Cytochrome P450 1A1 MspI Polymorphisms Research Articles

Association between the combined effects of GSTM1 present/null and CYP1A1 MspI polymorphisms with lung cancer risk: an updated meta-analysis.

Background: Many studies have been performed to explore the combined effects of glutathione-S-transferase M1 (GSTM1) present/null and cytochrome P4501A1 (CYP1A1) MspI polymorphisms with lung cancer (LC) risk, but the results are contradictory. Two previous meta-analyses have been reported on the issue in 2011 and 2014. However, several new articles since then have been published. In addition, their meta-analyses did not valuate the credibility of significantly positive results.Objectives: We performed an updated meta-analysis to solve the controversy following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Methods: False-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and the Venice criteria were used to verify the credibility of meta-analyses.Results: Twenty-three publications including 5734 LC cases and 7066 controls met the inclusion criteria in the present study. A significantly increased risk of LC was found in overall analysis, Asians and Indians. However, all positive results were considered as ‘less-credible’ when we used the Venice criteria, FPRP, and BFDP test to assess the credibility of the positive results.Conclusion: These positive findings should be interpreted with caution and results indicate that significant associations may be less-credible, there are no significantly increased LC risk between the combined effects of GSTM1 present/null and CYP1A1 MspI polymorphisms.

The cytochrome P4501A1 gene polymorphisms and endometriosis: a meta-analysis.

Cytochrome P450 1A1 (CYP1A1) polymorphisms were implicated in endometriosis risk, but individual published studies showed inconclusive results. Thus, a meta-analysis was performed to clarify the effect of CYP1A1 polymorphisms on endometriosis risk. PubMed, Embase, and CNKI databases were searched to identify the eligible studies focusing on the associations between CYP1A1 MspI and Ile462Val polymorphisms and susceptibility to endometriosis. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for CYP1A1 polymorphisms and endometriosis were calculated. Pooled analysis of 12 studies involved a total of 1555 cases and 2868 controls showed that in all genetic models, no significant association between CYP1A1 MspI polymorphism and endometriosis risk was observed in the overall, Asians and Caucasians population, respectively. Interestingly, increased endometriosis risk was associated with carrying the C allele of CYP1A1 combined with GSTM1 null genotypes. For CYP1A1 Ile462Val polymorphism, eight studies were available (878 cases and 1991 controls). In the overall analysis, CYP1A1 Ile462Val polymorphism had a statistically significant association with increased endometriosis risk in allele contrast and all genetic models except the model of Val/Ile vs. Ile/Ile. In the subgroup analysis by ethnicity, significant elevated endometriosis risk was associated with CYP1A1 Ile462Val polymorphism in Asians but not in Caucasians under all genetic models. No publication bias was found in the present studies. This meta-analysis suggested that CYP1A1 Ile462Val polymorphism was associated with an increased risk of endometriosis, particularly in Asians. CYP1A1 MspI polymorphism may not be associated with endometriosis risk, but GSTM1 and CYP1A1 MspI polymorphism may have a joint effect on endometriosis risk.

Association between cytochrome P450 1A1 (CYP1A1) gene polymorphisms and the risk of renal cell carcinoma: a meta-analysis.

Cytochrome P450 1A1 (CYP1A1) usually metabolizes carcinogens to their inactive derivatives but occasionally converts the chemicals to more potent carcinogens. To date, many studies have evaluated the association between the CYP1A1 MspI and Ile462Val polymorphisms and renal cell carcinoma (RCC) risk, but the results have been conflicting. To more precisely evaluate the potential association, we carried out a meta-analysis of seven published case-control studies. The meta-analysis indicated that the MspI polymorphism was associated with an increased RCC risk (allele model: OR = 1.49, 95%CI 1.03–2.16; homozygous model: OR = 1.64, 95%CI 1.13–2.40; dominant model: OR = 1.72, 95%CI 1.07–2.76). No significant associations were found for the Ile462Val polymorphism for all genetic models. When stratified by smoking status, smokers carrying the variant Vt and Val allele were more susceptible to RCC (Vt allele: OR = 3.37, 95%CI = 2.24–5.06; Val allele: OR = 2.07, 95%CI = 1.34–3.19). These data indicate that the CYP1A1 MspI polymorphism significantly increased RCC risk, while the Ile462Val polymorphism was not associated with RCC. Among smokers, individuals with the CYP1A1 Vt allele and Val allele showed a significantly increased risk of RCC. More well-designed studies with larger samples are warranted to show the underlying mechanisms of CYP1A1 in the development of RCC.

