The association between Toll-like receptor 2 (TLR2) -196 to -174del polymorphism and Toll-like receptor 4 (TLR4) polymorphisms (Asp299Gly, Thr399Ile, and 3725G>C) and gastric cancer risk are still conflicting. For better understanding of the effects of these four polymorphisms on gastric cancer risk, a meta-analysis was performed.

Previous studies have focused on the association of signal-induced proliferation associated 1 gene (SIPA1) with carcinogenesis of many cancers, including breast cancer. It has been suggested that SIPA1 polymorphisms are associated with susceptibility to breast cancer. In the present study, we performed a meta-analysis to systematically summarize the possible association between SIPA1 and the risk for breast cancer. We conducted a search of case-control studies on the associations of SPIA1 with susceptibility to breast cancer in PubMed, Embase, International Statistical Institute Web of Science, Wanfang Database in China, and Chinese National Knowledge Infrastructure databases. Data from eligible studies were extracted for meta-analysis. Breast cancer risk associated with SIPA1 was estimated by pooled odds ratios and 95% confidence intervals. Four studies on SIPA1 and breast cancer were included in our meta-analysis. Our results showed that rs746429 was associated with the risk of breast cancer. However, rs931127 and rs3741378 were not found to be associated with breast cancer in our analysis. This meta-analysis suggests that rs746429 is associated with the risk of breast cancer. Well-designed studies with larger sample size and more ethnic groups are required to further validate the results.

The goal of this study was to explore whether vitamin D receptor (VDR) polymorphisms are associated with susceptibility to ovarian cancer.

Testing for BRCA1 mutation has important clinical implications such as identifying risk of second primary cancers and risk of cancer in the family. This study seeks to quantify the risk of having BRCA1 mutation in female breast cancer patients with triple-negative phenotype compared with those with other phenotypes. We undertook a search of MEDLINE and EMBASE databases for relevant studies through 10 May 2013. Outcomes were calculated and reported as risk ratio and risk difference. 12 studies comprising 2533 breast cancer patients were included in the analysis. It was found that almost all eligible studies were performed on high-risk population with breast cancer. By analyzing the incidence rates of BRCA1 mutation in patients with triple-negative breast cancer (TNBC) and non-TNBC, our meta-analysis provides a relative risk of 5.65 [95% confidence interval (CI), 4.15-7.69] and risk difference of 0.22 (95% CI, 0.15-0.29). This implies that, in selected population with high-risk features, women with TNBC are approximately five and a half times more likely to have BRCA1 mutation compared with non-TNBC phenotype, and approximately two in nine women with TNBC harbor BRCA1 mutation. Triple-negative phenotype significantly increases the risk of having BRCA1 mutation in high-risk breast cancer patients compared with non-TNBC.

Acute lymphoblastic leukemia (ALL) is the major pediatric cancer diagnosed in economically developed countries with B-cell precursor (BCP)-ALL, accounting for approximately 70% of ALL. Recent genome-wide association studies (GWAS) have provided the first unambiguous evidence for common inherited susceptibility to BCP-ALL, identifying susceptibility loci at 7p12.2, 9p21.3, 10q21.2, and 14q11.2. To identify additional BCP-ALL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1658 cases and 4723 controls, with validation in 1449 cases and 1488 controls. Combined analysis identified novel loci mapping to 10p12.2 (rs10828317, odds ratio [OR] = 1.23; P = 2.30 × 10(-9)) and 10p14 marked by rs3824662 (OR = 1.31; P = 8.62 × 10(-12)). The single nucleotide polymorphism rs10828317 is responsible for the N215S polymorphism in exon 7 of PIP4K2A, and rs3824662 localizes to intron 3 of the transcription factor and putative tumor suppressor gene GATA3. The rs10828317 association was shown to be specifically associated with hyperdiploid ALL, whereas the rs3824662-associated risk was confined to nonhyperdiploid non-TEL-AML1 + ALL. The risk allele of rs3824662 was correlated with older age at diagnosis (P < .001) and significantly worse event-free survivorship (P < .0001). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to BCP-ALL and the influence of constitutional genotype on disease development.

