Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene Ala222Val and susceptibility to ovary cancer: a systematic review and meta-analysis

Many studies have reported the role of methylenetetrahydrofolate reductase (MTHFR) gene Ala222Val polymorphism with ovary cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95 % confidence intervals (CIs) were estimated to assess the association between MTHFR Ala222Val polymorphism and ovary cancer risk. A total of 8 studies including 3,723 cases and 4,001 controls were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, no significant association between ovary cancer risk and MTHFR Ala222Val polymorphism was found in all genetic models [codominant model: OR?=?0.980, 95 % CI?=?0.756–1.270, P _h?=?0.088, P?=?0.877; dominant model: OR?=?1.022, 95 % CI?=?0.864–1.208, P _h?=?0.033, P?=?0.803; recessive model: OR?=?1.050, 95 % CI?=?0.803–1.373, P _h?=?0.032, P?=?0.723; allele comparison model: OR?=?1.028, 95 % CI?=?0.898–1.178, P _h?=?0.012, P?=?0.685]. In the stratified analysis by ethnicity, no evidence of any associations of this polymorphism with ovary cancer was found in the Caucasian populations. Our meta-analysis supports that the MTHFR Ala222Val polymorphism is not contributed to the risk of ovary cancer from currently available evidence.     

Associations between MTHFR Ala222Val polymorphism and risks of hepatitis and hepatitis-related liver cancer: a meta-analysis

Chronic infection of viral hepatitis is the main cause of liver cancer. There were many studies assessing the associations of methylenetetrahydrofolate reductase (MTHFR) Ala222Val polymorphism with risks of hepatitis and hepatitis-related liver cancer, but no consistent results were reported. To investigate the associations of MTHFR Ala222Val polymorphism with risks of hepatitis and hepatitis-related liver cancer, we performed a meta-analysis of published case–control studies. Eligible studies were searched from PubMed and Chinese National Knowledge Infrastructure (CNKI) databases. The odds ratio (OR) and corresponding 95 % confidence interval (95 %CI) were used to assess the associations. Twenty-one individual studies with a total of 8,187 subjects were included. Overall, MTHFR Ala222Val polymorphism was not significantly associated with risks of liver cancer, hepatitis-related liver cancer, and non-hepatitis-related liver cancer. However, MTHFR Ala222Val polymorphism was significantly associated with risk of hepatitis infection (Val vs. Ala: OR?=?1.15, 95 %CI 1.01–1.32, P?=?0.03; ValVal/AlaVal vs. AlaAla: OR?=?1.37, 95 %CI 1.11–1.68, P?=?0.003). Therefore, MTHFR Ala222Val polymorphism is significantly associated with risk of hepatitis infection but not liver cancer. More studies are needed to further assess the association between MTHFR Ala222Val polymorphism and hepatitis-related liver cancer.     

Lack of association between MHTFR Glu429Ala polymorphism and breast cancer susceptibility: a systematic review and meta-analysis of 29 research studies

The association between MHTFR Glu429Val polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 29 studies including 8,649 cases and 18,672 controls were involved in this meta-analysis. Overall, no significant associations were found between MTHFR Glu429Ala polymorphism and breast cancer risk when all studies were pooled into the meta-analysis (Glu/Glu vs Ala/Ala: OR?=?0.891, 95 % CI?=?0.782–1.015; Glu/Ala vs Ala/Ala: OR?=?0.874, 95 % CI?=?0.760–1.006; dominant model: OR?=?0.885, 95 % CI?=?0.775–1.012; and recessive model: OR?=?0.989, 95 % CI?=?0.931–1.051). In the subgroup analysis by ethnicity, significantly elevated breast cancer risk was associated with Glu/Glu variant genotype in homozygote comparison and recessive genetic model (Glu/Glu vs Ala/Ala: OR?=?0.78, 95 % CI?=?0.63–0.97; Glu/Glu vs Glu/Ala: OR?=?0.92, 95 % CI?=?0.85–0.99; recessive model: OR?=?0.91, 95 % CI?=?0.85–0.97), while no significant associations were found for all comparison models in other ethnicity populations. In conclusion, this meta-analysis suggests that the MTHFR Glu429Ala polymorphism may be not associated with breast cancer development.     

