p53 is a tumor suppressor gene, which is activated in response to several forms of cellular stress and exerts multiple antiproliferative functions, making it the most frequent target for genetic alteration in cancer. Various studies have evaluated the association between p53 codon 72 G > C (rs1042522) polymorphism and risk of cancer. However, results from the published studies remained inconclusive. The aim of this study is to investigate the precise association between this variant and a risk of cancer in a large-scale meta-analysis. We searched the PubMed (MEDLINE) and Google Scholar web databases for studies regarding the association of p53 codon 72 G > C polymorphism and risk of cancer in the Indian population. Pooled odds ratio (OR) with 95 % confidence interval (CI) were calculated by using random effect model to assess the association. Twenty studies with 3,258 cancer cases and 4,260 healthy controls were included. Overall, no significant association was detected for C allele carrier (C vs. G: OR = 1.135, 95 % CI = 0.930 to 1.386, p = 0.211) and homozygous (CC vs. GG: OR = 1.200, 95 % CI = 0.810 to 1.779, p = 0.364), heterozygous (CG vs. GG: OR = 1.204, 95 % CI = 0.921 to 1.575, p = 0.175), dominant (CC + CG vs. GG: OR = 1.231, 95 % CI = 0.932 to 1.625, p = 0.144), and recessive (CC vs. GG + GC: OR = 1.078, 95 % CI = 0.792 to 1.468, p = 0.632) genetic models, respectively. No significant publication bias was observed by using Begg's funnel plot and Egger's test. Present meta-analysis indicated that the p53 codon 72 G > C polymorphism was not associated with cancer risk. This suggests that this polymorphism may not be an independent risk factor for cancer in the Indian population.

Recent studies suggested that two common polymorphisms, miR-146a G>C and miR-196a2 C>T, may be associated with individual susceptibility to hepatocellular carcinoma (HCC). However, the results remain conflicting rather than conclusive. Object. The aim of this study was to assess the association between miR-146a G>C and miR-196a2 C>T polymorphisms and the risk of HCC.

The RAD51 gene is essential for the repair of damaged DNA related to tumor development. Although a number of genetic studies have attempted to link the 135G/C polymorphism of RAD51 gene to the risk of cancer, the results were inconclusive. The present study aimed at investigating the pooled association using the more comprehensive meta-analysis. The PubMed, EBSCO, and BIOSIS databases were searched to identify eligible studies which were published in English before March 2014. Data were extracted using standardized methods. The association was assessed by odds ratio (OR) with 95 % confidence interval (CI). Begg's test was used to measure publication bias. Sensitivity analyses were also performed to assess the stability of the results. A total of 45 eligible studies with 28,956 patients and 28,372 controls were included in this meta-analysis. Overall, significant association was detected between 135G/C polymorphism and increased cancer risk (C allele vs. G allele: OR 1.23, 95 % CI 1.18-1.28; CC vs. GG: OR 2.41, 95 % CI 2.12-2.74; CC vs. CG: OR 3.86, 95 % CI 3.41-4.37; recessive model: OR 3.57, 95 % CI 3.19-4.00). In further stratified analysis, significantly elevated cancer risk was observed among Caucasians but not Asians. Subgroup analysis by different cancers also showed their significant associations in breast cancer, hematologic malignances, ovarian cancer, colorectal cancer and endometrial cancer, but not in head and neck cancer. Our results indicated that the RAD51 135G/C polymorphism was a candidate for susceptibility of cancer. The effect of the variants on the expression levels and the possible functional role of the variants in different cancers should be addressed in further studies.

Estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) may play a role in the development of prostate cancer. Many studies focused on ESR1 rs9340799 and ESR2 rs1256049 polymorphisms to explore associations with prostate cancer risk. These studies showed inconsistent and conflicting results. The aim of this meta-analysis was to investigate the pooled association of ESR1 rs9340799 and ESR2 rs1256049 polymorphisms with prostate cancer risk. A systematic literature search was conducted to identify related studies (up to February 2014) in several online databases including PubMed, Google Scholar, CNKI and Wanfang online libraries. A total of 16 eligible articles were enrolled in this updated meta-analysis. The result suggested that ESR1 rs9340799 polymorphism was significantly associated with prostate cancer in overall populations (GG+GA vs. AA: P = 0.002; G vs. A: P = 0.004), Caucasians (GG+GA vs. AA: P = 0.008; G vs. A: P = 0.016) and Africans (GG+GA vs. AA: P = 0.005; G vs. A: P = 0.006), but not in Asians (GG+GA vs. AA: P = 0.462; G vs. A: P = 0.665). The result also showed that there was a significant association between ESR2 rs1256049 polymorphism and prostate cancer in Caucasians (AA+AG vs. GG: P = 0.016; A vs. G: P = 0.005), but no association in overall populations (AA+AG vs. GG: P = 0.826; A vs. G: P = 0.478), Asians (AA+AG vs. GG: P = 0.177; A vs. G: P = 0.703) and Africans (AA+AG vs. GG: P = 0.847; A vs. G: P = 0.707). The cumulative meta-analysis and sensitivity analysis showed the results were robust. In conclusion, this meta-analysis indicated that ESR1 rs9340799 polymorphism was associated with prostate cancer risk in overall populations, Caucasians and Africans, while ESR2 rs1256049 polymorphism was associated with prostate cancer risk in Caucasians. However, the biological mechanisms need to be further investigated.

Tumor necrosis factor-α (TNF-α) is an immunoregulatory cytokine involved in B- and T-cell function, and also plays an important role in inflammation and cancer. TNF-α-308G>A has been associated with constitutively elevated TNF-α expression. Several studies have reported the association between the TNF-α-308G>A polymorphism and non-Hodgkin lymphomas (NHL) risk, however, results are still inconsistent. To solve these conflicts, we conducted the first meta-analysis to assess the effect of TNF-α-308G>A polymorphism on the risk of NHL and various subtypes (additive model) including 10,619 cases and 12,977 controls in Caucasian and Asian populations. Our meta-analysis indicated that TNF-α-308G>A polymorphism is not associated with NHL risk when pooling all studies together (OR=1.06, 95% CI: 0.92-1.23, p=0.413). In stratified analyses, we found TNF-α-308A allele was significantly associated with higher risk of NHL, B-cell lymphomas (BCL), T-cell lymphomas (TCL) and diffuse large B-cell lymphomas (DLBCL) in Caucasians (OR=1.22, 95% CI: 1.06-1.40, p=0.007; OR=1.18, 95% CI: 1.03-1.34, p=0.014; OR=1.20, 95% CI: 1.01-1.42, p=0.040; OR=1.21, 95% CI: 1.11-1.32, p<0.001, respectively). Interestingly, it was associated with decreased risk of NHL, BCL and DLBCL in Asians (OR=0.75, 95% CI: 0.66-0.86, p<0.001; OR=0.70, 95% CI: 0.52-0.94, p=0.018; OR=0.70, 95% CI: 0.57-0.86, p=0.001). These findings also suggest TNF-α might play a distinct role in pathogenesis of NHL in different populations.