Recent evidences suggest that common functional polymorphisms in the promoter region of the Calpain-10 gene may have an impact on an individual's susceptibility to polycystic ovary syndrome (PCOS), but individually published results are inconclusive. Our meta-analysis is aimed to provide a more precise estimation of the relationships between Calpain-10 genetic polymorphisms and PCOS risk. An extensive literature search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from inception through April 1st, 2013. This meta-analysis was performed using the STATA 12.0 software. The crude odds ratio (OR) with 95% confidence interval (CI) was calculated. Fourteen case-control studies were included with a total of 2123 PCOS patients and 3612 healthy controls. Nine common SNPs in the Calpain-10 gene were addressed. Our meta-analysis indicated that UCSNP-19, UCSNP-63 and UCSNP-45 polymorphisms in the Calpain-10 gene might be associated with increased PCOS risk. However, no statistically significant association was observed in UCSNP-43, UCSNP-22, UCSNP-43, UCSNP-45, UCSNP-56, UCSNP-58, and UCSNP-110 polymorphisms. Further subgroup analysis by ethnicity revealed that UCSNP-19, UCSNP-63 and UCSNP-45 polymorphisms might decrease the risk of PCOS among Asian populations, but not among Caucasian populations. The current meta-analysis indicates that UCSNP-19, UCSNP-63 and UCSNP-45 polymorphisms in the Calpain-10 gene may be risk factors for PCOS, especially among Asian populations.

The m.10398G>A polymorphism in the MT-ND3 gene has been linked to the manifestation of several neurodegenerative disorders and cancers. Several research groups have analyzed the association between m.10398G>A polymorphism and breast cancer; however, the results do not follow a consensus. We have studied this polymorphism in three Dravidian populations from South India. Analysis on 716 cases and 724 controls found no association between m.10398G>A polymorphism and breast cancer [OR = 0.916 (0.743-1.128); P = 0.409]. Menopausal stratification also revealed no significant association in either pre-menopausal or post-menopausal breast cancer groups. In addition, we undertook a meta-analysis on 16 study groups, comprising a total of 7202 cases and 7490 controls. The pooled odds ratio suggested no significant association of m.10398G>A substitution with breast cancer [OR = 1.016 (0.85-1.22); P = 0.86]. In conclusion, there is no evidence of association between m.10398G>A polymorphism and breast cancer risk among South Indian women. Meta-analysis suggested no overall correlation between this polymorphism and breast cancer risk.

The ability to respond properly to Toll-like receptor (TLR) ligands may be impaired by polymorphisms within the TLR family of genes, which results in an altered susceptibility to cancers. However, the results of epidemiological studies remained inconsistent. To assess the effect of four selected polymorphisms (rs5743708, -196 to -174 del polymorphism, rs3804099, and rs3804100) in TLR-2 on cancer, we conducted a meta-analysis, up to November 2012; 20 case-control studies were available. Summary odds ratios (OR) and corresponding 95% confidence intervals (CIs) for polymorphisms in TLR-2 and cancer risk were estimated. Our meta-analysis identified that elevated cancer risk was statistically associated with -196 to -174 del allele in -196 to -174 del polymorphism (OR=1.63, 95% CI=1.10-2.41 for allele comparison; OR=1.64, 95% CI=1.05-2.57 for dominant model; OR=2.26, 95% CI=1.24-4.12 for recessive model; OR=2.57, 95% CI=1.30-5.08 for DD vs. II and OR=1.53, 95% CI=1.01-2.32 for ID vs. II in codominant model); whereas rs3804099 in TLR-2 was associated with decreased cancer risk. Moreover, in terms of stratified analyses by cancer type for -196 to -174 del polymorphism, significantly elevated risk was observed to be associated with -196 to -174 del allele in "other cancers." These findings indicate that polymorphisms in TLR-2 may play a role, although modest, in cancer development.

