Ile105Val Polymorphism Research Articles

GSTP1 Ile105Val polymorphism and colorectal cancer risk: An updated analysis

BackgroundMany studies have investigated the association between the Glutathione S transferase-P1 (GSTP1) Ile105Val polymorphism and colorectal cancer (CRC) susceptibility, but the results were conflicting. The aim of this study is to quantitatively summarize the relationship between this polymorphism and CRC risk. MethodsTwo investigators independently searched the Medline, Embase, China National Knowledge Infrastructure (CNKI) and Chinese Biomedicine databases for studies published before December 2012. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for GSTP1 polymorphism and CRC were calculated in a fixed-effects model (the Mantel–Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. ResultsThis meta-analysis included 29 case–control studies, which included 8160 CRC cases and 10,450 controls. Overall, the variant genotypes (ValVal and IleVal) of the Ile105Val were not associated with CRC risk when compared with the wild-type IleIle homozygote. Similarly, no associations were found in the dominant and recessive models. When stratifying for ethnicity, source of controls, study sample size and genotyping methods, no evidence of significant association was observed in any subgroup, except among those studies taking others as genotyping methods (recessive model, OR=0.71, 95%CI=0.52–0.96). Limiting the analysis to the studies within Hardy–Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study. ConclusionThis updated meta-analysis suggests that the GSTP1 Ile105Val polymorphism may not be associated with CRC risk, while the observed decrease in risk of CRC may be due to small-study bias.

The GSTP1 105Val Allele Increases Breast Cancer Risk and Aggressiveness but Enhances Response to Cyclophosphamide Chemotherapy in North China

The glutathione-S-transferase (GST) family contributes to the inactivation of various toxic compounds formed as secondary metabolites during oxidative stress. GSTP1 accounts for the majority of the GST family enzymatic activity, and the activity of GSTP1 enzyme can be altered by the presence of the Ile105Val polymorphism. In this study, we examined the polymorphic frequency of GSTP1 Ile105Val genotype in 920 breast cancer patients and 783 healthy controls in women of North China. Results showed that GSTP1 105Val allele (Ile/Val and Val/Val) was associated with a higher breast cancer risk (OR = 1.38, 95% CI: 1.14–1.69; P = 0.001) and more aggressive tumors with histological grade III (OR = 1.15, 95% CI: 1.05–1.26; P = 0.001), lymph node metastases (OR = 2.35, 95% CI: 1.72–3.21; P < 0.001), as well as ER negative (OR = 1.77, 95% CI: 1.31–2.39; P < 0.001) than those carrying the Ile/Ile allele. However, the patients with the GSTP1 105Val genotype had a better disease free survival after cyclophosphamide (CTX)-based chemotherapy than those with Ile/Ile (HR = 0.77, 95% CI: 0.45–0.91; P < 0.001). Furthermore, in vitro cellular experiments demonstrated that breast cancer cells with the GSTP1 105Val allele were significantly more sensitive to CTX-induced proliferation inhibition. Thus, we conclude that the GSTP1 105Val allele increases breast cancer risk and aggressiveness and enhance response to CTX-based chemotherapy in women of North China. Detection of the GSTP1 Ile105Val genotype may help screen for high-risk populations and direct individualized therapy.

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.

The polymorphisms in the MGMT gene and the risk of cancer: a meta-analysis

Polymorphisms in the MGMT gene have been implicated in susceptibility to cancer, but the published studies have reported inconclusive results. The objective of the current study was to investigate the genetic risk of polymorphisms in the MGMT gene for cancer. A meta-analysis was carried out to analyze the association between polymorphisms in the MGMT gene and cancer risk. Five polymorphisms (Leu84Phe, Leu53Leu, Ile143Val, Lys178Arg, and -485C/A) with 98 case-control studies from 49 articles were analyzed. The results indicated that individuals who carried the Phe/Phe homozygote genotype of Leu84Phe had a 31 % increased risk of cancer compared with the Leu allele (Leu + Leu/Phe) carriers (odds ratio [OR] = 1.32, 95 % confidence interval [CI] = 1.15-1.52, P < 0.0001 for Phe/Phe vs. Phe/Leu + Leu/Leu). However, there was no significant association between the risk of cancer and the other four polymorphisms (Leu53Leu, Ile143Val, Lys178Arg, and -485C/A). In further stratified analyses for the Leu84Phe and Ile143Val polymorphisms, the increased risk of cancer remained in subgroups of Caucasians, patients with esophageal cancer for the Leu84Phe polymorphism, and patients with lung cancer for the Ile143Val polymorphism. Results from the current meta-analysis suggested that Leu84Phe and Ile143Val in the MGMT gene are risk factors for cancer. In the future, more studies should be performed to validate our results.

