CC: OR = 1.19, P = 0.01; TT vs. CT+CC: OR = 1.19, P <0.001). Furthermore, stratified analyses revealed a significant association between the rs1001179 polymorphism and prostate cancer in all models except the homozygote comparison. An association of the rs794316 polymorphism with cancer risk was detected in two genetic models . Additional well-designed studies with large samples should be performed to validate our results.Recent studies have focused on the associations of catalase polymorphisms with various types of cancer, including cervical and prostate cancers. However, the results were inconsistent. To obtain a more reliable conclusion, we evaluated the relationship between the two common catalase gene polymorphisms (rs1001179 and rs794316) and cancer risk by a meta-analysis. Our meta-analysis included 37 published studies involving 14,942 cancer patients and 43,285 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the cancer risk. The results demonstrated that the rs1001179 polymorphism was associated with an increased cancer risk in the recessive and homozygote models (TT  Worldwide, cancer is currently the main cause of death and a public health problem that seriously threatens human health . BiologiCAT gene may play an important role in substance metabolism. CAT is located on the nuclear chromosome 11p13, and polymorphisms in this gene have been reported to associate with the development of many types of cancer, such as invasive cervical cancer and prostate cancer  = 1.19, 95% confidence interval [CI] = 1.04-1.37, P = 0.01; TT vs. CT+CC: OR = 1.19, 95% CI = 1.06- 1.34, P < 0.001.) In the cancer-specific analysis, the results showed significant correlations between the rs1001179 polymorphism and prostate cancer risk in different comparison models . However, no meaningful correlations were observed in analyses stratified by ethnicity or the source of controls.The main results of this meta-analysis are listed in Table vs. AA: OR = 1.34, 95% CI = 1.03-1.74, P < 0.001; TT vs. AT+AA: OR = 1.39, 95% CI = 1.09-1.77, P = 0.01; Figure The association of the rs794316 polymorphism with cancer risk was investigated in 4 studies involving 1,188 cases and 1,186 controls. This polymorphism was associated with an increased cancer risk in the overall population under the two models (TT P = 0.134). Furthermore, the results revealed that the publication year, ethnicity, genotype method and the source of controls were all not the factors that could impact on our results . We also performed a funnel plot and Egger's test to assess publication bias. As shown in Figure P > 0.05). Therefore, the results revealed that publication bias was not significant in this meta-analysis.In this meta-analysis, Q-statistic test was used to detect between-study heterogeneity that arose from methodological or clinical dissimilarity across studies. When the P value of the heterogeneity test was more than 0.1 (P ≥0.1), a fixed-effects model was performed. Otherwise, the random-effects model was used. To explore the other factors which may influence our results, we performed a meta-regression analysis. As shown in the Table CAT polymorphisms  was not considered. Third, the overall outcomes were based on individual unadjusted ORs, whereas a more precise evaluation should be adjusted using other potentially suspect factors. Fourth, the genotyping methods used in the eligible studies differed widely, which might have influenced the results. Moreover, although we have summarized all data on rs794316 polymorphism and cancer risk, the number of relative studies still needs further expansion.CAT rs1001179 and rs794316 polymorphisms with an increased cancer risk. Additional larger-scale multicenter studies with larger sample sizes are needed to further validate the possible roles of these polymorphisms in cancers.In summary, this meta-analysis has shown associations of the CAT polymorphism and cancer risk; (b) published data must have been sufficient to allow OR estimation with a 95% CI; and (c) for multiple publications reporting the same data or overlapping data, the largest or most recent publication was selected.The PubMed, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) databases were searched for publications from 2002 to January 2016 using the terms “cancer” or “tumor”, “CAT” or “Catalase”, “polymorphism” or “SNP”, “rs1001179” or “C-262T”, and “rs794316” or “A-15 T”. We also used the “Related Articles” option in PubMed to identify additional studies of the same topic. The reference lists of the retrieved articles were also screened. All included studies were selected using the following criteria: (a) studies must have featured a case-control design and focused on Initially, 2 investigators (Liu K and Liu XH) independently checked all potentially relevant studies, and disagreements were resolved through discussions with a third researcher. We extracted the following items from each article: first author, year of publication, country of origin, ethnicity, cancer types, control source, genotyping method, total numbers of cases and controls, and numbers of different genotypes among cases and controls. All data were extracted from published articles. All cancers were confirmed by histology or pathology. The non-cancer controls had no evidence of any malignant disease at the time of the study.CAT polymorphisms. Heterogeneity between studies was evaluated using the I2 test, with a higher I2 value indicating a higher level of heterogeneity . During the heterogeneity evaluation, the fixed-effects model would be used if the P value was ≥0.10; otherwise, the random-effects model was used. Subgroup analyses were performed according to cancer type, control source, and ethnicity. A sensitivity analysis was performed to assess the stability of the final results by sequentially omitting each individual study at a time. Egger's test and Begg's test were adopted to assess publication bias. The meta-analysis assessed the following genetic models: dominant model (AB+BB vs. AA), recessive model (BB vs. AA + AB), homozygote comparison (BB vs. AA), heterozygote comparison (AB vs. AA), and allele comparison (B vs. A). All analyses were performed using the Stata software, version 12.0 . A P value < 0.5 was considered statistically significant, and all P values were 2-sided.We used ORs and 95% CIs to evaluate the cancer risks associated with


Base excision repair (BER) pathway is a DNA repair pathway that is important in carcinogenesis and in response to DNA-damaging chemotherapy. XRCC1 is one of important molecular markers for BER. So far, the role of XRCC1 polymorphisms with clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy is inconclusive. To explore the relationship between XRCC1 polymorphisms and platinum-based chemotherapy in advanced NSCLC patients, we performed this meta-analysis.I2 test were used for the assessment of heterogeneity. Subgroup analyses were conducted when heterogeneity exists. Begg’s funnel plots and Egger’s linear regression test were used to estimate publication bias. Sensitivity analysis was performed to evaluate the stability of the result.Crude odds ratios (ORs), Cox proportional hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were adopted to assess the strength of association between XRCC1 polymorphisms and response rate, Overall survival (OS) and progression free survival (PFS) of advanced NSCLC treated with platinum-based chemotherapy. Q test and A total of 19 studies including 2815 individuals were eligible for the analysis, results showed XRCC1 194Arg allele was negatively associated with the objective response rate relative to 194Trp, and results of homozygous model, dominant model and heterozygous model suggested a gene dosage effect negative correlation between 194Arg allele and objective response rate(ArgArg vs TrpTrp: OR = 0.64(95%CI: 0.44-0.91); ArgArg + TrpArg vs TrpTrp: OR = 0.79(95%CI: 0.57-1.11); TrpArg vs TrpTrp: OR = 1.05(95%CI: 0.73-1.51)). XRCC1 399Gln may indicate favorable overall survival (GlnGln + GlnArg vs ArgArg: HR = 0.65(95%CI: 0.43–0.98)) and favorable PFS (GlnGln vs ArgArg: HR = 0.72(95%CI: 0.48–0.97)) in Asian patients; while in Caucasian patients, XRCC1 399Gln indicated poorer overall survival (GlnGln vs ArgArg: HR = 2.29(95%CI: 1.25–3.33)).Our results indicated that in NSCLC patients treated with platinum-based regimen, XRCC1 194Arg allele suggest poor objective response rate, the GlnGln genotype of XRCC1 399 suggest poorer overall survival in Caucasian patients, and longer PFS in Asian patients.The online version of this article (doi:10.1186/s12885-017-3487-y) contains supplementary material, which is available to authorized users. Lung cancer, with growing incidence, is becoming one of the most prevalent cancer types all over the world. And it’s the leading cause of cancer death in males and second leading cause of cancer death in females, approximate 17.6% of the cancer deaths was due to lung cancer.  For decaapoptosis. [Anti-tumor mechanism of cisplatin and carboplatin is generally acknowledged as follows: cisplatin and carboplatin enter cell nucleus, bind to DNA and form DNA adducts which lead to intrastrand or interstrand cross-links, result in DNA synthesis/replication dysfunction and DNA structure disruption, which ultimately brings about cell proliferation inhibition and cell optosis. , 6 Resisoptosis. , 8 In otpolymerase beta and poly (ADP-ribose) polymerase, and forms a repair complex to participate in the BER pathway [Base excision repair (BER) pathway is a DNA repair pathway that repairs damaged DNA throughout the cell cycle, and it is important in carcinogenesis and in response to DNA-damaging chemotherapy. X-ray repair cross-complementing protein 1 (XRCC1), which located on chromosome no. 19q13.2–13.3, undertook the DNA repair mission of single-strand breaks formed by ionizing radiation and alkylating agents. This protein interacts with DNA ligase III,  pathway .So far, a number of studies have investigated the role of XRCC1 polymorphisms with clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy, but the results were quite controversial, some studies supported that there were some association between XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy (treatment response(TR), overall survival(OS) or progression-free survival(PFS)), –28 but oWe carried out this meta-analysis based on the PRISMA statement, all data was extracted from published papers, so that ethical approval was not required per our institutional ethics committee.Eligible studies were identified by searching the PubMed, CNKI, EBSCO and Cochrane databases (prior to July 2015) using “XRCC1” or “X-ray repair cross-complementing protein 1”, “lung”, “polymorphism” and “platinum”. Additional articles were identified through the reference cited in the first series of articles selected. Only research articles with human subjects were included and the language was not limited. The included studies have to be designed to evaluate the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC (no opportunity of surgery) treated with platinum-based chemotherapy. And a study was excluded if any of the following cases occurred: (i) the study did not report any clinical outcome; (ii) studies using XRCC1 polymorphisms either to predict lung cancer’s risk or to predict treatment toxicity; (iii) studies reported with the same data or overlapping data by the same authors; (iv) the response rate or overall survival reported in the study was either not specific to polymorphism or could not be attributed to a specific polymorphism; (v) the response rate or overall survival stratified by SNP was neither reported in nor derivable from the original article, and the principal investigator declined or was unable to provide this information on request.Upon carefully reading through all articles of eligible studies, information was carefully extracted. For each study, characteristics such as name of first author, year of publication, original country and ethnicity of the patients, tumor stage, sample size (case no.), genotyping method, genotype distribution and clinical outcomes were collected. For studies including different subpopulations according to ethnicity or experiment design, we considered each subpopulation as a separate study in the meta-analysis. For example, the study carried out by Liao et al.  includedI2 test were used for the assessment of heterogeneity. The fixed effects model was applied when the effects were assumed to be homogenous , otherwise a random effects model was applied for meta-analysis. When heterogeneity was present, and the number of the studies included was large enough to perform the multivariable regression analysis, a meta-regression analysis was employed to explore the sources of heterogeneity. Furthermore, subgroup analyses were conducted by ethnicity and sample size (n > 100). Hardy-Weinberg Equilibrium (HWE) were assessed by http://www.oege.org/software/hwe-mr-calc.shtml [The strength of association between XRCC1 polymorphisms and response rate of advanced NSCLC treated with platinum-based chemotherapy was assessed by Crude odds ratios (ORs) with the corresponding 95% confident intervals (CIs).  