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

ABSTRACT: 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.

SUBMITTER: Mao Y

PROVIDER: S-EPMC5558171 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Mao Yingying Y Yan Caiwang C Lu Qun Q Zhu Meng M Yu Fei F Wang Cheng C Dai Juncheng J Ma Hongxia H Hu Zhibin Z Shen Hongbing H Jin Guangfu G

European journal of human genetics : EJHG 20170621 9

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 con ...[more]

PMID: 28635950

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Project description:BACKGROUND:Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors. METHODS:We applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases? = ?46,325, controls? = ?42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively. RESULTS:In the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR]? = ?0.65 per 5 kg/m2 increase, 95% confidence interval [CI]: 0.56-0.75, p = 3.32?×?10-10). The associations were similar for both premenopausal (OR?? = ??0.44, 95% CI:0.31-0.62, p? = ?9.91?×?10-8) and postmenopausal breast cancer (OR? = ?0.57, 95%?CI: 0.46-0.71, p? = ?1.88?×?10-8). This association was replicated in the data from the DRIVE consortium (OR? = ?0.72, 95%?CI: 0.60-0.84, p?? = ??1.64?×?10-7). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p?<?0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk. CONCLUSIONS:BMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer.

Dataset Information

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

Publications

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

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