Association between GSTP1 Ile105Val polymorphism and oxaliplatin-induced neuropathy: a systematic review and meta-analysis

The association between glutathione-S-transferase P1 (GSTP1) Ile105Val polymorphism and oxaliplatin-induced neuropathy has been investigated in a number of published studies. However, most of these studies were based on small sample sizes and the results remained inconsistent. To assess the relationship between GSTP1 gene Ile105Val polymorphism and its susceptibility to oxaliplatin-induced neuropathy, a meta-analysis of previous studies was conducted. Two investigators independently searched studies published up to December 2012 from the databases of PubMed, EMBASE and The Cochrane Library. The pooled effect was calculated as odds ratio (OR) and corresponding 95% confidence intervals (CIs) using fixed-effect or random-effect model. Twelve prospective trials and two retrospective clinical trials involving 2,191 participants met the inclusion criteria. Combined analyses of these studies showed no significant associations between GSTP1 Ile105Val polymorphism and oxaliplatin-induced neuropathy, yielding OR of 1.08 (95%CI 0.67-1.74, P=0.754) in dominant model. Similar results were also obtained in recessive model (OR=1.67, 95%CI 0.56-4.93, P=0.357) and allelic analysis (OR=1.22, 95%CI 0.67-2.24, P=0.513). Since significant heterogeneity across studies, the pooled effects were calculated by random-effect model. No evidence of publication biases was identified in this meta-analysis. This meta-analysis did not support the hypothesis that GSTP1 Ile105Val polymorphism was related to the occurrence of neurotoxicity in oxaliplatin-treated patients. Given the limited number of studies and potential bias, large-scale and well-designed clinical trials should be needed to confirm these hypotheses.

Glutathione S‐transferase P1 Ile105Val polymorphism modulates allergen‐induced airway inflammation in human atopic asthmatics in vivo

Glutathione S-transferase P1 is a Phase II cytoprotective and detoxifying enzyme that is widely expressed in human airways. The glutathione S-transferase P1 Ile105Val polymorphism has been linked with atopic disorders and asthma. Yet, little remains known about the regulation of allergic inflammation by glutathione S-transferase P1 in human asthmatics. To establish the effect of the glutathione S-transferase P1 Ile105Val polymorphism on allergen-induced airway inflammation and oxidant stress, and non-specific bronchial hyperresponsiveness to methacholine and reactivity to specific allergen in mild human atopic asthmatics in vivo. Five Val(105)/Val(105) , twelve Val(105)/Ile(105) and twenty Ile(105)/Ile(105) mild atopic asthmatics underwent methacholine challenge, inhaled allergen challenge and endobronchial allergen provocation through a bronchoscope. A panel of inflammatory cytokines and chemokines, F2 -isoprostanes and isofuranes, markers of oxidative stress, thromboxane B2 and immunoglobulin E were measured in bronchoalveolar lavage fluid at baseline and 24 h after allergen instillation. Asthmatics with glutathione S-transferase P1 Val(105)/Val(105) compared with asthmatics with the glutathione S-transferase P1 Val(105)/Ile(105) and Ile(105)/Ile(105) had greater generation of acute phase cytokines (TNF-α, IL-6, CXCL8), IL-12, CCL11, thromboxane B2 and immunoglobulin E at 24 h after local allergen challenge. The GSTP1 genotype had no effect on airway hyperresponsiveness to methacholine and the reactivity to specific allergen. The glutathione S-transferase P1 Ile105Val polymorphism markedly modifies allergen-provoked airway inflammation in atopic asthmatics in vivo. Modulation of the biochemical milieu in response to allergen provides a mechanistic explanation for regulatory effects of glutathione S-transferase P1 polymorphism on airway pathophysiology, and may guide improvement of future therapeutic methods in human atopic asthmatics. These findings must me confirmed in a larger study population of asthmatics with various ethnicities.

