Journal Article•
Relationship between susceptibility to lung cancer and genetic polymorphism in CYP1A1 and GSTM1
TL;DR: CYP1A1 Val/Val and GSTM1 null genotypes may be the susceptible factors of lung cancer in Chinese Han nationality of Shandong and there may be a synergetic interaction between smoking and susceptible genotypes.
Abstract: Objective To explore the relationship between CYP1A1,GSTM1 gene polymorphisms and genetic susceptibility to lung cancerMethods In this study,110 lung cancer patients and 125 age-matched healthy controls in Chinese Han nationality of Shandong were enrolledAll DNA samples from peripheral blood were genotyped for genetic polymorphisms of CYP1A1 and GSTM1 genes by oligonucleotidechip techniqueResults The significant differences for distributions of CYP1A1 m2 and GSTM1 genotype were observed between lung cancer cases and healthy controlsThe individuals carried CYP1A1 Val/Val or GSTM1 null genotype had an increased risk for lung cancerThere was an elevated risk for smokers in lung cancer cases having CYP1A1 Val/Val or GSTM1 null genotypeConclusions CYP1A1 Val/Val and GSTM1 null genotypes may be the susceptible factors of lung cancer in Chinese Han nationality of ShandongThere may be a synergetic interaction between smoking and susceptible genotypes
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TL;DR: Evidence of an association between the CYP1A1 variant and GSTM1 null genotypes and increased risk of lung cancer is found in 46 published studies in Chinese populations.
114 citations
TL;DR: Results showed that the male lung cancer morbidity increased significantly from western to eastern China, except for the far north region, which is in line with the spatial distribution of PM2.5 concentration, manifesting a significant relationship between PM1.7 concentration level and lungcancer morbidity in Chinese males.
64 citations
TL;DR: It is demonstrated that the MspI and Ile-Val polymorphism of CYP1A1 is a risk factor associated with increased lung cancer susceptibility, but these associations vary in different ethnic populations.
Abstract: The cytochrome P450 1A1 (CYP1A1) is a phase I enzyme involved in many oxidative reactions that has attracted considerable attention as a candidate gene for lung cancer susceptibility based on its function as a key factor required for bioactivation of carcinogenic polycyclic aromatic hydrocarbons and catechol oestrogen formation. In the past decade, the relationship between CYP1A1 and lung cancer has been reported in various ethnic groups; however, these studies have yielded contradictory results. To investigate this inconsistency, we performed a meta-analysis of 71 studies involving a total of 30 368 subjects for the MspI and Ile-Val polymorphism of the CYP1A1 gene to evaluate the effect of CYP1A1 on genetic susceptibility for lung cancer. In a combined analysis, the summary per-allele odds ratios for lung cancer of the MspI and Ile-Val polymorphism were 1.19 [95% confidence interval (CI): 1.11-1.28] and 1.20 (95% CI: 1.08-1.33), respectively. Significant results were also observed using dominant or recessive genetic model. In the subgroup analysis by ethnicity, significantly increased risks were found for the MspI and Ile-Val polymorphism among East Asians in almost all genetic models. However, only marginal significant associations were detected for the MspI polymorphism among Caucasians and other population, while no significant associations were observed for the Ile-Val polymorphism in Caucasians and other population. This meta-analysis demonstrated that the MspI and Ile-Val polymorphism of CYP1A1 is a risk factor associated with increased lung cancer susceptibility, but these associations vary in different ethnic populations.
40 citations
TL;DR: It is suggested that GSTM1 deletion polymorphism may contribute to lung cancer risk in Chinese population and well-designed studies with larger sample sizes are required to verify the results.
Abstract: Previous studies have reported the association of glutathione S-transferase M1 (GSTM1) deletion polymorphism with genetic susceptibility of lung cancer in Chinese population. However, the results remained controversial. The aim of this study was to clarify the association of GSTM1 deletion polymorphism with lung cancer risk in Chinese population. Systematic searches were performed through the search engines of Medline/Pubmed, Web of Science, EMBASE, CNKI and Wanfang Medical Online. The pooled effects were calculated by STATA 10.0 software package and Review Manager 5.0.24. Overall, we observed an association of GSTM1 deletion polymorphism with increased lung cancer risk in Chinese population (odds ratio (OR) = 1.46, 95% confidence interval (95%CI): 1.32–1.66 for null genotype vs. present genotype) based on 53 studies including 7,833 cases and 10,353 controls. We also observed an increased risk of GSTM1 null genotype for lung cancer in stratified analyses by source of control, smoking status and histological type. The findings suggest that GSTM1 deletion polymorphism may contribute to lung cancer risk in Chinese population. Further, well-designed studies with larger sample sizes are required to verify the results.
27 citations
TL;DR: A stable and reliable result of the relationship between GSTM1 null genotype and lung cancer risk was demonstrated and a wide range of gene-environment and gene-gene interaction analysis should be taken into consideration in future studies.
Abstract: Background
The genetic polymorphisms of glutathione S-transferase (GSTs) have been suspected to be related to the development of lung cancer while the current results are conflicting, especially in the Chinese population.
Methods
Data on genetic polymorphisms of glutathione S-transferase Mu 1 (GSTM1) from 68 studies, glutathione S-transferase theta 1 (GSTT1) from 17 studies and GSTM1-GSTT1 from 8 studies in the Chinese population were reanalyzed on their association with lung cancer risk. Odds ratios (OR) were pooled using forest plots. 9 subgroups were all or partly performed in the subgroup analyses. The Galbraith plot was used to identify the heterogeneous records. Potential publication biases were detected by Begg's and Egger's tests.
Results
71 eligible studies were identified after screening of 1608 articles. The increased association between two vital GSTs genetic polymorphisms and lung cancer risk was detected by random-effects model based on a comparable heterogeneity. Subgroup analysis showed a significant relationship between squamous carcinoma (SC), adenocarcinoma (AC) or small cell lung carcinoma (SCLC) and GSTM1 null genotype, as well as SC or AC and GSTT1 null genotype. Additionally, smokers with GSTM1 null genotype had a higher lung cancer risk than non-smokers. Our cumulative meta-analysis demonstrated a stable and reliable result of the relationship between GSTM1 null genotype and lung cancer risk. After the possible heterogeneous articles were omitted, the adjusted risk of GSTs and lung cancer susceptibility increased (fixed-effects model: ORGSTM1 = 1.23, 95% CI: 1.19 to 1.27, P<0.001; ORGSTT1 = 1.18, 95% CI: 1.10 to 1.26, P<0.001; ORGSTM1-GSTT1 = 1.33, 95% CI: 1.10 to 1.61, P = 0.004).
Conclusions
An increased risk of lung cancer with GSTM1 and GSTT1 null genotype, especially with dual null genotype, was found in the Chinese population. In addition, special histopathological classification of lung cancers and a wide range of gene-environment and gene-gene interaction analysis should be taken into consideration in future studies.
23 citations