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.

Meta-analysis of association studies of CYP1A1 genetic polymorphisms with digestive tract cancer susceptibility in Chinese.

A great number of studies have shown that cytochrome P450 1A1 (CYP1A1) genetic polymorphisms, CYP1A1 Msp I and CYP1A1 Ile/Val, might be risk factors for digestive tract cancers, including esophageal cancer (EC), gastric cancer (GC), hepatic carcinoma (HC), as well as colorectal cancer (CC), but the results are controversial. In this study, a meta-analysis of this literature aimed to clarify associations of CYP1A1 genetic polymorphisms with digestive tract cancer susceptibility in Chinese populations. Eligible case-control studies published until December 2013 were retrieved by systematic literature searches from PubMed, Embase, CBM, CNKI and other Chinese databases by two investigators independently. The associated literature was acquired through deliberate search and selection based on established inclusion criteria. Fixed- effects or random-effects models were used to estimate odds ratios (ORs and 95%CIs). The meta-analysis was conducted using Review Manager 5.2 and Stata 12.0 softwares with stability evaluated by both stratified and sensitivity analyses. Moreover, sensitivity analysis and publication bias diagnostics confirmed the reliability and stability. Eighteen case control studies with 1, 747 cases and 2, 923 controls were selected for CYP1A1 MspI polymorphisms, and twenty case-control studies with 3, 790 cases and 4, 907 controls for the CYP1A1 Ile/ Val polymorphisms. Correlation associations between CYP1A1 Ile/Val polymorphisms and digestive tract cancers susceptibility were observed in four genetic models in the meta-analysis (GG vs AA:OR= 2.03, 95%CI =1.52- 2.72; AG vs AA: OR=1.26, 95%CI =1.07-1.48; [ GG+AG vs AA] :OR =1.42, 95%CI=1.20-1.68, [GG vs AA+AG ]:OR=1.80, 95%CI =1.40-2.31). There was no association between CYP1A1 Msp I polymorphisms and digestive tract cancer risk. Subgroup analysis for tumor type showed a significant association of CYP1A1 Ile/Val genetic polymorphisms with EC in China. However, available data collected by the study failed to reveal remarkable associations of GC or HC with CYP1A1 Ile/Val genetic polymorphisms and EC, GC or CC with CYP1A1 MspI genetic polymorphisms. Our results indicated that CYP1A1 Ile/Val genetic polymorphisms, but not CYP1A1 Msp I polymorphisms, are associated with an increased digestive tract cancer risk in Chinese population. Additional well-designed studies, with larger sample size, focusing on different ethnicities and cancer types are now warranted to validate this finding.

Association between cytochrome P450 1A1 MspI polymorphism and endometrial cancer risk: a meta-analysis

Many studies proposed that cytochrome P450 1A1 (CYP1A1) MspI polymorphism may be associated with endometrial cancer risk, but the findings from previous studies reported conflicting results. A meta-analysis of all relevant studies was performed to get a comprehensive assessment of the association between CYP1A1 MspI polymorphism and endometrial cancer risk. Eligible studies were searched in PubMed and China National Knowledge Infrastructure databases. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to evaluate the association. Twelve studies with a total of 2,111 cases and 2,894 controls were finally included into the meta-analysis. Overall, meta-analysis of a total of 12 studies showed that there was no obvious association between CYP1A1 MspI polymorphism and endometrial cancer risk (ORC vs. T = 0.97, 95 % CI 0.77-1.22, P OR = 0.808; ORCC vs. TT = 1.00, 95 % CI 0.57-1.76, P OR = 0.994; ORCC vs. TT/TC = 0.88, 95 % CI 0.65-1.20, P OR = 0.425; ORCC/TC vs. TT = 0.98, 95 % CI 0.74-1.29, P OR = 0.861). Subgroup analyses by ethnicity further showed that there was no obvious association between CYP1A1 MspI polymorphism and endometrial cancer risk in both Caucasians and Asians. There was no obvious risk of publication bias. Therefore, the meta-analysis suggests that CYP1A1 MspI polymorphism is not associated with endometrial cancer risk.