Assessment of the XPC (A2920C), XPF (T30028C), TP53 (Arg72Pro) and GSTP1 (Ile105Val) polymorphisms in the risk of cutaneous melanoma

We examined the influence of XPC A2920C, XPF T30028C, TP53 Arg72Pro and GSTP1 Ile105Val polymorphisms in the risk of cutaneous melanoma (CM). DNA from 146 CM patients and 146 controls was analysed by polymerase chain reaction (PCR)--restriction fragment length polymorphism (RFLP). The frequencies of XPC CC (15.1 vs. 6.9 %, P = 0.02), TP53 ArgArg (59.6 vs. 45.9 %, P = 0.02), XPC CC plus TP53 ArgArg (19.7 vs. 5.2 %, P = 0.01) and TP53 ArgArg plus GSTP1 IleIle (50.7 vs. 35.6 %, P = 0.03) genotypes were higher in patients than in controls. Carriers of the respective genotypes were under a 2.51 (95 % CI: 1.13-5.55), 1.76 (95 % CI: 1.09-2.83), 4.52 (95 % CI: 1.35-15.16), and 2.01 (95 % CI: 1.04-3.90)-fold increased risks for CM than others, respectively. An excess of TP53 ArgArg genotype was seen in patients with excessive sun exposure compared to patients with standard sun exposure (69.2 vs. 44.1 %, P = 0.02) and also compared to controls (69.2 vs. 45.9 %, P = 0.002). Individuals with TP53 ArgArg genotype and highly exposed to sunlight had 2.65 (95 % CI: 1.42-4.92)-fold increased risk for CM than others. XPC CC (27.8 vs. 10.4 %, P = 0.02) and the GSTP1 IleIle (58.3 vs. 36.8 %, P = 0.04) genotypes were more common in patients with advanced tumours than in patients with localized tumours and were also more common in these patients than in controls (27.8 vs. 6.9 %, P = 0.001; 58.3 vs. 37.0 %, P = 0.02, respectively). Individuals with the respective genotypes had 5.23 (95 % CI: 1.97-13.82)-fold and 2.38 (95 % CI: 1.13-5.01)-fold increased risks for advanced tumour than others, respectively. Our data suggest that inherited abnormalities of XPC, XPF, TP53 and GSTP1 pathways of the DNA repair, apoptosis and metabolism of reactive oxygen species are important determinants of CM in individuals from south-eastern Brazil.

Gene Frequencies of the Human GSTT1 (Null Allele) and GSTP1 (Ile105Val) Polymorphisms among South Indian Populations

Background: Glutathione S-transferases (GSTs) are members of the phase II biotransformation enzymes that play a key role in cellular detoxification of chemical carcinogens and xenobiotics. Variations at GST genes have been reported in different human populations, and some association studies have reported increased risk for cancers and other disease end points. The present study was conducted to investigate the allele frequency variations in south Indian populations. Methods: GSTT1 null allele and GSTP1 Ile105Val polymorphisms were genotyped in two hundred and twelve subjects (aged 34 to 60 years old) belong to six populations using PCR and PCR-RFLP techniques respectively. Results: Both GSTT1 ins-del and GSTP1 Ile105Val are polymorphic in all populations. GSTP1 Ile105Val followed the Hardy-Weinberg equilibrium. The GSTT1 null allele frequencies ranged from 11.6% to 22.2% and GSTP1 Ile105Val “Val” allele frequency ranged from 20.0% to 38.2% in the study populations. HapMap data showed the highest frequency of Val105 allele in African populations followed by European populations. East Asian populations showed the lowest frequency of Val105 allele. Conclusion: The variations observed in allelic distribution of GST genes may presumably be due to the selective pressure exerted on populations of that region. In conclusion, the present study reports the frequency of GSTT1 null allele and GSTP1 Ile105Val polymorphisms in Indian populations which provides foundation for potential epidemiological and clinical studies.

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.

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.

