CYP1A1 Ile462Val polymorphism and susceptibility to lung cancer

Department of Center for Disease Control and Prevention of Shaanxi Province, Xi'an, China.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) (Impact Factor: 3.03). 11/2011; 20(6):445-52. DOI: 10.1097/CEJ.0b013e328345f937
Source: PubMed


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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    • "The second polymorphism rs1048943 (2454A> G; m2 polymorphism ) results in an amino acid change (Ile462Val) [13]. This variant is frequent in Asians and is associated with lung cancer risk even though rare in Caucasians [12] [14] [15]. The combination of rs4646903 and rs1048943 forms the CYP1A1*2B allele with individual alleles positive for the single SNPs only referred to as CYP1A1*2A and CYP1A1*2C [10]. "
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    ABSTRACT: Background: CYP1A1, CYP2A6andCHRNA5are biologically plausible genes as risk factors for lung cancer but no studies have been reported in the Bangladeshi population. Methods:We conducted this study to determine the prevalence and role ofCYP1A1, CYP2A6andCHRNA5poly-morphisms together with tobacco smoking in the development of lung cancer in Bangladesh. A case–control study was carried out on 106 lung cancer patients and 116 controls to investigate three allelic variants of the CYP1A1gene—rs4646903, rs1048943 and rs1799814; 2 variants of CYP2A6(CYP2A6*1B1, CYP2A6*4)and1 variant ofCHRNA5(rs16969968) using Polymerase Chain Reaction Restriction Fragment Length Polymorphism. Results:Lung cancer risk was estimated as odds ratio (OR) and 95% confidence interval (CI) using unconditional logistic regression models adjusting for age, sex and smoking. A significantly elevated lung cancer risk was associated with heterozygous, mutant and combined heterozygous plus mutant variants of CYP1A1 rs4646903. Asignificant association was also found for heterozygous and heterozygous plus mutant variants of rs1048943 which was in linkage disequilibrium with rs4646903. The risk of lung cancer was decreased significantly in individuals carrying at least one CYP2A6 deletion (CYP2A6*4) allele. No association with lung cancer risk was found forCHRNA5rs16969968. When stratified by smoking, the effects of CYP1A1 and CYP2A6 polymorphisms on lung cancer susceptibility were found to be significant only in heavy smokers who had smoked 40 pack years or more (54% of all cases) but no associations were seen for lighter smokers. No association was also found with any polymorphism in the non-smokers in this study. Conclusions:Our results indicate that the CYP1A1*2B allele (rs4646903 and rs1048943) is associated with an in-creased lung cancer risk and CYP2A6*4 is associated with a decreased lung cancer risk in the study population
    Clinica chimica acta; international journal of clinical chemistry 02/2013; 416:11-19. · 2.82 Impact Factor
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    • "Genetic factors involved in lung cancers have been extensively studied and to date several genetic polymorphisms have been identified as candidates by meta-analyses. Previous studies indicated that variations of some genes such as CYP1A1 [5], GSTM1 [6], CYP1B1 [7] and TP53 [8] may be associated with increased susceptibility to lung cancer. Conversely, polymorphisms of NAT2 [9], ERCC1 [10] and TNF alpha [11] might not have significant association with tumorigenesis of lung cancer. "
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    ABSTRACT: Evidence suggests that MDM2 T309G polymorphism may be a risk factor for several cancers. Increasing investigations have been conducted on the association of MDM2 T309G polymorphisms with lung cancer risk and have yielded conflicting results. Previous meta-analyses on this issue have reported inconclusive data. The aim of the present study was to derive a more precise estimation of the relationship. Updated meta-analyses examining the association between MDM2 T309G polymorphism and lung cancer risk were performed. Separate analyses on ethnicity, smoking status, histological types and gender as well as source of controls were also implemented. Eligible studies were identified for the period up to Feb 2012. Lastly, ten publications including eleven case-control studies were selected for analysis. The overall data failed to indicate a significant association between MDM2 T309G polymorphism and lung cancer risk (GG vs TT OR = 1.14; 95%CI = 0.95-1.37; dominant model: OR = 1.05; 95%CI = 0.92-1.19; recessive model: OR = 1.12; 95%CI = 0.99-1.27). In a subgroup analysis by smoking status, increased lung cancer risk was shown among never-smokers (GG vs TT: OR = 1.76; 95%CI = 1.36-2.29; dominant model: OR = 1.48; 95%CI = 1.22-1.81; recessive model: OR = 1.37; 95%CI = 1.11-1.69). In subgroup analysis by gender, elevated risk was presented among women under a recessive model (OR = 1.29; 95%CI = 1.04-1.59). In the subgroup analysis by ethnicity, histological types and source of controls, no marked associations were observed. Compared to the previous meta-analyses, the results of this study confirmed that MDM2 T309G polymorphism might be a risk factor for lung cancer among never-smokers. However, the data failed to suggest a marked association between the G allele of MDM2 T309G and lung cancer risk among Asians. More interestingly, subgroup analysis by gender indicated that homozygous GG alleles might raise lung cancer risk among females.
    PLoS ONE 07/2012; 7(7):e41546. DOI:10.1371/journal.pone.0041546 · 3.23 Impact Factor
  • European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 12/2011; 21(4):317-22. DOI:10.1097/CEJ.0b013e32834ef1de · 3.03 Impact Factor
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