Genetic variants of MnSOD and GPX1 and susceptibility to bladder cancer in a Turkish population

This study was conducted to investigate the association of genetic polymorphisms in the MnSOD and GPX1 genes with the risk and invasiveness of bladder cancer in a Turkish population. This prospectively designed study enrolled 157 patients with bladder cancer (mean age 63.2 ± 10.86 years) and 224 healthy controls (mean age 61.7 ± 8.39 years). Genotyping of the MnSOD Ala-9Val and GPX1 Pro198Leu polymorphisms was carried out by PCR-RFLP. No significant difference was found in MnSOD genotype distributions between the controls and the bladder cancer patients. However, the Leu/Leu genotype of GPX1 was associated with a significantly higher risk of bladder cancer than the Pro/Pro genotype. When stratified according to tumor stage, the Leu/Leu genotype of GPX1 was more frequently observed in bladder cancer patients with high-stage tumors than those with low-stage tumors. Additionally, patients carrying both Ala/Ala of MnSOD and Leu/Leu of GPX1 had the highest risk of developing bladder cancer. In conclusion, the present study indicates that the GPX1 Pro198Leu polymorphism may be associated with the risk and development of invasive bladder cancer. In addition, the combination of the MnSOD Ala/Ala and GPX1 Leu/Leu genotypes may have a synergistic effect on disease risk.     

GPX1 Pro198Leu基因多态性与肿瘤易感性的Meta分析

目的:探讨GPX1Pro198Leu基因多态性与肿瘤易感性关系。方法:利用万方、维普、CNKI、Pubmed和Web ofScience检索1990-01-2011-01公开发表的关于谷胱甘肽过氧化物酶1(GPX1)Pro198Leu基因多态性与肿瘤易感性关系的文献,利用Stata11计算纳入文献的合并值及95%可信区间(95%CI),并依据入选文献的研究人群来源和肿瘤类型进行亚组分析。结果:纳入30篇文献共33项研究,累积病例13 280例,对照16 946名。经Meta整体分析GPX1Pro198Leu基因多态性与肿瘤易感性无关。亚组分析显示,亚洲人中携带TC基因型者患肿瘤的危险性是CC基因型携带者的1.55倍,T等位基因是C等位基因的1.48倍。TC和TT基因型携带者患膀胱癌的危险性是CC基因型的1.52和9.7倍。结论:GPX1Pro198Leu基因多态性与亚洲人肿瘤易感性相关,与高加索人、非洲人肿瘤易感性可能无关;GPX1Pro198Leu基因多态性与膀胱癌易感性相关,与乳腺癌、肺癌、结直肠癌等无关。     

Polymorphisms in oxidative stress-related genes are not associated with prostate cancer risk in heavy smokers.

Oxidative stress, associated with aging and inflammation, is likely to play a role in the etiology of prostate cancer. We evaluated potential associations between gene variants that result in reduced neutralization of reactive oxygen species (ROS; MnSOD Ala-16Val, CAT -262 C>T, and GPX1 Pro200Leu) and prostate cancer risk among 724 men with incident prostate cancer who participated in the Carotene and Retinol Efficacy Trial (CARET) cohort, a randomized trial for the prevention of lung cancer among men with a history of smoking and/or asbestos exposure. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression. Nested case-control analyses included study participants with available DNA (n = 533 cases and 1,470 controls), matched for race, age, and length of follow-time. Overall, there were no associations between genotypes of MnSOD, CAT, and GPX1 and prostate cancer risk, although among men diagnosed before age 65, CAT TT genotype was associated with increased risk (OR, 2.0; 95% CI, 0.97-3.95). Further analyses stratified by factors related to environmental oxidative stress exposures did not modify associations. When calculating the number of risk alleles of MnSOD, CAT, and GPX1 hypothetically related to reduced protection against ROS, there was a nonsignificant relationship between prostate cancer and carriage of five or more risk alleles, in comparison to men with less than five risk alleles (OR, 2.0; 95% CI, 0.90-4.42). In conclusion, it does not seem that variants in MnSOD, CAT, or GPX1 have an influence on prostate cancer risk in this cohort of men who were smokers or exposed to asbestos, although it is possible that cumulative defects in protection from oxidative stress may result in increased risk of the disease.     