Researchers have provided evidence that telomere dysfunction play an important role in cancer development. MNS16A is a polymorphic tandem repeats minisatellite of human telomerase (hTERT) gene that influences promoter activity of hTERT and thus implicates to relate with risk of several malignancies. However, results on association between MNS16A and cancer risk remain controversial. We therefore conduct a meta-analysis to derive a more precise estimation of association between MNS16A and cancer risk.

Growing studies have revealed the association between polymorphisms in the Toll-like receptor 9 (TLR9) and susceptibility to cancer, however, the results remained inconsistent.

Many studies have reported the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln, Arg194Trp, Arg280His, -77T>C, and X-ray repair cross-complementing group 3 (XRCC3) T241M polymorphisms with lung cancer risk, but the results remained controversial. Hence, we performed a meta-analysis to investigate the association between lung cancer risk and XRCC1 Arg399Gln (14,156 cases and 16,667 controls from 41 studies), Arg194Trp (7,426 cases and 9,603 controls from 23 studies), Arg280His (6,211 cases and 6,763 controls from 16 studies), -77T>C (2,487 cases and 2,576 controls from 5 studies), and XRCC3 T241M (8,560 cases and 11,557 controls from 19 studies) in different inheritance models. We found that -77T>C polymorphism was associated with increased lung cancer risk (dominant model: odds ration [OR] = 1.45, 95% confidence interval [CI] = 1.27-1.66, recessive model: OR = 1.73, 95% CI = 1.14-2.62, additive model: OR = 1.91, 95% CI = 1.24-1.94) when all the eligible studies were pooled into the meta-analysis. In the stratified and sensitive analyses, significantly decreased lung cancer risk was observed in overall analysis (dominant model: OR = 0.83, 95% CI = 0.78-0.89; recessive model: OR = 0.90, 95% CI = 0.81-1.00; additive model: OR = 0.82, 95% CI = 0.74-0.92), Caucasians (dominant model: OR = 0.82, 95% CI = 0.76-0.87; recessive model: OR = 0.89, 95% CI = 0.80-0.99; additive model: OR = 0.81, 95% CI = 0.73-0.91), and hospital-based controls (dominant model: OR = 0.81, 95% CI = 0.76-0.88; recessive model: OR = 0.89, 95% CI = 0.79-1.00; additive model: OR = 0.80, 95% CI = 0.71-0.90) for XRCC3 T241M. In conclusion, this meta-analysis indicates that XRCC1 -77T>C shows an increased lung cancer risk and XRCC3 T241M polymorphism is associated with decreased lung cancer risk, especially in Caucasians.

Previous published data on the association between X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and clinical outcome of platinum-based chemotherapy in patients with lung cancer reported conflicting results. A meta-analysis was performed to provide a systematic review of the published data. We retrieved the relevant studies from PubMed and Embase databases. The primary outcome was overall survival, and the hazard ratio (HR) with 95% confidence interval (95% CI) was estimated. Seven studies with a total of 1,514 patients were included into the meta-analysis. Overall, XRCC3 Thr241Met polymorphism had no influence on the overall survival of lung cancer patients receiving platinum-based chemotherapy (MetMet vs. ThrThr: HR = 0.82, 95% CI 0.52-1.31, P = 0.410; MetThr vs. ThrThr: HR = 0.93, 95% CI 0.79-1.10, P = 0.339; MetMet/MetThr vs. ThrThr: HR = 1.07, 95% CI 0.88-1.31, P = 0.480). There was no obvious risk of publication bias. Therefore, currently available data suggest that there is no predictive effect of XRCC3 Thr241Met polymorphism on platinum-based chemotherapy in lung cancer patients.