XPC gene polymorphisms contribute to bladder cancer susceptibility: a meta-analysis

Numerous studies have investigated the association between three polymorphisms (Lys939Gln, Ala499Val and PAT?/+) of Xeroderma pigmentosum group C (XPC) gene and bladder cancer susceptibility; however, the findings are inconclusive. In order to acquire a more precise estimation of the relationship, we performed a meta-analysis based on 10 studies including 3,934 cases and 4,269 controls for Lys939Gln, five studies including 2,113 cases and 2,249 controls for Ala499Val, and seven studies including 2,834 cases and 3,048 controls for PAT?/+ polymorphism. We searched publications from EMBASE, MEDLINE, and Chinese Biomedical. We calculated pooled odds ratio (OR) and 95 % confidence interval (CI) by using either fixed-effects or random-effects model according to the between-study heterogeneity. We found that all studied polymorphisms were individually associated with increased overall cancer risks, as shown by ORs (95 % CIs) below: the Lys939Gln (Gln/Gln vs. Lys/Lys: OR?=?1.39, 95 % CI?=?1.08–1.79; recessive model: OR?=?1.42, 95 % CI?=?1.11–1.83; and allele comparing: OR?=?1.12, 95 % CI?=?1.003–1.24), the Ala499Val (Val/Val vs. Ala/Ala: OR?=?1.82, 95 % CI?=?1.19–2.79; recessive model: OR?=?1.70, 95 % CI?=?1.18–2.46; and allele comparing: OR?=?1.23, 95 % CI?=?1.01–1.50), and the PAT?/+ (+/+ vs. ?/?: OR?=?1.36, 95 % CI?=?1.03–1.79 and recessive model: OR?=?1.34, 95 % CI?=?1.06–1.70). Furthermore, stratification analyses demonstrated an increased risk for Asian populations as to the Lys939Gln and PAT?/+ whereas for Caucasian populations as to the Ala499Val polymorphism in the homozygous and recessive models. Despite some limitations, this meta-analysis suggests that XPC polymorphisms are associated with bladder cancer risk, but this association warrants further validation in well-designed studies with large sample sizes.     

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.     

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 XPG Asp1104His polymorphism and bladder cancer risk

Published data regarding the association between XPG Asp1104His polymorphism and bladder cancer risk remained controversial. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. We systematically searched PubMed, Embase, and Web of Science with a time limit of June 22, 2013. Summary odds ratios (ORs) with 95 % CIs were used to assess the strength of the association between XPG Asp1104His polymorphism and bladder cancer risk using random effects model. A total of eight case–control studies including 2,613 cases and 2,934 controls were included for analysis. Overall, no significant association was found between XPG Asp1104His polymorphism and bladder cancer susceptibility for CC vs. GG (OR?=?1.12, 95 % CI?=?0.74–1.69), GC vs. GG (OR?=?1.12, 95 % CI?=?0.86–1.46), the dominant model CC + GC vs. GG (OR?=?1.08, 95 % CI?=?0.85–1.38), and the recessive model CC vs. GC + GG (OR?=?0.92, 95 % CI?=?0.66–1.29). In the subgroup analysis, no significant associations were found in either Asian or non-Asian population. This meta-analysis suggested that XPG Asp1104His polymorphism was not associated with bladder cancer risk.     

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.     

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.     

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.     

XPD Asp312Asn and Lys751Gln polymorphisms and breast cancer susceptibility: A meta-analysis

