Cell cycle checkpoint kinase 2 (CHEK2) is a checkpoint kinase that plays an important role in the DNA damage signaling network. Numerous epidemiological studies have evaluated the association between the CHEK2 I157T variant and cancer susceptibility. However, the results of these studies on the association remain conflicting. The main purpose of this study was to integrate previous results and explore whether the CHEK2 I157T variant is associated with cancer susceptibility. PubMed, Embase (before 2012-10-1), Google Scholar, and CBMdisc were searched for studies on the relationship of the CHEK2 I157T variant and the incidence of cancer. Eligible articles were included for data extraction. The main outcome was the frequency of CHEK2 I157T polymorphisms between cases and controls. Comparison of the distribution of SNP was mainly performed using Review Manager 5.0. The odds ratio (OR) and its 95% confidence interval (95% CI) were used to assess the strength of association. In total, 26,336 cases and 44,219 controls from 18 case-control studies were used in this meta-analysis, and significant associations of the CHEK2 I157T variant with cancer susceptibility were found (OR, 1.39; 95% CI, 1.19-1.63; p<0.0001), breast cancer (OR=1.58, 95% CI=1.42-1.75, p<0.00001) and colorectal cancer (OR=1.67, 95% CI=1.24-2.26, p=0.0008). We also found an association of the CHEK2 I157T variant with familial cases (OR=1.85, 95% CI=1.51-2.26, p<0.00001). However, the association was not established for other types of cancer (OR=1.09, 95% CI=0.75-1.57, p=0.66). This meta-analysis demonstrates that the CHEK2 I157T variant was an important cancer gene, which increases cancer risk, especially in breast and colorectal cancer in Caucasian, and the bioinformatic analysis showed this change was mainly attributed to the decreased hydrophobicity of CHEK2 157T.

Previous studies investigating the association between X-ray repair cross-complementation group 1 (XRCC1) Arg399Gln polymorphism and colorectal cancer risk in Chinese provided inconsistent findings. To assess the association in Chinese population, a meta-analysis was performed. Eligible studies were searched in Pubmed, Emabse, and China National Knowledge Infrastructure databases. Odds ratios (OR) with the corresponding 95 % confidence intervals (95 %CI) were pooled to assess the association. Seven case-control studies involving a total of 2136 colorectal cancer cases and 3168 controls were finally included in the meta-analysis. Our analysis suggested that the variant genotypes of XRCC1 Arg399Gln were associated with an increased risk of colorectal cancer in Chinese population (Gln vs. Arg: random effect model OR = 1.24, 95 %CI = 1.01-1.52, P = 0.041; GlnGln vs. ArgArg: random effect model OR = 1.52, 95 %CI = 1.07-2.15, P = 0.019; and Recessive model: fixed effect model OR = 1.37, 95 %CI = 1.12-1.67, P = 0.002). There was low risk of publication bias in present meta-analysis. Our meta-analysis provides an evidence for the association between XRCC1 Arg399Gln polymorphism and colorectal cancer risk in Chinese population, and XRCC1 Arg399Gln variant genotypes contribute to increased risk of colorectal cancer in Chinese.

Glioma, especially its most aggressive histological type glioblastoma, is a challenge to human health due to its poor prognosis. Identifying glioma risk factors will improve early diagnosis to prevent tumor progression. Three polymorphisms of X-ray repair cross-complementing groups 1 (XRCC1) Arg399Gln, Arg194Trp, and Arg280His have drawn attention because of their potential associations with the development of glioma. However, the conclusions from different studies are inconsistent. Here, we performed XRCC1 polymorphism-glioma association analyses on data gathered through searching PubMed, ISI Web of Knowledge, Cochrane, and EBSCO databases and meta-analyzing extracted eligible studies. For XRCC1 Arg399Gln (G>A) polymorphism, there were 12 studies with 4,356 cases and 6,616 controls; for Arg194Trp (C>T) polymorphism, there were nine studies with 3,760 cases and 5,971 controls; and for Arg280His (G > A) polymorphism, there were five studies with 1,883 cases and 3,144 controls. Odds ratios as well as their 95 % confidence intervals in three genetic models were used to estimate the strength of the association between XRCC1 genotypes and glioma risk. Based on our main analyses, increased risk was observed in Arg399Gln codominant and dominant models and Arg194Trp homozygous codominant and recessive models. In the stratified analyses for some genetic models, Arg399Gln and Arg194Trp were recognized as risk factors in the Asian but not in the Caucasian population. No associations were detected for Arg280His in any genetic model. This meta-analysis indicates that XRCC1 399Gln and 194Trp variants increase glioma risk. Both of these polymorphisms might raise the susceptibility of glioma in Asian populations.

