A common genetic variant, rs4939827, located in SMAD7, was identified by two recent genome-wide association (GWA) studies to be strongly associated with the risk of colorectal cancer (CRC). However, the following replication studies yielded conflicting results.

To improve the risk stratification of patients with rhabdomyosarcoma (RMS) through the use of clinical and molecular biologic data.

Toll-like receptor 4 (TLR4) is critical in the recognition of Gram-negative bacteria serving as a key immune system effector. Recently, a number of case-control studies were conducted to investigate the association between TLR4 gene polymorphism and cancer risk, especially Asp299Gly and Thr399Ile polymorphisms. However, published data were still conflicting. In this paper, we summarized 9463 cancer cases and 10,825 controls from 22 studies and attempted to assess the susceptibility of TLR4 gene polymorphism to cancers by a synthetical meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. Our results suggested that Asp299Gly represented a risk factor on cancers in digestive system (G allele versus A allele, OR=1.64, 95% CI: 1.02-2.64; GA+GG versus AA, OR=1.64, 95% CI: 1.00-2.71) but tend to have a protective effect on prostate cancer (GG versus AA, OR=0.37, 95% CI: 0.14-0.98; GG versus GA+AA, OR=0.37, 95% CI: 0.14-0.98). Thr399Ile polymorphism was significantly associated with an elevated cancer risk in overall analysis (T allele versus C allele, OR=1.72, 95% CI: 1.27-2.33; TC versus CC, OR=1.63, 95% CI: 1.18-2.26; TT+TC versus CC, OR=1.70, 95% CI: 1.24-2.34) and especially in gastrointestinal subgroup (T allele versus C allele, OR=2.01, 95% CI: 1.40-2.89; TC versus CC, OR=1.86, 95% CI: 1.26-2.74; TT+TC versus CC, OR=1.97, 95% CI: 1.35-2.88). Further prospective researches with larger numbers of worldwide participants are warranted to draw comprehensive and true conclusions.

Potential functional allele T/C single nucleotide polymorphism (SNP) of Interleukin 10 (IL-10) promoter -819 (rs1800871) has been implicated in gastric cancer risk. We aimed to explore the role of T/C SNP of IL-10 -819 in the susceptibility to gastric cancer through a systematic review and meta-analysis.

Evidence is accumulating that chronic inflammation may have an important role in prostate cancer (PCa). The COX-2 polymorphism rs2745557 (+202 C/T) has been extensively investigated as a potential risk factor for PCa, but the results have thus far been inconclusive. This meta-analysis was performed to derive a more precise estimation of the association.

Breast cancer susceptibility may be modulated partly through polymorphisms in oxidative enzymes, one of which is myeloperoxidase (MPO). Association of the low transcription activity variant allele A in the G463A polymorphism has been investigated for its association with breast cancer risk, considering the modifying effects of menopausal status and antioxidant intake levels of cases and controls.

Many studies have reported that prostate stem cell antigen (PSCA) polymorphisms (rs2294008 and/or 2976392) are significantly associated with gastric cancer (GC) risk, although the published results are inconsistent. We conducted a systematic review and meta-analysis for relevant literatures to quantitatively evaluate the relationship between PSCA polymorphisms and GC susceptibility.

Estrogen receptor-α is a key mediator of the estrogen response in endometrial tissue. The most-studied gene variants are the PvuII and XbaI polymorphisms, which may be associated with altered sensitivity to estrogen. However, studies evaluating the associations between these polymorphisms and endometrial cancer risk have produced controversial conclusions. To explore a more robust estimate of the role of estrogen receptor-α polymorphisms in endometrial carcinogenesis, we searched all published articles indexed in PubMed, Web of Science, EBSCO, Highwire and the CNKI database from 1995 to 2010. Data were independently extracted by two reviewers using a standardized data extraction form. Overall, the meta-analysis included 1944 cases and 3075 controls for PvuII polymorphisms, and 1831 cases and 2875 controls for XbaI polymorphisms. Our results did not show any statistically significant association between endometrial cancer risk and either PvuII or XbaI polymorphisms. However, PvuII polymorphisms, both the CT and the CC genotypes, significantly increased the risk of endometrial cancer in an Asian-Australian population (pooled OR = 1.50, 95%CI 1.09-2.08 and pooled OR = 1.55, 95%CI 1.08-2.22, respectively). The CC genotype significantly decreased the risk of endometrial cancer (pooled odds ratio 0.77, 95% confidence interval 0.64-0.94) in a European population. In contrast, the stratified analysis suggested that the XbaI polymorphism was not significantly associated with endometrial cancer between different populations. This meta-analysis provides evidence that PvuII polymorphisms in the ESR1 gene, which encodes for estrogen receptor-α, could modify the susceptibility to endometrial cancer. However, the genetic effect varied between different geographical regions for unknown reasons.

