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: A great number of studies regarding the association between MspI and Ile462Val polymorphisms in the CYP1A1 gene and gastric cancer have been published. However, the results have been inconsistent. In this study, a meta-analysis was performed to investigate the associations. Published literature from PubMed, ISI Web of Science and other Chinese databases were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random or fixed effect model. Nine studies (860 cases/2183 controls) for CYP1A1 MspI polymorphism and nine studies (1161 cases/3273 controls) for CYP1A1 Ile462Val polymorphism were included in this meta-analysis. MspI polymorphism was not associated with gastric cancer risk (dominant model, OR = 0.95, 95%CI 0.80-1.14; recessive model, OR = 1.01, 95%CI 0.76-1.35; CC vs. TT, OR = 1.03, 95%CI 0.76-1.41; TC vs. TT, OR = 0.95, 95%CI 0.78-1.15). Similarly, there was no association between Ile462Val polymorphism and gastric cancer risk (dominant model, OR = 0.93, 95%CI 0.79-1.10; recessive model, OR = 1.34, 95%CI 0.90-2.00; GG vs. AA, OR = 1.27, 95%CI 0.84-1.90; AG vs. AA, OR = 0.87, 95%CI 0.71-1.07). In the subgroup analysis, no significant association was found in ever smokers, never smokers, Asians and Caucasians. This meta-analysis suggested that there were no associations between CYP1A1 polymorphisms and gastric cancer.Tumor Biology 02/2012; 33(4):1125-32. · 2.52 Impact Factor
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ABSTRACT: The association of two cytochrome P4501A1 (CYP1A1) polymorphisms, m1 (T6235C transition) and m2 (A4889G transition), with gastric cancer risk is inconclusive. We conducted a meta-analysis of all available studies to evaluate the potential role of the polymorphisms and their interactions with tobacco smoking in gastric cancer susceptibility. Published literature from PubMed was retrieved by two investigators independently. Fourteen case-control studies with 2,032 gastric cancer cases and 5,099 controls were selected. A fixed effects model or a random-effects model was used to estimate the odds ratio (OR) for the CYP1A1 polymorphisms and the occurrence of gastric cancer. Significant associations between CYP1A1 m1 and m2 polymorphisms and gastric cancer susceptibility were not observed in all genetic models in the overall analyses. Subgroup analyses by ethnicity and source of controls did not reveal significant associations with gastric cancer risk. Stratification analysis by smoking status found that carriers of the heterozygous and homozygous m1 genotypes decreased the susceptibility of gastric cancer among ever-smokers (pooled OR = 0.56, 95 % CI 0.36-0.89, fixed effects). In contrast, the m2 genotypes (G/G and A/G) did not show any relevance to gastric cancer risk among the smoking population (pooled OR = 1.30, 95 % CI 0.84-2.00, fixed effects). Overall, we found that the CYP1A1 polymorphism itself, either m1 or m2, did not represent an independent genetic risk factor influencing gastric cancer. However, subgroup analyses suggest that carriers of the heterozygous and homozygous m1 genotype who are exposed to tobacco smoke have a significantly lower risk of developing gastric cancer. To explain the observed reduction of gastric cancer risk, we proposed a novel hypothesis of "observation bias". This hypothesis is also applicable to explain the combined effects of other genetic polymorphisms and environmental factors on the risk of developing cancers, and the rationality of the hypothesis needs to be further investigated.Molecular Biology Reports 06/2012; 39(8):8335-44. · 2.51 Impact Factor
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ABSTRACT: Evidence indicates CCND1 G870A polymorphisms as a risk factor for a number of cancers. Increasing studies have been conducted on the association of CCND1 G870A polymorphism with lung cancer risk. However, the results were controversial. The aim of the present study was to derive a more precise estimation of the relationship. Meta-analyses examining the association between CCND1 G870A polymorphism and lung cancer were performed. Subgroup analyses regarding ethnicity, smoking status, histological types and source of controls were also implemented. All eligible studies for the period up to May 2012 were identified. The overall data from ten case-control studies including 5,008 cases and 5,214 controls indicated that variant A allele may have an association with increased lung cancer risk (AA vs GG: OR = 1.21; 95 % CI = 1.08-1.36, dominant model: OR = 1.09; 95 % CI = 1.00-1.19, recessive model: OR = 1.23; 95 % CI = 1.01-1.49). In the subgroup analysis by ethnicity, A allele may elevate lung cancer risk among Asians but not Caucasians or Mixed ethnicities. In smoking status subgroup, A allele was shown to associate with increased lung cancer risk among smokers but not non-smokers. In the subgroup analysis by histological types, increased cancer risks were shown in adenocarcinoma but not squamous cell carcinoma, under the homozygote comparison and recessive models. Collectively, the results of the present study suggest that CCND1 G870A polymorphism might be a low-penetrant risk factor for lung cancer, particularly among Asians and smokers. Moreover, homozygous AA alleles might have a correlation with increased lung adenocarcinoma susceptibility.Molecular Biology Reports 05/2013; · 2.51 Impact Factor