Lung cancer is one of the most common cancers worldwide, but its etiology is still unclear. Superoxide dismutase 2 (SOD2) plays an essential role in oxidative stress and may be involved in the development of lung cancer. The association between SOD2 C47T polymorphism and lung cancer risk has been widely investigated, but the results of previous studies are contradictory. We conducted a meta-analysis to comprehensively assess the association between SOD2 C47T polymorphism and lung cancer. The association was estimated by odds ratio (OR) with 95 % confidence interval (95 % CI). A total of 10 studies with 5,146 cases and 6,173 controls were identified. The results showed that SOD2 C47T polymorphism was significantly associated with lung cancer (T versus C: OR = 0.88, 95 % CI = 0.83-0.93, P < 0.001; TT versus CC: OR = 0.74, 95 % CI = 0.66-0.83, P < 0.001; TT versus

A few case-control studies were performed to assess the association between X-ray repair cross-complementing group 3 (XRCC3) rs861539 C/T polymorphism and lung cancer susceptibility, but no consistent finding was reported. In the present study, we performed a meta-analysis of 14 case-control studies with a total of 7,869 lung cancer cases and 10,778 controls to provide a comprehensive assessment of the association between XRCC3 rs861539 C/T polymorphism and lung cancer risk. Pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the strength of the association. Overall, there was no significant association between XRCC3 rs861539 C/T polymorphism and lung cancer risk under all genetic models [OR (95 % CI) for T versus C, 1.00 (0.89-1.13), P = 0.99; OR (95 % CI) for TT versus CC, 1.07 (0.81-1.41), P = 0.62; OR (95 % CI) for TT/CT versus CC, 0.95 (0.84-1.07), P = 0.39; OR (95 % CI) for TT versus CT/CC, 1.10 (0.86-1.39), P = 0.62]. In the subgroup analyses of both Asians and Caucasians, there was still no significant association between XRCC3 rs861539 C/T polymorphism and lung cancer risk under all genetic models (All P values were more than 0.05). However, there was an obvious association between XRCC3 rs861539 C/T polymorphism and decreased risk of lung cancer in the subgroup analysis of the mixed population (All P values were less than 0.05). In addition, there was some risk of publication bias in the meta-analysis, and there was obvious discrepancy in the findings between studies with large sample size and studies with small sample size in the meta-analysis. The meta-analysis indicates that the association between XRCC3 rs861539 C/T polymorphism and lung cancer risk is still uncertain owing to the obvious discrepancy in the findings between studies with large sample size and studies with small sample size. More studies with large sample size are needed to further assess the association.

Ras-association domain family 1A (RASSF1A), a candidate tumor suppressor gene, is frequently silenced and inactivated by hypermethylation of its promoter region in several human tumors. However, the association between RASSF1A promoter methylation and gastric cancer risk remains conflicting. The aim of this study was to assess the association of RASSF1A promoter methylation with gastric cancer risk by a comprehensive meta-analysis. Relevant studies were identified by searches of PubMed and Web of Science databases with no restrictions. Combined odds ratio (OR) and 95 % confidence interval (CI) were used to assess the strength of the association between RASSF1A promoter methylation and gastric cancer risk. A chi-square-based Q test and sensitivity analyses were performed to test the between-study heterogeneity and the contributions of single studies to the final results, respectively. Funnel plots were carried out to evaluate publication bias. Overall, a significant association was observed between RASSF1A promoter methylation and gastric cancer risk (OR, 12.67; 95 % CI, 8.12-19.78; p < 0.001) with no between-study heterogeneity. Subgroup analyses further revealed that gastric cancer risk was increased for individuals carrying the methylated RASSF1A compared with those with unmethylated RASSF1A. In addition, no publication bias was detected in the overall and subgroup analyses. This study identified a strong association between RASSF1A promoter methylation and risk of gastric cancer and highlighted a promising potential for RASSF1A promoter methylation in gastric cancer risk prediction.

