Glutathione S-transferase P1 Ile105Val polymorphism and colorectal cancer risk: A meta-analysis and HuGE review

Colorectal cancer is the third most common form of cancer and the fourth most frequent cause of cancer deaths worldwide. Its development is influenced by both environmental and genetic factors. The glutathione S-transferase P1 gene (GSTP1) is a particularly attractive candidate for colorectal cancer susceptibility because it codes the enzyme involved in the metabolism of environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs). However, epidemiologic findings have been inconsistent. To investigate a putative association of GSTP1 Ile105Val polymorphism with the risk of colorectal cancer, we performed a meta-analysis and HuGE review of 16 published case-control studies (involving a total of 4386 colorectal cancer patients and 7127 controls). We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, the comparison of Val versus Ile allele showed no differential susceptibility to colorectal cancer (OR = 0.98, 95% CI: 0.92–1.04). A protective effect was found in recessive, with an OR of 0.86 (95% CI: 0.76–0.98). Whereas no significant association was observed in either dominant or codominant model. In stratified subgroup analysis, no effect of Val allele was seen in subjects of Caucasian and Asian descent, and in healthy and hospital controls. In conclusion, the meta-analysis suggests that the GSTP1 Ile105Val polymorphism is unlikely to increase considerably the risk of sporadic colorectal cancer, and it should be confirmed in further studies.     

Glutathione S-transferase P1 Ile105Val polymorphism, cigarette smoking and prostate cancer

The enzyme glutathione S-transferase P1 (GSTP1) detoxifies carcinogenic products of tobacco smoke. This exploratory case-control study evaluates the possible effect modification by the GSTP1 Ile105Val polymorphism (replacement of isoleucine by valine at codon 105) on smoking and prostate cancer. Because the Val variant possesses up to a five-fold greater enzymatic activity towards the carcinogenic metabolites of tobacco smoke, the Ile allele is expected to be related to an increase in the risk of prostate cancer among smokers. GSTP1 genotype and epidemiological data were obtained from 122 cases of prostate cancer and 135 healthy males as controls. A logistic regression model was used to estimate odds ratios and 95% confidence intervals. The adjusted OR of homozygous Ile compared to other genotypes for prostate cancer was 1.21 (95% CI: 0.61-2.83). Smoking was not significantly associated with prostate cancer with an adjusted OR of 1.56 (95% CI: 0.78-3.12). However, among individuals with the Ile/Ile genotype, smoking was strongly associated with an increased risk of prostate cancer with an adjusted odds ratio of 4.09 (95% CI: 1.25-13.35). A potential multiplicative interaction was suggested between GSTP1 and smoking on the risk of prostate cancer with the adjusted OR for the interaction of 4.52 (95% CI: 1.07-19.17). To our knowledge, this is the first time that a potential effect modification by the GSTP1 Ile/Ile genotype on smoking and the risk of prostate cancer is suggested.     

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.     

Glutathione S-transferase M1 polymorphism and breast cancer susceptibility: a meta-analysis involving 46,281 subjects

Published data on the association between present/null polymorphism of glutathione S-transferase M1 (GSTM1) and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the GSTM1 present/null polymorphism and breast cancer risk. The pooled ORs were performed for null versus present genotype. A total of 59 studies including 20,993 cases and 25,288 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with null genotype when all studies were pooled into the meta-analysis (OR = 1.10, 95% CI = 1.04–1.16). In the subgroup analysis by ethnicity, significantly increased risks were found for Caucasians (OR = 1.05, 95% CI = 1.00–1.10) and Asians (OR = 1.21, 95% CI = 1.08–1.35). When stratified by population-based studies or hospital-based studies, statistically significantly elevated risks were found among population-based studies (OR = 1.11, 95% CI = 1.03–1.20). In the subgroup analysis by menopausal status, statistically significantly increased risks were found among postmenopausal women (OR = 1.15, 95% CI = 1.04–1.28). In conclusion, this meta-analysis suggests that the GSTM1 null genotype is a low-penetrant risk factor for developing breast cancer.     

