The Ser326Cys polymorphism in the human 8-oxogunaine DNA glycosylase (hOGG1) gene had been implicated in cancer susceptibility. Studies investigating the associations between the Ser326Cys polymorphism and digestion cancer susceptibility showed conflicting results. Therefore, a meta-analysis was performed to derive a more precise estimation of the relationship. We conducted a meta-analysis of 48 studies that included 12,073 cancer cases and 19,557 case-free controls. We assessed the strength of the association using odds ratios (ORs) with 95% confidence intervals (CIs). In our analysis, the hOGG1 Ser326Cys polymorphism was significantly associated with the risk of digestive system cancers (Cys/Cys vs. Ser/Ser: OR = 1.17, 95% CI = 1.00-1.35, P < 0.001; Cys/Cys vs. Cys/Ser + Ser/Ser: OR = 1.14, 95% CI = 1.00-1.29, P < 0.001). In subgroup analyses by cancer types, we found that the hOGG1 Ser326Cys polymorphism may increase hepatocellular cancer and colorectal cancer risks, but decrease the risk of oral cancer. These findings supported that hOGG1 Ser326Cys polymorphism may contribute to the susceptibility of digestive cancers.

Mouse Double Minute 2 (MDM2) has emerged as a pivotal cellular antagonist of p53 by destructing the suppressive function of p53 against tumorigenesis. The MDM2 309 T > G polymorphism has been studied for its association with oral squamous cell carcinoma (OSCC) susceptibility, but the evidence was confusing and inconclusive. Here, we performed a meta-analysis to estimate the effects of the 309 T > G polymorphism on the development of OSCC. The relevant studies were searched on both PubMed and Embase. We estimated the risk of OSCC using odds ratio (OR) and 95 % confidence interval (CI). In addition, between-study heterogeneity was measured by the χ (2)-based statistic test; sensitivity analysis, and the funnel plots and Egger's test were also performed in this meta-analysis. Based on five case-control studies with a total of 1,369 OSCC cases and 2,167 control subjects, the meta-analysis result showed neither increased nor decreased risk of OSCC associated with any genetic model of the 309 T > G polymorphism. Similar results were observed in the subgroup of Asians. No significant heterogeneity and publication bias were detected in the meta-analysis. The evidence provided in our study indicated that the 309 T > G polymorphism might have no significant contribution to susceptibility toward OSCC.

Published data on the association between CYP17 rs743572 polymorphism and risk of PC showed inconclusive results. The aim of this study was to further estimate the pooled effect size of rs743572 polymorphism and PC progression via large-scale meta-analysis. We searched the case-control studies of rs743572 polymorphism and PC risk in PubMed, Embase, and Web of Science databases up to February 2014. Odds ratios (ORs) along with 95 % confidence intervals (CIs) were pooled by means of both fixed effects model and random effects model. A total of 38 publications consisting of 42 studies with 15,735 cases and 17,825 controls were included in this meta-analysis. Overall, no significant association was found between rs743572 polymorphism and PC risk. Stratified analyses by control source and sample size did not provide significant results. However, there was a borderline association in African population under A2A2 versus A1A2 + A1A1 genetic model (OR = 1.39, 95 % CI: 1.01-1.92, P = 0.975, I (2) = 0.0 %). Results from the current meta-analysis suggested that CYP17 rs743572 polymorphism might modify the risk of PC in the subjects of African decent.

To evaluate the accuracy of methylation of genes in stool samples for diagnosing colorectal tumours.

Polymorphisms of LIG4 gene may influence DNA repair ability, thus altering the genetic stability and resulting in carcinogenesis. A growing number of studies have investigated the relevance of LIG4 T9I (rs1805388) and D501D (rs1805386) polymorphisms with cancer risk, however, the results are conflicting. To obtain a comprehensive conclusion, we searched relevant literatures from PubMed, Web of Science, Ovid and Embase databases on May 15, 2014 and performed a meta-analysis. In this meta-analysis, a total of 17 articles were included. Of them, there were 15 studies with 5873 cases and 5771 controls for rs1805388 and 6 studies with 4161 cases and 4881 controls for rs1805386. Overall, our results suggested that there was no obvious relevance of LIG4 T9I polymorphism with cancer susceptibility. However, in subgroup analysis, we found the LIG4 T9I was associated with a slightly decreased cancer risk among Caucasians. As to the rs1805386, the genetic variant had no significant association with cancer risk. In conclusion, despite several limitations, this meta-analysis suggested that LIG4 T9I genetic variant is associated with a decreased risk of cancer among Caucasians, however, the rs1805386 gene polymorphism is not a risk factor of cancer.

