Body Composition in Relation to Clinical Outcomes in Renal Cell Cancer: A Systematic Review and Meta-analysis. Eur Urol Focus. 2018;4:420–34.Article PubMed Google Scholar 
102. Maurits JSF, Sedelaar JPM, Mulders PFA, Aben KKH, Kiemeney L, Vrieling A。骨骼肌放射密度和內臟脂肪組織指數與腎細胞癌的生存率相關——一項多中心基於人群的隊列研究。臨床營養。2022;41:131–43。
     Maurits JSF, Sedelaar JPM, Mulders PFA, Aben KKH, Kiemeney L, Vrieling A. Skeletal muscle radiodensity and visceral adipose tissue index are associated with survival in renal cell cancer—A multicenter population-based cohort study. Clin Nutr. 2022;41:131–43.Article PubMed Google Scholar 
103. Stevens J, Bradshaw PT, Truesdale KP, Jensen MD。肥胖悖論不應干擾公共衛生努力。國際肥胖期刊。2015;39:80–1。
     Stevens J, Bradshaw PT, Truesdale KP, Jensen MD. Obesity Paradox should not interfere with public health efforts. Int J Obes. 2015;39:80–1.Article CAS Google Scholar 
104. Glymour MM, Vittinghoff E。評論：選擇偏差作為肥胖悖論的解釋：僅僅因為它是可能的並不意味著它是合理的。流行病學。2014;25:4–6。
     Glymour MM, Vittinghoff E. Commentary: Selection bias as an explanation for the obesity paradox: just because it’s possible doesn’t mean it’s plausible. Epidemiology. 2014;25:4–6.Article PubMed Google Scholar 
105. Bradshaw PT, Zevallos JP, Wisniewski K, Olshan AF。貝葉斯敏感性分析將身體質量指數劃分為身體組成的組成部分：應用於頭頸癌生存率。美國流行病學雜誌。2019；188：2031–9。
     Bradshaw PT, Zevallos JP, Wisniewski K, Olshan AF. A Bayesian Sensitivity Analysis to Partition Body Mass Index Into Components of Body Composition: An Application to Head and Neck Cancer Survival. Am J Epidemiol. 2019;188:2031–9.Article PubMed PubMed Central Google Scholar 
106. Caan BJ, Cespedes Feliciano EM, Kroenke CH。身體組成在解釋癌症中的超重悖論的重要性——反方觀點。癌症研究。2018；78：1906–12。
     Caan BJ, Cespedes Feliciano EM, Kroenke CH. The Importance of Body Composition in Explaining the Overweight Paradox in Cancer-Counterpoint. Cancer Res. 2018;78:1906–12.Article CAS PubMed PubMed Central Google Scholar 
107. MacDonald AJ, Greig CA, Baracos V。橫斷面身體組成分析的優勢和局限性。當前支持性和緩和醫療意見。2011；5：342–9。
     MacDonald AJ, Greig CA, Baracos V. The advantages and limitations of cross-sectional body composition analysis. Curr Opin Support Palliat Care. 2011;5:342–9.Article PubMed Google Scholar 
108. 多元族群合作組。體重-身高關係和身體質量指數：來自多元族群合作的觀察。美國人類學雜誌。2005；128：220–9。
     Diverse Populations Collaborative, G. Weight-height relationships and body mass index: some observations from the Diverse Populations Collaboration. Am J Phys Anthropol. 2005;128:220–9.Article Google Scholar 
109. Kyle UG, Schutz Y, Dupertuis YM, Pichard C. 身體組成解釋。無脂肪質量指數和體脂質量指數的貢獻。營養學。2003;19:597–604。
     Kyle UG, Schutz Y, Dupertuis YM, Pichard C. Body composition interpretation. Contributions of the fat-free mass index and the body fat mass index. Nutrition. 2003;19:597–604.Article PubMed Google Scholar 
110. Brown JC, Heymsfield SB, Caan BJ. 將計算機斷層掃描的身體組成與身高進行標定：在結直腸癌患者中身高標準化指數的相關性。肌肉消耗症與肌肉雜誌。2022;13:203–9。
     Brown JC, Heymsfield SB, Caan BJ. Scaling of computed tomography body composition to height: relevance of height‐normalized indices in patients with colorectal cancer. J Cachexia Sarcopenia Muscle. 2022;13:203–9.Article PubMed Google Scholar 
111. Dewey M, Bosserdt M, Dodd JD, Thun S, Kressel HY. 臨床影像研究：更高的證據、全球合作、改善報告和數據共享是重大挑戰。放射學。2019;291:547–52。
     Dewey M, Bosserdt M, Dodd JD, Thun S, Kressel HY. Clinical Imaging Research: Higher Evidence, Global Collaboration, Improved Reporting, and Data Sharing Are the Grand Challenges. Radiology. 2019;291:547–52.Article PubMed Google Scholar 
112. Cooper AB, Slack R, Fogelman D, Holmes HM, Petzel M, Parker N 等。描述在可切除胰腺癌的術前治療期間發生的人體測量變化。《外科腫瘤學年鑑》。2015;22:2416–23。
     Cooper AB, Slack R, Fogelman D, Holmes HM, Petzel M, Parker N, et al. Characterization of Anthropometric Changes that Occur During Neoadjuvant Therapy for Potentially Resectable Pancreatic Cancer. Ann Surg Oncol. 2015;22:2416–23.Article PubMed Google Scholar 
113. Anderson AS, Martin RM, Renehan AG, Cade J, Copson ER, Cross AJ 等。癌症生存、過多體脂肪和減重干預——到 2020 年我們在哪裡？《英國癌症雜誌》。2021;124:1057–65。
     Anderson AS, Martin RM, Renehan AG, Cade J, Copson ER, Cross AJ, et al. Cancer survivorship, excess body fatness and weight-loss intervention-where are we in 2020? Br J Cancer. 2021;124:1057–65.Article PubMed Google Scholar