CYP1A1 MspI polymorphism is associated with prostate cancer susceptibility: evidence from a meta-analysis

Cytochrome P450 1A1 (CYP1A1), an important phase I xenobiotic metabolizing enzyme, is responsible for metabolizing numerous carcinogens, particularly polycyclic aromatic hydrocarbons. The genetic polymorphism of CYP1A1 at the site of MspI (CYP1A1 MspI) has been implicated in prostate cancer risk, but the results of individual studies remain conflicting and inconclusive. The aim of this meta-analysis was to investigate the association of CYP1A1 MspI polymorphism with prostate cancer risk more precisely. We performed a comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases from their inception up to September 20, 2012 for relevant publications. The pooled odds ratios with the corresponding 95% confidence intervals (95% CIs) were calculated to assess the association of CYP1A1 MspI polymorphism with prostate cancer risk. In addition, stratified analyses by ethnicity and sensitivity analyses were conducted for further estimation. Sixteen eligible publications with 6,411 subjects were finally included into the meta-analysis after checking the retrieved papers. Overall, meta-analysis of total studies suggested that individuals carrying the TC genotype and a combined C genotype (CC + TC) were more susceptible to prostate cancer (OR(TC vs. TT) = 1.33, 95% CI 1.10-1.61, P(OR) = 0.004; OR(CC+TC vs. TT) = 1.27, 95% CI 1.05-1.55, P(OR) = 0.016). Stratified analysis of high quality studies also confirmed the significant association (OR(TC vs. TT) = 1.32, 95% CI 1.04-1.67, P(OR) = 0.024; OR(CC+TC vs. TT) = 1.30, 95% CI 1.02-1.66, P(OR) = 0.035). In subgroup analyses by ethnicity, a significant association between the CYP1A1 MspI polymorphism and risk of prostate cancer was found among Asians (OR(TC vs. TT) = 1.44, 95% CI 1.20-1.72, P(OR) < 0.001; OR(CC+TC vs. TT) = 1.33, 95% CI 1.12-1.58, P(OR) = 0.001), but not in Caucasians or mixed populations. The meta-analysis suggests an important role of the CYP1A1 MspI polymorphism in the risk of developing prostate cancer, especially in Asians.

Does cytochrome P450 1A1 MspI polymorphism increase acute lymphoblastic leukemia risk? Evidence from 2013 cases and 2903 controls

Previous studies indicated that cytochrome P450 1A1 (CYP1A1) MspI polymorphism might be a possible risk factor for several malignancies. Increasing investigations have been conducted on the association of CYP1A1 MspI polymorphisms with acute lymphoblastic leukemia (ALL). However, the results were controversial. The goal of the present study was to address this controversy by pooling and analyzing the published data. Therefore, quantitative meta-analyses evaluating the association of CYP1A1 MspI variation with ALL were performed and subgroup analyses on ethnicity, age groups and source of controls were further carried out. After a rigorous search in the Medline, EMBASE, OVID, ScienceDirect, and CNKI databases, all eligible studies for the period up to May 2012 were identified and screened according to the inclusion and exclusion criteria. Consequently, a total of fourteen case–control studies including 2013 cases and 2903 controls were selected for analysis. The overall data indicated a significant association of CYP1A1 MspI polymorphism with ALL risk (CC+TC vs TT: OR=1.33; 95%CI=1.05–1.69). In a subgroup analysis according to ethnicity, no associations were shown among Asians, Caucasians and Mixed ethnicity subgroups. In the subgroup analysis regarding age groups, increased risk was observed in the childhood ALL subgroup (C vs T: OR=1.23; 95%CI=1.04–1.45; CC+TC vs TT: OR=1.31; 95%CI=1.08–1.59). In the subgroup analysis stratified by source of controls, significant associations were observed in the population-based subgroup (CC+TC vs TT: OR=1.33; 95%CI=1.03–1.71). In conclusion, the results of the present study suggest that CYP1A1 MspI polymorphism might be a risk factor for ALL, particularly childhood ALL. Future well-designed high quality investigations with large sample sizes are required to elucidate the gene polymorphism–ALL relationship and gene–environment interactions.