Data on the association between -1607 1G > 2G polymorphism in the promoter region of matrix metalloproteinase-1 (MMP1) and nasopharyngeal carcinoma (NPC) are conflicting. The aim of this study was to confirm whether this polymorphism was a causative factor of NPC. We searched PubMed, Embase, and China National Knowledge Infrastructure (CNKI) for studies on the present topic. A total of four publications (1,044 NPC patients and 1,284 healthy control subjects) were included and meta-analysis was performed to assess the association between -1607 1G > 2G polymorphism and NPC risk. Odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated for 1G1G versus 2G2G, 1G1G + 1G2G versus 2G2G, 1G1G versus 1G2G + 2G2G, 1G versus 2G, and 1G2G versus 2G2G contrast models. Meta-analysis results showed significantly reduced risk of NPC associated with the 1G1G versus 2G2G, 1G versus 2G and 1G2G versus 2G2G contrast models (OR = 0.61, 95 % CI 0.49-0.77; OR = 0.78, 95 % CI 0.65-0.92; OR = 0.86, 95 % CI 0.74-0.99, respectively). When we continued to perform subgroup analysis by ethnicity, the significant association persisted in Asian population and was most pronounced under the 1G2G versus 2G2G model (OR = 0.85, 95 % CI 0.73-0.99). These data suggested that MMP1 -1607 1G > 2G polymorphism was associated with reduced risk of NPC, particularly in the population of Asian descent.

Inconsistent association of microsomal epoxide hydrolase (mEH) polymorphisms (Tyr113His, His139Arg) and lung cancer susceptibility have been reported in earlier studies. This study was undertaken to assess if mEH Tyr113His and His139Arg represent risk factors for lung cancer in Asian population. We exhaustively searched multiple databases to identify all eligible studies. Odds ratios were calculated to estimate the strength of genetic associations. This meta-analysis finally combined 2,522 subjects for Tyr113His and 2,725 subjects for His139Arg. In the analysis of Tyr113His, the His/His genotype carriers were found to have 29 % higher risk of lung cancer compared to the Tyr/Tyr carriers (His/His vs. Tyr/Tyr, odds ratio, 1.29, 95 % confidence interval, 1.06-1.58). A significantly increased risk was also seen in His/His versus His/Tyr + Tyr/Tyr (odds ratio, 1.29, 95 % confidence interval, 1.07-1.55). Likewise, His139Arg demonstrated a significant association with lung cancer (Arg/His vs. His/His, odds ratio, 1.2 6, 95 % confidence interval, 1.06-1.49; odds ratio, 1.24, 95 % confidence interval, 1.05-1.46). Stratified analysis by ethnicity showed both of the polymorphisms were associated with lung cancer in Chinese populations. These results suggest that the genetic associations exist between mEH polymorphisms and lung cancer susceptibility in Asian populations.

This study is to evaluate the association between IL-8 -251A/T polymorphism and lung cancer risk in diverse populations. We performed a meta-analysis of six case-control studies that included 3,265 lung-cancer cases and 3,607 case-free controls. Overall, results showed that the IL-8 -251A/T polymorphism was not associated with a significantly increased risk of lung cancer in all genetic models. However, stratified by ethnicity, a significantly increased risk was found among Asians. In conclusion, IL-8 -251A/T polymorphism is associated with lung cancer susceptibility in Asians and the -251 A allele may increase risk of lung cancer in Asians.

Multifactorial predisposition to melanoma includes genes involved in pigmentation, immunity and DNA repair. Nonetheless, missing heritability in melanoma is still important. We studied the role of 335 candidate SNPs in melanoma susceptibility by using a dedicated chip and investigating 110 genes involved in different pathways. A discovery set was comprised of 1069 melanoma patients and 925 controls from France. Data were replicated using validation phases II (1085 cases and 801 controls from Spain) and III (1808 cases and 1894 controls from Germany and a second set of Spanish samples). In addition, an exome sequencing study was performed in three high-risk French melanoma families. Nineteen SNPs in 17 genes were initially associated with melanoma in the French population. Six SNPs were replicated in phase II, including two new SNPs in the WNT3 (rs199524) and VPS41 (rs11773094) genes. The role of VPS41 and WNT3 was confirmed in a meta-analysis (3940 melanoma cases and 3620 controls) with two-side p values of 0.002, (OR = 0.86) and 4.07 × 10(-10) (OR = 0.80), respectively. Exome sequencing revealed a non-synonymous VPS41 variant in one family that was shown to be strongly associated with familial melanoma (OR = 4.46, p = 0.001) in an independent sample of 178 melanoma families. WNT3 belongs to WNT pathway known to play a crucial role in melanoma, whereas VPS41 regulates vesicular trafficking and is thought to play a role in pigmentation. Our work identified two new pathways involved in melanoma predisposition. These results may be useful in the future for identifying individuals highly predisposed to melanoma.