The oddslc.shtml  on SepteAll the statistical analyses were performed using STATA version 12.0 .Overall 1569 potential studies were selected during the first step of systematic literature review, and a further review of the searched trials excluded 1448 studies, including 105 review articles, 258 studies on non-human beings, 1023 studies on other tumors, and 62 studies for other reasons. The remaining 121 studies were evaluated further, 96 studies were excluded, including 89 studies on lung cancer susceptibility, 3 studies on SCLC, 4 studies on treatment toxicity. Through detailed assessment, in the end, 19 follow-up studies were considered to meet all in inclusion criteria  were eligible for XRCC1 399 analysis, and 8 studies  were eligible for XRCC1 194 analysis. Table p = 0.190, PBegg = 0.368, PEgger = 0.943, Fig. p = 0.190, PBegg = 0.368, PEgger = 0.943; ArgArg + TrpArg vs TrpTrp: OR = 0.79(95%CI: 0.56-1.11), p = 0.324, PBegg = 0.230, PEgger = 0.337; TrpArg vs TrpTrp: OR = 1.05(95%CI: 0.73-1.51), p = 0.347, PBegg = 0.035, PEgger = 0.088; Table p = 0.013, PBegg = 0.072, PEgger = 0.065; Fig. p = 0.028, PBegg = 0.368, PEgger = 0.317; Fig. Seven studies including 1208 individuals referred the predictive value of XRCC1 Arg194Trp with respect to the sensitivity of lung cancer to platinum-based treatment. All the studies were carried out based on Asian population. In the homozygous model, the Arg genotype was inverse associated with objective response in all patients (ArgArg vs TrpTrp: OR = 0.64(95%CI: 0.44-0.91), p = 0.90). The pooled results showed no significant association between XRCC1 Arg194Trp polymorphism and PFS under either kinds of genetic model (Table Data from 3 included studies (including 721 patients) were applicable for the analysis. As shown in Table p = 0.000, PBegg = 0.077, PEgger = 0.093; Fig. Eighteen studies including 2814 individuals were qualified for analyzing the association between XRCC1 Arg399Gln polymorphism and treatment response to platinum-based treatment of NSCLC. No significant association was found between the 399Gln allele and response rate relative to the 399Arg allele in either kinds of genetic model , p = 0.136; Fig. Begg = 1, PEgger = 0.989; Fig. Only six studies  were applicable for the analysis. The results show GlnGln genotype of XRCC1 399 was associated with longer PFS than ArgArg genotype in patients treated with platinum-based regimen (GlnGln vs ArgArg: HR = 0.7295%CI: 0.48–0.97), 8–0.97, pExamining genotype frequencies in the controls, significant deviation from HWE was detected in the two articles. , 23 WhenPlatinum-based combination chemotherapy remains the first-line treatment regimen for advanced NSCLC. However, platinum (cisplatin or carboplatin) may cause severe toxic side effect, such as gastrointestinal reaction, neutropenia, anemia, renal toxicity and hepatic toxicity ect. Studies were carried out to explore whether non-platinum-based chemotherapy could achieve comparable efficacy as platinum-based chemotherapy. , 37 MetaFinding predictive markers to guide personalized treatment is essential. The XRCC1 polymorphisms have been widely investigated in lung cancer, and it was reported that different genotype of XRCC1 could predict different lung cancer risk, also it was reported that different genotype of XRCC1 could predict different clinical outcomes . Meanwhile, others might have different opinions. To explore the relationship between XRCC1 polymorphism and clinical outcomes to platinum-based regimen, and further guide our clinical strategic decision, we conduct this analysis.Our results showed that XRCC1 194Arg allele was negatively associated with the objective response rate relative to 194Trp, and interestingly, results of homozygous model, dominant model and heterozygous model suggested a gene dosage effect negative correlation between 194Arg allele and objective response rate. This further confirms the robustness of our results. But no association was found between 194Arg allele and either overall survival or PFS. That may due to too few eligible studies. Hence, the conclusions drawn in this meta-analysis about the association between 194Arg allele and both overall survival and PFS should be cautiously considered. More studies need to be carried out and applied for further analysis.Analysis showed that XRCC1 399Gln allele played different roles in different ethnicity. Although under fixed models, association was found between XRCC1 399Gln allele and not only overall survival, but also objective response rate and progress free survival. As heterogeneity was detected in the analysis of overall survival and objective response rate, after random model was adopted, no significant association was found between XRCC1 399Gln allele and the objective response rate relative to 399Arg allele. XRCC1 399Gln allele indicated better overall survival in Asian patients in dominant model; while in Caucasian patients, the GlnGln genotype of XRCC1 399 was associated with poorer overall survival in homozygous model. Furthermore, in homozygous model, 399GlnGln genotype was associated with longer PFS than 399ArgArg genotype in Asian patients treated with platinum-based regimen. According to the analysis results, it seemed that XRCC1 339Gln allele had contradictory results on different ethnic groups. Maybe there were other reasons that may influence the results of OS and PFS. Because we know that response rate more directly reflects pharmacogenomics roles, while OS and PFS may be influenced by many other factors, such as supportive care, dietary habits, living habits, constitutional factors and so on. In addition to those factors, more studies with much larger sample size are required to be able to draw more definitive conclusions.HWE states that allele and genotype frequencies in a population will remain constant from generation to generation in the absence of other evolutionary influences. It is not uncommon that quality of studies may vary in meta-analysis of genetic association studies in genetic epidemiology. As reports showed that XRCC1 was associated with lung cancer risk, we considered that violation of HWE was not necessarily be excluded in this analysis, and furthermore, no genotyping error was detected in those studies.Heterogeneity was detected in parts of the analysis, through random effects model, some of them generated a significant OR/HR results, and all the results were confirmed by sensitive analysis. The existence of heterogeneity indicated variability, which may have been caused by different characteristics, such as ethnicity, region, sample size, gender, method of genotyping used among patient populations. Hence, stratified analyses of subpopulations are needed to reduce such variability, and much larger studies should be undertaken to ensure sufficient statistical power.Many proteins involved in DNA damage repair system have a role in repairing the cross links by platinum. Nucleotide excision repair (NER) and base excision repair (BER) pathway are major DNA repair systems. Besides XRCC1, other DNA base excision repair genes including OGG1,  APE1, 1, 39–41 XDNA repair genetic polymorphisms may be better used in the future to predict clinical outcomes from treatments in cancer care  and helpAlthough interesting results have been achieved in this meta-analysis, there are several limitations. First, a systematic review should ideally be conducted using individual patient data. However, it’s not practical because individual patient data from studies are not always easily obtainable, lacking of the original data of the included studies limited our further evaluation of potential interactions. Second, we only included the studies published in English and Chinese, studies published in other languages were difficult to get. Last, our results were based on unadjusted published estimates. Without data limitations, we could adjust them such as age, smoking condition, pathological type, gender et al., and get more definitive and detailed conclusions. Overall, our results indicated that in NSCLC patients treated with platinum-based regimen, XRCC1 194Arg allele suggest poor objective response rate, the GlnGln genotype of XRCC1 399 suggest poorer overall survival in Caucasian patients, and longer PFS in Asian patients.Additional file 1:Dominant model of association between 399Gln and overall survival relative to 399Arg. (DOCX 73 kb)Additional file 2:Dominant model of association between 399Gln and overall survival relative to 399Arg in Asian population. (DOCX 62 kb)


