CYP1A1 MspI and exon7 gene polymorphisms and lung cancer risk: an updated meta-analysis and review

Abstract

Background: Many studies have examined the association between the CYP1A1 MspI and exon 7 gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent.

Methods: To assess this relationship more precisely, a meta-analysis and review were performed. The PubMed, Embase, Web of Science, and CNKI database was searched for case-control studies published up to June 2010. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.

Results: Ultimately, 64 studies, comprising 18,397 subjects from 49 case-control studies of the MspI genotype and 18,518 patients from 40 case-control studies of the exon 7 genotype, were included. A significantly elevated lung cancer risk was associated with 2 MspI genotype variants (for type C vs. Type A: OR = 1.26, 95% CI = 1.12-1.42; for types B and C combined vs. Type A: OR = 1.20, 95% CI = 1.13-1.28) in overall population. In the stratified analysis, a significant association was found in Asians, Caucasians, lung SCC, lung AC and Male population, not in mixed population, lung SCLC and female population. However, inconsistent results were observed for CYP1A1 exon7 in our meta-analysis, two variants of the exon 7 polymorphism were associated with a significantly higher risk for lung cancer (for Val/Val vs. Ile/Ile: OR = 1.24, 95% CI = 1.09-1.42; for (Ile/Val +Val/Val) vs. Ile/Ile: OR = 1.15, 95% CI = 1.07-1.24) in overall population. In the stratified analysis, a significant assocation was found in Asians, Caucasians, lung SCC and Female population, not in mixed population, lung AD, lung SCLC and Male population. Additionally, a significant association was found in smoker population and not found in non-smoker populations for CYP1A1 MspI and exon7 gene.

Conclusions: This meta-analysis suggests that the MspI and exon 7 polymorphisms of CYP1A1 correlate with increased lung cancer susceptibility and there is an interaction between two genotypes of CYP1A1 polymorphism and smoking, but these associations vary in different ethnic populations, histological types of lung cancer and gender of case and control population.

Figure 1

The flow diagram of search strategy.

Figure 2

Forest plot (random-effects model) of lung cancer risk associated with CYP1A1 MspI for the combined types B and C vs Type A. Each box represents the OR point estimate, and its area is proportional to the weight of the study. The diamond (and broken line) represents the overall summary estimate, with CI represented by its width. The unbroken vertical line is set at the null value (OR = 1.0).

Figure 3

Forest plot (random-effects model) of lung cancer risk associated with CYP1A1 MspI for the combined types B and C vs Type A stratified by histological types of lung cancer.

Figure 4

Forest plot (random-effects model) of lung cancer risk associated with CYP1A1 MspI for the combined types B and C vs Type A stratified by gender of population.

Figure 5

Forest plot (random-effects model) of lung cancer risk associated with CYP1A1 MspI for the combined types B and C vs Type A stratified by smoking status of population.

Figure 6

Forest plot (random-effects model) of lung cancer risk associated with CYP1A1 exon7 genotype for the combined Ile/Val and Val/Val vs Ile/Ile.

Figure 7

Forest plot (random-effects model) of lung cancer risk associated with CYP1A1 exon7 genotype for the combined Ile/Val and Val/Val vs Ile/Ile by histological types of lung cancer.

Figure 8

Forest plot (random-effects model) of lung cancer risk associated with CYP1A1 exon7 genotype for the combined Ile/Val and Val/Val vs Ile/Ile stratified by gender of population.

Figure 9

Forest plot (random-effects model) of lung cancer risk associated with CYP1A1 exon7 genotype for the combined Ile/Val and Val/Val vs Ile/Ile stratified by smoking status of population.

Figure 10

Begg's funnel plot of CYP1A1 MspI gene polymorphism and lung cancer risk for the combined types B and C vs Type A.

Figure 11

Begg's funnel plot of CYP1A1exon7 gene polymorphism and lung cancer risk for the combined Ile/Val and Val/Val vs Ile/Ile.