Long non-coding RNA has been involved in cancer progression, and high HOX transcript antisense intergenic RNA (HOTAIR) is thought to be a poor prognostic indicator in tumorigenesis of multiple types of cancer. Hence, the present study further reveals its prognostic value in tumor malignancy. A systematic review of PubMed and Web of Science was carried out to select literatures relevant to the correlation between HOTAIR expression levels and clinical outcome of various tumors. Overall survival (OS), metastasis-free survival (MFS), recurrence-free survival (RFS), and disease-free survival (DFS) were subsequently analyzed. Data from studies directly reporting a hazard ratio (HR) and the corresponding 95% confidence interval (CI) or a P value as well as survival curves were pooled in the current meta-analysis. A total of 2255 patients from 19 literatures almost published in 2011 or later were included in the analysis. The results suggest that HOTAIR was highly associated with HR for OS of 2.33 (95%CI = 1.77-3.09, Pheterogeneity = 0.016). Stratified analyses indicate that elevated levels of HOTAIR appears to be a powerful prognostic biomarker for patients with colorectal cancer (HR = 3.02, 95CI% = 1.84-4.95, Pheterogeneity = 0.699) and esophageal squamous cell carcinomas (HR = 2.24, 95CI% = 1.67-3.01, Pheterogeneity = 0.711), a similar effect was also observed in analysis method and specimen, except for ethnicity. In addition, Hazard ratios for up-regulation of HOTAIR for MFS, RFS, and DFS were 2.32 (P<0.001), 1.98 (P = 0.369), and 3.29 (P = 0.001), respectively. In summary, the high level of HOTAIR is intimately associated with an adverse OS in numerous cancers, suggesting that HOTAIR may act as a potential biomarker for the development of malignancies.

More clinically meaningful diagnostic tests are needed in pancreatic cancer (PC). K-ras mutations are the most frequently acquired genetic alteration.

Glutathione S-transferase Omega (GSTO) plays an important role in the development of cancer. Recently, a number of studies have investigated the association between single nucleotide polymorphisms on GSTO and susceptibility to cancer; however, the results remain inconclusive. We performed a meta-analysis of 20 studies, involving 4770 cases and 5701 controls to identify the strength of association by pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Overall, the pooled results revealed a significantly increased risk of susceptibility for GSTO2 polymorphism (GG vs. AA: OR = 1.20, 95%CI: 1.02-1.41, Pheterogeneity = 0.116), but no significant association was found for GSTO1 polymorphism. Subgroup analysis showed that GSTO2 polymorphism significantly increased cancer risk in Caucasian population (GG vs. AA: OR = 1.32, 95%CI 1.06-1.64, Pheterogeneity = 0.616) and GSTO2 polymorphism was significantly associated with elevated risk of breast cancer (GG vs. AA OR = 1.37, 95%CI: 1.06-1.77; Pheterogeneity = 0.281). This meta-analysis demonstrates that GSTO2 polymorphism may significantly increase cancer risk in Caucasian population and is associated with elevated risk of breast cancer; while GSTO1 polymorphism is not associated with cancer risk.

Emerging evidence suggests that a common functional polymorphism, rs4444903 (A>G), in the EGF gene might impact an individual's susceptibility to liver cancer; however, individually published results are inconclusive. This meta-analysis aimed to derive a more precise estimation of the relationship between the EGF rs4444903 polymorphism and liver cancer risk. A literature search was conducted in the PubMed, Embase, Web of Science, and CBM databases from inception through May 1st, 2013. Seven case-control studies were included with a total of 1408 liver cancer cases and 1343 healthy controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Our meta-analysis results indicated that the G variant of the rs4444903 polymorphism might be associated with an increased risk of liver cancer (G allele vs A allele: OR = 1.25, 95%CI = 1.01-1.56, P = 0.040; GG + AG vs AA: OR = 1.65, 95%CI = 1.27-2.15, P < 0.001; GG vs AA: OR = 1.77, 95%CI = 1.34-2.35, P < 0.001). Further subgroup analysis by ethnicity also showed significant associations between the G variant of the rs4444903 polymorphism and an increased risk of liver cancer among Asian, Caucasian, and African populations. No publication bias was detected in this meta-analysis. In conclusion, the current meta-analysis suggests that the G variant of the rs4444903 polymorphism may increase the risk of liver cancer. The EGF rs4444903 (A>G) polymorphism can be useful as a biomarker in predicting the development of liver cancer.