The association between xeroderma pigmentosum complementation group D (XPD) Asp312Asn and Lys751Gln gene polymorphisms and breast cancer risk has been widely reported, but the results were inconsistent. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. A comprehensive search strategy was conducted towards the electronic databases including Medline, PubMed, Web of Science, Embase, and Chinese Biomedical Literature Database (Chinese). The association between the XPD polymorphism and breast cancer risk was conducted by odds ratios (ORs) and 95 % confidence intervals (95 % CIs). A total of 22 studies with 18,136 cases and 18,351 controls were included in our meta-analysis. Among these, 12 studies with 7,667 cases and 7,480 controls for Asp312Asn polymorphism and 20 studies with 10,469 cases and 10,871 controls for Lys751Gln polymorphism. With regard to Asp312Asn polymorphism, no significantly associated was found with breast cancer risk. However, significant association was found between Lys751Gln polymorphism and breast cancer risk under all genetic models in overall populations (C vs. A—OR?=?1.10, 95 % CI?=?1.04–1.17, P?=?0.002; CC vs. AA—OR?=?1.17, 95 % CI?=?1.06–1.30, P?=?0.003; AC vs. AA—OR?=?1.06, 95 % CI?=?1.01–1.12, P?=?0.032; CC vs. AC/AA—OR?=?1.17, 95 % CI?=?1.04–1.32, P?=?0.009; CC/AC vs. AA—OR?=?1.07, 95 % CI?=?1.02–1.12, P?=?0.005). In subgroup analysis base on ethnicity, significance was found in Caucasians and mix. The results suggest that XPD Asp312Asn polymorphism was not associated with breast cancer. The XPD Lys751Gln polymorphism significantly increased breast cancer risk, especially for Caucasian and mix.     

The rs1050450 C > T polymorphism of GPX1 is associated with the risk of bladder but not prostate cancer: evidence from a meta-analysis

Glutathione peroxidase (GPX) is an endogenous antioxidant enzyme counteracting oxidative stress. Accumulating evidence has demonstrated that the GPX1 rs1050450 C?>?T polymorphism may modulate cancer risk, but the association of GPX1 rs1050450 polymorphism with bladder cancer (BC) and prostate cancer (PCa) is still inconclusive. This meta-analysis was designed to determine the exact association of GPX1 rs1050450 C?>?T polymorphism with the risk of bladder cancer and prostate cancer. Odds ratios (ORs) and 95 % confidence intervals (CI) were calculated to estimate the association strength. Databases of PubMed, EMBASE, and China National Knowledge Infrastructure were searched to retrieve eligible studies. In total, ten eligible studies with 6,194 participants were included. By pooling all eligible studies, we found that carriers of the variant T allele were associated with a significantly increased risk of urinary tract cancer (T vs. C: OR?=?1.459 and 95 % CI, 1.086–1.962; CT/TT vs. CC: OR?=?1.411 and 95 % CI, 1.053–1.891). In stratified analysis, we observed that the rs1050450 C?>?T polymorphism was significantly associated with an increased risk of BC (T vs. C: OR?=?2.111 and 95 % CI, 1.020–4.368; CT/TT vs. CC: OR?=?1.876 and 95 % CI, 1.011–3.480), while the association was not significant for PCa. Egger’s test and Begg’s test revealed no publication bias. The present meta-analysis provides evidence that the GPX1 rs1050450 C?>?T polymorphism leads to an increased risk of BC but not the risk of PCa.     

Xeroderma pigmentosum complementation group D (XPD) gene polymorphisms contribute to bladder cancer risk: a meta-analysis

Numerous epidemiological studies have been conducted to investigate the association between Xeroderma pigmentosum complementation group D (XPD) Asp312Asn (rs1799793 G?>?A) and Lys751Gln (rs13181 A?>?C) polymorphisms and bladder cancer risk; however, the conclusions remain controversial. With this in mind, we performed this meta-analysis with 11 studies including 3,797 cases and 5,094 controls for Asp312Asn and 21 studies including 6,360 cases and 7,894 controls for Lys751Gln polymorphism. We searched available literatures from PubMed, Embase, and CBM databases. Crude odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to assess the strength of the associations. Moreover, to validate biological plausibility of our findings, the effects of these two polymorphisms on XPD gene expression within three ethnicities was determine by gene expression analysis based on imputed genotypes from HapMap. Overall, the variant allele of Asp312Asn polymorphism was associated with an increased risk of bladder cancer (Asn/Asn vs. Asp/Asp: OR?=?1.51, 95 % CI?=?1.19–1.91; Asp/Asn vs. Asp/Asp: OR?=?1.23, 95 % CI?=?1.12–1.35; recessive model: OR?=?1.33, 95 % CI?=?1.10–1.61; dominant model: OR?=?1.32, 95 % CI?=?1.14–1.52; and allele comparing: OR?=?1.26, 95 % CI?=?1.11–1.42). We found the Lys751Gln was associated with increased bladder cancer risk only under the recessive model (OR?=?1.14, 95 % CI?=?1.01–1.29). Stratification analyses demonstrated an increased risk for Asians and hospital-based studies under all genetic models while only under the dominant model for Caucasians as to the Asp312Asn polymorphism and for Caucasians under the recessive model as to the Lys751Gln polymorphism. We also found the Asp312Asn polymorphism can significantly influence mRNA expression levels among Asians and Caucasians, and the Lys751Gln polymorphism has a similar effect for Caucasians. Despite some limitations, this meta-analysis suggests that polymorphisms in XPD gene may contribute to bladder cancer susceptibility. These findings need further validation by large well-designed prospective studies.     