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.

Functional CYP1A1 genetic variants, alone and in combination with smoking, contribute to development of head and neck cancers

CYP1A1 plays an essential role in pathogenesis of head and neck cancers. Functional CYP1A1 Ile462Val and MspI single nucleotide polymorphisms (SNP) are considered to have significant effects on risk of head and neck cancers. Several case-control studies have examined how these genetic polymorphisms are involved in development of this group of malignancies, but the conclusions are inconsistent. Therefore, we conducted this meta-analysis to systematically examine the associations between these functional genetic variants and head and neck cancer risk. A total of 28 studies are eligible for CYP1A1 Ile462Val SNP (4639 patients and 4701 controls), and 22 studies for MspI SNP (4168 patients and 4638 controls). Pooled odds ratios (ORs) and the 95% confidence interval (95% CI) were appropriately calculated using either fixed-effect model or random-effect model. There was no association between Ile462Val polymorphism and head and neck cancer risk (OR=1.23, 95% CI=0.99–1.53, P=0.062). However, in a stratified analysis, a statistically significant correlation between this SNP and pharyngeal cancer risk was observed (OR=1.76, 95% CI=1.32–2.33, P<0.001). For MspI SNP, our data indicated that carriers of TC and CC genotypes had a 34% increased risk to develop head and neck cancers compared to TT carriers (95% CI=1.15–1.57, P<0.001). This effect was even more pronounced in smokers (OR=2.98, 95% CI=1.69–5.26, P<0.001), demonstrating that gene–smoking interaction intensifying carcinogenesis may exist. These findings reveal that the functional CYP1A1 MspI genetic variant, alone and in combination with smoking, plays a more important role in pathogenesis of head and neck cancers.

Quantitative synthesis of the association between the cytochrome P450 1A1 Ile462Val polymorphism and prostate cancer risk

The association between the cytochrome P450 1A1 (CYP1A1) Ile462Val polymorphism and prostate cancer risk remains inconclusive owing to the conflicting findings from previous studies. To get a more precise estimate of the possible association, we performed the present meta-analysis. We searched the PUBMED, EMBASE, and Wanfang databases for the studies which met the inclusion criteria. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was used to estimate the association between CYP1A1 Ile462Val polymorphism and prostate cancer risk. A total of 13 studies with 2,350 cases and 2,992 controls were included in the meta-analysis. The results indicated that there was an obvious association between CYP1A1 Ile462Val polymorphism and increased risk of prostate cancer (for Val versus Ile: OR=1.27, 95 % CI 1.13-1.43, P<0.001; for ValVal versus IleIle: OR=1.51, 95 % CI 1.14-2.01, P=0.004; for ValVal + ValIle versus IleIle: OR=1.31, 95 % CI 1.14-1.51, P<0.001; for ValVal versus IleIle + ValIle: OR=1.38, 95 % CI 1.05-1.81, P=0.020). Subgroup analyses by ethnicity suggested that CYP1A1 Ile462Val polymorphism was associated with prostate cancer risk in Asians but not in Caucasians. This meta-analysis suggests that there is an association between CYP1A1 Ile462Val polymorphism and increased risk of prostate cancer. More studies with large sample are needed to further assess the association in Caucasians.

Glutathione S-transferase P1 Ile105Val Polymorphism and Oral Cancer Risk: A Meta-Analysis

Objective The glutathione S-transferase P1 (GSTP1) gene has been suggested to play an important role in the pathogenesis of oral cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of GSTP1 Ile105Val polymorphisms with oral cancer risk.Methods Published literature from PubMed and EMBASE were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model.Results 13 studies (1803 oral cancer cases and 2998 controls) for GSTP1 Ile105Val polymorphism were included in the meta-analysis. The results indicated that there was no significant association between GSTP1 Ile105Val polymorphism and oral cancer in the overall population (OR=1.30, 95%CI=0.92-1.38, I2=48.0%, p for heterogeneity=0.027). Further subgroup analysis by ethnicity suggested that GSTP1 Ile105Val polymorphism was significantly associated with oral cancer only in East Asians (OR=1.64, 95%CI=1.16-2.31, I2=0.0%, p for heterogeneity=0.525), but not in Caucasians (OR=1.16, 95%CI=0.73-1.82, I2=7.5%, p for heterogeneity=0.299), Africans (OR=1.10, 95%CI=0.37-3.28), South Asians (OR=1.20, 95%CI=0.69-2.08, I2=74.3%, p for heterogeneity=0.021) and mixed population (OR=0.91, 95%CI=0.70-1.20, I2=39.7%, p for heterogeneity=0.174).Conclusions The present meta-analysis has limited evidence to support the association of GSTP1 Ile105Val polymorphism with HCC risk in the overall population. However, GSTP1 Ile105Val polymorphism might be associated with risk of oral cancer in East Asians.