Association between survival after treatment for breast cancer and glutathione S-transferase P1 Ile105Val polymorphism

A glutathione S-transferase (GST) P1 polymorphism results in an amino acid substitution, Ile105Val; the Val-containing enzyme has reduced activity toward alkylating agents. Cancer patients with the variant enzyme may differ in removal of treatment agents and in outcomes of therapy. We evaluated survival according to GSTP1 genotype among women (n = 240) treated for breast cancer. Women with the low-activity Val/Val genotype had better survival. Compared with Ile/Ile, hazard ratios for overall survival were 0.8 (95% confidence interval, 0.5-1.3) for Ile/Val and 0.3 (95% confidence interval, 0.1-1.0) for Val/Val (P for trend = 0.04). Inherited metabolic variability may influence treatment outcomes.     

Glutathione S-transferase P1 gene Ile105Val polymorphism might be associated with lung cancer risk in the Chinese Han population

Genetic variations in glutathione S-transferase P1 (GSTP1) gene have been suggested to be involved in the development of cancer. However, the results from the studies regarding the association between GSTP1 Ile105Val polymorphism and lung cancer risk in the Chinese population have been inconsistent. Thus, we conducted a meta-analysis to investigate the association. Published literature from PubMed, Chinese Biomedical Literature Database, Chinese Wanfang Data, and Chinese National Knowledge Infrastructure databases were searched for eligible publications. Pooled odds ratios (ORs) with 95?% confidence intervals (CIs) were calculated using random or fixed effect model. Ten studies (1,506 cases/1,714 controls) were included in the meta-analysis. The results suggested that GSTP1 Ile105Val polymorphism was marginally associated with lung cancer risk in the Chinese Han population under a multiplicative model (G vs. A, odds ratio (OR)?=?1.22, 95?% confidence interval?=?1.02?C1.46), under a homogeneous codominant model (GG vs. AA, OR?=?1.67, 95?% CI?=?1.14?C2.45), under a heterogeneous codominant model (GA vs. AA, OR?=?1.15, 95?% CI?=?0.98?C1.35), under a dominant model (GG + GA vs. AA, OR?=?1.21, 95?% CI?=?1.04?C1.39), and under a recessive model (GG vs. GA + AA, OR?=?1.59, 95?% CI?=?1.09?C2.31), respectively. Moreover, after adjusted for age, gender, and smoking status, the significant association under dominant model remained (OR?=?1.27, 95?% CI?=?1.07?C1.51). This meta-analysis suggested that there might be an association between GSTP1 Ile105Val polymorphism and lung cancer in the Chinese Han population.     

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 polymorphism (Ile105Val) predicts cumulative neuropathy in patients receiving oxaliplatin-based chemotherapy.

PURPOSE: Glutathione S-transferases (GST) are xenobiotic metabolizing enzymes involved in the detoxification of a variety of chemotherapeutic drugs, including platinum derivatives. Genetic polymorphisms of GSTs have been associated with enzyme activity variations. Thus, a study was done to investigate the relationship between GST polymorphisms and oxaliplatin-related cumulative neuropathy in gastrointestinal cancer patients treated with oxaliplatin-based chemotherapy. EXPERIMENTAL DESIGN: Ninety patients were included. Clinical neurologic evaluation was done at baseline and before each cycle of treatment. We determined genetic variants for GSTP1 exon 5 (Ile105Val), GSTP1 exon 6 (Ala114Val), GSTM1 (homozygous deletion), and GSTT1 (homozygous deletion). We conducted analyses in a subgroup of 64 patients receiving a minimal cumulative dose of 500 mg/m2 of oxaliplatin to examine whether the GST polymorphisms are associated with oxaliplatin-related cumulative neuropathy. RESULTS: Among patients receiving a minimal cumulative dose of 500 mg/m2 of oxaliplatin, 15 patients showed clinically evident oxaliplatin-related cumulative neuropathy scored grade 3 according to an oxaliplatin-specific scale. The oxaliplatin-related cumulative neuropathy scored grade 3 was significantly more frequent in patients homozygous for the GSTP1 105Ile allele than in patients homozygous or heterozygous for the GSTP1 105Val allele (odds ratio, 5.75; 95% confidence interval, 1.08-30.74; P = 0.02). No association was found with respect to any of the GSTM1, GSTT1, or GSTP1 exon 6 genotypes. Conclusions: The results of the current study suggest that the 105Val allele variant of the GSTP1 gene at exon 5 confers a significantly decreased risk of developing severe oxaliplatin-related cumulative neuropathy.     

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.     