Several studies have evaluated the association between statin use and endometrial cancer risk. We carried out a meta-analysis of randomized controlled trials (RCTs) and non-randomized studies to evaluate the effect of statins on endometrial cancer risk. A comprehensive search of electronic databases, conference abstracts and clinical trial registers was conducted for published and unpublished results. Studies that evaluated exposure to statins and endometrial cancer risk were considered. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using either a fixed-effects or a random-effects model. Two RCTs and eleven non-randomized studies (four cohort and seven case-control studies) involving 9,517 cases of endometrial cancer were included in the analysis. There was no evidence of an association between statin use and endometrial cancer risk either among RCTs  or among non-randomized studies . Combined analysis of all included studies also showed that statin use did not significantly affect endometrial cancer risk . The sensitivity analysis confirmed the stability of our results. Our findings do not support a protective effect of statins against endometrial cancer at the population level. Endometrial cancer is the most common malignancy of the female genital tract in the United States, with 60,050 new cases estimated in 2016 [Statins or 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are widely used to reduce plasma cholesterol levels and prevent cardiovascular diseases. Statins block the HMG-CoA reductase, the enzyme required for conversion of HMG-CoA to the cholesterol precursor mevalonic acid . Satins in vitro and in vivo in many recent laboratory studies, which prevent cancer growth and development. Statins have anti-proliferative and anti-metastatic effects in endometrial cancer cells, possibly through regulation of the MAPK and AKT/mTOR pathways [Debate regarding the association between statin use and cancer risk is ongoing. In a review of rodent carcinogenicity tests, an association betweeen lipid-lowering drugs, including statins, and increased cancer incidence was reported in rats and mice . In contpathways , 9. Evenpathways –13, whilpathways –18.Recently, a number of studies have also evaluated the relationship between statin use and endometrial cancer risk –31. HoweIn our initial search, 294 records were identified through database searching, no additional records were found from conference proceedings or trial registers. After screening the titles and abstracts, 13 potentially relevant papers were retrieved for full-text review. Of these, we excluded 7 studies for the following reasons: 2 were narrative review studies , 33, 5 dThe studies were published between 2001 and 2016. Of these, 7 studies were carried out in North America , 26–29, The risk of bias assessment for the included 2 RCTs is presented in Figure p value of 0.43, and the corresponding I2 was 0.0%, both indicating that there was no evidence of heterogeneity . The Chi-square test resulted in a s Figure .To date, most of the available results of statin use and endometrial cancer risk are from observational studies, only two RCTs reported endometrial cancer risk as a secondary end point , 22. ThuIn the present meta-analysis, both the synthesis of RCTs and non-randomized studies showed no evidence that statin use is associated with a significant relative decreased or increased risk of endometrial cancer. The results were not affected in subgroup analysis regarding study design and sensitivity analysis, which confirmed the validity of the conclusion. In addition, several meta-analyses also have found that statin use does not substantially affect overall cancer risk –41. AlthThe present study has several merits. We performed a comprehensive search, including electronic databases, conference abstracts and clinical trial registers for published and unpublished results. We sought articles without language restrictions and did not exclude any article regarding methodological characteristics or place of publication. Hence, the likelihood of important selection or publication bias was small in the review process. Systematic reviews have found that the estimates of effect derived from RCTs and non-randomized studies are likely to be different . FailureNevertheless, the present meta-analysis had several limitations. First, the available relevant RCTs were limited, which mainly investigated cardiovascular outcomes and assessed the incidence of endometrial cancer only as a secondary end point. Second, there was significant heterogeneity in meta-analysis of non-randomized studies, which might partly due to the extra sources of methodological diversity and bias compared to RCTs. Third, all studies did not adjust for the same potential confounding factors. In addition, the limited data made it impractical to evaluate dose, duration, and type effects of statins.In conclusion, despite the chemopreventive potential of statins demonstrated in several laboratory studies, our findings do not support a protective effect of statins against endometrial cancer at the population level. Due to the limited data regarding the association between statin use and endometrial cancer risk, further high quality clinical studies are needed to validate our findings.This meta-analysis was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement .ClinicalTrials.gov , World Health Organization International Clinical Trials Registry Platform , Chinese Clinical Trial Registry (http://www.chictr.org.cn/searchproj.aspx). We also searched the following sources for conference reports and abstracts by handsearching and electronic searching from 2006 to 2016: Annual Meeting of the American Society of Clinical Oncology, Biennial Meeting of the International Journal of Gynecological Cancer Society, Biennial Meeting of the European Society of Gynaecological Oncology, and Annual Meeting on Women's Cancer of the Society of Gynecologic Oncology. In addition, we screened the reference lists from selected articles and relevant reviews retrieved in the initial search for additional studies.We searched for all published and unpublished randomized controlled trials (RCTs) and non-randomized studies, without language restrictions. We searched the following electronic databases from inception to 28 January 2017: the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and PubMed. The search strategies are presented in We downloaded all titles and abstracts retrieved by electronic searching into the reference management database NoteExpress. Two reviewers (JY and QZ) removed duplicates and screened the remaining references independently. The full text of potentially relevant references were obtained and evaluated in detail to determine their eligibility. Any disagreements were resolved by discussion between the two reviewers or in consultation with a third reviewers (WX). Studies considered in this meta-analysis were either RCTs or non-randomized studies that met the following inclusion criteria: (1) evaluated exposure to statins and endometrial cancer risk, (2) reported risk ratio (RR) and a 95% confidence interval (CI) or provided data for their calculation. Articles were excluded if they were: (1) editorials, letters, reviews, and case reports; (2) studies without appropriate data for determining an estimate of RR and 95% CI. In cases of duplicate publications from the same population, only the largest and the most informative studies were included.Studies reporting different measures of RR, including relative risk, rate ratio, odds ratio, hazard ratio, and incidence rate ratio, were included in this meta-analysis. Actually, these effect measures yield similar estimates of RR because of the low prevalence of endometrial cancer.Two reviewers (JY and QL) extracted data independently. The following variables were collected from each study: publication data , study design, participants’age, sample size, RR and 95% CI, definition of statin exposure, and adjustment factors, if applicable. In non-randomized studies, when multiple estimates of effect (RR) were presented, the most adjusted estimate was extracted; when adjusted estimate was not available, crude estimate was extracted. As the important information was presented in all included studies, we did not contact the original authors for extra data or impute data for any outcomes.Three reviewers  assessed the quality of included studies independently. The risk of bias in included RCTs was assessed using the Cochrane Collaboration’s tool . It is aFor examining consistency of results across different study designs with different potential biases, we conducted two separate meta-analyses base on the study design: one meta-analysis of RCTs and a second meta-analysis of non-randomized studies. Then, we conducted a meta-analysis of all included studies.2, or Chi2) and I2 test. When significant heterogeneity  was found, a random-effects model was applied to calculate the pooled effect; otherwise, a fixed-effects model was used. Once significant heterogeneity was found, we attempted to determine the causes of heterogeneity by examining individual study and conducting subgroup analysis by study design and study location if possible. To assess the stability of the results, we performed the leave-one-out sensitivity analysis. All analysis was performed using Stata version 12.0 software .Heterogeneity was measured using the Chi-square (χ


ACE) gene and chronic obstructive pulmonary disease (COPD) has been examined in many previous studies. However, their results were controversial. Therefore, we performed a meta-analysis to evaluate the relationship between the ACE gene and the risk of COPD. Fourteen case-control studies were included in this meta-analysis. The pooled p value, odds ratio (OR), and 95% confidence interval (95% CI) were used to investigate the strength of the association. The meta-analysis was performed using comprehensive meta-analysis software. Our meta-analysis results revealed that ACE polymorphisms were not related to the risk of COPD (p > 0.05 in each model). In further analyses based on ethnicity, we observed an association between insertion/deletion polymorphism of the ACE gene and risk of COPD in the Asian population  but not in the Caucasian population (p > 0.05 in each model). In conclusion, the present meta-analysis indicated that the insertion/deletion polymorphism of the ACE gene may be associated with susceptibility to COPD in the Asian population but not in the Caucasian population. However, the results of the present meta-analysis need to be confirmed in a larger sample.The relationship between polymorphism of the angiotensin I converting enzyme ( COPD isreceptor  were rep ACE gene is located on the chromosome 17q23 and it encodes angiotensin-converting enzyme (ACE) which plays a role in converting angiotensin I into angiotensin II. One of the well-known polymorphisms in the ACE gene is the insertion/deletion polymorphism, which is 287 bp long and results in three genotypes . The genotypes have been shown to be associated with ACE activity and levels in plasma and tissues [ ACE polymorphism and COPD susceptibility, but several studies have reported conflicting results. Therefore, the aim of this meta-analysis was to investigate the possible association between ACE polymorphism and COPD risk based on all available relevant studies.ACE has been one of the most studied candidate genes –16 due t tissues . A previ tissues . In COPD tissues . InhibitAll studies which were published from January 1, 1998, to March 1, 2016, and which examined the association between ACE insertion/deletion polymorphism and COPD risk were carefully searched. Case-control studies were searched in PubMed, Google, Embase, and Korean databases  up to March 2015. The following keywords were used: “angiotensin-converting enzyme” or “ACE” AND “polymorphisms” AND “chronic obstructive pulmonary disease or COPD.” Only human studies were selected. Additional studies were identified by a manual search of the reference of the related original studies or review articles. If data or data subsets were published in more than one article, only the publication with the largest sample size was included.The inclusion criteria were as follows: (1) the studies should have evaluated the relationship between the ACE insertion/deletion polymorphism and COPD risk; (2) the study design should be a case-control study; and (3) the authors should have provided sufficient data on genotype distributions in the COPD group and the control group to estimate the odds ratio (OR) with a 95% confidence interval (CI). Studies were excluded if the genotype distribution in the control groups deviated from the Hardy-Weinberg equilibrium. ACE insertion/deletion polymorphism.Two investigators independently extracted data and created an analysis. When the investigators differed in their conclusions, they rechecked the data and reached a consensus through discussion. Data extracted from the selected articles included the first author's name, the year of publication, country of origin, ethnicity of the study population, the number of cases and controls, and the genotype frequency ofp value, OR, and 95% CI were used to investigate the association between the risk of COPD and ACE insertion/deletion polymorphism. In the present meta-analysis, we adopted the following genetic models [Meta-analysis was performed