Epidemiological studies investigating the association between the insulin receptor substrate 1 (IRS1) gene Gly972Arg (rs1801278) polymorphism and various carcinomas risk reported conflicting results. Thus, a systemic review and meta-analysis of published studies were performed to assess the possible association. A comprehensive search was conducted to identify all eligible studies of IRS1 Gly972Arg polymorphism and cancer risk. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the associations. A total of 16 independent studies, including 11,776 cases and 11,654 controls, were identified. When all studies were pooled, we found a significant association between IRS1 Gly972Arg polymorphism and increased cancer risk under dominant model (OR = 1.16, 95 %CI = 1.04-1.30, P = 0.007) and allelic model (OR = 1.16, 95 %CI = 1.02-1.30, P = 0.02). In subgroup analysis based on cancer type, increased cancer risk was found in ovarian cancer (dominant: OR = 1.55, 95 %CI = 1.17-2.05, P = 0.002; allelic: OR = 1.55, 95 %CI = 1.19-2.01, P = 0.001), breast cancer (allelic: OR = 1.12, 95 %CI = 1.00-1.26, P = 0.05), and other cancers (allelic: OR = 1.31, 95 %CI = 1.00-1.71, P = 0.05). When stratified by study types, significant associations were observed in both cohort studies (dominant: OR = 1.25, 95 %CI = 1.06-1.47, P = 0.007; allelic: OR = 1.25, 95 %CI = 1.07-1.46, P = 0.005) and case-control studies (dominant: OR = 1.15, 95 %CI = 1.01-1.31, P = 0.04). In the subgroup analyses by ethnicity, significantly increased cancer risk was suggested among both Caucasians (dominant: OR = 1.13, 95 %CI = 1.02-1.26, P = 0.02; allelic: OR = 1.13, 95 %CI = 1.03-1.25, P = 0.01) and mixed population (dominant: OR = 1.22, 95 %CI = 1.01-1.46, P = 0.04). Our investigations demonstrate that IRS1 Gly972Arg polymorphism was associated with an increased risk of cancer, and additional well-designed studies are warranted to validate these findings.

We conducted a meta-analysis to investigate the association of 2 single nucleotide polymorphisms in the cytochrome P450, family 1, subfamily 1A1 gene (CYP1A1), CYP1A1*2A and CYP1A1*2C, with the risk of developing different subtypes of leukemia in adults and children. A total of 26 studies published between 1999 and 2011 were identified by searching the PubMed, EMBASE, Medline, and Web of Science databases. The odds ratios for the CYP1A1 polymorphisms and leukemia risk were calculated. The cumulative evidence in genetic associations was graded by using the Venice criteria of the Human Genome Epidemiology Network (Atlanta, Georgia). The results showed that the cumulative evidence was moderate for the association of the CYP1A1*2A variant with leukemia in Caucasians and with childhood acute lymphoid leukemia in Caucasians. In addition, there was moderate evidence that children who carry both the CYP1A1*2A variant and the glutathione S-transferase M1 null genotype have an increased risk of acute lymphoid leukemia. For the CYP1A1*2C polymorphism, the cumulative evidence of an association with leukemia risk was moderate for adults and weak for children. Logistic regression analysis demonstrated an interaction between the CYP1A1*2C polymorphism and age. This meta-analysis showed that the CYP1A1*2A and CYP1A1*2C polymorphisms were associated with an increased risk of leukemia, and that the associations might vary by ethnicity, gene-gene interactions, age, and leukemia subtype.

TERT-CLPTM1L genomic region has been extensively associated with several types of cancer. However, results were inconsistent. We performed this meta-analysis to estimate the association between TERT (rs2736100, rs2736098), as well as CLPTM1L (rs402710, rs401681) polymorphisms and cancer risk.

Transportation of anticancer drugs such as anthracyclines across the membrane is regulated by P-glycoprotein encoded by the human multidrug resistance gene 1 (ABCB1). Polymorphisms in the ABCB1 gene (1236C>T, 2677G>T/A, 3435C>T) have been found to be associated with intrinsic and acquired cross resistance to these anticancer drugs. Therefore, the aim of this study is to evaluate the influence of ABCB1 gene polymorphisms in breast cancer treatment outcomes in terms of response and toxicity.

A lot of studies have investigated the correlation between x-ray cross complementing group 1 (XRCC1) polymorphisms and bladder cancer risk, but the results in Asian population were still inconclusive. We conducted a meta-analysis to ascertain the association of XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms with bladder cancer risk in Asian population.