The addition of adjuvant chemotherapy to hormonal therapy is recommended for patients with estrogen receptor-positive (ER+), node-positive (N+) early breast cancer (EBC). Some of these patients, however, are not likely to benefit from treatment and may, therefore, be overtreated while also incurring unnecessary treatment-related adverse events and health care costs. The 21-gene Recurrence Score assay has been clinically validated and recommended for use in patients with ER+, node-negative (N0) EBC to assess the 10-year risk of distant disease recurrence and predict the likelihood of response to adjuvant chemotherapy. A growing body of evidence from several large phase III clinical trials reports similar findings in patients with ER+, N+ EBC. A systematic review of published literature from key clinical trials that have used the 21-gene breast cancer assay in patients with ER+, N+ EBC was performed. The Recurrence Score has been shown to be an independent predictor of disease-free survival, overall survival, and distant recurrence-free interval in patients with ER+, N+ EBC. Outcomes from decision impact and health economics studies further indicate that the Recurrence Score affects physician treatment recommendations equally in patients with N+ or N0 disease. It also indicates that a reduction in Recurrence Score-directed chemotherapy is cost-effective. There is a large body of evidence to support the use of the 21-gene assay Recurrence Score in patients with N+ EBC. Use of this assay could help guide treatment decisions for patients who are most likely to receive benefit from chemotherapy.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear chromatin-associated enzyme involved in several important cellular processes, particularly in the DNA repair system. PARP-1 rs1136410: C>T is among the most studied polymorphisms and likely involved in human carcinogenesis. However, results from previous studies are inconclusive. Thus, a meta-analysis was conducted to derive a more precise estimation of the effects of this enzyme.

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) have been involved in the risk of hepatocellular carcinoma (HCC). However, the interactive effect of GSTM1 and GSTT1 has not been reported previously. The aim of this work was to investigate the interaction and synergism of their variants. We identified nine publications including 1,085 cases and 2,396 controls containing both GSTM1 and GSTT1, and the bi-factor variance analysis of equal repeated test, binary class logistic regression analysis, meta-analysis and probability method were used in this analysis. Data showed there was no interaction between GSTM1 and GSTT1 null genotype variation in HCC development. In addition, individuals with at least one null genotype of GSTM1 and GSTT1 had higher susceptibility to HCC (OR = 2.99, 95 % CI 2.21-4.02). In the control group, the probability of individuals with at least one null genotype of GSTM1 and GSTT1 was 0.6624, while in the case group, the probability to develop HCC with at least one null genotype of GSTM1 and GSTT1 increased to 0.1760, which was considered as the changing characteristics of HCC occurrence in Chinese population. Our result suggests that there would be no direct interaction of GSTM1 and GSTT1 genotype in HCC risk. We speculate that GSTM1 and GSTT1 genotype variations have their own independent function in HCC development and may mutate independently to cause HCC. The synergism variants of the two genes in HCC development have bigger risk in Chinese population.

We conducted the present meta-analysis of relevant cohort studies to evaluate whether promoter methylation of the high in normal-1 (HIN-1) gene contributes to breast cancer. The MEDLINE (1966 ~ 2013), Cochrane Library (Issue 12, 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of Science (1945 ~ 2013), and Chinese Biomedical (CBM) (1982 ~ 2013) databases were searched without any language restrictions. Meta-analyses were conducted using Stata software (version 12.0; Stata Corporation, College Station, TX, USA). Crude odds ratios (ORs) with their 95 % confidence interval (CI) were calculated. Nine clinical cohort studies that enrolled a total of 693 breast cancer patients were included in the meta-analysis. The results of our meta-analysis demonstrated that HIN-1 methylation frequency in cancer tissue was significantly higher than that of normal and benign tissues (cancer tissue vs. normal tissue: OR = 52.60, 95 % CI = 33.77 ~ 81.92, P < 0.001; cancer tissue vs. benign tissue: OR = 2.38, 95 % CI = 1.53 ~ 3.70, P < 0.001; respectively). Ethnicity-stratified analysis indicated that HIN-1 promoter methylation was correlated with the pathogenesis of breast cancer among both Asians and Caucasians (all P < 0.05). Our findings provide empirical evidence that aberrant HIN-1 promoter methylation may contribute to the pathogenesis of breast cancer. Thus, aberrant HIN-1 promoter methylation could be an independent and important biomarker used in predicting the prognosis and progression of breast cancer.

