We conducted a meta-analysis to identify new susceptibility loci for testicular germ cell tumor (TGCT). In the discovery phase, we analyzed 931 affected individuals and 1,975 controls from 3 genome-wide association studies (GWAS). We conducted replication in 6 independent sample sets comprising 3,211 affected individuals and 7,591 controls. In the combined analysis, risk of TGCT was significantly associated with markers at four previously unreported loci: 4q22.2 in HPGDS (per-allele odds ratio (OR) = 1.19, 95% confidence interval (CI) = 1.12-1.26; P = 1.11 × 10(-8)), 7p22.3 in MAD1L1 (OR = 1.21, 95% CI = 1.14-1.29; P = 5.59 × 10(-9)), 16q22.3 in RFWD3 (OR = 1.26, 95% CI = 1.18-1.34; P = 5.15 × 10(-12)) and 17q22 (rs9905704: OR = 1.27, 95% CI = 1.18-1.33; P = 4.32 × 10(-13) and rs7221274: OR = 1.20, 95% CI = 1.12-1.28; P = 4.04 × 10(-9)), a locus that includes TEX14, RAD51C and PPM1E. These new TGCT susceptibility loci contain biologically plausible genes encoding proteins important for male germ cell development, chromosomal segregation and the DNA damage response.

The association between the Cyclin D1 gene (CCND1) G870A polymorphism and esophageal cancer has been widely evaluated, with conflicting results. As meta-analysis is a reliable approach to resolving discrepancies, we aimed to evaluate this association. Data were available from 9 study populations incorporating 1898 cases and 3046 controls. Overall, the allelic/genotypic association between the G870A polymorphism and esophageal cancer was nonsignificant [for allele: odds ratio (OR) = 1.14, 95% confidence interval (95%CI) = 0.94-1.38, P = 0.184; for genotype homozygous comparison: OR = 1.36, 95%CI = 0.90-2.06, P = 0.140; for dominant model: OR = 1.24, 95%CI = 0.88-1.75, P = 0.222; for recessive model: OR = 1.13, 95%CI = 0.90-1.43, P = 0.292]. Moreover, subgroup analyses according to study designs, geographic areas, types of esophageal cancer, genotyping methods, and ethnicities failed to demonstrate a significant association between this polymorphism and esophageal cancer. In addition, there was significant publication bias as reflected by funnel plots and the Egger test (P = 0.042). Taken together, our results suggest that the CCND1 G870A polymorphism might not be a potential candidate for predicting esophageal cancer risk.

Differential diagnosis of pancreatic solid masses with EUS-guided FNA (EUS-FNA) is still challenging in about 15% of cases. Mutation of the K-ras gene is present in over 75% of pancreatic adenocarcinomas (PADC).

Common genetic polymorphisms on chromosome 5p15.33, including rs401681 in cleft lip and palate transmembrane 1-like gene (CLPTM1L), have been implicated in susceptibility to lung cancer through genome-wide association studies (GWAS); however, subsequent replication studies yielded controversial results.

There were many studies performed to assess the association between X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp polymorphism and lung cancer risk in Chinese Han population, but contradictory results were reported. To provide a comprehensive and objective assessment of the association, a meta-analysis of all eligible case-control studies was carried out. After searching the databases and reading the abstracts, 12 case-control studies on the association between XRCC1 Arg194Trp polymorphism and lung cancer risk were finally included into this meta-analysis. Those 12 studies included a total of 4,385 cases and 4,545 controls. XRCC1 Arg194Trp polymorphism was associated with increased risk of lung cancer in Chinese Han population under three main models (allele contrast model, odds ratio (OR) = 1.12, 95 % confidence interval (CI) 1.00-1.26, P = 0.049; homozygote model, OR = 1.27, 95 % CI 1.09-1.48, P = 0.003; recessive model, OR = 1.26, 95 % CI 1.09-1.46, P = 0.003). However, there was no obvious association between XRCC1 Arg194Trp polymorphism and lung cancer risk under the dominant model (OR = 1.06, 95 % CI 0.98-1.16, P = 0.146). Sensitivity analysis suggested the stability and liability of this meta-analysis. Therefore, this meta-analysis suggests that XRCC1 Arg194Trp polymorphism is associated with increased risk of lung cancer in Chinese Han population.

Evidence indicates CCND1 G870A polymorphisms as a risk factor for a number of cancers. Increasing studies have been conducted on the association of CCND1 G870A polymorphism with lung cancer risk. However, the results were controversial. The aim of the present study was to derive a more precise estimation of the relationship. Meta-analyses examining the association between CCND1 G870A polymorphism and lung cancer were performed. Subgroup analyses regarding ethnicity, smoking status, histological types and source of controls were also implemented. All eligible studies for the period up to May 2012 were identified. The overall data from ten case-control studies including 5,008 cases and 5,214 controls indicated that variant A allele may have an association with increased lung cancer risk (AA vs GG: OR = 1.21; 95 % CI = 1.08-1.36, dominant model: OR = 1.09; 95 % CI = 1.00-1.19, recessive model: OR = 1.23; 95 % CI = 1.01-1.49). In the subgroup analysis by ethnicity, A allele may elevate lung cancer risk among Asians but not Caucasians or Mixed ethnicities. In smoking status subgroup, A allele was shown to associate with increased lung cancer risk among smokers but not non-smokers. In the subgroup analysis by histological types, increased cancer risks were shown in adenocarcinoma but not squamous cell carcinoma, under the homozygote comparison and recessive models. Collectively, the results of the present study suggest that CCND1 G870A polymorphism might be a low-penetrant risk factor for lung cancer, particularly among Asians and smokers. Moreover, homozygous AA alleles might have a correlation with increased lung adenocarcinoma susceptibility.

