Association of Body Mass Index and the Risk of Gastro-Esophageal Cancer: A Mendelian Randomization Study in a Japanese Population

Abstract

There are growing concerns that body mass index (BMI) is related to cancer risk at various anatomical sites, including the upper gastrointestinal tract, and the existence of a causal relationship remains unclear. The Mendelian randomization (MR) method uses instrumental genetic variables of risk factors to explore whether a causal relationship exists while preventing confounding. In our study, genome-wide association study (GWAS) data from the BioBank Japan (BBJ) project were used. Genetic variants were chosen as instrumental variables using inverse-variance weighting (IVW), MR–Egger regression and weighted-median methods to estimate the causal relationship between BMI and the risk of gastro-esophageal cancer. We found no evidence to support a causal association between BMI and risk of gastric cancer [odds ratio (OR) =0.99 per standard deviation (SD) increase in BMI; 95% confidence interval (CI): (0.76–1.30); P = 0.96] or esophageal cancer [0.78(0.50–1.22); P = 0.28] using the IVW method. Sensitivity analysis did not reveal any sign of horizontal pleiotropy. Additionally, in the gender-stratified analysis, no causal association was found. Findings from this study do not support a causal effect of BMI on gastro-esophageal cancer risk. However, we cannot rule out a modest or nonlinear effect of BMI.

Ethical Approval

Ethical approval was not required for this study in accordance with the local legislation and institutional requirements.

Disclosure Statement

No potential conflict of interest was reported by the authors.

Data Availability Statement

All the GWAS data can be downloaded directly from the website of https://humandbs.biosciencedbc.jp/en/. The instrumental variables data can be found from the paper mentioned in the article.

Additional information

Funding

BBJ was supported by the Tailor-Made Medical Treatment Program (the BioBank Japan Project) of the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) and the Japan Agency for Medical Research and Development (AMED). This work was supported by grants from the National Natural Science Foundation of China (81874277).