No association between CYP1B1 Val432Leu polymorphism and breast cancer risk: a meta-analysis involving 40,303 subjects

Breast cancer is the most common cancer in women. To date, many publications have evaluated the association between Cytochrome P450 1B1 (CYP1B1) Val432Leu polymorphism and breast cancer risk. However, the results remain inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was performed in this study. By searching Medline, Pubmed, and ISI Web of Knowledge databases, 26 studies including 19,028 cases and 21,275 controls were collected for CYP1B1 Val432Leu polymorphism. Crude ORs with 95% CIs were used to assess the strength of association between CYP1B1 Val432Leu polymorphism and breast cancer risk. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Overall, no significant associations between CYP1B1 Val432Leu polymorphism and breast cancer susceptibility were found for Val/Val versus Leu/Leu (OR = 0.98; 95% CI: 0.90–1.06), Val/Leu versus Leu/Leu (OR = 1.01; 95% CI: 0.93–1.09), Val/Val + Val/Leu versus Leu/Leu (OR = 1.00; 95% CI: 0.93–1.08) and Val/Val versus Val/Leu + Leu/Leu (OR = 0.96; 95% CI: 0.91–1.01). In the stratified analysis by ethnicity, menopausal status and sources of controls, significant associations were still not observed in all genetic models. In conclusion, this meta-analysis provides strong evidence that CYP1B1 Val432Leu polymorphism is not associated with breast cancer risk.     

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.     

Lack of association between MnSOD Val16Ala polymorphism and breast cancer risk: a meta-analysis involving 58,448 subjects

Published data on the association between MnSOD Val16Ala polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MnSOD Val16Ala polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (Val/Ala vs. Val/Val, Ala/Ala vs. Val/Val), dominant model (Ala/Ala + Val/Ala vs. Val/Val), and recessive model (Ala/Ala vs. Val/Ala + Val/Val), respectively. A total of 32 studies including 26,022 cases and 32,426 controls were involved in this meta-analysis. Overall, no significant associations were found between MnSOD Val16Ala polymorphism and breast cancer risk when all studies pooled into the meta-analysis (Val/Ala vs. Val/Val: OR = 1.022, 95% CI = 0.981–1.064; Ala/Ala vs. Val/Val: OR = 1.006, 95% CI = 0.934–1.083; dominant model: OR = 1.013, 95% CI = 0.962–1.066; and recessive model: OR = 0.985, 95% CI = 0.931–1.042). In the subgroup analysis by ethnicity or study design, still no significant associations were found for all comparison models. In conclusion, this meta-analysis suggests that the MnSOD Val16Ala polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.     

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

Background and aims

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.

Methods

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.

Results

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.

Conclusion

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.     

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.     

Cyclin D1 G870A polymorphism and breast cancer risk: a meta-analysis involving 23,998 subjects

Cyclin D1 (CCND1) plays an essential role in tumor development and progression through regulating the cell transition from G1 to the proliferative S phase. The CCND1 G870A polymorphism has been associated with an increased susceptibility to squamous cell carcinoma of the head and neck, bladder, prostate, and gastric cardiac cancers. There are a number of studies that explored the relationship between CCND1 G870A polymorphism and breast cancer risk, with inconsistent conclusions. In order to better define the predictive value of CCND1 G870A polymorphism in breast cancer, we searched PubMed and EBSCO for relevant publications. A total of 13 studies were indentified, which included 11,235 cases and 12,763 controls. We calculated the summary odds ratios and the corresponding 95% confidence interval. Our meta-analysis showed that carriers of AA genotype have a significantly higher risk in developing breast cancer compared with that of GG genotype (OR = 1.08, 95% CI = 1.01-1.17, p > = 0.03) in overall population. Furthermore, in subgroup analysis, CCND1 G870A polymorphism was associated with a marginally increased risk of breast cancer for Chinese compared to Caucasian populations with an OR = 1.14, 95% CI = 1.00-1.20, p-trend = 0.06 for AA + GA versus GG, if the controls were hospital-based population with an OR = 1.21, 95% CI = 0.99-1.47, p = 0.06 for AA versus GG and if the distributions of genotypes in control groups were consistent with the Hardy-Weinberg equilibrium (HWE) with an OR = 1.08, 95% CI = 1.00-1.15, p = 0.04 for AA versus GA + GG. Our meta-analysis represents the largest study to date indicating that the G870A polymorphism in CCND1 confers an increased risk for breast cancer. Further studies are warranted to explore the preventive measures to detect and manage the breast cancers attributable to the G870A polymorphism.     

