CYP1A1 Ile462Val polymorphism and cervical cancer: evidence from a meta-analysis

Many publications have evaluated the correlation between Cytochrome P450 1A1 (CYP1A1) Ile462Val polymorphism and cervical cancer risk, but the results remain inconclusive. To provide a more robust estimate of this effect, a meta-analysis was carried out. We systematically searched PubMed, Embase and CBM databases for studies published before May 2012. The association between CYP1A1 Ile462Val polymorphism and cervical cancer risk was assessed by calculating pooled odds ratios (OR) with its 95?% confidence intervals (95?% CI). On the basis of our inclusion criteria, ten studies with a total of 2,423 individuals were included in the meta-analysis. Overall, CYP1A1 Ile462Val polymorphism was associated with increased risk of cervical cancer (Val versus Ile, OR?=?1.43; 95?% CI, 1.03?C1.97; ValVal versus IleIle, OR?=?2.43; 95?% CI, 1.19?C4.95; ValVal+ValIle versus IleIle, OR?=?1.59; 95?% CI, 1.00?C2.53). Ethnic subgroup analyses showed a significant association was found in Caucasians (Val versus Ile, OR?=?2.03; 95?% CI, 1.17?C3.51; ValVal versus IleIle, OR?=?2.74; 95?% CI, 1.30?C5.75; ValVal+ValIle versus IleIle, OR?=?2.50; 95?% CI, 1.33?C4.70), but not in Asians. In conclusion, this meta-analysis suggests that CYP1A1 Ile462Val polymorphism plays an important role in susceptibility to cervical cancer. Further studies with large sample size and careful design need performing to identify this association more comprehensively.     

Quantitative assessment of the association between GSTP1 gene Ile105Val polymorphism and susceptibility to hepatocellular carcinoma

Glutathione S-transferase P1 (GSTP1) gene Ile105Val polymorphism has been suggested to be involved in the development of cancer. However, the results from the studies regarding the association between GSTP1 Ile105Val polymorphism and hepatocellular carcinoma risk have been inconsistent. Thus, we performed a meta-analysis to investigate the association. Published literature from PubMed, Chinese Biomedical Literature, and Wanfang databases was searched for eligible publications. Pooled odds ratios (ORs) with 95 % confidence intervals (95 %CIs) were calculated using random- or fixed-effects model. Six studies with a total of 1,843 participants were finally included into this meta-analysis. The results suggested there was no association between GSTP1 Ile105Val polymorphism and hepatocellular carcinoma risk under all genetic models (for ValVal vs. IleIle, OR?=?0.79, 95 %CI 0.48–1.29, P?=?0.341; for IleVal vs. IleIle, OR?=?1.05, 95 %CI 0.84–1.30, P?=?0.678; for the dominant model, OR?=?0.91, 95 %CI 0.68–1.20, P?=?0.498; and for the recessive model, OR?=?0.76, 95 %CI 0.47–1.24, P?=?0.269). Subgroup analyses by ethnicity showed there was also no association between GSTP1 Ile105Val polymorphism and hepatocellular carcinoma risk in Asians under all genetic models (All P values were more than 0.05), but GSTP1 Ile105Val polymorphism was associated with decreased risk of hepatocellular carcinoma in European under the recessive model (ValVal vs. IleVal/IleIle) (OR?=?0.44, 95 %CI 0.20–0.98, P?=?0.044). In conclusion, the meta-analysis suggests that there is little evidence for the association between GSTP1 Ile105Val polymorphism and hepatocellular carcinoma risk. However, more well-designed studies are needed to further assess this association.     

