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: The rate of direct smoking, second hand smoking, and smokeless tobacco users as well as the amount of environmental pollutant like polycyclic aromatic hydrocarons is increasing in Bangladesh. Therefore, the prevalence of lung cancer is increasing day by day. To the best of our knowledge, no pharmacogentic study of CYP3A4, CYP3A5 genes has been reported on Bangladeshi population relating those with lung cancer. The present study was conducted to determine the association of CYP3A4, CYP3A5 gene polymorphisms and tobacco smoking in the development of lung cancer in Bangladeshi population. A case–control study was carried out on 106 lung cancer patients and 116 controls to investigate three allelic variants—CYP3A4*1B, CYP3A5*3, and CYP3A5*6 using Polymerase Chain Reaction Restriction Fragment Length Polymorphism. Risk of lung cancer was estimated as odds ratio (OR) and 95 % confidence interval (CI) using unconditional logistic regression models. The variant allele frequencies for CYP3A4*1B (*1A/*1B + *1B/*1B) were 2.83 % and 0.86 % and that of CYP3A5*3 (*1A/*3 + *3/*3) were 88.68 % and 85.34 % in cases and controls, respectively. Individual carrying at least one variant allele of CYP3A4*1B (CYP3A4*1A/1B + *1B/1B) has a 3.35 times more risk (OR = 3.35, 95 % Cl = 0.34-32.71, p = 0.271) for developing lung cancer whereas individual carrying at least one variant allele of CYP3A5 (CYP3A5*1A/3 + *3/3) has a 1.26 times more risk (OR = 1.35, 95 % Cl = 0.61–2.97) and both are statistically non-significant (p > 0.05). CYP3A5*6 was absent in the study population. No association of lung cancer with the mentioned polymorphisms was found both in heavy and light smokers. In the cases of all three major types of lung cancer—squamous cell carcinoma, adenocarcinoma, and small cell carcinoma—significantly strong relationships (p ˂ 0.05) have been found. To confirm the association of lung cancer with the mentioned polymorphisms, large number volunteers (patients and controls) will be required.Tumor Biology 10/2013; · 2.84 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