Glutathione S-transferase M1 status and gastric cancer risk: a meta-analysis

Susceptibility to gastric cancer may be in part attributable to inter-individual variability in metabolic activation or detoxification of carcinogens, and in this context the polymorphic GSTM1 gene has been extensively studied. Seventeen reports detailing a possible association between GSTM1 deletion and gastric cancer have been published so far. In order to examine the risk of gastric cancer associated with GSTM1 null genotype, a meta-analysis of published case-control studies was undertaken using a random effect model. Two studies were excluded because some data were missing in the results. The principal outcome measure was the odds ratio for the risk of gastric cancer. Pooling all the 15 studies identified, the overall odds ratio of gastric cancer risk associated with GSTM1 deficiency was 1.24 (95% confidence interval, 1.00-1.54). Furthermore, by pooling four studies detailing the possible interaction between GSTM1 status smoking habits and gastric cancer risk, an overall estimate of odds ratio of 2.93 (95% confidence interval, 1.56-5.47) for ever smokers with GSTM1 deficiency compared to non-smokers with GSTM1 normal genotype has emerged. These results suggest that GSTM1 status probably has no effect on the risk of gastric cancer per se, but may modulate tobacco-related carcinogenesis of gastric cancer. Greater attention should therefore be paid to the design of future studies: only well designed population-based control studies considering all the possible confounding risk factors and based on a sample size commensurate with the detection of small genotypic risk may allow a more definitive conclusion.     

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.     

Methionine synthase A2756G polymorphism and breast cancer risk: a meta-analysis involving 18,953 subjects

The A2756G polymorphism in the methionine synthase (MTR) gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Eleven published case–control studies, including 8,438 breast cancer cases and 10,515 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Overall, no significant associations between the MTR A2756G polymorphism and breast cancer risk were found for GG versus AA (OR = 0.98, 95% CI: 0.84–1.15), AG versus AA (OR = 0.95, 95% CI: 0.89–1.01), GG/AG versus AA (OR = 0.95, 95% CI = 0.89–1.01), and GG versus AG/AA (OR = 1.00, 95% CI: 0.86–1.17). However, in the stratified analysis, significantly decreased breast cancer risks were found among Europeans (AG versus AA, OR = 0.90, 95% CI = 0.83–0.98; GG/AG versus AA, OR = 0.90, 95% CI = 0.82–0.97) and studies with population-based controls (AG versus AA, OR = 0.93, 95% CI = 0.86–1.00; GG/AG versus AA, OR = 0.93, 95% CI = 0.86–1.00). When stratifying by the menopausal status, no significant result was observed in all genetic models. Taken together, the results suggest that the MTR A2756G polymorphism may contribute to susceptibility to breast cancer among Europeans.     

Glutathione S-transferase M1 status and lung cancer risk: a meta-analysis.

Interindividual differences in lung cancer susceptibility may be mediated in part through polymorphic variability in the bioactivation of procarcinogens. GSTM1 status has been extensively studied in this context as a lung cancer risk factor, although published studies have produced conflicting results. To clarify the impact of GSTM1 status on lung cancer risk a meta-analysis of 23 case-control studies from the literature has been carried out using a random effects model. The principal outcome measure was the odds ratio for the risk of lung cancer. There was heterogeneity between the studies attributable to differences in the methods of assigning GSTM1 status. Pooling the studies that were based on phenotyping methods, the overall odds ratio of lung cancer risk associated with GSTM1 deficiency was 2.12 (95% confidence interval, 1.43-3.13). The risk of lung cancer risk associated with GSTM1 deficiency derived from the studies based on genotyping methods was, however, lower. The overall odds ratio was 1.13 (95% confidence interval, 1.04-1.25). These findings suggest that the estimates of lung cancer risk associated with GSTM1 deficiency in the early studies, based on phenotyping, were overinflated. Moreover, it is conceivable, given publication bias, that GSTM1 status has no effect on the risk of lung cancer per se. A major concern in case-control studies of polymorphisms and cancer risk is bias. A review of the 23 case-control studies indicates that greater attention should, therefore, be paid to the design of future studies.