using a comprehensive meta-analysis software program . The pooled c models , 25: codχ2-test-based Q statistic test and the I2 test were applied. The random-effects Mantel-Haenszel method was adopted if the result of the Q test was p < 0.05 or the I2 statistic was >50%, which indicated a statistically significant degree of heterogeneity among studies. Otherwise, the fixed-effects Mantel-Haenszel method was adopted. Publication bias was evaluated by Egger's regression. A p value less than 0.05 was considered statistically significant.Firstly, we assessed the heterogeneity among studies to select the analysis model. The p < 0.001 and p = 0.004, resp., Q test was p < 0.05 or the I2 statistic was >50%. Otherwise, the fixed-effects method was adopted. Insertion/deletion polymorphism of the ACE gene did not show any significant association with susceptibility to COPD in each model, respectively  and p value and I2 for heterogeneity were 0.412 and < 0.001, respectively, in the fixed model. For the recessive model (D/D genotype versus I/D genotype + I/I genotype), OR was 3.326  and p value and I2 for heterogeneity were 0.203 and 3.835, respectively, in the fixed model. OR for the homozygote comparison (D/D genotype versus I/I genotype) was 3.126  and p value and I2 for heterogeneity were 0.358 and 6.964, respectively, in the fixed model. In the allele model, D allele of the ACE gene showed a significant association with the risk of COPD .We performed a meta-analysis in two subgroups based on ethnicity: Asian population and Caucasian population. Results of the analysis in the Asian subgroup and the Caucasian subgroup are presented in  ACE gene was significantly associated with a strong risk of COPD in the Asian population but not in the Caucasian population. Figures The present results obtained from these genetic models suggested that insertion/deletion polymorphism of thep > 0.05, To identify publication bias in the meta-analysis, funnel plots for all comparison models were generated to detect the presence of publication biases. The shapes of all of the funnels were symmetrical. We also evaluated publication bias using Egger's regression. There was no publication bias  but not in the Caucasian population. A previous study examined the ratio of the frequencies of ACE II, ID, and DD genotypes among various ethnicities. The study showed that the ratio of the frequencies of ACE II, ID, and DD genotypes was 1 : 2 : 1 in the Europeans; there was a tendency towards a higher D allele frequency in the Nigerians, and there was a tendency towards a higher I allele frequency in the Samoans and the Yanomami Indians [Previous two meta-analysis studies that assessed the relationship betweenpulation , 47. Our Indians . AlthougAccording to GBD study, age-standardized death rates for COPD are higher in low-income countries such as South Asian and Sub-Saharan African countries . But, th ACE polymorphism, but our study has some limitations. Our results showed the association between ACE polymorphism and COPD risk. However, we could not investigate various ethnic distributions because most of the studies included only the Caucasian and Asian populations. Also, environmental factors are key factors in COPD, but we could not consider the environmental factors in this meta-analysis. As mentioned above, our results showed no evidence of publication bias, but some results were influenced by the included articles.In the present study, we collected previous studies that assessed the relationship between COPD risk and ACE polymorphism and the development of COPD can be clarified.Despite some limitations, our results showed a statistically significant difference in the allele and genotype distribution in the Asian population. If more results in various populations are obtained in further studies, the relationship between


HIF1A) gene has been suggested to play a critical role in cancer progression, and the relationship between HIF1A rs11549465 polymorphism and risk of prostate cancer has been investigated in previous studies. Nevertheless, conflicting results have been obtained. Hence, we reevaluated this issue by means of this meta-analysis, with the purpose of providing more precise conclusion on this issue. The electronic databases of PubMed, EMBASE and Chinese National Knowledge Infrastructure (CNKI) as well as other sources were searched for relevant reports concerning on the role of HIF1A rs11549465 polymorphism in the occurrence of prostate cancer. The strength of the relationship was determined by calculating odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs). Besides, subgroup analyses by ethnicity and source of control were further performed to examine this relationship. All statistical analyses were performed using STATA software 12.0. Although HIF1A rs11549465 polymorphism showed a tendency of increasing the risk of prostate cancer, no statistical significance was detected under any genetic models. Similar results were also revealed in subgroup analyses on the basis of ethnicity and control source. Our findings indicate that HIF1A rs11549465 polymorphism may not independently play a significant role in the occurrence of prostate cancer.The hypoxia inducible factor 1-alpha ( Prostate cancer is the second most common cancer in men all over the world and the fourth most frequent cancer overall, accounting for 11% of male cancers and 9% of cancer-related mortality . The fivHIF1A gene has been proposed to be correlated with the occurrence risk of prostate cancer in several studies, but no definitive conclusion on the role of the single nucleotide polymorphism (SNP) in prostate cancer development has been drawn.Angiogenesis, referring to the formation of new blood cells from pre-existing cells –11, playHIF1A rs11549465 polymorphism on prostate cancer risk.In the present study, we incorporated previously published studies to more systematically explore the impact of n = 6), not involving HIF1A rs11549465 polymorphism (n = 13), and no controls (n = 5). As a consequence, a total of 4,570 cases and 4,820 controls were included in the present study [The selection process of eligible studies is presented in Figure nt study , 24–29. HIF1A rs11549465 polymorphism and susceptibility to prostate cancer is illustrated in Table vs. CC, TT+CT vs. CC, TT vs. CC+CT, T vs. C, and CT vs. CC [OR = 1.17, 95% CI = 0.61-2.23 , suggesting there was no significant publication bias.Publication bias across the selected studies was assessed with Begg's funnel plot and Egger's test. The funnel plots showed obvious symmetrical shapes Figure , and resHIF1A gene have been identified, and the variant allele of the rs11549465 polymorphism (C-to-T substitution at locus +1772) has been shown higher transcriptional activity under both normoxic and hypoxic conditions when compared with the wild allele [Prostate cancer is a rather common disease threatening the health of older males . Global d allele –42. TherHIF1A rs11549465 polymorphism to the occurrence of androgen-independent prostate cancer (AIPC), and found an apparent difference in the genotype distribution between AIPC patients and control subjects, so they concluded that the SNP might be involved in the susceptibility to AIPC [HIF1A rs11549465 polymorphism was not related to the risk of prostate cancer [Chau et al. investigated the contribution of  to AIPC . Similar to AIPC . Besides to AIPC . Neverthe cancer . In addie cancer , 26.HIF1A rs11549465 polymorphism in prostate cancer incidence may be due to several reasons. First of all, these studies described different types of prostate cancer. Secondly, the studies were carried out among people with different genetic backgrounds. Thirdly, different interfering environmental factors might be involved in the final results. Last but not least, studies with a small number of participants might get biased results.Above controversies over the role of HIF1A rs11549465 polymorphism and the prostate cancer risk under any genetic comparisons, which was also true for subgroup analyses according to ethnicity and control source. Compared to the above-mentioned studies, the present meta-analysis had the advantage of larger sample size. However, some limitations in this study still should be addressed. To begin with, the influences of other relevant components such as age, gender, and smoking as well as their interactions with HIF1A rs11549465 polymorphism on prostate cancer occurrence were not analyzed due to the lack of original information. Second, meta-analysis is a secondary analysis and the heterogeneity is the major issue in genetic studies [In the present study, we found no statistically significant relationship between  studies –44. In oHIF1A rs11549465 polymorphism may not be an independent risk factor for prostate cancer. However, due to the above limitations, our conclusions should be verified by multi-center studies with larger sample sizes based on multiple ethnic groups. Importantly, more attention should be paid to the roles of polymorphisms and their genetic variants in clinical aggressiveness and therapeutic response in future work.Taken together, the present meta-analysis manifests that This meta-analysis was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement  PRISMA .HIF1A rs11549465 polymorphism in the occurrence of prostate cancer. The following search terms were adopted: “HIF1A” or “HIF-1α”, “prostate cancer” or “prostatic cancer”, and “polymorphism” or “variant” or “mutation” or “SNP”. Additionally, the references of all pertinent articles were manually checked for other relevant articles.The electronic databases of PubMed, EMBASE and Chinese National Knowledge Infrastructure (CNKI) as well as other sources were searched for relevant reports concerning on the role of HIF1A rs11549465 polymorphism and risk of prostate cancer; (2) with a case-control design; (3) published in English or Chinese language; and (4) containing sufficient data on genotype and/or allele frequencies both in case and control groups. Studies with any one of the following characteristics were excluded: (1) with only cases; (2) comment, review, or abstract; (3) animal study; and (4) offering duplicated content.Eligible studies enrolled in the meta-analysis were required to fulfill the following criteria: (1) evaluating the association between P values for Hardy-Weinberg Equilibrium (HWE) in control groups. Conflicting opinions over extracted data were resolved by discussion between the two investigators so as to reach a consensus.The following items were extracted by two independent investigators using a specific sheet: name of the first author, publication year, country, ethnic line, control source, method for genotyping, total numbers of cases and controls, genotype and/or allele frequencies in cases and controls, and P < 0.05 was considered as statistical significance. Whether genotype distribution in control group was in accordance with HWE was assessed by Chi-square test. ORs and 95% CIs were calculated to examine the strength of correlation between HIF1A rs11549465 polymorphism and prostate cancer susceptibility. The significance of pooled ORs was determined by Z test. Degree of heterogeneity across studies was evaluated by Chi-square-based Q test. In case of P < 0.05, indicating significant heterogeneity, random-effects model was applied to calculate pooled ORs; otherwise, fixed-effects model was used. The stability of final results was assessed by conducting sensitivity analysis. Begg's funnel plots and Egger's linear regression test were carried out to determine the underlying publication bias.STATA software (version 12.0) was applied to perform all statistical calculations in this meta-analysis.


