CYP1B1 polymorphisms and susceptibility to prostate cancer: a meta-analysis

PLoS One. 2013 Jul 4;8(7):e68634. doi: 10.1371/journal.pone.0068634. Print 2013.

Abstract

Background: Studies investigating the association between single-nucleotide polymorphisms (SNPs) of the cytochrome P450 1B1 (CYP1B1) and prostate cancer (PCa) risk report conflicting results. To derive a more precise estimation of the relationship between CYP1B1 polymorphisms and PCa risk, a meta-analysis was performed.

Methodology/principal findings: A comprehensive literature search was conducted to identify all eligible studies of CYP1B1 polymorphisms and PCa risk. A total of 14 independent studies, including 6380 cases and 5807 controls, were identified. We investigated by meta-analysis the effects of 5 polymorphisms in CYP1B1 L432V (12 studies, 5999 cases, 5438 controls), R48G (6 studies, 1647 cases, 1846 controls), N453S (4 studies, 1407 cases, 1499 controls), -13C/T (4 studies, 1116 cases, 1114 controls), and A119S (4 studies, 1057 cases, 1018 controls). There was no evidence that L432V had significant association with PCa in overall population. After subgroup analyses by ethnicity, we found that L432V was significantly associated with PCa risk in Asians (additive: OR = 2.38, 95%CI = 1.31-4.33, P = 0.004; recessive: OR = 2.11, 95%CI = 1.17-3.79, P = 0.01; dominant: OR = 1.52, 95%CI = 1.14-2.01, P = 0.004; allelic: OR = 1.52, 95%CI = 1.20-1.92, P = 0.0006). When stratified by source of controls, significantly elevated PCa risk was found in all genetic models in population based studies (additive: OR = 1.34, 95%CI = 1.14-1.57, P = 0.0003; recessive: OR = 1.25, 95%CI = 1.09-1.43, P = 0.002; dominant: OR = 1.25, 95%CI = 1.11-1.41, P = 0.0002; allelic: OR = 1.18, 95%CI = 1.09-1.28, P<0.0001). For N453S, there was a significant association between N453S polymorphism and PCa risk in both overall population (dominant: OR = 1.18, 95%CI = 1.00-1.38, P = 0.04) and mixed population (domiant: OR = 1.31, 95%CI = 1.06-1.63, P = 0.01; allelic: OR = 1.27, 95%CI = 1.05-1.54, P = 0.01). For A119S, our analysis suggested that A119S was associated with PCa risk under recessive model in overall population (OR = 1.37, 95%CI = 1.04-1.80, P = 0.03).

Conclusions: The results suggest that L432V, N453S, and A119S polymorphisms of CYP1B1 might be associated with the susceptibility of PCa. Further larger and well-designed multicenter studies are warranted to validate these findings.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Asian People
  • Black People
  • Case-Control Studies
  • Cytochrome P-450 CYP1B1
  • Databases, Bibliographic
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Models, Statistical*
  • Polymorphism, Single Nucleotide*
  • Prostatic Neoplasms / ethnology
  • Prostatic Neoplasms / genetics*
  • Risk Factors
  • White People

Substances

  • Aryl Hydrocarbon Hydroxylases
  • CYP1B1 protein, human
  • Cytochrome P-450 CYP1B1

Grants and funding

This study was supported by the National Natural Science Foundation of China (No: 81172451), Tianjin Major Anti-Cancer Project (12ZCDZSY17200), and Science Foundation of Tianjin Medical University (No: 2009GSI18). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.