Cytochrome P450 1A1 (CYP1A1) polymorphisms and breast cancer risk in Korean women

Cytochrome P450 1A1 (CYP1A1) is involved in the 2-hydroxylation of estrogen, the hormone that plays a critical role in the etiology of breast carcinoma. We evaluated the associations between two CYP1A1 polymorphisms [MspI (rs4646903); Ile462Val (rs1048943)] and breast cancer in a multicenter case-control study of 513 breast cancer cases and 447 controls in Korea. Women carrying the T allele of the CYP1A1 MspI polymorphism were found to have a 1.72-fold (95% CI 1.11-2.68) greater risk of developing breast cancer. No association was found between any CYP1A1 Ile462Val polymorphism and breast cancer. Haplotype analysis of the two loci showed that the CA haplotype was associated with the lowest risk of breast cancer, and CA/CA diplotypes were associated with a lower risk of breast cancer [OR=0.28 (0.13-0.61)] than others/others diplotypes. Moreover, this reduced risk was more pronounced among women with a lower body mass index (BMI) [OR=0.18 (0.06-0.58)] or with a shorter lifetime exposure to estrogen [OR=0.23 (0.07-0.81)]. The results obtained suggest that the CYP1A1 MspI polymorphisms could affect susceptibility to breast cancer.

Cytochrome P450 1A1 and 1B1 in Human Blood Lymphocytes Are Not Suitable as Biomarkers of Exposure to Dioxin-like Compounds: Polymorphisms and Interindividual Variation in Expression and Inducibility

Cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1) are phase I enzymes, the expression of which can be affected by many environmental compounds, including dioxins and dioxin-like compounds. Because CYP1A1 and CYP1B1 expression can easily be determined in peripheral blood lymphocytes, it is often suggested as biomarker of exposure to these compounds. In this study we investigated the interindividual differences in constitutive and induced CYP1A1-catalyzed ethoxyresorufin-O-deethylase (EROD) activity and CYP1A1 and CYP1B1 gene expression in human blood lymphocytes in a group of ten non-smoking females. Freshly isolated lymphocytes were cultured in medium containing the mitogen PHA and were exposed to the most potent dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or the less potent dioxin-like polychlorinated biphenyl 126 (PCB126). In addition, we determined the occurrence of the CYP1A1 MspI and CYP1B1 Leu432Val polymorphisms. All individuals showed a concentration-dependent increase of EROD activity by TCDD, which was significantly correlated with an increase in CYP1A1, but not CYP1B1 expression. The maximum induced EROD activity by TCDD was very different among the individuals, but the EC50 values were about the same. PCB126 also caused a concentration-dependent increase of EROD activity, but was a factor 100-1000 less potent than TCDD among the individuals. The allele frequencies for CYP1A1 MspI and CYP1B1 Leu432Val reflected a normal Caucasian population and in this study the polymorphisms had no apparent effect on the expression and activity of these enzymes. Our study shows a large interindividual variability in constitutive and induced EROD activity, and CYP1A1 and CYP1B1 expression in human lymphocytes. In addition, dioxin concentrations at which effects were observed in our in vitro study are about 10-fold higher than the human blood levels found in vivo, indicating that EROD activity and CYP1A1 and CYP1B1 expression in human lymphocytes might not be applicable as biomarkers of exposure to dioxin and dioxin-like compounds.

A case-control study of cytochrome P450 1A1, glutathione S-transferase M1, cigarette smoking and lung cancer susceptibility (Massachusetts, United States)

Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genetic polymorphisms are involved in the activation and detoxification of chemical carcinogens found in tobacco smoke; thus they may influence host susceptibility to lung cancer. In this study at Massachusetts General Hospital (Boston, MA, USA) of 416 cases and 446 controls (mostly White) we evaluated the association between the CYP1A1 MspI and GSTM1 polymorphisms and lung cancer risk, and their interaction with cigarette smoke. The CYP1A1 MspI heterozygous genotype was present in 18 percent of cases and 16 percent of controls, and one percent of cases and controls were CYP1A1 MspI homozygous variant. The GSTM1 null genotype was detected in 54 percent of cases and 52 percent of controls. After adjusting for age, gender, pack-years of smoking, and years since quitting smoking, while neither the CYP1A1 MspI heterozygous genotype alone nor the GSTM1 null genotype alone were associated with a significant increase in lung cancer risk, having both genetic traits was associated with a twofold increase in risk (95 percent confidence interval [CI] = 1.0-3.4). Our data did not provide enough evidence for a substantial modification of the effect of pack-years on lung cancer risk by the CYP1A1 MspI and GSTM1 genotypes. However, limitations of our study preclude a conclusion about this potential interaction.