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

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, Pheterogeneity = 0.068; homozygote comparison: OR = 1.41; 95% CI = 1.08–1.85, Pheterogeneity = 0.071; dominant model comparison: OR = 1.26; 95% CI = 1.04–1.51, Pheterogeneity = 0.019; and recessive model comparison: OR = 1.17; 95% CI = 1.02–1.34, Pheterogeneity = 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; Pheterogeneity = 0.092), and dominant model (OR = 1.35; 95% CI = 1.03–1.77; Pheterogeneity = 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; Pheterogeneity = 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.