Interactive effect of TLR SNPs and exposure to sexually transmitted infections on prostate cancer risk in Jamaican men

Prostate. 2020 Nov;80(15):1365-1372. doi: 10.1002/pros.24067. Epub 2020 Sep 7.

Abstract

Background: Prostate cancer (PC) risk increases with African ancestry and a history of sexually transmitted infections (STIs). Also, single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes influence PC risk. This pilot study explores interactions between STIs and TLR-related SNPs in relation to PC risk among Jamaican men.

Methods: This case-control study evaluates two TLR related SNPs in 356 Jamaican men (194 controls and 162 cases) with or without history of STIs using stepwise penalized logistic regression in multivariable analyses.

Results: Age (odds ratio [OR] = 1.08; 95% confidence interval [CI]: 1.04-1>.12; p < .001) and IRF3_rs2304206 GG genotype (OR = 0.47; 95% CI: 0.29-0<.78; p = .003) modulated PC risk in people with history of STIs. In the population with no history of STIs, resulting interactions between risk factors did not survive correction for multiple hypothesis testing.

Conclusion: Overall, an interaction between the IFR3_rs2304206 variant and a history of exposure to STIs leads to greater decrease of PC risk than the presence of polymorphic genotype alone. These findings are suggestive and require further validation. Identification of gene variants along with detection of lifestyle behaviors may contribute to identification of men at a greater risk of PC development in the population.

Keywords: StepPLR; black; prostate cancer; sexually transmitted infections; single nucleotide polymorphisms; toll-like receptor (TLR).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Genetic Predisposition to Disease*
  • Genotype*
  • Humans
  • Jamaica
  • Male
  • Middle Aged
  • Pilot Projects
  • Polymorphism, Single Nucleotide*
  • Prostatic Neoplasms / etiology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Risk Assessment
  • Risk Factors
  • Sexually Transmitted Diseases / complications*
  • Toll-Like Receptors / genetics*

Substances

  • Toll-Like Receptors