Glutathione S-transferase P1 Ile105Val polymorphism contributes to increased risk of gastric cancer in East Asians

Glutathione S-transferase P1 (GSTP1) is an important enzyme playing critical roles in the phase II detoxification pathway. There were many studies investigating the association between GSTP1 gene Ile105Val polymorphism and gastric cancer risk, but studies from East Asians reported inconsistent findings. We performed a meta-analysis to investigate the association in East Asians. Published literature from PubMed and Chinese Biomedical Literature databases were searched for eligible publications. Pooled odds ratios (ORs) with 95 % confidence intervals (95 %CIs) were calculated using random or fixed-effect model according the between-study heterogeneity. A total of 12 studies with 2,552 cases and 5,474 controls were finally included into the meta-analysis. Meta-analysis of those 12 studies showed that there was an obvious association between GSTP1 Ile105Val polymorphism and gastric cancer risk in East Asians under three genetic models (for valine vs. isoleucine, OR?=?1.32, 95 %CI 1.05–1.66, P?=?0.015; for ValVal vs. IleIle, OR?=?2.00, 95 %CI 1.34–2.98, P?=?0.001; for the recessive model, OR?=?1.96, 95 %CI 1.35–2.83, P?<?0.001). Sensitivity analysis by removing one study at a time suggested the pooled results were stable under the three genetic models above. There was no risk of publication bias. In conclusion, the meta-analysis suggests that there is a strong evidence for the association between GSTP1 Ile105Val polymorphism and increased risk of gastric cancer in East Asians and contributes to increased risk of gastric cancer in East Asians.     

Quantitative assessment of the association between glutathione S-transferase P1 Ile105Val polymorphism and bladder cancer risk

Previous studies investigating the association between glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and bladder cancer risk reported controversial results. This study aimed to quantify the strength of the association between GSTP1 Ile105Val polymorphism and bladder cancer risk by performing a meta-analysis. We searched the PubMed, Embase, and Wanfang databases for publications on the association between GSTP1 Ile105Val polymorphism and bladder cancer risk. We estimated the pooled odds ratios (ORs) with their confidence intervals (95 %CIs) to assess the association. Twenty-five individual studies with a total of 12,360 subjects were finally included. Meta-analysis of all 25 studies showed that GSTP1 Ile105Val polymorphism was associated with increased risk of bladder cancer risk under four genetic comparison models (for G versus A, random-effect OR?=?1.19, 95 %CI 1.05–1.35; for GG versus AA, random-effect OR?=?1.49, 95 %CI 1.12–1.97; for GG/GA versus AA, random-effect OR?=?1.20, 95 %CI 1.03–1.39; for GG versus GA/AA, random-effect OR?=?1.41, 95 %CI 1.10–1.80). Sensitivity analysis showed that GSTP1 Ile105Val polymorphism was still associated with bladder cancer risk under three genetic comparison models (for G versus A, random-effects OR?=?1.13, 95 %CI 1.01–1.26; for GG versus AA, random-effects OR?=?1.29, 95 %CI 1.01–1.65; for GG versus GA/AA, random-effects OR?=?1.19, 95 %CI 1.04–1.35). No evidence of publication bias was observed. This meta-analysis shows that there is an obvious association between GSTP1 Ile105ValIle105Val polymorphism and bladder cancer risk, and GSTP1 ILE105VAL polymorphism contributes to bladder cancer risk.     

Cytochrome P450 1A1 Ile462Val polymorphism and oral carcinoma risk: an updated meta-analysis including 1,515 cases and 2,233 controls

Cytochrome P450 (CYP) 1A1 Ile462Val (exon7) polymorphism has been suggested to be a risk factor for several cancers. Published data on its association with oral cancer risk have generated conflicting results. Our previous meta-analysis containing data from prior to Jan 2008 regarding this issue failed to find a significant association between CYP1A1 Ile462Val variation and oral cancer susceptibility. An updated meta-analysis with eligible studies for the period up to May 2012 was conducted. Separate analyses on ethnicity and source of controls were also performed. A total of 13 case?Ccontrol studies comprising 1,515 cases and 2,233 controls were lastly selected for analysis. Compared with the previous meta-analysis, the overall data also failed to indicate a significant association of CYP1A1 Ile462Val polymorphism with oral cancer risk (Val/Val vs. Ile/Ile??OR?=?1.46; 95?% CI?=?0.96?C2.24; dominant model??OR?=?1.01; 95?% CI?=?0.81?C1.25; and recessive model??OR?=?1.46; 95?% CI?=?0.96?C2.23). However, in the subgroup analysis by ethnicity, increased cancer risk was observed among Asians under the additive and recessive models (Val/Val vs. Ile/Ile??OR?=?1.74; 95?% CI?=?1.04?C2.90 and recessive model??OR?=?1.73; 95?% CI?=?1.04?C2.87), inconsistent with the previous meta-analysis. Collectively, the data of the present study suggest that CYP1A1 variant Val/Val alleles might modify the susceptibility to oral cancer among Asians. Further well-designed investigations with large sample sizes are required to confirm this conclusion.     