Epidemiological studies have evaluated the association between transforming growth factor-β1 (TGF-β1) -509C/T polymorphisms and breast cancer risk. However, the results remain conflicting rather than conclusive. The aim of this study was to comprehensively clarify the association between TGF-β1 -509C/T polymorphisms and breast cancer risk. All relevant studies were searched in the electronic databases. The potential sources of heterogeneity were detected with the chi-square-based Q test. The strength of associations between TGF-β1 -509C/T polymorphisms and breast cancer risk was measured by odds ratio (OR) and 95 % confidence intervals (CI). Publication bias was tested by Begg's test and Egger's test. A total of 10 studies including 10,913 cases and 14,187 controls were included in the meta-analysis. Overall, there was no evidence of significant association of TGF-β1 -509C/T polymorphisms with breast cancer risk (TT vs. CC [OR = 0.97, 95 % CI = 0.83-1.14]; CT vs. CC [OR = 1.05, 95 % CI = 0.90-1.22]; TT + CT vs. CC [OR = 0.99, 95 % CI = 0.91-1.08]; T allele vs. C allele [OR = 0.99, 95 % CI = 0.93-1.06]). Similar results were also found in the subgroup analyses by ethnicity and source of control. When stratified by estrogen receptor (ER) status, TT genotype and T allele were associated with a decreased ER-positive breast cancer risk (OR = 0.66, 95 % CI = 0.49-0.90 and OR = 0.85, 95 % CI = 0.75-0.96, respectively). The present meta-analysis results suggest that TGF-β1 -509C/T variants may not contribute to the risk of breast cancer overall. However, T allele may be a potential protective factor for developing ER-positive breast cancer. Well-designed studies with larger sample size were required to verify our findings further.

The aim of this meta-analysis is to generate large-scale evidence on whether common vascular endothelial growth factor (VEGF) gene polymorphisms (-2578C/A [dbSNP: rs699947] and -460C/T [dbSNP: rs833061]) are associated with lung cancer. A literature search of PubMed, Embase, Web of Science, Cochrane Library, and CBM databases was conducted to identify all eligible studies published before May 3, 2013. Crude odds ratios (ORs) with their corresponding confidence intervals (95% CIs) were used to evaluate the strength of the association. Eleven case-control studies were included with a total of 3,861 lung cancer cases and 3,676 controls in this meta-analysis. For the VEGF -2578C/A polymorphism, the combined results showed that there exist highly significant risk factors for individuals carrying the A allele resulting in lung cancer, and the magnitude of this effect was similar in smoker patients and squamous cell carcinoma (SCC) patients. Unlike the situation with the -2578C/A polymorphism, the VEGF -460C/T polymorphism is not associated with the risk of lung cancer in neither Asians nor Caucasians. However, when stratified according to smoking status and histological types of lung cancer, we found that the T allele (-460C/T) was associated with decreased lung cancer risk among nonsmoker patients and SCC patients. Our findings showed that the -2578C/A polymorphism may increase lung cancer risk, especially in smoker patients and SCC patients, whereas the -460C/T polymorphism may decrease lung cancer risk, especially in nonsmoker patients and SCC patients.

Common functional polymorphisms in the promoter region of microRNAs (miRNAs), based on multiple lines of evidence, might participate in transcriptional regulation and other biological processes, which interact to increase the risk of developing breast cancer. Since 2005, many studies have investigated the association between breast cancer risk and common single nucleotide polymorphisms (SNPs) in miRNAs. However, the findings of several meta-analyses are inconclusive or ambiguous. The aim of this Human Genome Epidemiology meta-analysis was to determine more precisely the relationship between common miRNA polymorphisms and breast cancer risk. Twelve case-control studies with a total of 7,170 breast cancer patients and 8,783 healthy controls were included. Eight SNPs in miRNA genes were examined. When all eligible studies were pooled in the meta-analysis, the miR-196a-2 rs11614913*T, miR-499 rs3746444*T, and miR-605 rs2043556*A alleles predicted a decreased risk of breast cancer among Asians, while not Caucasians. In addition, the miR-27a rs895919*C allele might be a protective factor for breast cancer among Caucasians. However, for the miR-146a rs2910164 (G>C), miR-149 rs2292832 (G>T), miR-373 rs12983273 (C>T), and miR-423 rs6505162 (C>A) polymorphisms, we failed to find any significant association with the risk of breast cancer in any genetic model. In conclusion, the current meta-analysis supports that the miR-196a-2 rs11614913*T, miR-499 rs3746444*T, miR-605 rs2043556*A, and miR-27a rs895919*C alleles might be protective factors for breast cancer.