Association of GSTP1 Ile105Val Polymorphism and Risk of Head and Neck Cancers: A Meta-Analysis of 28 Case-Control Studies

Background and AimsThe Glutathione S-transferase P1 (GSTP1) polymorphism have been considered a risk modifier for developing head and neck cancer (HNC) in many studies; however, the results of such studies are inconsistent. The aim of this study was to evaluate the possible association between the GSTP1 Ile105Val polymorphism and risk of HNC.MethodWe performed a search in the relevant electronic database and a meta-analysis based on 28 published case–control studies that included 6,404 cases and 6,523 controls. To take into account the possibility of heterogeneity across the studies, a Chi-square based I2-statistic test was performed. Crude pooled odds ratios (ORs) with 95% confidence intervals (CIs) were assessed using both fixed-effects and random-effects models.ResultsThe results of this meta-analysis showed that the GSTP1 Ile105Val polymorphism was not significantly associated with risk of HNC in the overall study population (pooled OR 1.00, 95% CI 0.92–1.09) or in subgroup analyses stratified by ethnicity, sample size, tumor site or publication year. Moreover, substantial evidence of heterogeneity among the studies was observed. Publication year was identified as the main cause of heterogeneity.ConclusionThis meta-analysis does not support a significant association between the GSTP1 Ile105Val polymorphism and risk of HNC.

Association between CYP1A1 Ile462Val variation and acute leukemia risk: meta-analyses including 2164 cases and 4160 controls.

BackgroundPreviously, CYP1A1 Ile462Val polymorphism has been indicated to be a risk factor for several malignancies. Increasing reports have focused on the association of CYP1A1 Ile462Val polymorphisms with susceptibility to acute leukemia and have generated controversial results. The goal of the present study was to derive a more precise estimation of the relationship.MethodsRelevant literature has been rigorously searched and screened. Eligible studies were identified for the period up to Apr 2012. Meta-analyses evaluating the association of CYP1A1 Ile462Val variation with acute leukemia were carried out. Subgroup analyses on ethnicity, clinical types and source of controls were further performed.ResultsA total of thirteen publications including fourteen case-control studies with 2164 cases and 4160 controls were selected for analysis. The overall data indicated a significant association of CYP1A1 Ile462Val polymorphism with acute leukemia risk (Val/Val vs Ile/Ile OR = 1.49; 95% CI = 1.11–1.98; dominant model: OR = 1.26; 95% CI = 1.05–1.51; recessive model: OR = 1.38; 95% CI = 1.04–1.83). In subgroup analysis on ethnicity, increased risk was shown among mixed ethnicities (Val/Val vs Ile/Ile: OR = 2.36; 95% CI = 1.46–3.82; dominant model: OR = 1.37; 95% CI = 1.01–1.86; recessive model: OR = 2.20; 95% CI = 1.37–3.53) but not Asians or Caucasians. In subgroup analysis on clinical types, increased risk was observed in the acute lymphocytic leukemia (ALL) subgroup (Val/Val vs Ile/Ile: OR = 2.06; 95% CI = 1.42–3.01; recessive model: OR = 1.91; 95% CI = 1.32–2.76) but not in the acute myeloid leukemia (AML) subgroup.ConclusionThe results of the present study suggest that CYP1A1 Ile462Val polymorphism might be a low-penetrant risk factor for acute leukemia. Subgroup analyses suggest that homozygous Val/Val alleles might modify the susceptibility to ALL.