The CYP1B1 Leu432Val polymorphism and risk of urinary system cancers

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

Quantitative assessment of the influence of CYP1B1 polymorphisms and head and neck squamous cell carcinoma risk

The associations between CYP1B1 polymorphisms and head and neck squamous cell carcinoma (HNSCC) risk have been conflicting. We therefore performed a meta-analysis to derive a more precise relationship. Six published case–control studies were collected; odds ratios (ORs) with 95 % confidence interval (CI) were used to assess the association between CYP1B1 Leu432Val, Asn453Ser polymorphisms, and HNSCC risk. The Sensitivity analysis and publication bias also were performed to guarantee the statistical power. Overall, the pooled OR with 95 % CIs indicated that CYP1B1 Leu432Val polymorphism was significantly related with HNSCC risk (for Val vs. Leu: OR = 1.13, 95 % CI = 1.03–1.25, P?=?0.014, P _{heterogeneity}?=?0.141; for Val/Val vs. Leu/Leu: OR = 1.30, 95 % CI = 1.06–1.60, P?=?0.013, P _{heterogeneity}?=?0.253; for Val/Val vs. Leu/Leu + Leu/Val: OR = 1.23, 95 % CI = 1.05–1.46, P?=?0.013, P _{heterogeneity}?=?0.456). The similar results were also been found in succeeding analysis of HWE and stratified analysis of Caucasian population. Furthermore, no significant association between CYP1B1 Asn453Ser polymorphism and HNSCC risk was found in this meta-analysis. In conclusion, our meta-analysis demonstrates that CYP1B1 Leu432Val polymorphism may be a risk factor for developing HNSCC.     

Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study

Breast cancer may be related to oxidative stress. Breast cancer patients have been reported to have lower antioxidant enzyme activity than healthy controls and the polymorphism GPX1 Pro198Leu has been associated with risk of lung and breast cancer. The purpose of the present nested case-control study was to determine whether GPX1 Pro198Leu and glutathione peroxidase (GPX) activity in prospectively collected blood samples are associated with breast cancer risk among postmenopausal women and whether GPX activity levels are associated with other known breast cancer risk factors. We matched 377 female breast cancer cases with 377 controls all nested within the prospective 'Diet, Cancer and Health' study of 57 000 Danes. Carriers of the variant T-allele of GPX1 Pro198Leu were at 1.43-fold higher risk of breast cancer compared with non-carriers (95% CI=1.07-1.92). Pre-diagnostic GPX activity tended to be lower in cases compared with controls. GPX activity was positively correlated with intake of alcohol (P<0.0001) and the catalytic activity was lowered 5% for each additional copy of the variant T-allele (P=0.0003). Alcohol intake was correlated with increased GPX activity for the C-allele but not for the T-allele. Results from this prospective study suggest that the GPX1 Pro198Leu-associated lowered GPX activity is associated with higher breast cancer risk among Danish women.     

CYP1B1 基因 Leu432Val 位点多态性与头颈癌易感性的 Meta 分析

目的：运用Meta分析方法研究CYPlBl基因Leu432Val位点多态性与头颈癌易感性的发生风险。方法：检索CNKI和PubMed数据库中有关CYPlBl基因Leu432Val位点多态性与头颈癌易感性关联研究的文献。对符合纳入标准的文献进行资料提取后，以OR值和95％可信区间为效应指标，应用STATA11．0软件进行Meta分析，并对发表偏倚进行检测。结果：纳入5个对照研究，共计1580例头颈癌患者和2076例正常对照人群。Meta分析结果显示，总人群中，CYPlBl基因Leu432Val位点多态性与头颈癌易感性之间有显著关联（ValVS．Leu：OR=1．13，95％CI=1．03—1．25，P=0．014；Val／ValV8．Leu／Leu：OR=1．30。95％CI=1．06—1．60，P=0．013；Val／ValVS．Leu／Leu＋Leu／Val：OR=1．23，95％CI：1．05—1．46，P=0．013）。在针对种族的亚组分析中，发现CYPlBl基因Leu432Val位点多态性可能会增加欧洲人群发生头颈癌的风险。结论：CYPlBl基因Leu432Val位点多态性可能是增加欧洲人群发生头颈癌易感性的危险因素。     

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.     