Lack of Association Between the CYP1A1 Ile462Val Polymorphism and Endometrial Cancer Risk: a Meta-analysis

Purpose: Any association between the CYP1A1 Ile462Val polymorphism and endometrial cancer risk remainsinconclusive. For a more precise estimate, we performed the present meta-analysis. Methods: PUBMED, OVIDand EMBASE were searched for the studies which met inclusion criteria. Data in all eligible studies wereevaluated and extracted by two authors independently. The meta-analysis estimated pooled odds ratio (OR) with95% confidence interval (CI) for endometrial cancer risk attributable to the CYP1A1 Ile462Val polymorphism.Results: A total of 7 studies were included in this meta-analysis. The results indicated no association betweenendometrial cancer risk and the CYP1A1 Ile462Val polymorphism (for Val vs Ile allele model [OR 1.09, 95%CI 0.73-1.62]; for Val.Val vs Ile.Ile genotype model [OR 1.54, 95% CI 0.56-4.23]; for (Ile.Val + Val.Val) vs Ile.Ilegenotpye model [OR 1.08, 95% CI 0.71-1.63]; for Val.Val vs (Ile.Ile + Ile.Val) genotype model [OR 1.46, 95% CI0.53-4.04]). Conclusions: This meta-analysis suggests that there is no association between endometrial cancerrisk and the CYP1A1 Ile462Val polymorphism.     

Cytochrome P450 1A1 (CYP1A1) polymorphism and susceptibility to esophageal cancer: an updated meta-analysis of 27 studies

Cytochrome P450 1A1 (CYP1A1) polymorphisms are known to play a crucial role in the development and metastasis of malignant diseases including esophageal cancer. However, the results of previous studies investigating the association between CYP1A1 polymorphisms and esophageal cancer risk have been inconsistent. This meta-analysis of 27 eligible studies, encompassing 4,215 esophageal cancer cases and 6,339 control subjects, pooled the odds ratios (ORs) with corresponding 95 % confidence intervals (95 % CI) to assess this association. The effects of ethnicity (Caucasian and Asian) and histopathology type (esophageal squamous cell carcinoma and esophageal adenocarcinoma) were considered in subgroup analyses. A significant association was observed between the CYP1A1 Ile/Val gene polymorphism and esophageal cancer in all of the genetic models (Ile/Val vs. Ile/Ile, OR?=?1.41, 95 % CI?=?1.25–1.58; Val/Val vs. Ile/Ile, OR?=?1.94, 95 % CI?=?1.34–2.82; Ile/Val?+?Val/Val vs. Ile/Ile, OR?=?1.49, 95 % CI?=?1.33–1.66). The subgroup analysis based on ethnicity showed that the association between the CYP1A1 Ile/Val polymorphism and esophageal cancer existed in Asian and Caucasian populations. However, no association was observed between the CYP1A1 MspI polymorphism and esophageal cancer in either subgroup or in the overall population. These results suggested that the CYP1A1 Ile/Val polymorphism was associated with an increased risk of esophageal cancer, whereas the CYP1A1 MspI polymorphism may not have increased susceptibility to esophageal cancer. Further studies are required to confirm these findings.     