Ser447X XX genotype  was also associated with CAD risk. However, PvuII polymorphism was found to have no significant association with CAD risk. Conclusions: LPL HindIII polymorphism was significantly associated with the risk of CAD. For Ser447X polymorphism, it was found that only XX genotype was significantly associated with CAD risk. Furthermore, PvuII polymorphism had no significant association with CAD risk. It was considered that LPL HindIII polymorphism might serve as a potential biomarker for CAD risk.Background: In recent years, the lipoprotein lipase (LPL) polymorphism has been extensively investigated as a potential risk factor for coronary artery disease (CAD). However, the results of these studies have been inconsistent. Therefore, we performed this meta-analysis to explore the association between LPL polymorphism and CAD risk. Methods: The literature was searched from electronic databases such as Embase, China Biological Medicine Database, PubMed, Knowledge Infrastructure, and China National Web of Science by the key words “coronary artery disease”, “lipoprotein lipase” and “polymorphism”. All of the studies included in this manuscript met the inclusion and exclusion criteria. An odds ratio (OR) analysis using a 95% confidence interval (CI) was employed to assess the association of the LPL polymorphism with CAD susceptibility. Results: We performed a meta-analysis of 14 case-control studies including HindIII, Ser447X and PvuII polymorphism. A statistically significant increase in the risk of CAD was associated with LPL HindIII polymorphism. This included HindIII H Coronary artery disease (CAD) is one of the greatest causes of morbidity and mortality throughout the world. It accounts for roughly one-half of all cardiovascular deaths ,2. AlthoLPL is a key enzyme for lipid metabolism. It can hydrolyze the triglycerides of chylomicrons and very-low-density lipoprotein (VLDL) to provide free fatty acids for oxidation and utilization in the heart and other tissues, as well as for storage in adipose tissue ,8. The aIn this study, we performed the meta-analysis to explore these inconsistencies between LPL gene variants and the risk of CAD. The results confirmed that the LPL HindIII polymorphism is significantly associated with increased risk of CAD. This polymorphism might serve as a potential biomarker for CAD risk. The literature included in this study was searched from electronic databases including Embase, China Biological Medicine Database, PubMed, Knowledge Infrastructure, and China National Web of Science. The key words were as follow: “coronary artery disease”, “lipoprotein lipase” and “polymorphism”. The relative of the references from the retrieved studies were also included. The last search was updated on 15 December 2015, with publication years ranging from 2000 to 2015.The studies were selected based on the following inclusion criteria: the case-control studies discussed the polymorphism of LPL and the risk of CAD; the studies supplied the number of individual genotypes for the LPL polymorphisms in the CAD cases and controls; and the studies conform to the Hardy–Weinberg equilibrium (HWE). In addition, the following exclusion criteria were used: the study did not provide the detailed data that are typically presented in abstracts, meeting reports and reviews; the genotype frequency was not reported; and the studies repeated or overlapped other publications.The information was drawn out according to a standard protocol. Repeated publications were only adopted once and studies violating the inclusion criteria or providing insufficient data were excluded. The extracted data in p value less than 0.05. If there was heterogeneity among the individual studies, the random effects model was adopted to calculate the overall OR value [p < 0.05 level [Deviation from the Hardy–Weinberg equilibrium was examined by the Chi-square test. The odds ratio (OR) and the corresponding 95% confidence interval (CI) between the case and control groups was used to assess the strength of the association between the LPL polymorphisms and the risk of CAD. For the HindIII, Ser447X and PvuII polymorphisms, we pooled the OR by comparing the risk allele carrier genotypes versus the wild-type genotype for low frequency of the homozygous variant. The statistical significance of the summary OR was determined by the Z test with the significance set as OR value . OtherwiOR value . To dete05 level ,21. All The databases of Embase, China Biological Medicine Database, PubMed, Knowledge Infrastructure, and China National Web of Science were used to identify literature for inclusion in this study. The following key words were entered: “coronary artery disease”, “lipoprotein lipase” and “polymorphism”. Originally, 224 potentially relevant studies were identified and screened. Then, these studies were carefully analyzed and 14 case-control studies were selected ,28,29,30+H+ genotype had a significantly increased CAD risk compared with those who carried the HindIII H+H− and H−H− genotypes in all subjects , the fixed-effects model was conducted. In addition, we found that the H+ allele genotype was significantly associated with increased CAD risk when compared with the H− allele genotype , the fixed-effects model was used. It was determined that the individuals who carried the Ser447X XX genotype had a significantly increased CAD risk compared with those who carried the Ser447X other genotypes in all subjects , and the random-effects model was used for analysis. It was found that X allele genetic model had no significant association with CAD risk . In addition, we analyzed other genetic models and found that the heterozygous and dominant genetic models had no association with the risk of CAD.Eight studies examining CAD were included for the evaluation of the association with the LPL Ser447X polymorphism. As the heterogeneity was not significant (p = 0.45). It was determined that this genetic model had no significant association with the risk of CAD . It was also determined that the allele genetic model and the heterozygous and recessive genetic models had no associations with the risk of CAD.Data from six studies that included 1064 cases and 832 controls were pooled together to analyze the association between the PvuII polymorphism and the risk of CAD. For the dominant genetic model, the fixed-effects model was conducted because the heterogeneity was not significant . To assess the publication bias of the meta-analysis, Begg’s funnel plot and Egger’s test were performed. The funnel plot shapes were symmetrical for all the polymorphisms of HindIII and PvuII genotypes (data not shown). The statistical results did not suggest any evidence of publication bias among these studies. However, for Ser447X genotype, it was found that when the study by Ahmadi and colleagues was deleted, the sensitivity analysis was unstable and publication bias existed . TherefoIn this study, we first performed a meta-analysis for the association between LPL polymorphism and CAD risk. It was found that the LPL HindIII polymorphism was positively correlated with CAD risk. In contrast, the LPL PvuII polymorphism had no association with CAD risk. Further research on the association between LPL Ser447X polymorphism and CAD risk is still needed.The LPL gene spans over 30 kb, comprising 10 exons and nine introns on chromosome 8p22. Its cDNA is translated to a 475 amino acid proteins, including a 27 amino acid signal peptide. Several sequence variations, including BamHI, PvuII, HindIII, BstNI and Ser447X sites, have been identified by restriction fragment length polymorphisms (RFLPs) in the LPL gene ,32,33. A+H+ genotype and the H+ allele genotype were significantly associated with the risk of CAD. These results were consistent with previous reports that HindIII is the most common polymorphism of LPL associated with CAD risk. However, for the Ser447X polymorphism, the association with CAD was only found in the XX genotype; the other genotype had no significant association. The difference in the XX genotype may have been caused by publication bias because two studies reported no events in the XX genotype [The association between the LPL polymorphism and CAD has been researched for thirty years. However, the results to date have been inconsistent. Currently, there are no large scale case control studies for LPL polymorphism and CAD risk. Thus, we performed a meta-analysis to study the association between LPL polymorphism and CAD risk. To analyze the association between the HindIII polymorphism and CAD risk, we reviewed seven studies including 1853 cases and 1171 controls that were conducted from 2000 to 2015. As shown in genotype . More stHowever, there are some limitations in this study. First, based on our inclusion and exclusion criteria, the available studies that could be included in this meta-analysis were moderate. Thus, the results may be influenced by factors such as random error. Second, the results were based on individual unadjusted effect estimates, whereas a more precise evaluation would be adjusted by other potential risk factors, including age, sex, drinking status, cigarette consumption, etc. Third, the lack of individual-level data prevented further analyses to identify interactions between the genetic variations and the metabolic traits.+H+ genotype and H+ allele genotype were significantly associated with the risk of CAD. The Ser447X XX genotype was also significantly associated with the risk of CAD. However, more studies are needed to confirm these findings. In contrast, the PvuII polymorphism had no association with the risk of CAD. We have concluded that LPL HindIII polymorphism might serve as a potential biomarker for CAD risk.In conclusion, we found that the LPL polymorphisms HindIII H