Associations between methylenetetrahydrofolate reductase polymorphisms and hepatocellular carcinoma risk in Chinese population

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene are considered to have some influence on both folate metabolism and cancer risk. Previous studies on the associations of MTHFR genetic polymorphisms with hepatocellular carcinoma (HCC) risk in Chinese population reported inconsistent results. We performed this meta-analysis to comprehensively assess the associations. Finally, 12 individual case–control studies were included into the meta-analysis. There were seven studies (6,384 subjects) on the MTHFR C677T polymorphism and five studies (4,502 subjects) on the MTHFR A1298C polymorphism. Overall, MTHFR C677T polymorphism was significantly associated with susceptibility to HCC in Chinese population (T versus C, odds ratio (OR)?=?1.09, 95 % confidence interval (95 % CI) 1.01–1.17; TT versus CC, OR?=?1.17, 95 % CI 1.00–1.38; TT/CT versus CC, OR?=?1.12, 95 % CI 1.00–1.26). MTHFR A1298C polymorphism was conversely associated with HCC risk in Chinese population (CC versus AA, OR?=?0.65, 95 % CI 0.46–0.91; CC versus AA/AC, OR?=?0.64, 95 % CI 0.46–0.90). The sensitivity analysis confirmed the reliability and stability of the meta-analysis. Thus, the findings from our meta-analysis support the associations of MTHFR C677T and A1298C polymorphisms with HCC risk in Chinese population.     

GSTP1 Ala114Val polymorphism and colorectal cancer risk: a meta-analysis

Studies investigating the association between cytochrome glutathione S-transferase P1 (GSTP1) Ala114Val polymorphism and colorectal cancer (CRC) risk report conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine databases. 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. The pooled ORs were performed for co-dominant model (ValVal vs. AlaAla, AlaVal vs. AlaAla), dominant model (ValVal + AlaVal vs. AlaAla), and recessive model (ValVal vs. AlaVal + AlaAla). This meta-analysis included seven case–control studies, which included 3,173 CRC cases and 3,323 controls. Overall, the variant genotypes (ValVal and AlaVal) of the Ala114Val were not associated with CRC risk when compared with the wild-type AlaAla homozygote. Similarly, no associations were found in the dominant and recessive models. When stratifying for ethnicity, Hardy–Weinberg equilibrium in controls, study sample size, and source of controls, a significantly increased risk was observed among Asians (AlaVal vs. AlaAla, OR?=?1.67, 95 % CI?=?1.08–2.59; dominant model, OR?=?1.74, 95 % CI?=?1.14–2.67). No heterogeneity or publication bias was found in the present study. This meta-analysis suggests that the GSTP1 Ala114Val polymorphism may not be associated with CRC risk, while the observed increase in risk of CRC may be due to small-study bias.     

Association between NAD(P)H:quinone oxidoreductase 1 rs1800566 polymorphism and risk of bladder cancer

