CYP1A1 Ile462Val polymorphism and susceptibility to lung cancer: a meta-analysis based on 32 studies.
ABSTRACT Lung cancer is the second most common human malignant disease and the leading cause of cancer-related mortality worldwide. The effect of CYP1A1 IleVal polymorphism on susceptibility to lung cancer has been researched extensively over the last two decades. However, controversial results were obtained. To provide a more robust estimate of the effect, a meta-analysis was carried out. We systematically searched the PubMed database for studies published before August 2010, without language restriction. On the basis of our search criteria, a total of 32 studies (5126 patients and 6974 controls) were included in the meta-analysis. Overall, CYP1A1 IleVal polymorphism is associated with lung cancer risk (GG vs. AG+AA: odds ratio=1.61, 95% confidence interval: 1.19-2.17; GG vs. AA: odds ratio=1.70, 95% confidence interval: 1.23-2.35). Ethnic subgroup analyses showed that a significant association was found in Asians, but not in Africans, Caucasians, or other populations. In subgroup analyses by histology, the result is not reliable. In conclusion, this meta-analysis suggests that the CYP1A1 IleVal polymorphism might play a modest role in susceptibility to lung cancer, especially in Asians.
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ABSTRACT: Abstract Background: Although many epidemiology studies have investigated the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and their associations with lung cancer (LC), definite conclusions cannot be drawn. To clarify the effects of MTHFR polymorphisms on the risk of LC, we performed a meta-analysis in Chinese populations. Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) until 16 February 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. A total of 11 studies with 2487 LC cases and 3228 controls were included in this meta-analysis. Overall, no significant association was found between MTHFR C677T polymorphism and LC risk when all studies in Chinese populations were pooled into this meta-analysis. In subgroup analyses stratified by geographical location and source of controls, significantly increased risk was found in North China (T vs. C: OR=1.28, 95% CI: 1.14-1.44; TT vs. CC: OR=1.67, 95% CI: 1.33-2.10; TT + CT vs. CC, OR=1.39, 95% CI=1.15-1.69; TT vs. CC + CT: OR=1.46, 95% CI: 1.03-2.06) and in population-based studies (TT vs. CC: OR=1.37, 95% CI: 1.14-1.65; TT vs. CC + CT: OR=1.25, 95% CI: 1.07-1.45). This meta-analysis provides evidence that MTHFR C677T polymorphism may contribute to LC development in North China. Studies with larger sample sizes and wider spectrum of populations are warranted to verify this finding.Medical science monitor: international medical journal of experimental and clinical research 01/2014; 20:2817-23. · 1.22 Impact Factor
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ABSTRACT: Lung cancer (LC) is the leading cause of mortality caused by neoplasias worldwide. Although cigarette smoking is the primary cause, not all smokers develop LC. Polymorphic variations in genes associated with carcinogen metabolism, DNA repair, and cell-cycle dysregulation may alter an individual risk of developing LC. A polygenic cancer model was proposed, which considers genetic susceptibility to cancer is a global mechanism and suggests that it might be defined by the contributions of low-risk alleles in several candidate genes. This study focused on the analysis of 15 polymorphisms in 12 low-penetrance genes in a case-control study of a sample of Mexican Mestizo population. A case-control study was performed with a total of 572 unrelated individuals, including 190 cases with a primary LC diagnosis and 382 healthy controls. The polymorphic status of the individuals was determined by TaqMan probe and RFLP techniques. The association between LC and genotype score (GS) was assessed by logistic regression. The results suggests a protective effect of the genotypes Arg/Lys of AhR rs2066853 (odds ratio [OR] 0.55, p = 0.03), Ile/Val of CYP1A1 rs1048943 (OR 0.49, p = 0.009), Tyr/His of EPHX1 rs1051740 (OR 0.53, p = 0.03), and A/A of CCND1 rs603965 (OR 0.44, p = 0.02). Analyses using the GS suggest that average cases have a larger number of risk alleles than controls (Student's t test -4.85, p = 0.001; OR 1.25, p < 0.001). Our results suggest significant differences between the GS for the cases and controls, which support the hypothesis underlying the additive and polygenic models for lung cancer risk depending on the polymorphisms in low-penetrance genes.Beiträge zur Klinik der Tuberkulose 12/2013; · 2.17 Impact Factor
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ABSTRACT: With the widespread use of O-alkoxyresorufin dealkylation assays since the 1990s, thousands of inhibitors of cytochrome P450 family 1 enzymes (P450s 1A1, 1A2, and 1B1) have been identified and studied. Generally, planar polycyclic molecules such as polycyclic aromatic hydrocarbons, stilbenoids, and flavonoids are considered to potentially be effective inhibitors of these enzymes, however, the details of the structure-activity relationships and selectivity of these inhibitors are still ambiguous. In this review, we thoroughly discuss the selectivity of many representative P450 family 1 inhibitors reported in the past 20 years through a meta-analysis.Molecules 12/2013; 18(12):14470-95. · 2.10 Impact Factor