Excessive estrogenic influence is known to be associated with initiation/promotion of endometrial cancer (EC). Common variants among genes coding for enzymes in sex steroid biosynthetic pathways may influence the risk of EC. Cytochrome P450c17α (CYP17), a gene that codes for a key enzyme (cytochrome P450c17α) in a rate-limiting step of estrogen biosynthesis has attracted considerable attention as a candidate gene for EC. The relationship between CYP17 and EC has been reported in various ethnic groups; however, these studies have yielded contradictory results. To investigate this inconsistency, we performed a meta-analysis of 13 studies involving a total of 3,258 cases and 4,614 controls for -34T>C (rs743572) polymorphism of the CYP17 gene to evaluate the effect of CYP17 on genetic susceptibility for EC. An overall random effects odds ratio of 0.71 (95% confidence interval 0.58-0.88, P=0.001) was found under recessive genetic model. Stratified analysis based on ethnicity, sample size and Hardy-Weinberg equilibrium status was conducted to explore potential heterogeneity. This meta-analysis demonstrated that the C allele of -34T>C in CYP17 is a protective factor associated with decreased EC susceptibility, but these associations vary in different ethnic populations.

The Cdx-2 polymorphism in VDR gene has been extensively investigated for association with cancer risk, however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of the Cdx-2 polymorphism in VDR and cancer risk by meta-analysis. All eligible case-control studies were searched in Pubmed, Embase, CNKI and Wanfang databases. Odds ratios (OR) with the 95 % confidence intervals (CI) were used to assess the association. A total of 12,906 cases and 13,700 controls in 18 case-control studies were included. The results indicated that the AA homozygote carriers had a 16 % increased risk of cancer, when compared with the homozygote GG and heterozygote AG (OR = 1.16, 95 % CI 1.05-1.29 for AA vs. GG+AG). In the subgroup analysis by ethnicity, significant elevated risks were associated with AA homozygote carriers in Caucasians (OR = 1.16, 95 % CI 1.01-1.33, and P = 0.04) and African Americans (OR = 1.31, 95 % CI 1.07-1.61, and P = 0.01). In the subgroup analysis by cancer types, the polymorphism was associated with increased risk of breast cancer (OR = 1.23, 95 % CI 1.04-1.46, and P = 0.02). This meta-analysis suggested that the Cdx-2 polymorphism of VDR gene would be a risk factor for cancer. To further evaluate gene-to-gene and gene-to-environmental interactions between polymorphisms of VDR gene and cancer risk, more studies with large groups of patients are required.

Cytochrome P450 2A6 (CYP2A6) is an enzyme involved in the metabolism of some tobacco carcinogens, which is an important risk factor of lung cancer. Among CYP2A6 allelic variants, CYP2A6*4 presents a whole gene deletion that accounts for the majority of poor metabolizer. In this study, a meta-analysis was performed to assess the association between CYP2A6*4 and risk of lung cancer. Literature searches were conducted to identify peer-reviewed manuscripts published up to December 20, 2012. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated in a fixed-effects model and a random-effects model when appropriate. Eight eligible studies with 3,203 lung cancer cases and 2,839 controls were included in this study. Overall, no significant association was observed in CYP2A6*4 with the risk of lung cancer under any genetic model for all samples after correction. However, subgroup analysis showed that significant associations were observed in Asian with pooled OR (95 %CI) of 0.761 (0.672-0.861) for allele comparison, 0.769 (0.668-0.886) for dominant model, and 0.522 (0.359-0.760) for recessive model. Furthermore, after stratifying Asian samples according to smoking status, significant associations were only observed in smokers with pooled OR (95 %CI) of 0.713 (0.607-0.838) for allele comparison, 0.720 (0.596-0.869) for dominant model, and 0.444 (0.275-0.715) for recessive model. This meta-analysis suggests that the CYP2A6*4 polymorphism was associated with susceptibility of lung cancer for smokers in Asian. The whole gene deletion of CYP2A6 might decrease the risk of tobacco-related lung cancer in Asian.

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

Nonpolypoid colorectal neoplasms (NP-CRNs) are proposed as a major contributor to the occurrence of interval cancers, but their underlying biology remains controversial. We conducted a systematic review and meta-analysis to clarify the major biological events in NP-CRNs.