In this case-cohort study, we examined the association between bulky DNA adducts and the risk of lung cancer within the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort with an average 7-year follow-up, including 98 cases of primary lung cancer and 296 subjects randomly selected from the cohort. Aromatic adducts were measured using (32)P-postlabeling in leukocyte DNA from blood samples collected at enrollment. The association between DNA adducts and the risk of lung cancer was estimated using a Cox proportional hazards model with a modified partial likelihood. There was an overall significant increased risk for developing lung cancer when DNA adduct concentrations were doubled, with relative risk (RR) adjusting for all relevant confounders of 1.36 with 95% confidence interval (CI) 1.18-157. There was a significant increased risk for developing lung cancer when DNA adduct concentrations were doubled for current smokers and among subjects exposed to PAH at work; there was also a slightly higher increase among males than females. However, no statistically significant differences were observed for the effect of adduct levels across smoking status, sex or occupational exposure to PAH. A meta-analysis combined four prospective studies, including this study, resulting in a significant association among current smokers, with an overall estimate of 34% increase in the risk of lung cancer when doubling the level of aromatic DNA adducts in leukocytes.

The results from the published studies on the association between leptin (LEP) genetic polymorphism and cancer risk are conflicting. The common A19G (rs2167270) genetic polymorphism has been reported to be functional and may contribute to genetic susceptibility to cancers. However, the association between LEP A19G (rs2167270) genetic polymorphism and cancer risk remains inconclusive. To better understand the role of LEP A19G (rs2167270) genetic polymorphism in global cancer, we conducted this comprehensive meta-analysis encompassing 5,679 cases and 7,443 controls. Overall, the LEP A19G (rs2167270) genetic polymorphism was associated with lower cancer risk. In the stratified analysis, significant associations were found between the LEP A19G (rs2167270) genetic polymorphism and colorectal cancer and non-Hodgkin's lymphoma. For colorectal cancer, there was no significant association of LEP A19G (rs2167270) variant with this disease under heterozygous codominant model [odds ratio (OR) = 1.11 (0.97-1.27)], dominant genetic model [OR = 1.03 (0.91-1.17)], and additive genetic model [OR = 0.94 (0.86-1.03)]; however, there was a marginal association under homozygous codominant model [OR = 0.80 (0.66-0.97)] and recessive genetic model [OR = 0.75 (0.63-0.90)]. For non-Hodgkin's lymphoma, there was a significant association of LEP A19G (rs2167270) variant with the disease under homozygous codominant model [OR = 0.74 (0.59-0.94)], recessive genetic model [OR = 0.76 (0.61-0.94)], and additive genetic model [OR = 0.89 (0.80-0.99)], but not under heterozygous codominant model [OR = 0.95 (0.82-1.10)] and dominant genetic model [OR = 0.91 (0.79-1.04)]. Moreover, a significantly decreased cancer risk was found in recessive genetic model among Latin American population. When stratified by study design, significantly elevated susceptibility to cancer was not found among any studies. No significantly differences in genotype method and sample size in cases were found among genotypes. These findings suggest that the LEP A19G (rs2167270) genetic polymorphism may decrease the susceptibility to cancers in colorectal cancer and non-Hodgkin's lymphoma, when assuming a homozygote codominant model and a recessive genetic model among Latin American population. The phenomenon also indicates that the SNP functions as a recessive mutation, which needs to be verified or linked with functional studies.