<Emphasis Type="Italic">GPX1 Pro198Leu</Emphasis> polymorphism and breast cancer risk: a meta-analysis

A genetic polymorphism at codon 198 in the human glutathione peroxidase 1 gene was reported to be associated with several cancers. However, this relationship remains controversial, especially in breast cancer. For better understanding the effect of GPX1 Pro198Leu polymorphism on breast cancer, a meta-analysis was performed. By searching relevant literatures, a total of six case–control studies, containing 5,509 breast cancer cases and 6,542 healthy controls, were included. The strength of association between GPX1 Pro198Leu polymorphism and breast cancer risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95%CI). And the results strongly suggested that there was no significant association between variant Leu allele and breast cancer susceptibility in overall comparisons in all genetic models [additive model: OR, 1.04; 95% CI, 0.92–1.18; P = 0.555; dominant model: OR, 1.01; 95% CI, 0.94–1.09; P = 0.777; recessive model: OR, 1.04; 95% CI, 0.92–1.18; P = 0.536]. However in subgroup analysis, an elevated risk in African population with variant Leu allele was revealed in additive (OR, 1.91; 95% CI, 1.02–3.58; P = 0.044) and recessive (OR, 2.09; 95% CI, 1.16–3.76; P = 0.014) genetic model. No apparent association between this polymorphism and different menopausal status (premenopausal and postmenopausal) and the other ethnicities (almost Caucasians) was showed. In conclusion, this meta-analysis strongly suggests that GPX1 Pro198Leu polymorphism is not associated with breast cancer risk in Caucasians, and an elevated risk in Africans needs large-scale investigations to confirm.     

Association between MTHFR Ala222Val (rs1801133) polymorphism and bladder cancer susceptibility: a systematic review and meta-analysis

Folate metabolism is thought to play an important role in carcinogenesis through its involvement in both DNA methylation and nucleotide synthesis. The association between the MTHFR Ala222Val polymorphism and bladder cancer has been widely reported, however, in general the data from published studies with individually low statistical power were controversial and underpowered. Hence, we performed a meta-analysis to investigate the association between bladder cancer and MTHFR Ala222Val in different inheritance models. Fourteen studies including a total of 3,570 bladder cancer cases and 3,926 controls for MTHFR rs1801133 polymorphism were included in the meta-analysis. Data were extracted from these studies and odds ratios with corresponding 95 % confidence intervals (95 % CI) were computed to estimate the strength of the association. Overall, the MTHFR Ala222Val polymorphism was not associated with the development of bladder cancer in all genetic models (Ala/Ala vs. Val/Val—OR?=?0.961, 95 % CI?=?0.763–1.209; Ala/Ala vs. Ala/Val—OR?=?0.918, 95 % CI?=?0.795–1.060—Ala/Val vs. Val/Val—OR?=?1.022, 95 % CI?=?0.852–1.227; dominant model—OR?=?0.998, 95 % CI?=?0.869–1.145; recessive model—OR?=?0.921, 95 % CI?=?0.794–1.069; Ala allele vs. Val allele—OR?=?0.957, 95 % CI?=?0.857–1.067). In the stratified analyses, no significant associations were found among different descent populations and sources of controls. Our meta-analysis suggests that the MTHFR Ala222Val polymorphism not contributes to the development of bladder cancer.     

MnSOD polymorphism and breast cancer in a population-based case-control study

A polymorphism in the signal sequence (Ala-9Val) of the gene encoding the free radical-quenching manganese superoxide dismutase (MnSOD) has been reported to alter the risk for breast cancer. We evaluated this relationship in a population-based case-control study (476 breast cancer cases and 502 controls). Overall, relative risks were not significantly elevated in women with one (RR: 1.27; 95% CI: 0.91-1.77) or two (RR: 1.18; 95% CI: 0.81-1.73) Ala alleles compared to those homozygous for the wild-type Val genotype. Results do not support any overall association of the Ala-9Val MnSOD polymorphism to the development of breast cancer.     

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.     

