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Several studies have focused on the correlation between the programmed death-1 (PD-1) rs2227981 C > T polymorphism and the risk of cancer; however, the results of such studies remain conflicting. To address this gap, we performed this meta-analysis to identify the potential association. Search strategies were performed in PubMed and EMBASE using appropriate terms. In total, 2,977 cancer cases and 2,642 controls from seven publications were recruited in our study. According to the seven eligible publications, the odds ratios (ORs) and 95% confidence intervals (CIs) on the risk of cancer for the TT vs. CC and TT vs. CT+CC genotypes were 0.67 and 0.50-0.91 and 0.65 and 0.47-0.90, respectively. In a subgroup analysis by cancer type, PD-1 rs2227981 C > T polymorphism was associated with a significantly decreased risk of breast cancer (OR, 0.82; 95% CI, 0.71-0.95; P = 0.009 for T vs. C and OR, 0.76; 95% CI, 0.63-0.92; P = 0.005 for TT+CT vs. CC) and of other cancer (OR, 0.58; 95% CI, 0.36-0.92; P = 0.004 for TT vs. CT+CC). In a subgroup analysis by ethnicity, a significant decreased cancer risk was identified among Asians (OR, 0.74; 95% CI, 0.63-0.86; P < 0.001 for T vs. C and OR, 0.71; 95% CI, 0.59-0.87; P = 0.001 for TT+CT vs. CC) and among Caucasians (OR, 0.66; 95% CI, 0.44-0.99; P = 0.047 for TT vs. CT+CC). These findings highlight the fact that the T allele of PD-1 rs2227981 C > T polymorphism modestly decreases the susceptibility of cancer. Nevertheless, further large and well-designed studies are needed to enrich the evidence of this association.

The correlation between insulin receptor substrate-1 (IRS-1) rs1801278G>A polymorphism and polycystic ovary syndrome (PCOS) has been widely studied. However, the results of these studies are conflicting. The current study provides an assessment of the association between the genetic susceptibilities of IRS-1 rs1801278G>A polymorphism and PCOS. A comprehensive meta-analysis was carried out in over 4,555 subjects included in twenty publications which were published up to June 26, 2015. Our findings suggested that the IRS-1 rs1801278G>A genotype was correlated with the susceptibility of PCOS in the allele comparison, heterozygote comparison and the dominant genetic model. In the dominant genetic model, variant A allele carriers (AA+GA) of IRS-1 rs1801278G>A polymorphism increased the susceptibility of PCOS comparing to the homozygote GG [odds ratio (OR)=1.82, 95% confidence interval (CI) 1.30-2.53 for AA+GA vs. GG]. The analysis by different ethnicity groups highlighted that Caucasian population (OR=1.96, 95% CI 1.26-3.04 for AA+GA vs. GG) had significant increased PCOS susceptibility. Bias diagnosis indicated there are slight publication biases in some genetic models, suggesting that these findings should be interpreted with very caution. In summary, our findings suggested that IRS-1 rs1801278G>A polymorphism may be a risk factor for PCOS.

The aim of this study was to evaluate the association between CTLA-4 +49 G>A polymorphism and esophageal cancer (EC) susceptibility in a hospital based case-control study and a subsequent meta-analysis. We implemented genotyping analyses for CTLA-4 +49 G>A polymorphism with 629 esophageal squamous cell carcinoma cases and 686 controls in a Chinese Han population. Polymerase chain reaction ligase detection reaction (PCR-LDR) method was used to identify genotypes of CTLA-4 +49 G>A polymorphism. We first assessed the association between CTLA-4 +49 G>A polymorphism and EC risk in a hospital based case-control study, and then performed a comprehensive meta-analysis to derive a more precise estimation. Our results demonstrated that CTLA-4 +49 G>A polymorphism was not associated with EC risk. This case-control study and further meta-analysis, failed to identify the association between CTLA-4 +49 G>A polymorphism and EC risk. And additional, further well designed studies with large sample sizes and detailed gene-environment data are required.

Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms are associated with many types of cancers. The purpose of our study was to evaluate the effect of MTHFR single nucleotide polymorphisms (SNPs) on gastric cardia adenocarcinoma (GCA). We conducted a hospital-based case-control study. Three hundred and thirty cases with GCA and 608 controls were recruited. The ligation detection reaction (LDR) method was used to determine genotypes. The genotype MTHFR rs1801133 TT was significantly more frequent in cases than in controls (adjusted odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.04-2.05, P = 0.029) in a recessive model, after adjusting for age, sex and smoking and alcohol use. The haplotype MTHFR Grs4845882Ars4846048Trs1801133Crs9651118Ars3753584 was more frequent in cases than in controls (crude OR = 5.32, 95% CI = 2.34-12.10, P < 0.001). No association between other genotypes and haplotypes was observed. Our results suggest that the genotype MTHFR rs1801133 TT and the MTHFR Grs4845882Ars4846048Trs1801133Crs9651118Ars3753584 haplotype may be associated with susceptibility to GCA. Further studies are needed to confirm these findings.

The possible association between CD28 IVS3 +17T>C (rs3116496) polymorphism and cancer susceptibility has been widely investigated. However, the results are conflicting. To verify the association more precisely, we performed a meta-analysis of 11 publications involving a total of 8,843 subjects. In this meta-analysis, 11 publications were included by searching PubMed and EMBASE databases up to May 23, 2014. The cancer susceptibility associated with the CD28 IVS3 +17T>C polymorphism was evaluated by odds ratios (ORs) with 95% confidence intervals (95% CIs). Heterogeneity, sensitivity and publication bias analyses were also assessed. The result suggested that the CD28 IVS3 +17T>C polymorphism is not associated with cancer susceptibility in overall cancer. In a stratified analysis by ethnicity, the association of CD28 IVS3 +17T>C polymorphism with cancer susceptibility was significant in Asians. In a stratified analysis by the origin of cancer cells and system of cancer, CD28 IVS3 +17T>C polymorphism was not associated with cancer susceptibility. In summary, this meta-analysis demonstrated that the CD28 IVS3 +17T>C polymorphism may be a cancer susceptibility factor in Asians.

Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. It is very aggressive with a poor prognosis. Besides environmental risk factors, genetic factors might contribute to the esophageal cancer carcinogenesis. To evaluate the association between the risk of esophageal squamous cell carcinoma (ESCC) and genetic variants in IGFBP3, we conducted a hospital-based case-control study to assess the genetic effects of these SNPs. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The genotypes were determined using a matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The IGFBP3 single nucleotide polymorphisms (SNPs) rs2270628 C>T, rs10282088 C>A, and rs3110697 G>A were associated with a significantly decreased risk of ESCC. However, our results were obtained with a limited sample size. To confirm the current findings, larger studies with other ethnic populations are required.

Objectives: The correlation between intercellular adhesion molecule 1 (ICAM-1) common polymorphisms (rs5498 A>G and rs3093030 C>T) and cancer susceptibility has been explored in various ethnic groups and different cancer types; however, these investigations have yielded contradictory results. To address the relationship more precisely, we performed this meta-analysis., Design and Methods: EmBase, PubMed and China National Knowledge Infrastructure (CNKI) databases were searched by two authors independently for eligible publications before April 8, 2015. Random-effects or fixed-effects model was harnessed to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) when appropriate., Results: The result suggested that the ICAM-1 rs5498 A>G polymorphism is not associated with cancer susceptibility in overall cancer. In a stratified analysis by ethnicity, a significant increased cancer risk was identified among Asians, but the inverse association was found among Caucasians. In a stratified analysis by cancer type, ICAM-1 rs5498 A>G polymorphism was associated with a significantly increased risk of oral cancer, but with protection from colorectal cancer and melanoma. ICAM-1 rs3093030 C>T polymorphism is not correlated with cancer susceptibility., Conclusions: In summary, this meta-analysis highlights that the ICAM-1 rs5498 A>G polymorphism probably contributes to decreased susceptibility to cancer, especially in Caucasians, in melanoma and colorectal cancer subgroup, but it may be a risk factor for oral cancer and Asians.