Interleukin-1 beta (IL-1β), a pro-inflammatory cytokine, is emerging as a key mediator of carcinogenesis that characterizes host-environment interactions. Epidemiological studies investigating the association between two polymorphisms of IL-1B (-511C/T and +3954C/T) and cancer susceptibility have shown conflicting results. The aim of this study is to derive a more precise estimation of the relationship.

To identify the genetic factors that influence overall survival in never smokers who have non-small cell lung carcinoma (NSCLC), we conducted a consistency meta-analysis study using genome-wide association approaches for overall survival in 327 never smoker patients with NSCLC from The University of Texas MD Anderson Cancer Center (Houston, TX) and 293 cases from the Mayo Clinic (Rochester, MN). We then conducted a two-pronged validation of the top 25 variants that included additional validation in 1,256 patients with NSCLC from Taiwan and assessment of expression quantitative trait loci (eQTL) and differential expression of genes surrounding the top loci in 70 tumors and matched normal tissues. A total of 94 loci were significant for overall survival in both MD Anderson and Mayo studies in the consistency meta-analysis phase, with the top 25 variants reaching a P value of 10(-6). Two variants of these 25 were also significant in the Taiwanese population: rs6901416 [HR, 1.44; 95% confidence interval (CI), 1.01-2.06] and rs10766739 (HR, 1.23; 95%CI, 1.00-1.51). These loci resulted in a reduction of median survival time of at least eight and five months in three populations, respectively. An additional six variants (rs4237904, rs7976914, rs4970833, rs954785, rs485411, and rs10906104) were validated through eQTL analysis that identified significant correlations with expression levels of six genes (LEMD3, TMBIM, ATXN7L2, SHE, ITIH2, and NUDT5, respectively) in normal lung tissue. These genes were also significantly differentially expressed between the tumor and normal lung tissue. These findings identify several novel, candidate prognostic markers for NSCLC in never smokers, with eQTL analysis suggesting a potential biologic mechanism for a subset of these observed associations.

The prognostic value of CDKN2A promoter hypermethylation in colorectal cancer remains controversial. We systematically reviewed the evidence for assessment of CDKN2A methylation in colorectal cancer to elucidate this issue.

We conducted a systematic review and a meta-analysis of observational studies to identify and summarise the level of colorectal cancer (CRC) screening participation for people at increased risk due to family history of the disease. Medline, Cinhal, Embase and PsychInfo databases were comprehensively searched between January 1995 and May 2012 to identify relevant articles. To be included, studies had to report on screening for people who had at least one first-degree relative with CRC and no previous personal diagnosis of the disease. Pooled screening participation levels were calculated for each screening modality. Seventeen studies, accounting for a total of 13,269 subjects with a family history of CRC met the inclusion criteria. Seven studies, including a total of 6,901 subjects had a pooled faecal occult blood testing screening participation (at least once) of 25 % (95 % CI 12-38). Five studies including a total of 5,091 subjects had a pooled sigmoidoscopy-based screening participation (at least once) of 16 % (95 % CI 7-27). Seven studies including a total of 9,965 subjects had pooled participation colonoscopy-based screening (at least once) of 40 % (95 % CI 26-54). There was a significant level of screening heterogeneity between studies. This review identified a substantial underuse of CRC screening for people at increased risk of developing the disease. It highlights the potential opportunity that exists for increasing screening participation among this segment of the population and the need to adjust the current CRC screening policies towards that objective.

The association between glutathione-S-transferase P1 (GSTP1) Ile105Val polymorphism and oxaliplatin-induced neuropathy has been investigated in a number of published studies. However, most of these studies were based on small sample sizes and the results remained inconsistent. To assess the relationship between GSTP1 gene Ile105Val polymorphism and its susceptibility to oxaliplatin-induced neuropathy, a meta-analysis of previous studies was conducted.

The C282Y and H63D polymorphisms in the HFE gene have been implicated in susceptibility of breast cancer, but a number of studies have reported inconclusive results. The aim of this study is to investigate the association between the C282Y and H63D polymorphisms in the HFE gene and breast cancer risk by meta-analysis. We searched PubMed and Embase databases, covering all related studies until March 2, 2013. Statistical analysis was performed using STATA 10.0. A total of 7 studies including 1,720 cases and 18,296 controls for HFE C282Y polymorphism and 5 studies including 942 cases and 1,571 controls for HFE H63D polymorphism were included in the meta-analysis. The results showed that HFE C282Y polymorphism was significantly associated with increased risk of breast cancer under homozygotes vs. wild-type model (OR = 2.06, 95%CI = 1.19-3.58) and recessive model (OR = 1.98, 95%CI = 1.14-3.44) but not under heterozygotes vs. wild-type model (OR = 0.97, 95%CI = 0.70-1.35), dominant model (OR = 1.00, 95%CI = 0.72-1.40) and multiplicative model (OR = 1.04, 95%CI = 0.76-1.42). However, we did not find any association between HFE H63D polymorphism and breast cancer risk under all genetic models. This current meta-analysis suggested that C282Y polymorphism rather than H63D might be associated with increased risk of breast cancer.

