The CYP1B1 Leu432Val polymorphism contributes to lung cancer risk: evidence from 6501 subjects

Lung Cancer. 2010 Dec;70(3):247-52. doi: 10.1016/j.lungcan.2010.03.011. Epub 2010 Apr 14.

Abstract

The polymorphism of cytochrome P4501B1 (CYP1B1) codon 432 (rs1056836, CYP1B1*3, or Leu432Val) is thought to have a significant effect on lung cancer risk, but the results are inconsistent. In this meta-analysis, we assessed 9 published studies involving 6501 subjects that investigated the association between the CYP1B1 codon 432 polymorphism and risk of lung cancer. Overall, the CYP1B1 Leu/Val and Val/Val-variant genotypes were associated with a significantly increased risk of lung cancer in different genetic models (heterozygote comparison: OR=1.22; 95% CI=1.02-1.45, P(heterogeneity)=0.068; homozygote comparison: OR=1.41; 95% CI=1.08-1.85, P(heterogeneity)=0.071; dominant model comparison: OR=1.26; 95% CI=1.04-1.51, P(heterogeneity)=0.019; and recessive model comparison: OR=1.17; 95% CI=1.02-1.34, P(heterogeneity)=0.429). In the stratified analysis by ethnicity, significantly increased risks were found among Caucasians for Leu/Val vs Leu/Leu (OR=1.30; 95% CI=1.03-1.64; P(heterogeneity)=0.092), and dominant model (OR=1.35; 95% CI=1.03-1.77; P(heterogeneity)=0.015). However, no significant associations were found in both Europeans and African-Americans for all genetic models. In the subgroup analyses by smoking status, a significantly increased risk of lung cancer was found among smokers (dominant model: OR=1.46; 95% CI=1.08-1.83; P(heterogeneity)=0.175). However, we did not find any statistically significant association by subgroup analyses of pathological type. This meta-analysis suggests that the CYP1B1 Val allele is a low-penetrant risk factor for developing lung cancer.

Publication types

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

MeSH terms

  • Adenocarcinoma / epidemiology*
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / physiopathology
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Cytochrome P-450 CYP1B1
  • Ethnic Groups
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Leucine / genetics
  • Lung Neoplasms / epidemiology*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / physiopathology
  • Penetrance
  • Polymorphism, Genetic
  • Risk
  • Smoking
  • Valine / genetics

Substances

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