Association between the GSTP1 Ile105Val polymorphism and prostate cancer risk: a systematic review and meta-analysis

Many studies have reported the role of glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism with prostate cancer (PCa) risk. However, these studies have yielded conflicting results. Hence, we performed this meta-analysis to investigate the association between GSTP1 Ile105Val polymorphism and PCa in different inheritance models. A total of 13 eligible studies were pooled into this meta-analysis. There was significant association between the GSTP1 Ile158Val variant genotypes and PCa for Ile/Ile vs Val/Val comparison [odds ratio (OR)?=?0.705; I ²?=?63.7 %; 95 % confidence interval (95 % CI)?=?0.508–0.977], Ile/Val vs Val/Val comparison (OR?=?0.736; I ²?=?8.0 %; 95 % CI?=?0.613–0.883), and dominant model (OR?=?0.712; I ²?=?45.5 %; 95 % CI?=?0.555–0.913). However, no associations were detected for other genetic models. In the stratified analysis by ethnicity, significant associations between GSTP1 Ile105Val polymorphism and PCa risk were also found among Caucasians (Ile/Ile vs Val/Val comparison OR?=?0.818, I ²?=?0.0 %, 95 % CI?=?0.681–0.982; Ile/Val vs Val/Val comparison OR?=?0.779, I ²?=?0.0 %, 95 % CI?=?0.651–0.933; and dominant model OR?=?0.794, I ²?=?0.0 %, 95 % CI?=?0.670–0.941), while there were no associations found for other genetic models. However, no associations were found in Asians and African-Americans for all genetic models when stratified by ethnicity. In conclusion, our meta-analysis indicates that GSTP1 Ile105Val polymorphisms contributed to the PCa susceptibility. However, a study with the larger sample size is needed to further evaluate gene–environment interaction on GSTP1 Ile105Val polymorphisms and PCa risk.     

Genetic polymorphisms in glutathione S-transferases P1 (GSTP1) Ile105Val and prostate cancer risk: a systematic review and meta-analysis

Numerous epidemiological studies have evaluated the association between the glutathione S-transferases P1 (GSTP1) Ile105Val polymorphisms and prostate cancer (PCa) risk. However, these studies have yielded conflicting results. A comprehensive search was conducted through researching MEDLINE, PubMed, Web of Science, and EMBASE, and a total of 13 studies including 3,227 cases and 3,945 controls were identified. A meta-analysis was performed to obtain a summary of estimated odds ratios (ORs) and 95 % confidence intervals (CIs) of GSTP1 polymorphisms for PCa, with attention to study quality and publication bias. The GSTP1 Ile158Val variant genotypes are less associated with increased risk of PCa for the homozygote model (Val/Val vs Ile/Ile: OR?=?1.42; I ²? =?63.7 %; 95 % CI?=?1.02–1.97) and the recessive model (OR?=?1.41; I ²? =?45.5 %; 95 % CI?=?1.10–1.80). However, no associations were detected for other genetic models. In the stratified analysis by ethnicity, significant associations between GSTP1 Ile105Val polymorphism and PCa risk were also found among Caucasians for Val/Val vs Ile/Ile comparison (OR?=?1.22; I ²? =?0.0 %; 95 % CI?=?1.02–1.47) and for the recessive model (OR?=?1.26; I ²? =?0.0 %; 95 % CI?=?1.06–1.49), while there were no associations found for other genetic models. However, no associations were found in Asians and African-Americans for all genetic models when stratified by ethnicity. In conclusion, our meta-analysis provides evidence that GSTP1 Ile105Val gene polymorphisms contributed to PCa susceptibility.     