MTHFR C677T and A1298C) and methionine synthase gene (MS A2756G) polymorphisms have shown an association with male infertility risk in several ethnic populations. Although several studies have evaluated these associations in Chinese populations, their small sample sizes and inconsistent outcomes have prevented strong conclusions. Therefore, the present meta-analysis was performed with published studies to evaluate the associations of the three single nucleotide polymorphisms (SNPs) and male infertility in a Chinese population.Methylenetetrahydrofolate reductase gene , China biology medical literature (CBM), VIP, and Chinese literature (Wan Fang) databases up to May 31, 2016. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were used to assess the strength of associations with a random-effect model or a fixed-effect model based on the heterogeneity analysis results. Sensitivity analysis was used to confirm the reliability and stability of the meta-analysis.MTHFR C667T polymorphism was significantly associated with increased risk of male infertility in the Chinese population in the allele model , the dominant model , the additive model  and the recessive model , whereas the MTHFR A1298C and MS A2756G polymorphisms were not risk factors. There was no significant heterogeneity in any genotype contrasts among the studies. The sensitivity analysis indicated that the results of this meta-analysis were relatively stable.A total of nine studies, including 1,713 cases and 1,104 controls, were included in the meta-analysis. The pooled results indicated that the MTHFR C667T polymorphism may contribute to the genetic susceptibility to male infertility in the Chinese population, whereas MTHFR A1298C and MS A2756G polymorphisms may be unrelated to male infertility. Studies with larger sample sizes and representative population-based cases and well-matched controls are needed to validate our results.This study suggests that the  FSHR, , FSHR[AR[PRM1[GST, the fol607093) gene polymorphisms , a methionine synthase  gene polymorphism , and a methionine synthase reductase  gene polymorphism . These SNPs can affect the activity, stability, and level of folate metabolism-related enzymes, which may affect folate metabolism and DNA synthesis[Folate plays an important role in DNA synthesis, RNA synthesis, methylation reactions, and protein synthesis, which contribute to the maintenance of genome integrity, 8. Sevesynthesis.MTHFR C677T polymorphism was associated with a significantly increased male infertility risk in the Asian and overall populations but not the Caucasian population[MS A2756G polymorphism may be a genetic risk factor for idiopathic male infertility[MTHFR A1298C and the risk of male infertility, the results were inconsistent[To date, several studies have explored the associations between these SNPs and male infertility risk; however, their results are conflicting. As a result, several meta-analyses addressing these associations have been performed. Three recent meta-analyses consistently showed that the opulation–13. Two fertility. Moreoveonsistent, 13. In onsistent–15. TherTwo authors independently conducted a systematic literature search of the PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature (CBM), VIP, and Chinese literature (Wan Fang) databases up to May 31, 2016. Search terms were as follows: “MTHFR or Methylenetetrahydrofolate reductase”, “MTR, MS or methionine synthase”, “SNP, polymorphism, mutation, or variant”, “male infertility”. In addition, the references of reviews and retrieved articles were reviewed to identify other eligible studies that were missed by the search. The search was limited to human subjects. The search strategy flowchart is shown in Only those studies meeting the following inclusive selection criteria were eligible: 1) The full text of the article was available. 2) The study was a case—control study evaluating at least one of the three SNPs. 3) The genotype distributions were available for both cases and controls. 4) There were no duplicate data. For studies that considered partially or fully duplicate data and that were by the same authors, we selected the study with the most subjects. 5) The published language was English or Chinese. 6) The study was of a Chinese population. 7) Genotypic distributions were available for the estimation of odds ratios (ORs) and 95% confidence intervals (CIs). Studies were excluded if any of the following criteria existed: 1) The study did not explore the association between any of the three SNPs and male infertility risk. 2) The article was an animal study, review article, meta-analysis, conference abstract or editorial article.The Newcastle-Ottawa Scale (NOS) was usedTwo authors extracted the relevant data independently in compliance with the inclusion criteria. Extracted data were entered into a collection form and checked by a third author. Disagreement was solved by discussion and consensus. Data on the following variables for each study were extracted: 1) first author’s name, year of publication, region, and genotyping method; 2) sample sizes of the case and control groups; 3) genotype and allele frequencies; and 4) results of the Hardy—Weinberg equilibrium test.MTHFR gene polymorphisms and male infertility risk were assessed using ORs and corresponding 95% CIs. The pooled ORs were calculated for the allele comparison model, dominant model, recessive model, and codominant model. The heterogeneity assumption was tested using the Chi-square-based Q test. Heterogeneity was considered significant at p<0.10, and I2 values of 25%, 50% and 75% corresponded to low, medium and high levels of heterogeneity, respectively. The significance of the pooled ORs were determined by the Z-test, and P<0.05 was considered statistically significant. The statistical analysis was performed with Reviewer Manager 5.3 and STATA 12.0. Potential publication bias was estimated using funnel plots and the Egger regression test. Sensitivity analysis was performed to evaluate the stability of the results. The pooled ORs were estimated by excluding one study each time to evaluate the influence of individual studies.The strength of the relationships between the MTHFR C667T polymorphism; 3 studies addressed MTHFR A1298C polymorphism, and 3 studies addressed the MS A2756G polymorphism. The year of publication ranged from 2007 to 2015. The Hardy-Weinberg test (HWE) was performed on all of the included studies, and HWE of the MTHFR C667T polymorphism was violated in one study[A total of 152 results were retrieved from the search of the PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature (CBM), VIP, and Chinese literature (Wan Fang) databases. Three studies were excluded because they were meta-analyses as determined from reading the title and abstract. An additional two publications contained duplicate data and were published by the same author; the one with the most subjects was included in the present analysis. Nine case-control studies considering 1,713 cases and 1,104 controls met the inclusion criteria–25Fig 1Fig 1. OfMTHFR C667T polymorphism on the risk of male infertility. Figs I2 value, representing the among-study heterogeneity, was 42%, 29%, 35%, and 0%, respectively. Thus, fixed-effects models were applied. Overall, the results revealed a significant association between the MTHFR C677T polymorphism and Chinese male infertility risk  , dominant model , additive model  or recessive model   or recessive model  and no association between the polymorphism and infertility risk with low heterogeneity in the allele model  or dominant model  . The results are consistent with recent meta-analysis studies that suggest a moderate to strong association between MTHFR C677T and male infertility, especially in Asian populations[In the present study, a meta-analysis was conducted of nine case-control studies to evaluate the association between three folate-related enzyme gene polymorphisms and male infertility in the Chinese population. Overall, we did not find the variant genotypes of the pulations–13, 32.MTHFR C667T polymorphism was not a risk factor for male infertility risk in a Chinese population, in contrast to the conclusions of a previous study. Similarly, Li et al. found no evidence an association of this polymorphism with male infertility risk. This difference among studies may be due to small sample sizes, study differences in genotyping method or population substructure, or other factors. The general Chinese population occupies a vast country such that cultures and habits, such as personality, diet, living environment, and customs, can vary greatly among regions, for example, between southern and northern China. In this meta-analysis, four of the included studies were from northern China, and the remaining five were from southern China. Xu et al. showed that the greatest genetic differentiation of the Chinese Han population occurred between the northern Han Chinese and the southern Han Chinese[MTHFR C677T, A1298C and MTRR A66G gene polymorphisms among different Chinese Han populations[MTHFR C667T polymorphism and male infertility risk may also be associated with variation in the nutritional status of people among different regions of China; for example, a higher vitamin intake can mask the biological effects of the MTHFR C667T polymorphism[MTHFR A1298C and MS A2576G polymorphisms, our results provided no evidence of either's association with male infertility risk in any genetic model, which is consistent with previous studies. Only three studies addressing the MTHFR A1298C and MS A2576G polymorphisms were included in the present meta-analysis; thus, studies with larger sample sizes are needed to further investigate the potential relationships of MTHFR A1298C and MS A2576G polymorphisms with male infertility risk.Ni et al. reported that the n Chinese. In addipulations. Differeymorphism. RegardiSome limitations of the present study should be considered when interpreting the results. First, only nine studies were included in the meta-analysis, and their sample sizes were small; therefore, limited data were available. Second, we did not estimate the potential gene—gene and gene—environment interactions due to the lack of information available in the original studies. Third, other clinical data, such as sources of control, subject age, and semen quality, were not considered here due to a lack of information. Finally, although the funnel plot and Egger’s test indicated no remarkable publication bias, some publication bias may exist in the results because only published studies were retrieved.MTHFR C667T polymorphism may contribute to genetic susceptibility to the risk of male infertility in the Chinese population, whereas MTHFR A1298C and MS A2576G polymorphisms may have no impact. Nevertheless, large-scale, well-designed and population-based studies are needed to investigate the combined effects of these variants within the MTHFR gene or other folate-related enzyme genes in the Chinese population, which may lead to a comprehensive understanding of their potential roles in infertility.In summary, this meta-analysis provides evidence that the S1 ChecklistThe PRISMA Checklist for our meta-analysis.(DOC)Click here for additional data file.S2 ChecklistMeta-analysis on Genetic Association Studies Checklist.(DOCX)Click here for additional data file.S1 FileThe PRISMA 2009 flow diagram for our meta-analysis.(DOC)Click here for additional data file.