Genetic polymorphisms in CYP1A1, GSTM1, GSTP1 and GSTT1metabolic genes and risk of lung cancer in Asturias

BackgroundMetabolic genes have been associated with the function of metabolizing and detoxifying environmental carcinogens. Polymorphisms present in these genes could lead to changes in their metabolizing and detoxifying ability and thus may contribute to individual susceptibility to different types of cancer. We investigated if the individual and/or combined modifying effects of the CYP1A1 MspI T6235C, GSTM1 present/null, GSTT1 present/null and GSTP1 Ile105Val polymorphisms are related to the risk of developing lung cancer in relation to tobacco consumption and occupation in Asturias, Northern Spain.MethodsA hospital-based case–control study (CAPUA Study) was designed including 789 lung cancer patients and 789 control subjects matched in ethnicity, age, sex, and hospital. Genotypes were determined by PCR or PCR-RFLP. Individual and combination effects were analysed using an unconditional logistic regression adjusting for age, pack-years, family history of any cancer and occupation.ResultsNo statistically significant main effects were observed for the carcinogen metabolism genes in relation to lung cancer risk. In addition, the analysis did not reveal any significant gene-gene, gene-tobacco smoking or gene-occupational exposure interactions relative to lung cancer susceptibility. Lastly, no significant gene-gene combination effects were observed.ConclusionsThese results suggest that genetic polymorphisms in the CYP1A1, GSTM1, GSTT1 and GSTP1 metabolic genes were not significantly associated with lung cancer risk in the current study. The results of the analysis of gene-gene interactions of CYP1A1 MspI T6235C, GSTM1 present/null, GSTT1 present/null and GSTP1 Ile105Val polymorphisms in lung cancer risk indicate that these genes do not interact in lung cancer development.

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, 1.03-1.97; ValVal versus IleIle, OR = 2.43; 95 % CI, 1.19-4.95; ValVal+ValIle versus IleIle, OR = 1.59; 95 % CI, 1.00-2.53). Ethnic subgroup analyses showed a significant association was found in Caucasians (Val versus Ile, OR = 2.03; 95 % CI, 1.17-3.51; ValVal versus IleIle, OR = 2.74; 95 % CI, 1.30-5.75; ValVal+ValIle versus IleIle, OR = 2.50; 95 % CI, 1.33-4.70), 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.

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

Any association between the CYP1A1 Ile462Val polymorphism and endometrial cancer risk remains inconclusive. For a more precise estimate, we performed the present meta-analysis. PUBMED, OVID and EMBASE were searched for the studies which met inclusion criteria. Data in all eligible studies were evaluated and extracted by two authors independently. The meta-analysis estimated pooled odds ratio (OR) with 95% confidence interval (CI) for endometrial cancer risk attributable to the CYP1A1 Ile462Val polymorphism. A total of 7 studies were included in this meta-analysis. The results indicated no association between endometrial 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.Ile genotype model [OR 1.08, 95% CI 0.71-1.63]; for Val.Val vs (Ile.Ile + Ile.Val) genotype model [OR 1.46, 95% CI 0.53-4.04]). This meta-analysis suggests that there is no association between endometrial cancer risk and the CYP1A1 Ile462Val polymorphism.

CYP1A1 Ile462Val polymorphism contributes to lung cancer susceptibility among lung squamous carcinoma and smokers: a meta-analysis.

Many studies have examined the association between the CYP1A1 Ile462Val gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. Ultimately, 43 case-control studies, comprising 19,228 subjects were included. A significantly elevated lung cancer risk was associated with 2 Ile462Val genotype variants (for Val/Val vs Ile/Ile: OR = 1.22, 95% CI = 1.08–1.40; for (Ile/Val +Val/Val) vs Ile/Ile: OR = 1.15, 95% CI = 1.07–1.23) in overall population. In the stratified analysis, a significant association was found in Asians, Caucasians and lung SCC, not lung AC and lung SCLC. Additionally, a significant association was found in smoker population and not found in non-smoker populations. This meta-analysis suggests that the Ile462Val polymorphisms of CYP1A1 correlate with increased lung cancer susceptibility in Asian and Caucasian populations and there is an interaction with smoking status, but these associations vary in different histological types of lung caner.