Microsomal epoxide hydrolase 1 (EPHX1) plays an important role in the detoxification of carcinogenic polycyclic aromatic hydrocarbons. EPHX1 Tyr113His and His139Arg polymorphisms have been reported to have some impacts on the EPHX1 activity. Previous case-control studies assessing the associations between EPHX1 polymorphisms and esophageal cancer risk reported conflicting results. To quantitatively summarize the associations of EPHX1 Tyr113His and His139Arg polymorphisms with esophageal cancer risk, a systemic review and meta-analysis of published studies were performed. Published literatures from PubMed, Embase, and China National Knowledge Infrastructure databases were searched. The strength of the associations between EPHX1 polymorphisms and esophageal cancer risk was estimated by the pooled odds ratios (ORs) with its 95 % confidence interval (95 %CI). This meta-analysis yielded nine case-control studies, which included nine studies for Tyr113His polymorphism (1,291 cases and 2,120 controls) and seven studies for His139Arg polymorphism (899 cases and 1,615 controls). Overall, meta-analysis showed that EPHX1 Tyr113His polymorphism was not associated with esophageal cancer risk under all genetic models. Meta-analysis of these seven studies for EPHX1 His139Arg polymorphism showed that EPHX1 His139Arg polymorphism was also not associated with esophageal cancer risk under all genetic models. However, subgroup analysis by ethnicity further showed that there was an obvious association between EPHX1 His139Arg polymorphism and decreased risk of esophageal cancer in Caucasians (ArgArg versus HisArg/HisHis: OR = 0.52, 95 %CI 0.27-0.97, P = 0.041). This meta-analysis suggests that EPHX1 His139Arg polymorphism is associated with decreased risk of esophageal cancer in Caucasians. In addition, more studies with large samples are needed to get a more precise estimation on the associations mentioned above.

Previous studies show that X-ray cross-complementing group 1 (XRCC1) Arg194Trp may result in variations in host's repair efficiency of DNA damage, and this repair deficit may eventually cause individual susceptibility to oral cancer. However, published data regarding the association between XRCC1 Arg194Trp polymorphism and oral cancer risk were contradictory. The aim of this study was to derive a more precise estimation of the association of XRCC1 Arg194Trp polymorphism with oral cancer by performing a meta-analysis. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to assess the strength of the association. Finally, a meta-analysis of nine eligible studies including 1,281 cases and 1,966 controls was performed. Overall, there was a significant association between XRCC1 Arg194Trp polymorphism and oral cancer risk (for Trp versus Arg: OR = 1.41, 95 % CI 1.08-1.83, P = 0.01; for TrpTrp versus ArgArg: OR = 1.50, 95 % CI 1.00-2.30, P = 0.05; for TrpTrp/ArgTrp versus ArgArg: OR = 1.49, 95 % CI 1.14-1.94, P = 0.003). After excluding those studies containing patients with oral leukoplakia, there was still an obvious association between XRCC1 Arg194Trp polymorphism and oral cancer risk (for TrpTrp/ArgTrp versus ArgArg: OR = 1.40, 95 % CI 1.14-1.71, P = 0.001). Subgroup analysis by ethnicity suggested that there was an obvious association between XRCC1 Arg194Trp polymorphism and oral cancer risk in Asians under three genetic models. In conclusion, the results from this meta-analysis suggest that XRCC1 Arg194Trp polymorphism is associated with oral cancer risk, especially in Asians.