The CYP1B1 Leu432Val polymorphism and risk of urinary system cancers

The cytochrome P450 1B1 (CYP1B1) gene plays a key role in the metabolism of various carcinogens. The CYP1B1 Leu432Val polymorphism leads to leucine to valine substitution at codon 432. A lot of studies have shown that the CYP1B1 Leu432Val polymorphism was associated with urinary system cancers, especially prostate cancer. However, the results were still inconclusive. In this meta-analysis, by searching online databases and references of related reviews, we identified 17 eligible studies to assess the relationship between CYP1B1 Leu432Val polymorphism and urinary system cancers, including 7,783 cancer cases and 7,238 controls. By pooling all eligible studies, we found that the CYP1B1 Leu432Val polymorphism was not associated with overall urinary system cancers. However, in subgroup analyses, we found that the variant 432Val allele significantly increased the risk of prostate cancer (Val vs. Leu, odds ratio (OR)?=?1.064, 95 % confidence interval (CI) 0.981–1.154; P _{heterogeneity}?=?0.002), while no association was found for bladder cancer (Val vs. Leu, OR?=?0.942, 95 % CI 0.853–1.041; P _{heterogeneity}?=?0.504). No evidence of publication bias was found (Begg’s test, P?=?0.053; Egger’s test, P?=?0.073). In conclusion, based on 17 eligible studies, we found that the CYP1B1 Leu432Val polymorphism was associated with an increased risk of prostate cancer, while no association of bladder cancer was observed.     

CYP1A1 exon7 polymorphism is associated with lung cancer risk among the female population and among smokers: a meta-analysis

The genetic polymorphism of the CYP1A1 exon7 (rs1048943) gene is thought to have a significant effect on lung cancer risk, but the results are inconsistent. To assess this relationship more precisely, a meta-analysis was performed. Ultimately, 45 case–control studies, involving 19,689 subjects were included. A significantly increased lung cancer risk was associated with two exon7 genotype variants (for Val/Val vs Ile/Ile: odds ratio [OR]?=?1.23, 95 % confidence interval [CI]?=?1.10–1.43; for (Ile/Val?+?Val/Val) vs Ile/Ile: OR?=?1.16, 95 % CI?=?1.08–1.24) in the overall population. In the stratified analysis by ethnicity, gender, and smoking status, a significant association was found in Asians, Caucasians, and the female population, not the male population. Additionally, a significant association was found in the smoker population, not in the nonsmoker population. This meta-analysis suggests that the exon7 polymorphisms of CYP1A1 correlate with increased lung cancer susceptibility and there is an interaction between CYP1A1 exon7 polymorphisms and smoking, but these associations vary in different genders of the case and control populations.     

Associations of CYP2E1 rs2031920 and rs3813867 polymorphisms with colorectal cancer risk: a systemic review and meta-analysis

Cytochrome P450 2E1 (CYP2E1) is a natural enzyme involved in the metabolic activation of many carcinogens, and the functional polymorphisms in the CYP2E1 gene might have impacts on colorectal cancer risk. Many studies were published to assess the associations of CYP2E1 rs2031920 and rs3813867 polymorphisms with colorectal cancer risk, but no consistent findings were reported. A systemic review and meta-analysis of eligible studies was performed to comprehensively assess the associations above. Odds ratios (ORs) with 95 % confidence interval (95 % CIs) were used to assess the strength of the associations. Seventeen studies from 15 publications with 17,082 individuals were finally included into this meta-analysis. Meta-analysis of the 13 studies on CYP2E1 rs2031920 polymorphism showed that there was a significant association between CYP2E1 rs2031920 polymorphism and colorectal cancer risk under two genetic models (c2 versus c1: OR?=?1.19, 95 % CI 1.03–1.37, P?=?0.022; c2c2/c2c1 versus c1c1: OR?=?1.16, 95 % CI 1.00–1.35, P?=?0.046). Meta-analysis of those four case–control studies on CYP2E1 rs3813867 polymorphism showed that there was no significant association between CYP2E1 rs3813867 polymorphism and colorectal cancer risk under all contrast models (c2 versus c1: OR?=?0.96, 95 % CI 0.80–1.16, P?=?0.672; c2c2 versus c1c1: OR?=?1.26, 95 % CI 0.43–3.67, P?=?0.672; c2c2/c1c2 versus c1c1: OR?=?0.95, 95 % CI 0.78–1.16, P?=?0.114; and c2c2 versus c1c2/c1c1: OR?=?1.17, 95 % CI 0.41–3.36, P?=?0.775). Therefore, the findings from this meta-analysis suggest that CYP2E1 rs2031920 polymorphism is associated with colorectal cancer risk, but CYP2E1 rs3813867 polymorphism is not associated with colorectal cancer risk. In addition, more well-designed studies with large sample size are needed to provide a more precise evaluation on the associations above.     