Association between p53 Arg72Pro polymorphism and thyroid cancer risk: a meta-analysis

The p53 is a tumor suppressor gene which may be involved in the development of thyroid cancer. Studies investigating the association between p53 Arg72Pro polymorphism and thyroid cancer risk reported conflicting results. The aim of the meta-analysis was to derive a more precise assessment of the association between p53 Arg72Pro polymorphism and thyroid cancer risk. A literature search of PubMed and Web of Science from their inception through March 2013 was conducted. Odds ratios (OR) with 95 % confidence intervals (95 % CI) were used to assess the strength of the association. Eight case–control studies were included with a total of 874 thyroid cancer cases and 1,891 controls. The meta-analysis results showed that the p53 Arg72Pro polymorphism was only associated with thyroid cancer risk under the recessive model (ProPro vs. ArgArg/ArgPro: OR?=?1.83, 95 % CI 1.05–3.20, P?=?0.034). However, there was no significant association between p53 Arg72Pro polymorphism and thyroid cancer risk under the other three genetic models (Pro vs. Arg: OR?=?1.20, 95 % CI 0.87–1.67, P?=?0.262; ProPro vs. ArgArg: OR?=?1.75, 95 % CI 0.88–3.50, P?=?0.113; ProPro/ArgPro vs. ArgArg: OR?=?1.01, 95 % CI 0.66–1.55, P?=?0.968). Subgroup by ethnicity showed that there was no significant association between p53 Arg72Pro polymorphism and thyroid cancer risk in both Caucasians and Asians. Thus, p53 Arg72Pro polymorphism may be associated with thyroid cancer risk, and ProPro genotype is likely to be a risk factor of thyroid cancer.     

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.     

P53 Arg72Pro polymorphism and bladder cancer risk--meta-analysis evidence for a link in Asians but not Caucasians

Objective: Individual studies of the associations between P53 codon 72 polymorphism (rs1042522) and bladdercancer susceptibility have shown inconclusive results. To derive a more precise estimation of the relationship,we performed this systemic review and meta-analysis based on 15 publications. Methods: We used odds ratios(ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Results: We found that therewas no association between P53 codon 72 polymorphism and bladder cancer risk in the comparisons of Pro/Pro vs Arg/Arg; Pro/Arg vs. Arg/Arg; Pro/Pro plus Pro/Arg vs. Arg/Arg; Arg/Arg vs. Pro/Arg plus Arg/Arg(OR=1.06 95%CI 0.81-1.39; OR=1.06 95%CI 0.83-1.36; OR=0.98 95%CI 0.78-1.23; OR=1.06 95%CI 0.84-1.32).However, a significantly increased risk of bladder cancer was found among Asians in the homozygote comparison(Pro/Pro vs. Arg/Arg, OR=1.36 95%CI 1.05-1.75, P=0.790 for heterogeneity) and the dominant model (Arg/Proplus Pro/Pro vs. Arg/Arg, OR=1.26 95%CI 1.05-1.52, P=0.564 for heterogeneity). In contrast, no evidence of anassociation between bladder cancer risk and P53 genotype was observed among Caucasian population in anygenetic model. When stratifying for the stage of bladder, no statistical association were found (Pro/Pro vs. Arg/Arg, OR=0.45 95%CI 0.17-1.21; Pro/Arg vs. Arg/Arg, OR=0.60 95%CI 0.28-1.27; Dominant model, OR=0.5695%CI 0.26-1.20; Recessive model, OR=0.62 95%CI0.35-1.08) between P53 codon 72 polymorphism and bladdercancer in all comparisons. Conclusions: Despite the limitations, the results of the present meta-analysis suggestthat, in the P53 codon 72, Pro/Pro type and dominant mode might increase the susceptibility to bladder cancerin Asians; and there are no association between genotype distribution and the stage of bladder cancer.     

Association between APE1 T1349G polymorphism and prostate cancer risk: evidence from a meta-analysis