Prospective and case-control studies which reported adjusted relative risk estimates and 95% confidence intervals of endometrial cancer associated with a hypertension diagnosis were included. Summary relative risks were estimated using a random effects model. Nineteen case-control studies and 6 cohort studies were included. The summary RR was 1.61  for all studies, 1.73  for case-control studies and 1.32  for cohort studies. The association between hypertension and endometrial cancer was weaker, but still significant, among studies with adjustment for smoking, BMI, oral contraceptive use, and parity, compared to studies without such adjustment. This meta-analysis suggest an increased risk of endometrial cancer among patients with hypertension, however, further studies with more comprehensive adjustments for confounders are warranted to clarify the association.A history of hypertension has been associated with increased risk of endometrial cancer in several studies, but the results have not been consistent. We conducted a systematic review and meta-analysis of case-control and cohort studies to clarify the association between hypertension and endometrial cancer risk. PubMed and Embase databases were searched up to 27 Hypertension is a major cause of morbidity and mortality worldwide and is an established risk factor for coronary heart disease and stroke158910Endometrial cancer is the eighth most common type of cancer in women with approximately 320 000 cases recorded in 2012, accounting for about 4.8% of all cancers in women 1420212223242526272829303132333435363739404142432021242526283032333435363738394222232729313942451620212533352021242528293335th February 2016 for eligible studies. We used the following search terms in the PubMed search: (hypertension OR high blood pressure OR blood pressure OR risk factor) AND . We followed standard criteria for reporting meta-analysesWe searched the PubMed and Embase databases up to 27We included published retrospective case-control studies and cohort studies that investigated the association between hypertension and the risk of endometrial cancer. Adjusted estimates of the relative risk  had to be available with the 95% CIs in the publication. A list of excluded studies and exclusion reasons is provided in The following data were extracted from each study: The first author’s last name, publication year, country where the study was conducted, study period, sample size, number of cases/controls, exposure and subgroups of tumor characteristics  or cancer type (type 1 vs. type 2), relative risks and 95% confidence intervals for the association and variables adjusted for in the analysis. Data were extracted by one reviewer (DA) and checked for accuracy by a second reviewer (AS).We calculated summary relative risks of developing endometrial cancer by history of hypertension using the random-effects model by DerSimonian and Laird2 statistics2 is a measure of how much of the heterogeneity that is due to between study variation rather than chance. I2-values of 25%, 50% and 75% indicates low, moderate and high heterogeneity respectively. We conducted main analyses  and stratified by study design  because of the greater potential for recall and selection bias in retrospective case-control studies and to investigate sources of potential heterogeneity. We also conducted subgroup analyses by other study characteristics such as sample size, number of cases, geographic location, and by adjustment for confounding factors. We also conducted a stratified analysis by whether the articles explicitly stated that participants with prevalent hysterectomies at baseline were excluded, and/or whether participants with incident hysterectomies were censored during follow-up in cohort studies, or excluded from the control group in case-control studies.Heterogeneity between studies was evaluated using Q and IPublication bias was assessed using Egger’s testOut of a total 7879 records identified by the search we included 25 studies with 28385 cases and 300598 participants in the meta-analysis of hypertension and endometrial cancer risk, including six cohort studies394041424320212223242526272829303132333435362 = 86%), and it was 1.73  for case-control studies and 1.32  for cohort studies  for studies with such exclusions or censoring and 1.81  for studies without such exclusions or censoring.In a further sensitivity analysis we also conducted a subgroup analysis by whether the studies explicitly stated that they excluded participants with prevalent hysterectomies at baseline and/or stated that they censored participants at the time of incident hysterectomy (cohort studies) or excluded participants who had undergone hysterectomy from the control group (case-control studies). The summary RR was 1.51  for all studies and 1.33  for cohort studies. Further including another cohort study2 = 85%) for all studies and summary RR = 1.28  for cohort studies. Mean (median) study quality scores were 7.3 (7.0) for all studies combined, 7.3 (7.0) for case-control studies, and 7.3 (7.0) for cohort studies).In a sensitivity analysis we also included a pooled analysis which assessed the association between quintiles of systolic blood pressure and endometrial cancer riskTo our knowledge this is the first meta-analysis of published observational studies of hypertension and the risk of endometrial cancer and our results confirm that hypertension is a strong risk factor for endometrial cancer with a 61% increase in the relative risk, however, the association was weaker in cohort studies (RR = 1.32) than among case-control studies (RR = 1.73). These findings are consistent with a large cohort study of 290 000 women in Austria, Norway and Sweden which found an increased endometrial cancer risk with increasing levels of diastolic blood pressure and in particular, systolic blood pressureThe present meta-analysis has some limitations. As hypertension is a condition that is strongly related to lifestyle factors and some medical conditions including diet, BMI, physical activity, and diabetes we cannot entirely exclude the possibility that the observed association between hypertension and endometrial cancer risk at least partly could be due to confounding. We found that the association was weaker, but still statistically significant, among studies that adjusted for smoking, BMI, oral contraceptive use, hormone replacement use, parity and age at menopause (RR = 1.14–1.34 for studies with such adjustment vs. 1.74–2.10 for studies without such adjustment). However, because there was still a significant association in subgroups that adjusted for these factors it could indicate that there is an adverse effect of hypertension on endometrial cancer risk, but that it may be slightly weaker than what was suggested from the overall summary estimates. Because the original studies did not stratify for BMI or diabetes it was not possible for us to investigate whether the association was limited to specific weight classes or if it was modified by diabetes status.We also found that the positive association between hypertension and endometrial cancer persisted when the studies were stratified by whether participants with prevalent hysterectomies at baseline were excluded and/or whether participants with incident hysterectomies were censored, or whether prevalent hysterectomies were excluded from the control group. Hypertension may also be related to hysterectomies5657Case-control studies are more likely to be affected by certain biases, such as recall bias and selection bias. Because we included both case-control and cohort studies there is a possibility that recall or selection bias might have affected the results in the case-control studies and the overall summary estimate. Although the association appeared to be stronger in case-control studies than among cohort studies, there was still a significant association among cohort studies, which suggest that recall bias or selection biases does not entirely explain the observed association. In addition, there was some indication of publication bias with Egger’s test, but this appeared to be restricted to the analyses of case-control studies and all studies combined, and was not observed among the cohort studies.The biological mechanism(s) that may explain an adverse effect of hypertension on endometrial cancer risk are unclear at present. It has been suggested that long-term hypertension may lead to cellular senescence and inhibition of apoptosisStrengths of the present meta-analysis include the comprehensive search strategy, the detailed subgroup and sensitivity analyses, and the large sample size providing a more robust estimate of the association between hypertension and endometrial cancer risk. To date relatively few studies have investigated the association between hypertensive disorders of pregnancy and endometrial cancer risk with one study suggesting an increased risk with hypertensive disorders overall66In conclusion, the results from this systematic review and meta-analysis suggest that women with hypertension may have a 61% increase in the relative risk of developing endometrial cancer. Any further studies should clarify potential effect modification by age, BMI and diabetes status, and the causality of the observed association, as well as the potential underlying mechanism(s).How to cite this article: Aune, D. et al. Hypertension and the risk of endometrial cancer: a systematic review and meta-analysis of case-control and cohort studies. Sci. Rep.7, 44808; doi: 10.1038/srep44808 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Xeroderma pigmentosum group G (XPG) gene is an essential gene in the nucleotide excision repair (NER) pathway. The association between XPG polymorphisms and cancer susceptibility has been the focus of attention in the molecular epidemiology of cancer. However, the conclusions have been divergent. Therefore, we conducted a comprehensive meta-analysis to precisely evaluate the association of 3 frequently investigated XPG polymorphisms  with cancer risk.Exposure to environmental carcinogens can cause damages to DNA. If not properly repaired, the DNA damages may increase the risk of carcinogenesis. Pubmed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) were searched for relevant studies in English and Chinese. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the association between XPG polymorphisms  and cancer risk.P = .045; TC vs CC: OR = 1.12, 95% CI = 1.00–1.24, P = .041; TC/TT vs CC: OR = 1.13, 95% CI = 1.02–1.26, P = .020). There was a significant correlation between rs873601 polymorphism and cancer risk under the homozygous model . Moreover, significant association with breast cancer was detected for rs873601 polymorphism under the allele contrast model . In the subgroup of Asian, rs873601 polymorphism was related to the susceptibility to cancer . Significant association between rs2296147 polymorphism and cancer risk were observed in Asian population .Twenty-three studies were included. Overall, there was no significant association between rs751402 polymorphism and overall cancer risk under the 5 gene models. However, we observed strong correlation between rs751402 polymorphism and gastric cancer (C vs T: OR=1.21, 95% CI = 1.00–1.26, Our meta-analysis suggested that the rs873601 polymorphism was significantly associated with overall cancer risk. The moderate effects of rs751402 and rs2296147 polymorphism on cancer susceptibility might be highly dependent on cancer type and ethnicity, respectively. Large studies are needed to validate our findings, especially in Caucasian and African population. Environmental carcinogens exposure can cause DNA damage, which may increase the risk of developing cancer, if not restored properly. In addition, during the process of DNA replication, DNA mismatch may occur and lead to genome instability. In human, the DNA repaired mechanism is a complex biological process, including several pathways and numerous proteins. If DNA damage cannot be properly and efficiently restored due to defects in DNA repair pathways, the risk of cancer could be elevated by many folds.To date, cancer remains a major health problem around the world with enormous health expenditure.,4 Among these pathways, NER removes helix-distorting DNA lesions and structures from the genome with 4 steps: lesion recognition, protein binding, oligonucleotide excision, and DNA fragment synthesis. Gene mutation in the NER pathway can lead to several diseases in human, including xeroderma pigmentosum (XP). XP is a prototypical DNA disorder featured by sensitivity to UV radiation and extremely increased susceptibility to skin cancer. The XP patients can be classified as 8 complementation groups, XPA through XPG.DNA damages caused by environment factors, such as ultraviolet (UV) radiation, tobacco, and diet, are closely related to human disease. DNA repair pathways play an important role in maintain genomic integrity and stability. There are 5 major DNA repair pathways, homologous recombinational repair (HRR), nonhomologous end joining (NHEJ), nucleotide excision repair (NER), base excision repair (BER), and mismatch repair (MMR).xeroderma pigmentosum group G (XPG) gene, also termed as excision repair cross-complementation group 5 (ERCC5) gene, is an essential gene in NER pathway. It encodes a structure-specific endonuclease that has multiple function during the NER. Previous studies indicated that XPG polymorphisms can influence the DNA repair ability for tobacco