N-Acetyltransferase (NAT) 2 is an important enzyme involved in the metabolism of different xenobiotics, including potential carcinogens, whose phenotypes were reported to be related to individual susceptibility to colorectal cancer (CRC). However, the results remain conflicting. To assess the relationship between NAT2 phenotypes and CRC risk, we performed this meta-analysis.

Hepatocarcinogenesis is a complex process that may be influenced by many factors, including polymorphism in the epidermal growth factor (EGF) gene. Previous work suggests an association between the EGF 61*A/G polymorphism (rs4444903) and susceptibility to hepatocellular carcinoma (HCC), but the results have been inconsistent. Therefore, we performed a meta-analysis of several studies covering a large population to address this controversy.

studies investigating the associations between UDP-glucuronosyltransferase 1A7 (UGT1A7) gene polymorphisms and various carcinomas risk reported conflicting results. To derive a more precise estimation of the association, we have conducted a meta-analysis.

Epidemiological studies have evaluated the association between polymorphic sites in the thymidylate synthase (TYMS) gene and non-Hodgkin lymphoma (NHL) risk, but the results remain controversial. Here we performed a meta-analysis to estimate the relationship between TYMS polymorphisms and the risk of NHL and two of its subtypes from all nine published case-control studies. Our meta-analysis suggested that both 1053C > T and IVS6-68C >T polymorphisms were significantly associated with decreased risks of NHL among Caucasians (for 1053C > T: TT vs. CC, odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.64-0.95; recessive model, OR = 0.81, 95% CI = 0.67-0.98 and for IVS6 - 68C > T: TT vs. CC, OR = 0.61, 95% CI = 0.40-0.92; recessive model, OR = 0.63, 95% CI = 0.42-0.93), whereas the TSER, 1122A > G and 1494del6 polymorphisms had no influence on the susceptibility to NHL. Further analysis revealed that the T allele of the 1053C > T polymorphism might provide protective effects in Caucasians against the risk of NHL (OR = 0.90, 95% CI = 0.82-0.98) and follicular lymphoma (FL) (OR = 0.81, 95% CI = 0.71-0.93), but not diffuse large B-cell lymphoma (DLBCL). Additionally, the IVS6 - 68C > T variant homozygote genotype was significantly associated with reduced risks for DLBCL (TT vs. CC: OR = 0.51, 95% CI = 0.28-0.94; recessive model: OR = 0.53, 95% CI = 0.29-0.96), but not FL. However, individuals carrying the T allele of the IVS6 - 68C > T polymorphism were not significantly associated with reduced risks for DLBCL and FL.

A recent genome-wide association study showed that the rs9939609 polymorphism in the fat mass and obesity-associated (FTO) gene was associated with body mass index (BMI)/obesity in Europeans. Subsequently, several studies have investigated the association between FTO polymorphism and cancer risk. However, the results have been inconsistent. In this study, a meta-analysis was performed to clarify the association between FTO polymorphism and cancer risk. Published literature from PubMed and Embase databases were retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed-effects model. A total of 13 studies involving 16,277 cases and 31,153 controls were identified. The results suggested that FTO rs9939609 polymorphism was not significantly associated with the increased risk of cancer (OR = 1.01, 95 %CI 0.98-1.04), with the exception that a statistically significant association was found for pancreatic cancer (OR = 1.10, 95 %CI 1.03-1.19). No publication bias was detected (Begg's test: P = 0.760; Egger's test: P = 0.553). Our meta-analysis indicated that there was no association between FTO rs9939609 polymorphism and the increased risk of cancer, although this polymorphism was marginally associated with pancreatic cancer. However, the conclusion should be made with caution since most included studies did not take BMI/obesity into account.

