Polymorphisms of Estrogen Metabolism-Related Genes and Prostate Cancer Risk in Two Populations of African Ancestry

PLoS One. 2016 Apr 13;11(4):e0153609. doi: 10.1371/journal.pone.0153609. eCollection 2016.

Abstract

Background: Estrogens are thought to play a critical role in prostate carcinogenesis. It has been suggested that polymorphisms of genes encoding enzymes involved in estrogen metabolism are risk factors for prostate cancer. However, few studies have been performed on populations of African ancestry, which are known to have a high risk of prostate cancer.

Objective: We investigated whether functional polymorphisms of CYP17, CYP19, CYP1B1, COMT and UGT1A1 affected the risk of prostate cancer in two different populations of African ancestry.

Methods: In Guadeloupe (French West Indies), we compared 498 prostate cancer patients and 565 control subjects. In Kinshasa (Democratic Republic of Congo), 162 prostate cancer patients were compared with 144 controls. Gene polymorphisms were determined by the SNaPshot technique or short tandem repeat PCR analysis. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).

Results: The AA genotype and the A allele of rs4680 (COMT) appeared to be inversely associated with the risk of prostate cancer in adjusted models for both Afro-Caribbean and native African men. For the A allele, a significant inverse association was observed among cases with low-grade Gleason scores and localized clinical stage, in both populations.

Conclusions: These preliminary results support the hypothesis that polymorphisms of genes encoding enzymes involved in estrogen metabolism may modulate the risk of prostate cancer in populations of African ancestry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Aromatase / genetics
  • Black People / genetics
  • Case-Control Studies
  • Catechol O-Methyltransferase / genetics
  • Cytochrome P-450 CYP1B1 / genetics
  • Democratic Republic of the Congo
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Glucuronosyltransferase / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prostatic Neoplasms / genetics*
  • Steroid 17-alpha-Hydroxylase / genetics
  • West Indies

Substances

  • Aromatase
  • CYP1B1 protein, human
  • Cytochrome P-450 CYP1B1
  • Steroid 17-alpha-Hydroxylase
  • COMT protein, human
  • Catechol O-Methyltransferase
  • UGT1A1 enzyme
  • Glucuronosyltransferase

Grants and funding

This work was supported by the French Health Directorate (LM) (no grant number), and Ligue contre le cancer (EE) (a doctoral fellowship). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.