Association between circulating alanine and cancer susceptibility using Mendelian randomization

Abstract Background Circulating alanine concentrations are associated with several cancers, but little is known about the causal direction of the associations. This study aims to explore whether there is a relationship between circulating alanine and ten common cancers. Methods We conducted two-sample Mendelian randomization (MR) analysis to assess the causal effects of circulating alanine on ten common cancers. According to published genome-wide association studies (GWASs), we obtained 36 alanine-related single nucleotide polymorphisms used as instrumental variables. For exposure data, genetic association data of lung, breast, pancreatic, liver, colorectal, esophageal, stomach, thyroid, prostate and ovarian cancer from GWAS Consortia were used, including up to 1,213,351 participants of European origin and 196,187 participants of East Asian. The inverse variance weighting (IVW) method was used for MR analysis, and MR-Egger and the weighted median method further evaluated the pleiotropic effect. Results Specific to cancer GWAS, we found that circulating alanine was significantly associated with increased squamous cell lung cancer (odds ratio [OR]: 1.37, 95% CI = 1.00-1.87; P = 0.048), pancreatic cancer (OR 3.02, 95% CI = 1.35 to 6.76; P = 0.007), low grade serous ovarian cancer (OR 1.81, 95% CI = 1.01 to 3.25; P = 0.047). We have no evidence of a convincing causal effect of circulating alanine concentrations predicted by genetics on other cancer risks. Conclusion We observed the possible causal relationship between circulating alanine and lung squamous cell carcinoma, pancreatic cancer, low-grade serial ovarian cancer. Further research is needed to verify this causal relationship.