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Eur J Hum Genet. 2017 Sep;25(9):1061-1066. doi: 10.1038/ejhg.2017.103. Epub 2017 Jun 21.

Genetically predicted high body mass index is associated with increased gastric cancer risk.

Mao Y1,2, Yan C1,3, Lu Q1, Zhu M1, Yu F1, Wang C1, Dai J1, Ma H1, Hu Z1,3, Shen H1,3, Jin G1,3.

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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.
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Centre For Cancer Medicine, Nanjing Medical University, Nanjing, China.


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 × 10-3). 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.

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