Background: Peroxisome proliferator-activated receptor gamma (PPARG), a nuclear hormone receptor, plays a critical role in the lipid and glucose homeostasis, adipocyte differentiation, as well as intracellular insulin-signaling events. Several studies have been conducted to explore the associations of PPARG polymorphisms with breast cancer (BC), yet the findings are inconsistent., Methods: Databases of Pubmed and Embase were searched until October 5, 2014. The association between PPARG polymorphisms and BC risk was determined by crude odds ratios (ORs) with their 95% confidence intervals (CIs)., Results: Finally, there are nine publications involving 3,931 BC cases and 5,382 controls included in this meta-analysis. No significant association was observed between PPARG rs1801282 C>G variants and overall BC risk in all genetic comparison models. However, in a subgroup analysis by ethnicity, significant association was observed between PPARG rs1801282 C>G variants and decreased BC risk in three genetic models: GG+CG vs. CC (OR, 0.83; 95% CI, 0.71-0.96; P = 0.011), CG vs. CC (OR, 0.82; 95% CI, 0.71-0.96; P = 0.011) and G vs. C (OR, 0.85; 95% CI, 0.75-0.97; P = 0.016) in Caucasians and in a subgroup analysis by menopausal status, significantly decreased BC risk was also found in two genetic models: GG+CG vs. CC (OR, 0.79; 95% CI, 0.67-0.95; P = 0.011) and CG vs. CC (OR, 0.77; 95% CI, 0.64-0.92; P = 0.005) in post-menopause subgroup. For PPARG rs3856806 C>T, we found no significant association between PPARG rs3856806 C>T polymorphism and breast cancer., Conclusions: In summary, despite some limitations, the results suggest that PPARG rs1801282 C>G polymorphism may be a protective factor for BC in Caucasians and in post-menopause women.

Studies examining the association between the cyclin D1 (CCND1) A870G (rs9344 G>A) polymorphism and esophageal squamous cell carcinoma (ESCC) have yielded inconsistent results. Here, we conducted a hospital-based case-control study in a Chinese Han population to assess the association between the CCND1 A870G polymorphism and ESCC. We then performed a meta-analysis to further investigate this association. We recruited 629 patients with ESCC and 686 cancer-free controls. Genotyping was performed with the polymerase chain reaction-ligase detection reactions (PCR-LDR) method. The meta-analysis was performed with the STATA 12.0 software. The case-control study showed no significant difference between the ESCC cases and controls in the allele frequencies or genotype distributions of the CCND1 A870G polymorphism. To obtain a more precise estimate of this relationship, we performed a meta-analysis of seven case-control studies involving a total of 2080 ESCC cases and 2833 controls. The meta-analysis suggested that the CCND1 A870G polymorphism is not associated with a risk of ESCC. A further subgroup analysis based on ethnicity also detected no association. This study suggests that the CCND1 A870G polymorphism is not associated with the risk of ESCC.

Polymorphisms in gene encoding programmed death-1 (PD-1) were suggested to be associated with the risk of multiple cancers. To the best of our knowledge, no investigation has been carried out for gastric cardia adenocarcinoma (GCA) and PD-1 polymorphisms. Thus, we studied PD-1 rs10204525 A>G, rs7421861 T>C and rs2227982 C>T single nucleotide polymorphisms (SNPs) in 330 GCA cases and 608 cancer-free controls. Genotypes of PD-1 SNPs were determined by ligation detection reaction (LDR) assays. The distributions of the allele and genotype were not statistically significant in two groups for the three PD-1 SNPs. However, in stratified analyses by various characteristics (eg., age, sex, smoking condition and alcohol consumption status), we found a significantly increased risk of GCA associated with the PD-1 rs2227982 C>T polymorphism was evident among ever drinking cases (TT vs. CC: adjusted OR = 2.53, 95% CI = 1.11-5.79, P = 0.028; TT+CT vs. CC: adjusted OR = 2.04, 95% CI = 1.01-4.13, P = 0.047). For the other SNPs, in stratified analyses, no correlation between the SNPs and susceptibility of GCA was observed. In conclusion, our results highlight that rs2227982 C>T polymorphism in PD-1 gene may contribute to the risk of GCA.