Genetically predicted levels of circulating cytokines and prostate cancer risk: A Mendelian randomization study

Inflammation is considered to play a pivotal role in the pathogenesis of cancer, and observational studies have reported a relationship between circulating inflammation markers and the risk of prostate cancer. Using summary data of >140 000 individuals, two-sample Mendelian randomization (MR) analyses were performed to evaluate whether circulating levels of 27 cytokines and growth factors have a causal effect on the risk of developing prostate cancer. Genetically predicted elevated levels of monocyte chemotactic protein-1 (MCP-1) were associated with an increased risk of prostate cancer (odds ratio (OR) per 1 SD increase = 1.06, 95% confidence interval (CI): 1.04-1.09) at Bonferroni-adjusted level of significance (P < 1.85 × 10-3). Results were stable across sensitivity analyses, and there was no evidence of directional pleiotropy. Under MR assumptions, our findings suggested a risk-increasing effect of circulating MCP-1 levels on prostate cancer. Whether targeting MCP-1 or its downstream effectors are useful in reducing prostate cancer incidence needs further investigation.