There are many studies performed to assess the associations of CD95 A670G and G1377A polymorphisms with gastric cancer, and the association of CD95L T844C polymorphism with gastric cancer risk, but the data are remaining controversial. To get a comprehensive assessment of the association above, we performed a meta-analysis of published studies. PubMed, Embase, Web of Science, and Wanfang Medicine databases were searched for eligible studies. There were eight studies including 3,790 subjects on CD95 A670G polymorphism, eight studies including 4,563 subjects on CD95 G1377A polymorphism, and eight studies including 4,563 subjects on CD95L T844C polymorphism. Overall, CD95 G1377A polymorphism was associated with a significantly increased risk of gastric cancer (for AA versus GG: odds ratio (OR) = 1.24, 95 % confidence interval (95 % CI) = 1.02-1.52, P = 0.030; for AA versus GG + GA: OR = 1.27, 95 % CI = 1.05-1.53, P = 0.012). However, there were no associations of CD95 A670G and CD95L T844C polymorphisms with gastric cancer. Subgroup analysis by ethnicity found similar associations in Asians, but the associations in Caucasians were still unclear owing to the lack of relevant data. Therefore, the outcomes of this meta-analysis show that there is a significant association between CD95 G1377A polymorphism and risk of gastric cancer.

The retinoic acid receptor beta2(RARβ2) is a type of nuclear receptor that is activated by both all-trans retinoic acid and 9-cis retinoic acid, which has been shown to function as a tumor suppressor gene in different types of human tumors. Previous reports demonstrated that the frequency of RARβ2 methylation was significantly higher in prostate cancer patients compared with controls, but the relationship between RARβ2 promoter methylation and pathological stage or Gleason score of prostate cancer remained controversial. Therefore, a meta-analysis of published studies investigating the effects of RARβ2 methylation status in prostate cancer occurrence and association with both pathological stage and Gleason score in prostate cancer was performed in the study. A total of 12 eligible studies involving 777 cases and 404 controls were included in the pooled analyses. Under the random-effects model, the pooled OR of RARβ2 methylation in prostate cancer patients, compared to non-cancer controls, was 17.62 with 95%CI = 6.30-49.28. The pooled OR with the fixed-effects model of pathological stage in RASSF1A methylated patients, compared to unmethylated patients, was 0.67 (95%CI = 0.40-1.09) and the pooled OR of low-GS in RARβ2 methylated patients by the random-effect model, compared to high-GS RARβ2 methylated patients, was 0.54 (95%CI = 0.28-1.04). This study showed that RARβ2 might be a potential biomarker in prostate cancer prevention and diagnosis. The detection of RARβ2 methylation in urine or serum is a potential non-invasive diagnostic tool in prostate cancer. The present findings also require confirmation through adequately designed prospective studies.

Cyclin D1 (CCND1), a key regulator of cell cycle progression, is overexpressed in many human cancers, including breast cancer. However, the impact of CCND1 overexpression in these cancers remains unclear and controversial. We conducted a systematic literature search in PubMed and EMBASE with the search terms "cyclin D1", "CCND1", "breast cancer", "prognosis", and potential studies for analysis were selected. Studies with survival data, including progression-free survival (PFS), overall survival (OS) or metastasis-free survival (MFS), were included in this meta-analysis. A total of 33 studies containing 8,537 cases were included. The combined hazard risk (HR) and its 95 % confidence interval (CI) of OS, PFS and MFS were 1.13 (95 % CI 0.87-1.47; P = 0.35), 1.25 (95 % CI 0.95-1.64; P = 0.12), and 1.04 (95 % CI 0.80-1.36; P = 0.76), respectively, for primary breast cancer patients with tumors exhibiting CCND1 overexpression. Interestingly, the impact of CCND1 expression on OS was a 1.67-fold (95 % CI 1.38-2.02; P = 0.00) increased risk for ER-positive breast cancer patients. However, CCND1 overexpression exhibited no association with the PFS or OS of patients who received epirubicin-based neoadjuvant chemotherapy, for which the P values were 0.63 and 0.47, respectively. In summary, CCND1 overexpression impacts the prognosis of ER-positive breast cancer patients, but not patients with unselected primary breast cancer or patients treated with neoadjuvant chemotherapy.

Testicular germ cell tumor (TGCT) is the most common cancer in young men and is notable for its high familial risks. So far, six loci associated with TGCT have been reported. From genome-wide association study (GWAS) analysis of 307,291 SNPs in 986 TGCT cases and 4,946 controls, we selected for follow-up 694 SNPs, which we genotyped in a further 1,064 TGCT cases and 10,082 controls from the UK. We identified SNPs at nine new loci (1q22, 1q24.1, 3p24.3, 4q24, 5q31.1, 8q13.3, 16q12.1, 17q22 and 21q22.3) showing association with TGCT (P < 5 × 10(-8)), which together account for an additional 4-6% of the familial risk of TGCT. The loci include genes plausibly related to TGCT development. PRDM14, at 8q13.3, is essential for early germ cell specification, and DAZL, at 3p24.3, is required for the regulation of germ cell development. Furthermore, PITX1, at 5q31.1, regulates TERT expression and is the third TGCT-associated locus implicated in telomerase regulation.