To evaluate the contribution of association studies of candidate polymorphisms to inherited predisposition to chronic lymphocytic leukemia (CLL), we conducted a systematic review and meta-analysis of published case-control studies. We identified 36 studies which reported on polymorphic variation in 19 genes and CLL risk. Out of the 23 polymorphic variants, significant associations (p < 0.05) were seen in pooled analyses for only four variants: MDR1, rs1045642; LTA, rs2239704; CD38, rs6449182; and IFNGR1, rs4896243. These findings should be interpreted cautiously, as the estimated false positive report probabilities (FPRPs) for each association were not noteworthy (i.e. FPRP > 0.2). While studies of candidate polymorphisms may be an attractive means of identifying risk factors for CLL, the limited power of published studies to demonstrate statistically significant associations makes it essential that future analyses be based on sample sizes well-powered to identify variants having modest effects on CLL risk.

Thymidylate synthetase is the major target of 5-fluorouracil (5-FU), which is widely used for the treatment of gastric cancer (GC) and colorectal cancer (CRC). This meta-analysis aimed to elucidate the effect of Ts polymorphisms on the efficacy of 5-FU-based chemotherapy in GC and CRC patients. Individual data were analyzed from 10 studies of 1102 GC and CRC patients treated with 5-FU-based regimens. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). Data were pooled using the program STATA version 10.0 (Stata Corporation, College Station, TX). The relationship between the Ts polymorphism and survival following 5FU-based treatment of GC and CRC patients was systematically summarized. Compared with the C allele, the G allele was associated with shorter PFS but with similar OS in Caucasian CRC patients. Compared with the 3R/3R genotype, the 2R/3R or 2R/2R genotype was associated with the same PFS, but with a shorter OS, particularly in Caucasian CRC patients. These results show a correlation between survival following 5-FU-based therapy and tumor genotype in Caucasian CRC patients. Larger studies and further clinical trials are required to confirm this observation.

Genetic variation in glutathione S-transferases (GSTs) may contribute to lung cancer risk. Many studies have investigated the correlation between the Glutathione S-transferase T1 (GSTT1) null genotype and lung cancer risk in Asian population but yielded inconclusive results.

The 1306 C>T, 1171 5A>6A, and 1562C>T polymorphisms of matrix metalloproteinase (MMP) 2, MMP3, and MMP9 genes, respectively, have been found to be functional and may contribute to head and neck carcinogenesis. However, the results of case-control studies examining associations between MMP polymorphisms and head and neck cancer (HNC) risk remain inconclusive. Therefore, we performed a meta-analysis to further evaluate the role of these polymorphisms in HNC development.

Gallstones (GS) is the major manifestation of gallbladder disease, and is the most common risk factor for gallbladder cancer (GBC). Previous studies investigating the association between ApoB-100 gene polymorphisms and the risks of GS and GBC have yielded conflicting results. Therefore, we performed a meta-analysis to clarify the effects of ApoB-100 gene polymorphisms on the risks of GS and GBC.

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

Previous studies suggest that genetic factors play important roles in the development of colorectal cancer. CYP2E1 T7632A and 9-bp insertion polymorphisms may influence the risk of colorectal cancer, but published results are conflicting. We therefore conducted a meta-analysis comprising 9 case-control studies with 4,592 cases and 5,918 controls. Odds ratios (ORs) with 95 % confidence interval (95 % CI) were used to assess the strength of the associations of CYP2E1 T7632A and 9-bp insertion polymorphisms with colorectal cancer. For CYP2E1 T7632A polymorphism, meta-analysis showed that there was no significant association between the CYP2E1 T7632A polymorphism and colorectal cancer risk under all contrast models (A vs. T: OR = 1.06, 95 % CI 0.88-1.29, P = 0.528; AA vs. TT: OR = 0.85, 95 % CI 0.61-1.19, P = 0.351; AA/TA vs. TT: OR = 1.08, 95 % CI 0.87-1.34, P = 0.484; and AA vs.

Previous studies published to evaluate the association between FAS-1377 G/A polymorphism and susceptibility to gastric cancer provided inconclusive outcomes. To derive a more precise estimation on this association, a meta-analysis of published case-control studies was performed. Eligible studies up to November 13, 2012 were identified from PubMed, Wanfang Medicine database, and Web of Science. Nine studies with a total of 2,086 cases and 2,701 controls were finally included into this meta-analysis. Overall, there was an obvious association between FAS-1377 G/A polymorphism and susceptibility to gastric cancer (for AA versus GG: odds ratio (OR) = 1.38; 95 % confidence interval (CI) 1.00-1.91, P = 0.05; for AA versus

Frequent deletions of the kinesin-like protein gene 1B (KIF1B) have been reported in neural tumors. Recently, a genome-wide association study revealed an association between polymorphisms in the KIF1B gene and the risk of hepatocellular carcinoma (HCC), and several case-control studies have further investigated this relationship. However, these studies have yielded controversial results. We therefore performed a meta-analysis to derive a more precise estimation of the association between the KIF1B gene polymorphisms and HCC risk.