CYP2E1 T7632A and 9-bp insertion polymorphisms and colorectal cancer risk: a meta-analysis based on 4,592 cases and 5,918 controls

Previous studies suggest that genetic factors play important roles in the development of colorectal cancer. CYP2E1 T7632A and 9-bp insertion polymorphisms may influence the risk of colorectal cancer, but published results are conflicting. We therefore conducted a meta-analysis comprising 9 case–control studies with 4,592 cases and 5,918 controls. Odds ratios (ORs) with 95 % confidence interval (95 % CI) were used to assess the strength of the associations of CYP2E1 T7632A and 9-bp insertion polymorphisms with colorectal cancer. For CYP2E1 T7632A polymorphism, meta-analysis showed that there was no significant association between the CYP2E1 T7632A polymorphism and colorectal cancer risk under all contrast models (A vs. T: OR?=?1.06, 95 % CI 0.88–1.29, P?=?0.528; AA vs. TT: OR?=?0.85, 95 % CI 0.61–1.19, P?=?0.351; AA/TA vs. TT: OR?=?1.08, 95 % CI 0.87–1.34, P?=?0.484; and AA vs. TT/TA: OR?=?0.87, 95 % CI 0.62–1.21, P?=?0.395). For CYP2E1 96-bp insertion polymorphism, meta-analysis showed that there was a significant association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk under the allele contrast model and the dominant contrast model (for the allele contrast model: OR?=?1.20, 95 % CI 1.06–1.36, P?=?0.005; for the dominant contrast model: OR?=?1.25, 95 % CI 1.07–1.45, P?=?0.005). Subgroup analysis by race suggested that there was an obvious association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk in Asians under the codominant contrast model. In conclusion, our meta-analysis demonstrates that there is a significant association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk, and CYP2E1 9-bp insertion polymorphism is a risk factor for developing colorectal cancer.     

CYP1A2 rs762551 polymorphism contributes to risk of lung cancer: A meta-analysis

Previous studies proposed that CYP1A2 rs762551 polymorphism might be associated with risk of lung cancer by influencing the function of CYP1A2. However, previous studies on the association between CYP1A2 rs762551 polymorphism and risk of lung cancer reported inconsistent findings. We performed a meta-analysis of the published case–control studies to assess the association between CYP1A2 rs762551 polymorphism and risk of lung cancer. PubMed and Embase were searched to identify relevant studies on the association between CYP1A2 rs762551 polymorphism and risk of lung cancer, and seven studies with a total of 3,320 subjects were finally included into the meta-analysis. The pooled odds ratio (OR) and 95 % confidence interval (95%CI) was calculated to evaluate the association. Meta-analysis of total studies showed that CYP1A2 rs762551 polymorphism contributed to risk of lung cancer under all four genetic models (C versus A: OR?=?1.26, 95%CI 1.13 to 1.40, P?<?0.001; CC versus AA: OR?=?1.61, 95%CI 1.28 to 2.04, P?<?0.001; CC versus AA/AC: OR?=?1.52, 95%CI 1.11 to 2.09, P?=?0.009; CC/AC versus AA: OR?=?1.28, 95%CI 1.10 to 1.48, P?=?0.001). Subgroup analysis based on ethnicity further suggested that CYP1A2 rs762551 polymorphism was associated with risk of lung cancer in Caucasians. These results from the meta-analysis suggest that CYP1A2 rs762551 polymorphism contributes to risk of lung cancer.     