To data, epidemiological studies have assessed the association between peptidyl-propyl-cis/trans isomerase 1 (PIN1) gene polymorphisms and cancer risk, including breast cancer, hepatocellular carcinoma, lung cancer, esophageal cancer, head and neck squamous cell carcinoma, and laryngeal squamous cell cancer. However, the results of these studies remain controversial. We aimed to examine the associations between two SNPs (rs2233678 and rs2233679) of PIN1 gene and cancer risk by conducting a meta-analysis of case-control studies. A total of seven publications were included in this meta-analysis for both rs2233678 and rs2233679. Overall, rs2233678 polymorphism was found to be associated with decreased cancer risk in four genetic models (C-allele vs. G-allele: odd ratio (OR) = 0.73, 95% confidence interval (CI): 0.60-0.88; CC vs. GG: OR = 0.55, 95% CI: 0.36-0.84; CC+CG vs. GG: OR = 0.72, 95% CI 0.58-0.90; CC vs. CG+GG: OR = 0.58, 95% CI 0.38-0.89). However, the rs2233679 polymorphism of PIN1 gene did not appear to have an influence on caner susceptibility. In the subgroup analysis by cancer type, we observed that the PIN1 rs2233678 polymorphism was significantly associated with decreased breast cancer risk (C-allele vs. G-allele: OR = 0.73, 95% CI: 0.60-0.89; CC+CG vs. GG: OR = 0.71, 95% CI 0.57-0.89). Further subgroup analyses showed that the PIN1 rs2233678 polymorphism was associated with decreased cancer risk among Asian people (C-allele vs. G-allele: OR = 0.63, 95% CI: 0.51-0.79; CC vs. GG: OR = 0.44, 95% CI: 0.25-0.80; CC+CG vs. GG: OR = 0.63, 95% CI 0.50-0.79; CC vs. CG+GG: OR = 0.47, 95% CI 0.26-0.86). In conclusion, PIN1 rs2233678 polymorphism might be a potential biomarker for cancer risk among Asians, especially for breast cancer. Further large and well-designed studies are needed to confirm this conclusion.

Although a number of studies have been conducted on the association between prostate cancer and CAG repeat polymorphisms of the androgen receptor gene, this association remains elusive and controversial. In this meta-analysis, we aimed to evaluate the effects of (CAG)n repeat genetic polymorphisms on the incidence of prostate cancer, particularly as regards race, study design and the number of (CAG)n repeats. To collect articles published on the association between CAG repeats and prostate cancer, publications were identified from the National Center for Biotechnology Information (NCBI) database of epidemiological studies published up to October 2011; our identification of publications was not limited by a language barrier. The following search keywords were used: prostate cancer risk, CAG repeat polymorphism, androgen receptor gene and human. Stata version 10 was used for the meta-analysis and the publication bias was measured through the Begg's test and Egger's test. This meta-analysis included 47 studies with 13,346 cases and 15,172 control or non-cases and consisted of 31 reports based on Caucasians, ten on Asians, one on Hispanics and four on combined ethnic groups. The carriers of a shorter CAG repeat sequence had an increased risk of prostate cancer (OR 1.21, 95% CI 1.10-1.34 for all subjects; OR 1.21, 95% CI 1.10-1.34 for prospective studies; OR 1.32, 95% CI 1.15-1.51 for retrospective studies) regardless of the exact length of the CAG repeat, compared with carriers of a longer repeat sequence. In terms of race, the risk of carrying a shorter CAG repeat sequence was 1.10- and 1.83-fold higher than that of a longer repeat sequence in Caucasians and Asians, respectively. For the specific number of CAG repeat polymorphisms, carriers of <22 repeats were observed to have a higher risk of prostate cancer (OR 1.16, 95% CI 1.04-1.29) compared with carriers with ≥ 22 CAG repeat polymorphisms, particularly for Asians (OR 2.06, 95% CI 1.00-4.24). This meta-analysis suggests that a shorter CAG repeat polymorphism may increase the risk of prostate cancer compared with the longer CAG repeat; in particular, the effect of shorter CAG repeats on the increased risk of prostate cancer was predominantly observed in Caucasians and Asians.