Genetically predicted levels of circulating cytokines and prostate cancer risk: A Mendelian randomization study
Xiaohui Sun, Ding Ye, Lingbin Du, Yu Qian, Xia Jiang, Yingying Mao
Abstract
Abstract 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.