Association between GSTP1 Ile105Val polymorphism and glioma risk: A systematic review and meta-analysis

Glutathione S-transferase P1 (GSTP1) gene Ile105Val polymorphism has been suggested to be involved in the development of glioma. However, the results from the studies regarding the association between GSTP1 Ile105Val polymorphism and glioma risk have been inconsistent. Thus, we performed a meta-analysis to investigate this association. Pooled odds ratios (ORs) with 95 % confidence intervals (95 %CIs) were calculated using random or fixed effects model. Nine studies with 2,078 cases and 3,970 controls were finally included into this meta-analysis. The results suggested there was no association between GSTP1 Ile105Val polymorphism and glioma risk under recessive model (OR?=?1.138, 95 %CI?=?0.966–1.341, P _{heterogeneity}?=?0.088, P?=?0.123). Subgroup analyses by ethnicity showed there was also no association between GSTP1 Ile105Val polymorphism and glioma risk in mixed populations under recessive model (OR?=?1.199, 95 %CI?=?0.928–1.549, P _{heterogeneity}?=?0.060, P?=?0.166) and Caucasian populations(OR?=?1.097, 95 %CI?=?0.885–1.360, P _{heterogeneity}?=?0.186, P?=?0.398). In conclusion, the meta-analysis suggests that there is no association between GSTP1 Ile105Val polymorphism and glioma risk. However, more well-designed and larger studies are needed to further assess this association.     

CYP1B1, CYP1A1, MPO, and GSTP1 polymorphisms and lung cancer risk in never-smoking Korean women

Polymorphisms in metabolic genes encoding phase I and phase II enzymes are thought to modulate the risk of lung cancer via changes in enzymatic activity. Recently, the effect of these metabolic enzymes and their interaction with environmental factors has been studied in both smokers and also never-smokers, since never-smokers are a good model in which to study genetic susceptibility at low-dose carcinogen exposure. Here, we investigated the association of CYP1A1 Ile462Val, CYP1B1 Leu432Val, GSTP1 Ile105Val, MPO G-463A polymorphisms and lung cancer risk in never-smoking Korean women. In this case-control study of 213 lung cancer patients and 213 age-matched healthy controls, we found that carrying one variant allele of the CYP1A1 Ile462Val polymorphism was associated with a significantly decreased risk of lung adenocarcinoma (adjusted odds ratio (OR)=0.63; 95% confidence interval (CI), 0.41-0.99). Furthermore, the combination of risk genotypes of CYP1B1 Leu432Val with CYP1A1 Ile462Val was associated with the risk of lung adenocarcinoma (adjusted OR=2.16; 95% CI, 1.02-4.57) as well as overall lung cancer (adjusted OR=2.23; 95% CI 1.01-4.89). The polymorphisms of GSTP1 Ile105Val and MPO G-463A showed no significant association with lung cancer. Theses results suggest that the CYP1A1 Ile462Val polymorphism is associated with a reduced risk of lung adenocarcinoma in never-smoking Korean women, whereas specific combinations of variant genotypes for metabolic enzymes increase lung cancer risk considerably.     

CYP1A1 and CYP2E1 genotypes and risk of esophageal squamous cell carcinoma in a high-incidence region,Kashmir

The study analyzed the relationship between genetic polymorphisms of phase I xenobiotic metabolizing enzymes, cytochromes P450 (CYP) 1A1 and CYP2E1 and esophageal squamous cell carcinoma (ESCC) in Kashmir, India. The different genotypes of CYP1A1 and CYP2E1 were analyzed by polymerase chain reaction and restriction fragment length polymorphism in 526 ESCC cases and equal number of matched controls. Conditional logistic regression models were used to assess the association of various genotypes with ESCC, gene–gene, and gene–environment interactions. High risk of ESCC was found in participants who carried CYP1A1 Val/Val genotype (OR?=?2.87; 95 % CI?=?1.00–8.44) and the risk increased in such individuals when c1/c1 of CYP2E1 genotype was also present (OR?=?5.68; 95 % CI?=?1.09–29.52). Risk due to CYP1A1 Val/Val genotype was further enhanced (OR?=?8.55; 95 % CI?=?1.86–42.20) when the analysis was limited to ever smokers. Participants who carried CYP2E1 c1/c2 genotype showed an inverse relation (OR?=?0.27; 95 % CI?=?0.17–0.43) with ESCC. The inverse association of CYP2E1 c1/c2 genotype was retained when CYP1A1 Ile/Ile was also present (OR?=?0.18; 95 % CI?=?0.09–0.32), as well as when analysis was limited to ever smokers (OR?=?0.45; 95 % CI?=?0.23–0.90). Significant interaction was found between CYP1A1 (Val/Val) and CYP2E1 (c1/c1) genotypes (OR?=?1.30; 95 % CI?=?1.12–1.51; P?=?0.001) and between CYP1A1 (Val/Val) and smoking (OR?=?1.31; 95 % CI?=?1.01–1.69; P?=?0.043). The study suggests CYP1A1 Val/Val and CYP2E1 c1/c1 genotypes are significantly associated with ESCC risk.     

