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

Int J Cancer. 2020 Nov 1;147(9):2469-2478. doi: 10.1002/ijc.33221. Epub 2020 Aug 12.

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.

Keywords: Mendelian randomization; cytokines; inflammation; monocyte chemotactic protein‐1; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Causality
  • Chemokine CCL2 / blood*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Incidence
  • Linkage Disequilibrium
  • Male
  • Mendelian Randomization Analysis
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / epidemiology*
  • Prostatic Neoplasms / genetics
  • Risk Factors
  • White People / genetics

Substances

  • Biomarkers, Tumor
  • CCL2 protein, human
  • Chemokine CCL2