and alcohol-induced DNA damage, thereby increasing the susceptibility to cancer.,10 For instances, Lu et al reported that XPG rs17655 polymorphism contributed to increased risk of laryngeal cancer; He et al indicated that another polymorphism in XPG gene, rs2094258, might be associated with neuroblastoma susceptibility. Moreover, a meta-analysis provided the evidence of the association between XPG rs17655 polymorphism and colorectal cancer risk. However, overall, the association between XPG polymorphisms and the risk of cancer remains conflicting. Therefore, it is necessary to conduct a comprehensive to reevaluate the association of interest.The 22.1Pubmed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) for relevant studies written in English and Chinese. The key words were as follows: “xeroderma pigmentosum group G or XPG or excision repair cross-complementation group 5 or ERCC5 or rs751402 or rs873601 or rs3742282 or 2296147 OR rs17326289,” “polymorphisms or SNP or variation,” and “carcinoma or tumor or neoplasm or cancer.” In addition, the references list of included studies and relevant reviews were manually searched for eligible studies. The last search was performed on December 30, 2016.We searched 2.2XPG polymorphisms and the risk of cancer; case–control studies; articles providing genotype distribution data or corresponding odds ratio (OR) and 95% confidence interval (CI); and articles published in English or Chinese. The exclusion criteria were as follows: letters, editorials, reviews, meta-analysis, or systematic reviews; published studies containing duplicate data; studies lacking of genotype distribution data or corresponding OR and 95% CI; and not case–control study or cohort study.Studies were included based on the following criteria: studies investigating the association between the 2.3P value of Hardy–Weinberg Equilibrium (HWE). The meta-analysis was approved by the Hospital Ethics Committee  to not reidentify the participants.Eligible studies were selected by 2 researchers independently according to the inclusion and exclusion criteria. All disagreements were discussed. All the researchers would vote if a consensus could not be reached. All the information was double checked by authors who were responsible for data extraction. The following data were extracted from the original studies: author, publish year, country or region, ethnicity, cancer types, sample size including case and control sample size, genotype data of rs751402, rs873601, and rs2296147, and 2.42 test. OR and 95% CI were used to estimate the association between XPG polymorphisms and cancer susceptibility. Pooled analysis was performed under the 5 genotype models, including allele contrast, homozygous, heterozygous, dominant, and recessive models. Chi-square-based Q statistic test was used to estimate the between-study heterogeneity via I2 value and P value. If I2 > 50%, random effects model was applied to calculate the pooled OR and 95% CI. Otherwise, fixed-effects model was adopted. Moreover, subgroup analyses were conducted by cancer type and ethnicity. All the P values were 2-sided. We referred to statistically significant as P < .05. Sensitivity analysis was applied to assess the stability of the results by sequentially removing one study at a time and recalculating OR and 95% CI. Funnel plot and Egger linear regression test were performed to estimate the publish bias. Asymmetrical funnel plot or P < .1 indicated that publication bias was significant. STATA 12.0  was applied to perform all the statistical analysis.The HWE in control subjects in all the articles was assessed by χ33.1XPG polymorphisms  and cancer risk were summarized in Table Based on the inclusion and exclusion criteria, 23 eligible articles were identified from 672 potential publications Fig. . Among t3.2P = .045; TC vs CC: OR = 1.12, 95% CI = 1.00–1.24, P = .041; TC/TT vs CC: OR = 1.13, 95% CI = 1.02–1.26, P = .020). Stratified analysis by ethnicity indicated there is an association between rs873601 polymorphism and cancer risk in Asian population . However, significant association between rs873601 polymorphism and gastric cancer risk were observed under the allele contrast model   .We conducted the sensitive analysis and the results suggested that no single study could significantly change the pooled risk estimates, which indicated our meta-analysis results were robust and stable. The Begg funnel plot and Eagger regression test were used to assess the publication bias. The results of Egger test suggested no significant publication bias in our meta-analysis  and transcription-coupled repair (TC-NER). In GG-NER, XPG interacts with transcription factor II H (TFIIH) and this interaction leads to the recruitment of XPG to NER complex at the sites of DNA damage caused by UV radiation.,16 Then the NER complex including XPG removes the lesion from DNA strand. Several investigations indicated that XPG is related to carcinogenesis and prognosis of various types of cancer.–19 Notably, genetic variations in the XPG gene show significant association with the risk of various cancers.–22 In addition, some meta-analysis focusing on one of XPG polymorphisms and cancer risk revealed that XPG rs17655 contributed to cancer susceptibility.,23 However, the association between other polymorphisms and cancer risk remains controversial.XPG protein serves as structure-specific endonuclease that cleaves several kinds of substrates with ss/ds DNA junction in NER.XPG polymorphisms  and cancer risk. Pooled analysis indicated that there was no significant association of XPG gene polymorphisms rs751402 and rs2296147 with cancer risk individually. However, there is association with cancer observed for the studied rs873601 polymorphism under the homozygous model. In the stratified analysis of Asian subgroup, there is a significant association between rs873601 polymorphism and cancer risk under the allele contrast, homozygous, dominant, and recessive models. The rs2296147 polymorphism was significantly associated with the decreased cancer risk in Asian population under the heterozygous model.To the best of our knowledge, this is the first meta-analysis that focused on ,24–26 In subgroup analysis by cancer type, there were strong correlation between rs751402 polymorphism and gastric cancer, while no relationship between rs751404 polymorphism and breast cancer was observed. The association with gastric cancer risk was based on 6 case–control studies, and our results were in accordance with Duan et al. However, the results were inconsistent with other studies, which failed to find significant association between rs751402 polymorphisms and gastric cancer.–30 Zhou et al found that TT genotype was associated with an increasing risk of gastric cardia adenocarcinoma. The controversial results might be partially due to the variations in the sample sizes and the control group sampling methods. In Duan et al’ studies, the sample size was relatively small, and the healthy controls were patients with mild superficial gastritis receiving endoscopic examination. And the selection bias in controls might be the major reason leading to the discrepancy.The results of current meta-analysis suggest that the rs751402 polymorphism was not associated with overall cancer risk, which is coincided with previous studies.ERCC5 gene polymorphism and found that rs751402 might not be the risk factor for breast cancer. Wang et al conducted another hospital-based case–control study in 2015 with 101 cases and 101 controls. In contrast, they reported that rs751402 was a strong protective factor against breast cancer.The meta-analysis indicated that no significant association was found between the rs751402 and breast cancer risk. Na et al conducted a hospital-based case–control study to explore the association between  In addition, Chen et al found that XPG rs873601 polymorphism was associated with gastric cancer susceptibility under the recessive model. As for ethnicity, 11 of 12 articles were performed in Asian population and only one article was conducted in Caucasian population. A significant association with cancer susceptibility was found in Asian population under the allele contrast, homozygous, dominant and recessive models. The results were consistent with those of previous studies.,33 However, other studies could not find any correlation between rs873601 polymorphism and cancer risk. This discrepancy may result from many factors, including the study designs, genotyping methods and sources of control and cases. Currently, the association between rs873601 polymorphism and cancer risk is mainly investigated among Asian population, while few studies conducted in other population such as Caucasian and African.With regard to rs873601 polymorphism, there was a significant association with total cancer risk observed under the homozygous model. When stratified by cancer type, rs873601 polymorphism was shown to significantly increase gastric cancer under the allele contrast model. This result was in accordance with the findings by He et al.,32,34,35 our meta-analysis results indicated that the rs2296147 polymorphism might not contribute to cancer susceptibility. However, Yang et al investigated the association between XPG gene polymorphisms and gastric cancer risk and found that rs2296147 CC genotype was related to increased risk of gastric cancer. In this study, the control group was recruited from other surgical department and selection bias might exist. Another study focusing on rs2296147 polymorphism and prostate cancer risk was conducted by Yang et al. They suggested that rs2296147 polymorphism T allele was strongly associated with prostate cancer risk. In this study, the sample size was relatively small with only 241 prostate cancer cases and 264 healthy controls. Na et al found that rs2296147 showed no association with breast cancer risk, but the genotype distribution was not in agreement with HWE. As for ethnicity, there was significant relationship between rs2296147 polymorphism and cancer risk in Asian population in heterozygous model. This result suggested that rs2296147 may be a protective factor against carcinogenesis in Asian population.Similar to previous studies, have summarize several hallmarks of cancer, including sustaining proliferative signaling, evading growth suppressors, avoiding immune destruction, enabling replicative immortality, tumor promoting inflammation, activating invasion and metastasis, inducing angiogenesis, genome instability and mutation, resisting cell death, and deregulating cellular energetics. Apart from common hallmarks, every type of cancer has its unique biological characteristics. Previous studies reported that XPG gene polymorphisms may affect XPG gene expression, leading to genomic instability and carcinogenesis.As we know, cancer can occur in the different sites of the body. Although cancer is a highly heterogeneous disease, different types of cancer share some similar mechanisms and pathogenesis. In 2011, Hanahan and WeinbergXPG polymorphisms are new genetic variations discovered recent years, the relationship between these SNPs and cancer risk is not clear. Thus, it is necessary to clarify such association. There are several meta-analysis focused on other XPG polymorphisms and cancer risk previously. Ding et al conducted a meta-analysis of the association between XPG Asp1104His polymorphism and breast cancer risk. This meta-analysis included 10 studies with 5235 cases and 5685 controls, but failed to find any significant association. Zhu et al reported that XPG Asp1104His polymorphism might have no correlation with susceptibility to overall cancer risk in a meta-analysis with 23,490 cases and 27,168 controls. Another meta-analysis investigating the association between XPG Asp1104His polymorphism and cancer risk suggested that XPG Asp1104His polymorphism may be a low-penetrant risk factor in some kinds of cancer. Jiang et al suggested that XPG Asp1104His polymorphism may increase the risk of head and neck cancer in a meta-analysis of 8 case–control studies. All these meta-analysis focused on XPG Asp1104His polymorphism and cancer risk.As Some limitations might exist in this study should be mentioned. First, the between-study heterogeneity was relatively large. This may be due to variations in the sample sizes, the genotyping methods or the selections of case among the original studies. Second, not all the studies included in our meta-analysis were in accordance with HWE. When we omitted this study deviated from HWE to recalculate risk estimates, the results were not altered substantially, suggesting that the results of our meta-analysis were reliable. Third, the control groups of some original studies were enrolled from other patients without malignant tumors, which may be a source of selection bias.XPG gene polymorphisms and cancer risk in the future.In conclusion, the results of our meta-analysis suggested that there was no any significant association between rs751402 and rs2296147 polymorphisms and overall cancer risk. There was a significant correlation between rs873601 polymorphism and cancer risk in homozygous model. The rs873601 polymorphism was shown to increase gastric cancer risk. In the subgroup of Asian, rs873601 polymorphism was related to the susceptibility of cancer. Moreover, there was significant relationship between rs2296147 polymorphism and cancer risk in Asian population. Additional large studies should be conducted to explore the association between