Mao Yingying, Yan Caiwang, Lu Qun, Zhu Meng, Yu Fei, Wang Cheng, Dai Juncheng, Ma Hongxia, Hu Zhibin, Shen Hongbing, Jin Guangfu
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
Department of Epidemiology and Biostatistics, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Eur J Hum Genet. 2017 Sep;25(9):1061-1066. doi: 10.1038/ejhg.2017.103. Epub 2017 Jun 21.
Epidemiological studies have linked body mass index (BMI) with risk of gastrointestinal cancers. However, for gastric cancer, the relationship is more controversial. In particular, it is unclear whether the observed association is due to confounding or bias inherent in conventional observational studies. To investigate whether BMI is causally associated with gastric cancer risk, we applied Mendelian randomization using individual-level data from 2631 gastric cancer cases and 4373 cancer-free controls. We derived a weighted genetic risk score (wGRS) using 37 BMI-associated genetic variants as an instrumental variable. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between genetically predicted BMI and gastric cancer risk. We observed that higher genetically determined BMI was associated with increased gastric cancer risk (per standard deviation (SD) increase in the wGRS: OR=1.07, 95% CI: 1.02-1.13, P=4.94 × 10). Compared with individuals in the bottom tertile of the BMI wGRS, those in the top tertile had 1.14-fold (95% CI: 1.01-1.29) increased risk of developing gastric cancer. Sensitivity analyses using alternative causal inference measures demonstrated consistent association. Our study indicated that genetically high BMI was associated with increased gastric cancer risk, suggesting that high BMI may have a causal role in the etiology of gastric cancer.
流行病学研究已将体重指数（BMI）与胃肠道癌症风险联系起来。然而，对于胃癌而言，这种关系更具争议性。特别是，尚不清楚观察到的关联是由于传统观察性研究中固有的混杂因素还是偏差所致。为了研究BMI是否与胃癌风险存在因果关系，我们使用来自2631例胃癌病例和4373例无癌对照的个体水平数据进行了孟德尔随机化分析。我们使用37个与BMI相关的基因变异作为工具变量，得出了一个加权遗传风险评分（wGRS）。我们使用逻辑回归来估计基因预测的BMI与胃癌风险之间关联的比值比（OR）和95%置信区间（CI）。我们观察到，基因决定的较高BMI与胃癌风险增加相关（wGRS每增加一个标准差（SD）：OR = 1.07，95% CI：1.02 - 1.13，P = 4.94×10）。与BMI wGRS处于最低三分位数的个体相比，处于最高三分位数的个体患胃癌的风险增加了1.14倍（95% CI：1.01 - 1.29）。使用替代因果推断方法的敏感性分析显示出一致的关联。我们的研究表明，基因决定的高BMI与胃癌风险增加相关，这表明高BMI可能在胃癌病因学中具有因果作用。