Quantitative assessment of the associations between CYP1A1 polymorphisms and gastric cancer risk

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.     

Association between NQO1 C609T polymorphism and colorectal cancer risk

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme, and the NQO1 C609T polymorphism is associated with the enzymatic activity of NQO1. Many studies were performed to assess the association between NQO1 C609T polymorphism and colorectal cancer risk, but no consensus was available up to now. We conducted a meta-analysis to examine the association between NQO1 C609T polymorphism and colorectal cancer risk, and the pooled odds ratios (OR) with their 95 % confidence intervals (95 % CI) were used to assess the association. Finally, 12 studies involving 4,026 cases and 4,855 controls were included into the meta-analysis. Overall, there was an obvious association between NQO1 C609T polymorphism and colorectal cancer risk (T versus C: OR?=?1.28, 95 % CI 1.08–1.51, P?=?0.005; TT versus CC: OR?=?1.60, 95 % CI 1.10–2.33, P?=?0.015; TT/CT versus CC: OR?=?1.36, 95 % CI 1.09–1.69, P?=?0.006; TT versus CT/CC: OR?=?1.37, 95 % CI 1.05–1.80, P?=?0.022). Subgroup analysis by ethnicity showed that the association was obvious in both Caucasians and Asians. Therefore, the meta-analysis provides strong evidence for the association between NQO1 C609T polymorphism and colorectal cancer risk, and the T allele of NQO1 C609T polymorphism is an important risk factor of colorectal cancer.     

Association between the CYP3A4 and CYP3A5 polymorphisms and cancer risk: a meta-analysis and meta-regression

Previously published data on the association between CYP3A4 A392G and CYP3A5 Met235Thr polymorphisms and the risk of cancer remained controversial. Thus, we performed a meta-analysis to investigate the association between cancer susceptibility and CYP3A4 A392G (18,629 cases and 22,323 controls from 49 studies) and CYP3A5 Met235Thr polymorphisms (14,334 cases and 18,183 from 39 studies) in different inheritance models. We used odds ratios with 95 % confidence intervals to assess the strength of the association. Overall, significant association was found between CYP3A4 A392G polymorphism and cancer susceptibility (dominant model, odds ratio (OR) = 1.19; 95 % confidence interval (CI) = 1.03–1.38). In the further stratified and sensitivity analyses, significant increased prostate cancer risk was found among Caucasians (dominant model, OR?=?1.88; 95 % CI?=?1.20–2.95; recessive model, OR?=?2.10; 95 % CI?=?1.23–3.60; additive model, OR?=?1.80, 95 % CI?=?1.24–2.63; homozygous model, OR?=?2.34, 95 % CI?=?1.36–4.03; heterozygote model, OR?=?1.79, 95 % CI?=?1.11–2.89) for CYP3A4 A392G. For CYP3A5 Met235Thr polymorphism, no significant association was found among overall analysis and any subgroup analysis. In summary, this meta-analysis suggests that CYP3A4 A392G polymorphism is associated with increased prostate cancer risk among Caucasians and CYP3A5 Met235Thr polymorphism is not associated with the risk of cancer.