NAD(P)H:quinone oxidoreductase 1 (NQO1) rs1800566 (Pro187Ser) is a functional polymorphism which leads to a proline-to-serine amino acid substitution at codon 187 in the NQO1 protein and enzyme activity changes. NQO1 rs1800566 polymorphism was implicated to be associated with a risk of bladder cancer, but published studies showed inconclusive results. We performed a meta-analysis of nine publications with a total of 2,661 cases and 2,738 controls on the association between NQO1 rs1800566 polymorphism and risk of bladder cancer. Data were extracted from those included studies, and the pooled odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) was calculated to assess the association. We found that there was no association between NQO1 rs1800566 polymorphism and risk of bladder cancer under all four genetic models (Ser vs. Pro, OR?=?1.06, 95 % CI?=?0.97–1.16, P?=?0.21, I ²?=?31 %; SerSer vs. ProPro, OR?=?1.12, 95 % CI?=?0.89–1.42, P?=?0.33, I ²?=?44 %; SerSer/ProSer vs. ProPro, OR?=?1.08, 95 % CI?=?0.96–1.21, P?=?0.20, I ²?=?27 %; SerSer vs. ProPro/ProSer, OR?=?1.06, 95 % CI?=?0.85–1.32, P?=?0.59, I ²?=?36 %). Meta-analysis of those eight studies from Europeans also showed that there was no association between NQO1 rs1800566 polymorphism and risk of bladder cancer under all four genetic models (Ser vs. Pro, OR?=?1.02, 95 % CI?=?0.93–1.13, P?=?0.66, I ²?=?20 %; SerSer vs. ProPro, OR?=?0.99, 95 % CI?=?0.75–1.30, P?=?0.93, I ²?=?38 %; SerSer/ProSer vs. ProPro, OR?=?1.04, 95 % CI?=?0.92–1.17, P?=?0.55, I ²?=?6 %; SerSer vs. ProPro/ProSer, OR?=?0.98, 95 % CI?=?0.75–1.28, P?=?0.87, I ²?=?39 %). This meta-analysis suggests that the NQO1 rs1800566 polymorphism is not associated with a risk of bladder cancer. Further studies with larger samples are needed, especially for studies in Asians and Africans.     

Vascular endothelial growth factor +936C/T polymorphism and breast cancer risk: a meta-analysis of 13 case–control studies

The association between vascular endothelial growth factor (VEGF) +936C/T polymorphism and breast cancer risk has been widely reported, but results were inconsistent. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Eligible articles were identified through search of databases including PubMed, Embase, and Chinese Biomedical Literature Database (CBM). The association between the VEGF +936C/T polymorphism and breast cancer risk was conducted by odds ratios (ORs) and 95 % confidence intervals (95 % CIs). Finally, a total of 13 studies with 6,879 cases and 7,219 controls were included in our meta-analysis. Overall, a significant association was found between VEGF +936C/T polymorphisms and the risk of breast cancer in overall populations under five models (T vs. C: OR?=?0.83, 95 % CI?=?0.73–0.94, P?=?0.002; TT vs. CC: OR?=?0.74, 95 % CI?=?0.61–0.91, P?=?0.004, Fig. 1a; TC vs. CC: OR?=?0.83, 95 % CI?=?0.71–0.96, P?=?0.014; TT vs. CC/CT: OR?=?0.77, 95 % CI?=?0.62–0.94, P?=?0.010; TT/TC vs. CC: OR?=?0.82, 95 % CI?=?0.72–0.95, P?=?0.006). In the subgroup analysis by ethnicity, there were also significant associations found between VEGF +936C/T polymorphism and breast cancer risk in Asians and Caucasians. In conclusion, the results of our meta-analysis suggest that the VEGF +936C/T polymorphism is significantly associated with breast cancer development and the VEGF 936T allele carriers may be associated with decreased breast cancer risk.     

Association between cytotoxic T lymphocyte antigen-4 +49A/G, −1722T/C,and −1661A/G polymorphisms and cancer risk: a meta-analysis