The associations between four common genetic polymorphisms of transforming growth factor-β1 (TGF-β1 -509 C > T, +869 T > C, +915 G > C, and -800 G > A) and risk of colorectal tumor (including adenoma and cancer) have been widely studied. To date, no conclusions could be available because of controversial results reported. Thus, we conducted a meta-analysis to further assess the associations. We searched the databases of Medline, Embase, and Wangfang to identify eligible studies, and latest update was on January 1, 2012. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated to present the associations. Our meta-analysis indicated that TGF-β1 -509 C > T, +869 T > C, +915 G > C, and -800 G > A were not associated with risk of colorectal adenoma (OR = 0.89 for C carriers vs. TT for -509 C > T, 1.03 for C carriers vs. TT for +869 T > C, 1.09 for C carriers vs. GG for +915 G > C, and 1.19 for A carriers vs. GG for 800 G > A). However, C allele of TGF-β1 -509 C > T and A allele of -800 G > A were associated with increased risk of colorectal cancer (CRC), and OR (95%CI) was 1.23 (0.99-1.52) for CC vs. TT for -509 C > T and 6.64 (3.46-12.72) for A carriers vs. GG. The positive association between -509 C allele and risk of CRC was more obvious when subgroup analyses were conducted for population-based and large sample-sized studies as well as Caucasians. In contrast, we did not observed any associations between TGF-β1 +869 T > C, +915 G > C, and risk of CRC. This study indicated that C allele of TGF-β1-509 C > T and A allele of -800 G > A might contribute to the increased risk of CRC, and could be used as two of genetic marks for screening individuals at high risk of CRC. Because of modest limitation, large sample-sized studies were required to confirm the findings.

Through a genome-wide association analysis with a total of 7,035 individuals with duodenal ulcer and 25,323 controls from Japan, we identified two susceptibility loci at the PSCA gene (encoding prostate stem cell antigen) at 8q24 and at the ABO blood group locus at 9q34. The C allele of rs2294008 at PSCA was associated with increased risk of duodenal ulcer (odds ratio (OR) = 1.84; P = 3.92 × 10(-33)) in a recessive model but was associated with decreased risk of gastric cancer (OR = 0.79; P = 6.79 × 10(-12)), as reported previously. The T allele of rs2294008 encodes a translation initiation codon upstream of the reported site and changes protein localization from the cytoplasm to the cell surface. rs505922 at ABO was also associated with duodenal ulcer in a recessive model (OR = 1.32; P = 1.15 × 10(-10)). Our findings demonstrate a role for genetic variants in the pathogenesis of duodenal ulcer.

The relationships between the NAD(P)H quinone oxidoreductase 1 (NQO1) C609T polymorphism and the risk of digestive tract (DT) cancer are controversial. Therefore, we performed a meta-analysis to assess the relationships. The databases of Medline, Embase, and WanFang (updated to 15 May 2011) were reviewed. Odds ratios and 95% confidence intervals were calculated to assess the strength of the associations. Overall, 21 individual case-control studies in 20 papers with 5340 cases and 5911 controls were included in this meta-analysis. The results of combined analyses indicated that the T allele of NQO1 C609T was significantly associated with increased risk of DT cancer [odds ratio (95% CI): 1.58 (1.22-2.07) for TT vs. CC and 1.13 (1.06-1.22) for T carriers vs. C carriers]. Subgroup analyses for different types of cancers indicated that the T allele was significantly associated with an increased risk of gastric cancer [1.19 (1.13-1.47) for T carriers vs. C carriers], but not with esophageal cancer [1.05 (0.86-1.27) for T carriers vs. C carriers] and colorectal cancer [1.09 (0.98-1.21) for T carriers vs. CC]. Subgroup analyses for ethnicities and countries indicated that the T allele was associated with risk of DT cancer among Europeans [1.52 (1.05-2.19) for TT vs. CC] and Asians [1.52 (1.05-2.19) for TT vs. CC], and German, Indian, and Chinese populations but not among English and Japanese populations. In addition, subgroup analyses also indicated that the T allele was significantly associated with risk of DT cancer in studies with large and small sample sizes and in population-based studies, but not in hospital-based studies. This meta-analysis suggests that NQO1 C609T is significantly associated with risk of DT cancer among both Europeans and Asians, especially gastric cancer. Because of the limited number of cases and controls in the subgroup analyses, more well-designed studies with a large sample of participants are needed to verify our findings.