APE1 T1349G polymorphism was considered to be associated with risk of cancer, but studies on the association between APE1 T1349G polymorphism and risk of prostate cancer remained inconclusive. A meta-analysis of published studies was performed to precisely assess the association between APE1 Asp148Glu polymorphism and prostate cancer risk. PubMed, Embase, and Wanfang databases were searched for published case–control studies investigating the association between APE1 T1349G polymorphism and prostate cancer risk. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to assess the strength of the association. Overall, seven studies with a total of 3,063 individuals were finally included into the meta-analysis. The heterogeneity analysis did not find obvious heterogeneity among those included studies. Meta-analysis of total seven studies did not find an obvious association between APE1 T1349G polymorphism and prostate cancer risk (G vs T OR (95 % CI)?=?1.11 (0.99–1.24); GG vs TT OR (95 % CI)?=?1.25 (0.96–1.62); TG vs TT OR (95 % CI)?=?1.11 (0.95–1.30); GG/TG vs T OR (95 % CI)?=?1.13 (0.97–1.32); GG vs TT/TG OR (95 % CI)?=?1.16 (0.91–1.48)). Subgroup analyses by ethnicity showed that APE1 T1349G polymorphism was associated with increased risk of prostate cancer in Caucasians (G vs T OR (95 % CI)?=?1.26 (1.02–1.56), P?=?0.033; TG vs TT OR (95 % CI)?=?1.44 (1.06–1.94), P?=?0.019; GG/TG vs T OR (95 % CI)?=?1.45 (1.08–1.94), P?=?0.013). The meta-analysis suggests that APE1 T1349G polymorphism is associated with increased risk of prostate cancer, especially in Caucasians. More studies are needed to further identify the obvious association above.     

<Emphasis Type="Italic">ARLTS1</Emphasis> polymorphism is associated with an increased risk of familial cancer: evidence from a meta-analysis

Adenosine diphosphate (ADP)-ribosylation factor-like tumour suppressor gene 1(ARLTS1) might be associated with an increased risk of several types of familial cancers. However, previous studies have shown that cancer susceptibility is not completely consistent with ARLTS1 polymorphisms, and the precise mechanism remains unknown. Therefore, we conducted a meta-analysis of case-control studies by searching the PubMed, Embase, OVID, Science Direct and Chinese National Knowledge Infrastructure (CNKI) databases. In total, 12 studies met the inclusion criteria and were included in this meta-analysis. Statistical analyses were performed using STATA 11.0 software. Overall, the Cys148Arg T?>?C variant significantly increased cancer risk (CC vs. TT: OR?=?1.27, 95% CI?=?1.15–1.41, P?<?0.05). The stratification indicated that the Cys148Arg variant is significantly associated with sporadic cancer (CC vs. TT: OR?=?1.36, 95% CI?=?1.18–1.55) and familial cancer (CC vs. TT: OR?=?1.26, 95% CI?=?1.12–1.43). Trp149Stop, Pro131Leu, Ser99Ser and Leu132Leu were not correlated with cancer susceptibility. Based on these results, we demonstrated that the ARLTS1 Cys148Arg polymorphism is associated with an increased risk of sporadic cancer and familial cancer, and there were no associations between the other four SNPs (i.e., Trp149Stop, Pro131Leu, Ser99Ser and Leu132Leu) and cancer risk.     

Genetic polymorphisms of MPO, COMT, MnSOD, NQO1, interactions with environmental exposures and bladder cancer risk

Tobacco smoking and occupational exposure are major risk factors of bladder cancer via exposure to polycyclic aromatic hydrocarbons (PAHs) and aromatic amines, which lead to oxidative stress and DNA damage. Several enzymes, which play key roles in oxidative stress are polymorphic in humans. Myeloperoxidase (MPO) produces a strong oxidant for microbicidal activity, and activates carcinogens in tobacco smoke. Catechol-O-methyltransferase (COMT) catalyzes the methylation of endo- and xenobiotics and prevents redox cycling. NAD(P)H:quinone oxidoreductase (NQO1) catalyzes the two-electron reduction of quinoid compounds, which also protects cells from redox cycling. Manganese superoxide dismutase (MnSOD) protects cells from free radical injury. To test the hypothesis that the risk of bladder cancer can be influenced by polymorphisms in the genes that modulate oxidative stress, in particular by interacting with environmental carcinogens, we conducted a hospital-based case-control study among men in Brescia, Northern Italy. We recruited and interviewed 201 incident cases and 214 controls from 1997 to 2000. Occupational exposures to PAHs and aromatic amines were coded blindly by occupational physicians. Unconditional multivariate logistic regression was applied to model the association between genetic polymorphisms and bladder cancer risk and the effect of modifications of smoking and occupational exposures were evaluated. MPO G-463A homozygous variant was associated with a reduced risk of bladder cancer with an OR of 0.31 (95% CI = 0.12-0.80). MnSOD Val/Val genotype increased the risk of bladder cancer with OR of 1.91 (95% CI = 1.20-3.04), and there was a combined effect with smoking (OR = 7.20, 95% CI = 3.23-16.1) and PAH (OR = 3.02, 95% CI = 1.35-6.74). We did not observe an effect of COMT Val108Met polymorphism. These findings suggest that individual susceptibility of bladder cancer may be modulated by MPO and MnSOD polymorphisms, and that the combination of genetic factors involved in oxidative stress response with environmental carcinogens may play an important role in bladder carcinogenesis.     