Cytotoxic T lymphocyte antigen-4 (CTLA-4), a key gene that contributes to the susceptibility and clinical course of cancer, is an important down-regulator of T cell activation and proliferation. The +49A/G polymorphism is commonly studied because of its association with cancer risks. However, other polymorphisms, such as ?1722T/C and ?1661A/G, have not been studied in detail. We performed a meta-analysis using 43 eligible case–control studies with a total of 19,089 patients and 21,388 controls to examine the association between CTLA-4 +49A/G, ?1722T/C, and ?1661A/G polymorphisms and cancer risk. We searched the PubMed and EMBASE databases for all articles published up to July 17, 2013. Individuals with the +49 A allele (AA/AG vs. GG, odds ratio (OR)?=?1.21, 95 % confidence interval (95 % CI)?=?1.16–1.27) and ?1661 G allele (AG/GG vs. AA, OR?=?1.52, 95 % CI?=?1.34–1.73) had increased cancer risk. However, no significant association between cancer risk and the ?1722T/C polymorphism was found (CC/CT vs. TT, OR?=?1.04, 95 % CI?=?0.92–1.16). In subgroup analysis for the +49A/G polymorphism, increased cancer risk remained in the subgroups of Asians (OR?=?1.25, 95 % CI?=?1.18–1.31), patients with breast cancer (OR?=?1.28, 95 % CI?=?1.15–1.42), and patients with lung cancer (OR?=?1.20, 95 % CI?=?1.07–1.35). For the ?1661A/G polymorphism, increased cancer risk remained in the subgroups of Asians (OR?=?1.52, 95 % CI?=?1.34–1.73), patients with breast cancer (OR?=?1.48, 95 % CI?=?1.07–2.03), and patients with oral cancer (OR?=?3.16, 95 % CI?=?1.84–5.45). However, no significant increase in cancer risk was found in the subgroups for the ?1722T/C polymorphism. In conclusion, the results suggest that +49A/G and ?1661A/G polymorphisms in CTLA-4 are risk factors for cancers, whereas the ?1722T/C polymorphism is not associated with an increased risk of cancer.     

NFKB1 -94 insertion/deletion polymorphism and cancer risk: a meta-analysis

Previous studies on the associations of the NFKB1 -94 insertion/deletion polymorphism with cancer risk have produced conflicting results. The purpose of this meta-analysis is to define the effect of the NFKB1 -94 insertion/deletion polymorphism on cancer risk. A search of the literature by PubMed was performed to identify studies based on the predetermined inclusion criteria. Twenty-three studies consisting of 6,494 cases and 9,884 controls were identified and analyzed. Overall, significant association was observed between the polymorphism and cancer risk under all genetic models. Subgroup analysis according to ethnicity and cancer type also detected significant association. The NFKB1 -94 insertion/deletion polymorphism was associated with cancer risk in Asian population (dominant model: OR?=?1.52, 95 % CI?=?1.17–1.98; recessive model: OR?=?1.50, 95 % CI?=?1.26–1.79; II vs. DD: OR?=?1.90, 95 % CI?=?1.37–2.65; ID vs. DD: OR?=?1.32, 95 % CI?=?1.05–1.66; I vs. D: OR?=?1.37, 95 % CI?=?1.17–1.60), but not in Caucasian population. In addition, significant associations in OC, HCC, and OSCC were observed, but significant associations were not found in BC and LC. The current meta-analysis suggested that NFKB1 -94 insertion/deletion polymorphism may influence cancer risk in Asian population.     

XRCC1 polymorphisms increase bladder cancer risk in Asians: a meta-analysis

X-ray cross complementing group 1 (XRCC1) polymorphisms and bladder cancer risk has been investigated for years, but the result in Asian population is till inconclusive. Thus, we performed this meta-analysis to determine the association of XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphisms with bladder cancer risk in the Asian population. PubMed, EMBASE, and China National Knowledge Infrastructure were searched up to January 2013 to identify eligible studies. The association strength was measured with odd ratios (ORs) and 95 % confidence intervals (95 % CIs). A total of nine eligible studies, including 1,931 bladder cancer patients and 2,192 controls, were identified. Significant increased risk of bladder cancer was observed for Arg194Trp polymorphism (allele comparison OR?=?1.20, 95 % CI: 1.06–1.36, P_{heterogeneity}?=?0.11; dominant model OR?=?1.20, 95 % CI: 1.02–1.41, P_{heterogeneity}?=?0.37) and Arg280His polymorphism (heterozygote comparison OR?=?1.87, 95 % CI: 1.21–2.90, P_{heterogeneity}?=?0.01; dominant model OR?=?1.75, 95 % CI: 1.05–2.90, P_{heterogeneity}?=?0.01); however, Arg399Gln was not associated with susceptibility to bladder cancer. No evidence of publication bias was detected. Our meta-analysis results suggest that XRCC1 Arg194Trp and Arg280His polymorphisms are associated with significantly increased risk of bladder cancer in Asians.