Leptin and Soluble Leptin Receptor in Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition Cohort
Leptin and Soluble Leptin Receptor in Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition Cohort
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DOI：
10.1158/0008-5472.can-12-0465
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发表时间：
2012-10-15
期刊：
影响因子：
11.2
通讯作者：
Pischon, Tobias
中科院分区：
文献类型：
--
作者：
Aleksandrova, Krasimira;Boeing, Heiner;Pischon, Tobias
瘦素是一种主要由脂肪细胞产生的肽类激素，被认为在结直肠癌（CRC）的发病机制中起作用。可溶性瘦素受体（sOB-R）可以调节瘦素的生理功能，但其与结直肠癌风险的关系尚不清楚。本研究在欧洲癌症与营养前瞻性研究（EPIC）队列中进行了一项前瞻性巢式病例对照研究，探讨瘦素和sOB-R与CRC风险的关系。共有1,129例CRC病例（713例结肠癌，416例直肠癌）与1,129例对照组相匹配。条件Logistic回归用于计算相对危险度（RR）和95%置信区间（CI）。在多变量校正后，包括体重指数（BMI）、腰围和基线瘦素浓度，sOB-R与CRC呈强负相关（RR比较最高五分位数与最低五分位数，0.55; 95% CI，0.40-0.76; P趋势= 0.0004）和结肠癌（RR，0.42; 95%CI，0.28-0.63，P趋势= 0.0001）;而直肠癌无相关性（经BMI和腰围校正的RR，0.83; 95%CI，0.48-1.44，P趋势= 0.38）。相比之下，瘦素与结直肠癌风险无关（经BMI和腰围校正的RR为0.85; 95%CI为0.56-1.29，P趋势= 0.23）。循环代谢生物标志物的额外调整不会减弱这些结果。这些新的发现表明循环sOB-R和CRC风险之间存在强烈的负相关性，独立于肥胖指标，瘦素浓度和其他代谢生物标志物。sOB-R在结直肠癌发病机制中的潜在重要作用有待进一步研究证实。Cancer Res; 72（20）; 5328-37. (C)2012年AACR。
Leptin, a peptide hormone produced primarily by the adipocytes, is hypothesized to play a role in the pathogenesis of colorectal cancer (CRC). Soluble leptin receptor (sOB-R) may regulate leptin's physiologic functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 1,129 incident CRC cases (713 colon, 416 rectal) were matched within risk sets to 1,129 controls. Conditional logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI). After multivariable adjustment including body mass index (BMI), waist circumference, and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile vs. the lowest, 0.55; 95% CI, 0.40-0.76; P-trend = 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28-0.63, P-trend = 0.0001); whereas no association was seen for rectal cancer (RR adjusted for BMI and waist circumference, 0.83; 95% CI, 0.48-1.44, P-trend = 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for BMI and waist circumference, 0.85; 95% CI, 0.56-1.29, P-trend = 0.23). Additional adjustments for circulating metabolic biomarkers did not attenuate these results. These novel findings suggest a strong inverse association between circulating sOB-R and CRC risk, independent of obesity measures, leptin concentrations, and other metabolic biomarkers. Further research is needed to confirm the potentially important role of sOB-R in CRC pathogenesis. Cancer Res; 72(20); 5328-37. (C) 2012 AACR.