Xeroderma pigmentosum group D (XPD) rs13181 may reduce DNA repair capacity (DRC) through modifying XPD protein product. Reduced DRC is reportedly related to an increase in the risk of lung cancer. To precisely estimate the association between XPD rs13181 and lung cancer risk, we carried out the current meta-analysis. We searched multiple databases (up to 31 October 2013) for studies investigating the association of XPD rs13181 and lung cancer. Odds ratio (OR) was estimated with the fixed effect model to assess the association. Heterogeneity between studies was measured using Q test. Subgroup analyses were conducted by ethnicity, histological type, and sample size. Meta-analysis of 30 studies suggested that individuals carrying Gln/Gln genotype were more likely than the individuals with Lys/Lys or Lys/Gln + Lys/Lys genotypes (homozygous model, OR 1.18, 95 % confidence interval (CI) 1.07-1.31; recessive model, OR 1.17, 95 % CI 1.06-1.29) to develop lung cancer, without any substantial heterogeneity. This significantly increased risk was also revealed in the individuals harboring Gln/Gln + Lys/Gln genotypes (dominant model, OR 1.07, 95 % CI 1.01-1.12). Further stratification by histological type, ethnicity, and sample size yielded statistically significant estimates in subgroup of Caucasian subjects, non-small cell lung cancer, and relatively large studies, but borderline association in Asians. Our analyses demonstrate that XPD rs13181 may be associated with an increase in the risk of lung cancer among Caucasian populations.

To evaluate the published data on association between present/null polymorphism of glutathione S-transferase M1 (GSTM1) and breast cancer risk in Chinese population in order to abttain a more precise and comprehensive estimation of the relationship.

Excision repair cross-complimentary group 1 (ERCC1) is an essential component of the nucleotide excision repair system that is responsible for repairing damaged DNA. Functional genetic variations in the ERCC1 gene may alter DNA repair capacity and modulate cancer risk. The putative roles of ERCC1 gene polymorphisms in lung cancer susceptibility have been widely investigated. However, the results remain controversial.

Breast cancer may be caused by several factors, including polymorphisms in the microsomal epoxide hydrolase (mEH) gene. Previous work suggested an association between mEH polymorphism and risk of breast cancer, but the results have been inconsistent. PubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure database were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between Tyr113His and His139Arg mEH polymorphisms and susceptibility to breast cancer. Odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to assess the strength of the association. Seven studies involving 6,357 cases and 8,089 controls were included in this study. The Tyr113His mEH polymorphism did not affect breast cancer risk in the allelic contrast model (OR = 0.99, 95 % CI = 0.94-1.04, P = 0.58), the dominant genetic model (OR = 1.14, 95 % CI = 0.88-1.48, P = 0.33), or the recessive genetic model (OR = 1.03, 95 % CI = 0.96-1.10, P = 0.43). Similarly, the His139Arg mEH polymorphism was not associated with breast cancer risk in the allelic contrast model (OR = 0.97, 95 % CI = 0.91-1.04, P = 0.44), the dominant genetic model (OR = 1.01, 95 % CI = 0.84-1.21, P = 0.94), or the recessive genetic model (OR = 1.04, 95 % CI = 0.96-1.12, P = 0.35). The mEH polymorphisms Tyr113His and His139Arg are not risk factors for breast cancer. Further, large and well-designed studies are required to confirm this conclusion.

Previous studies have shown the association of the Cyclin D1 (CCND1) G870A polymorphism with glioma risk, but the findings are inconsistent and inconclusive. To shed some light on the findings across individual studies and acquire a quantitative assessment of this association, we conducted a meta-analysis of all published case-control studies thus far. Four independent studies with a total of 690 cases and 1,014 controls were identified after a systematic search of the PubMed, Embase, Web of Science, and Wanfang databases. The strength of the association between the CCND1 G870A polymorphism and glioma risk was estimated by the pooled odds ratios (ORs) with 95 % confidence intervals (95 %CIs). Subgroup analysis by ethnicity was also performed. Overall, a statistically significant association was found between the CCND1 G870A polymorphism and glioma risk in three genetic models (ORA vs. G = 1.178, 95 %CI 1.025-1.354, P OR = 0.021; ORAA vs. GG = 1.328, 95 %CI 1.007-1.750, P OR = 0.045; ORAA + AG vs. GG = 1.253, 95 %CI 1.006-1.516, P OR = 0.044). In subgroup analysis, the pooled ORs suggested that the CCND1 G870A polymorphism was associated with an increased risk of glioma in Caucasians under the heterozygote and dominant genetic models (ORAG vs. GG = 1.329, 95 %CI 1.001-1.766, P OR = 0.049; ORAA + AG vs. GG = 1.332, 95 %CI 1.019-1.740, P OR = 0.036). The meta-analysis suggests that the CCND1 G870A polymorphism is a risk factor for the development of glioma.