P53 codon 72 polymorphism and lung cancer risk: evidence from 27,958 subjects

The role of p53 codon 72 polymorphism in the development of lung cancer remains obscure due to inconsistent findings of individual case–control studies published to date. A meta-analysis was conducted to better estimate the association between the p53 codon 72 variant and lung cancer risk. All relevant publications from the PubMed, Embase, Web of Science, and Wanfang databases were retrieved. Based on the inclusion criteria, 39 publications involving 44 independent case–control studies were finally included into this meta-analysis. Data were extracted and the pooled odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) was calculated. The overall pooled ORs showed no significant relationship of the p53 codon 72 polymorphism with increased or decreased risk of lung cancer in all gene contrast models (OR _{Pro vs. Arg}?=?1.04, 95 % CI?=?0.96–1.13, P _OR?<?0.001; OR _{Pro/Pro vs. Arg/Arg}?=?1.07, 95 % CI?=?0.91–1.25, P _OR?<?0.001; OR _{Arg/Pro vs. Arg/Arg} =1.04, 95 % CI?=?0.94–1.15, P _OR?<?0.001; OR _{Pro/Pro + Arg/Pro vs. Arg/Arg}?=?1.04, 95 % CI?=?0.94–1.16, P _OR?<?0.001; OR _{Pro/Pro vs. Arg/Arg + Arg/Pro}?=?1.07, 95 % CI?=?0.93–1.23, P _OR?<?0.001). According to the ethnicity, no significant association was observed in subgroup analyses of the Asians, Caucasians, Africans and the mixed population. Similar finding was found in subgroup analyses of hospital-based and population-based studies. Concerning the histological types of lung cancer, the p53 codon 72 variant exerts risk effect on the lung carcinogenesis in patients with adenocarcinoma (OR _{Arg/Pro vs. Arg/Arg}?=?1.10, 95 % CI?=?1.00–1.22, P _OR?=?0.048). Additionally, subgroup analysis by the smoking status demonstrated that the p53 codon 72 variant seemed to play a protective role in lung carcinogenesis among the non-smokers but not the smokers in the contrast model of Arg/Pro vs. Arg/Arg (OR _{Arg/Pro vs. Arg/Arg}?=?0.71, 95 % CI?=?0.50–1.00, P _OR?=?0.049). The present meta-analysis suggests the p53 codon 72 polymorphism may weakly modify the risk for lung cancer among the adenocarcinoma patients and non-smokers. Nevertheless, this association needs further confirmation in future studies with high quality.     

MGMT Leu84Phe gene polymorphism and lung cancer risk: a meta-analysis

Many studies have examined the association between the MGMT Leu84Phe polymorphism 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. The PubMed and CNKI database was searched for case–control studies published up to Nov. 2013. Data were extracted and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 7 studies, comprising 3,094 lung cancer cases and 4,216 controls, were included. Overall, for (Phe/Phe+Phe/Leu) versus Leu/Leu, the pooled OR for all studies was 1.08 (95 % CI?=?0.97–1.21 P?=?0.518 for heterogeneity); for Phe/Phe versus Leu/Leu and Phe versus Leu, the pooled OR was 1.10 (95 % CI?=?0.99–1.21 P?=?0.445 for heterogeneity) and 1.46 (95 % CI?=?1.05–2.02 P?=?0.352 for heterogeneity), respectively. In the stratified analysis by ethnicity, significantly risks were found among Caucasians not in Asians. This meta-analysis suggests that the MGMT Leu84Phe polymorphisms are associated with lung cancer risk among Caucasians not in Asians.