Genetically Predicted Circulating Concentrations of Alanine and Alanine Aminotransferase Were Associated with Prostate Cancer Risk

Clin Epidemiol. 2022 Oct 28:14:1255-1264. doi: 10.2147/CLEP.S382116. eCollection 2022.

Abstract

Object: Prostate cancer is one of the leading malignancies in men worldwide. Previous observational studies have linked amino acids and transaminase with altered risk of prostate cancer. However, whether these associations were causal remained unclear. Therefore, we conducted a Mendelian randomization (MR) to assess their potential causal associations.

Methods: Summary-level data for prostate cancer were obtained from a meta-analysis of genome-wide association studies (GWAS) including 79,148 prostate cancer cases and 61,106 controls of European descent. Instrumental variables (IVs) of amino acids and alanine aminotransferase (ALT) were obtained from a GWAS of 86,507 European individuals and a GWAS of 312,572 participants from the UK Biobank, respectively. MR analyses were performed using inverse-variance-weighted (IVW), likelihood-based, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test and MR-Egger regression.

Results: Genetically predicted circulating concentrations of alanine were associated with an increased risk of prostate cancer (odds ratio (OR): 1.16, 95% confidence interval (CI): 1.01-1.33, P=0.037 by IVW). Consistently, genetically predicted ALT was inversely associated with the risk of prostate cancer (OR: 0.43, 95% CI: 0.27-0.68, P=3.28×10-4 by IVW). MR-Egger regression did not indicate evidence of directional pleiotropy and sensitivity analyses yielded consistent associations.

Conclusion: Our study revealed that genetically predicted circulating alanine and ALT levels were associated with an altered risk of prostate cancer, suggesting their potential roles in the development of prostate cancer. Whether targeting alanine, ALT or its downstream effectors are helpful in reducing prostate cancer incidence warrants further investigation.

Keywords: Mendelian randomization; alanine; alanine aminotransferase; amino acids; prostate cancer.

Grants and funding

This work was jointly supported by grants from National Natural Science Foundation of China (82103936, 82174208, and 81973663) and Natural Science Foundation of Zhejiang Province (LQ20H260008 and LQ21H260001); Zhejiang Medical and Health Science and Technology Plan (2021KY081 and 2022KY671. The funder had no role in the study design, data analysis, interpretation of data, or preparation of the manuscript.