Cancer
Using genetics to assess the role of acetate in ischemic heart disease, diabetes, and sex hormone-related cancers: a Mendelian randomization study Jie Zhao* Jie Zhao
Acetate, a short chain fatty acid, has attracted increasing attention with dual reputation, a potential benefit on cardiovascular health whilst concern on cancer, especially sex hormone-related cancers. These effects have been rarely examined in humans. To fill in this research gap, we used Mendelian randomization to minimize confounding and test causal relationship. Specifically, we used genetic variants strongly (p<5×10-8) and independently (r2<0.001) associated with acetate, and applying to large genome-wide association studies of ischemic heart disease (IHD) (up to 154,373 cases), diabetes (109,731 cases), and five sex hormone-related cancers (prostate, breast, endometrial, ovarian and colorectal cancer, 8,679 to 122,977 cases). Several methods, including penalized inverse variance weighting (pIVW), IVW, weighted median and weighed mode were used in the analysis. This study shows acetate is related to lower risk of IHD (odds ratio (OR) 0.61 per SD increase in acetate, 95% confidence interval (CI) 0.39 to 0.98) but higher risk of breast cancer (OR 1.26, 95% CI 1.08 to 1.46), robust to different sensitivity analyses. Acetate or factors affecting the activity of acetate may serve as potential targets for IHD and breast cancer, with implications for new drug development.