Recent studies implicate single nucleotide polymorphisms (SNPs) within the 8q24 region as a risk factor for prostate cancer (PCa). New developments suggest that 8q24 encodes regulators of the nearby MYC gene, a known oncogene. In order to better understand the implications of SNPs in this region, we performed meta-analyses, stratified by race, of seven SNPs and one microsatellite marker previously identified as risk loci on the 8q24 region of the genome. In addition, we reviewed the literature examining the possible associations between these polymorphisms and clinicopathological features of PCa. The results of the meta-analyses indicate that rs6983267, rs1447295, rs6983561, rs7837688, rs16901979, and DG8S737 are significantly associated with a higher risk for PCa for at least one race, whereas the variants rs13254738 and rs7000448 are not. The degree of association and frequency of the causative allele varied among men of different races. Though several studies have demonstrated an association between certain 8q24 SNPs and clinicopathological features of the disease, review of this topic revealed conflicting results.

5,10-Methylenetetrahydrofolate reductase (MTHFR) polymorphisms implicated in the cancer development, but the published studies had yielded inconsistent results.

Colorectal cancer (CRC) that demonstrates microsatellite instability (MSI) is caused by either germline mismatch repair (MMR) gene mutations, or 'sporadic' somatic tumour MLH1 promoter methylation. MLH1 promoter methylation is reportedly correlated with tumour BRAF V600E mutation status. No systematic review has been undertaken to assess the value of BRAF V600E mutation and MLH1 promoter methylation tumour markers as negative predictors of germline MMR mutation status. A literature review of CRC cohorts tested for MMR mutations, and tumour BRAF V600E mutation and/or MLH1 promoter methylation was conducted using PubMed. Studies were assessed for tumour features, stratified by tumour MMR status based on immunohistochemistry or MSI where possible. Pooled frequencies and 95% CIs were calculated using a random effects model. BRAF V600E results for 4562 tumours from 35 studies, and MLH1 promoter methylation results for 2975 tumours from 43 studies, were assessed. In 550 MMR mutation carriers, the BRAF V600E mutation frequency was 1.40% (95% CI 0.06% to 3%). In MMR mutation-negative cases, the BRAF V600E mutation frequency was 5.00% (95% CI 4% to 7%) in 1623 microsatellite stable (MSS) cases and 63.50% (95% CI 47% to 79%) in 332 cases demonstrating MLH1 methylation or MLH1 expression loss. MLH1 promoter methylation of the 'A region' was reported more frequently than the 'C region' in MSS CRCs (17% vs 0.06%, p<0.0001) and in MLH1 mutation carriers (42% vs 6%, p<0.0001), but not in MMR mutation-negative MSI-H CRCs (40% vs 47%, p=0.12). Methylation of the 'C region' was a predictor of MMR mutation-negative status in MSI-H CRC cases (47% vs 6% in MLH1 mutation carriers, p<0.0001). This review demonstrates that tumour BRAF V600E mutation, and MLH1 promoter 'C region' methylation specifically, are strong predictors of negative MMR mutation status. It is important to incorporate these features in multifactorial models aimed at predicting MMR mutation status.

We have previously reported multiple loci associated with prostate cancer susceptibility in a Japanese population using a genome-wide association study (GWAS). To identify additional prostate cancer susceptibility loci, we genotyped nine SNPs that were nominally associated with prostate cancer (P < 1 × 10(-4)) in our previous GWAS in three independent studies of prostate cancer in Japanese men (2,557 individuals with prostate cancer (cases) and 3,003 controls). In a meta-analysis of our previous GWAS and the replication studies, which included a total of 7,141 prostate cancer cases and 11,804 controls from a single ancestry group, three new loci reached genome-wide significance on chromosomes 11q12 (rs1938781; P = 1.10 × 10(-10); FAM111A-FAM111B), 10q26 (rs2252004; P = 1.98 × 10(-8)) and 3p11.2 (rs2055109; P = 3.94 × 10(-8)). We also found suggestive evidence of association at a previously reported prostate cancer susceptibility locus at 2p11 (rs2028898; P = 1.08 × 10(-7)). The identification of three new susceptibility loci should provide additional insight into the pathogenesis of prostate cancer and emphasizes the importance of conducting GWAS in diverse populations.