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of renal cell carcinoma from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR ApaI (rs7975232), BsmI (rs1544410), TaqI (rs731236), and Fok1 (rs2228570) gene polymorphism and the risk of renal cell carcinoma using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Five reports were recruited into this meta-analysis for the association of VDR gene polymorphism with renal cell carcinoma susceptibility. In this meta-analysis, the ApaI AA genotype, BsmI BB genotype, Fok1 f allele, and Fok1 FF genotype were associated with the risk of renal cell carcinoma in Asians. However, VDR ApaI, BsmI, TaqI, and Fok1 gene polymorphism were not associated with the risk of renal cell carcinoma in overall populations and in Caucasians. In conclusion, the ApaI AA genotype, BsmI BB genotype, Fok1 f allele, and Fok1 FF genotype were associated with the risk of renal cell carcinoma in Asians. However, more studies should be conducted to confirm it.

We aimed to obtain a summary risk estimate for CD243 gene polymorphism associated with breast cancer. A total of nine case-control studies, including 5,073 cancer patients and 7,498 control subjects, were pooled in our fixed effects meta-analysis of the association between CD243 gene polymorphism and risk of breast cancer. All data were analyzed by using Stata software (version 12.0). We found significant risk effects under TT vs. TC + CC genetic model [odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.01-1.18, P = 0.516], but not in other comparisons. Stratifying the pooled data by ethnicity and source of controls revealed that the association between the T allele and an increased risk of breast cancer was more pronounced among Asians (TT vs. CC: OR = 1.26, 95 % CI = 1.02-1.57, P = 0.720; TT vs. TC + CC: OR = 1.31, 95 % CI = 1.07-1.61, P = 0.708) and hospital-based studies (TT vs. CC: OR = 1.25, 95 % CI = 1.02-1.53, P = 0.877; TT vs. TC + CC: OR = 1.27, 95 % CI = 1.05-1.53, P = 0.540). No notable heterogeneity was indicated across studies. Our meta-analysis demonstrates that CD243 gene polymorphism may act as a predisposition factor for breast cancer, particularly in Asian populations.

Published studies on the association between NQO1 C609T polymorphism and prostate cancer risk have yielded conflicting results. Thus, a systemic review and meta-analysis of published studies were performed to assess the possible association. All eligible studies of NQO1 C609T polymorphism and prostate cancer risk were collected from the PubMed and the Cochrane Library. Statistical analyses were performed by Review Manage 5.0 and Stata 11.0. A total of 6 available studies were considered in the present meta-analysis, with 717 cases and 1,794 controls. When all groups were pooled, there was no evidence that NQO1 C609T had significant association with prostate cancer under additive, recessive, dominant, and allelic models. When stratifying for the race, our analysis suggested that NQO1 C609T was associated with prostate cancer risk in Asians when using dominant (TT + CT vs CC: OR = 1.419, 95 % CI = 1.053 - 1.913, P = 0.021) and allelic models (OR = 1.337, 95 % CI = 1.014 - 1.763, P = 0.040) to analyze the data. However, no significant associations were found in Caucasians. This meta-analysis suggested that NQO1 C609T polymorphism most likely contributes to increased susceptibility to prostate cancer in the Asians. Further large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.

Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted a genome-wide association study of CRC in East Asians with 14,963 cases and 31,945 controls and identified 6 new loci associated with CRC risk (P = 3.42 × 10(-8) to 9.22 × 10(-21)) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcriptional regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9), and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC-associated loci. Our study provides insights into the genetic basis of CRC and suggests the involvement of new biological pathways.