Recent studies have provided new insights into the diagnostic value of circulating microRNAs (miRNAs) for breast cancer (BCa). However, the inconsistent results between studies have prevented the widespread usage of miRNAs in clinics. To systematically assess the potential diagnostic value of circulating miRNAs in BCa, we performed a comprehensive meta-analysis. Eligible studies were retrieved by searching electronic databases. The quality of the studies was assessed on the basis of quality assessment for studies of diagnostic accuracy (QUADAS) criteria. The bivariate meta-analysis model was employed to summarize the diagnostic indices and plot the summary receiver operator characteristic (SROC) curve. A total of 15 studies were included in this meta-analysis, involving 1368 BCa patients and 849 healthy controls. Our bivariate random effects meta-analysis yielded an area under curve (AUC) value of 0.9217, with a sensitivity of 0.82 (95 % confidence interval (CI) 0.80-0.83) and specificity of 0.82 (95% CI 0.80-0.85) for the use of miRNAs in differentiating BCa patients from healthy controls. Notably, our subgroup analysis suggested that a combination of multiple miRNAs (AUC, sensitivity, and specificity of 0.9518, 0.87, and 0.88, respectively) seemed to harbor higher accuracy than single miRNA-based assays (AUC, sensitivity, and specificity of 0.8923, 0.79, and 0.77, respectively). Altogether, our data indicate that circulating miRNA profiling has a potential to be used as a screening test for BCa, among which, the detection of a combined multiple miRNAs may be a more comprehensive indicator than individual miRNA.

Epidemiological studies indicate a genetic contribution to colorectal cancer (CRC) and colorectal adenoma (CRA) risk, but specific genetic variants remain unknown. Recently, genome-wide association studies have identified 8q23.3-rs16892766 as a new CRC susceptibility locus in populations of European descent. Since then, the relationship between 8q23.3-rs16892766 and CRC/CRA has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency and derive a more precise estimation of the relationship, we conducted a meta-analysis of 13 studies, including 41,728 patients and 44,393 controls for CRC, and 3,767 patients and 11,607 controls for CRA. An overall random-effects per-allele odds ratio of 1.19 (95 % CI: 1.13-1.25, P < 10(-5)) was found for the rs16892766 polymorphism and CRC/CRA risk. When stratified by outcome, the rs16892766 polymorphism was significantly associated with increased CRC risk with per-allele OR of 1.22 (95 % CI: 1.18-1.27, P < 10(-5)), while no associations were found for CRA (OR = 1.05, 95 % CI: 0.91-1.25, P = 0.49). In the subgroup analysis by ethnicity, significantly increased CRC risks were found among Caucasians (OR = 1.23, 95 % CI: 1.17-1.29, P < 10(-5)) and African American (OR = 1.18, 95 % CI: 1.07-1.29, P = 0.001); while no significant associations were found among other ethnic populations. Similar results were also observed under dominant and recessive genetic models. Ethnicity was identified as a potential source of between-study heterogeneity for rs16892766. When stratified by sample size and study design, significantly increased CRC risks were found for the polymorphism in all genetic models. Our findings demonstrated that rs16892766-C allele might be risk-conferring factors for the development of CRC, but not for CRA.

Catechol-O-methyltransferase (COMT) is involved in estrogen metabolism and is vital to estrogen-induced carcinogenesis, including that of ovarian cancer. Although many recent epidemiologic studies have investigated associations between the COMT rs4680 polymorphism and ovarian cancer risk, the results remain inconclusive. We therefore performed a meta-analysis to derive a more precise estimate of associations. Systematic searches of the PubMed, Embase, Web of Science, Cochrane Library, Wanfang, China National Knowledge Infrastructure, and Chinese Biomedicine databases were undertaken to retrieve eligible studies. Odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were pooled to assess the strength of the association. In total, 8 case-control studies involving 1,293 cases and 2,647 controls were included in the meta-analysis. Overall, the results showed no evidence of significant association between the COMT rs4680 polymorphism and ovarian cancer risk in any of the assessed genetic models. Subgroup analyses by ethnicity also did not reveal any significant association in any genetic model (p>0.05). In conclusion, our findings suggest that the COMT rs4680 polymorphism may not contribute to the risk of ovarian cancer.

Despite evidence suggesting roles for caspase-8 (CASP8) -652 6N del and D302H polymorphisms in prostate cancer (PCa), the association of these polymorphisms with PCa risk remains inconclusive. Therefore, a meta-analysis was performed to more precisely estimate the association of CASP8 -652 6N del and D302H polymorphisms with PCa susceptibility.

RESULTS from previous studies concerning the association of ERCC4 rs1800067 polymorphism with risk of cancer were inconsistent. To explore the exact relation with susceptibility, we conducted the present meta-analysis.

Colorectal cancer (CRC) is a major cause of cancer-related death and cancer-related incidence worldwide. The potential of microRNA-21 (miR-21) as a biomarker for CRC detection has been studied in several studies. However, the results were inconsistent. Therefore, we conducted the present meta-analysis to systematically assess the diagnostic value of miR-21 for CRC.