CYP1A1 MspI polymorphism is associated with prostate cancer susceptibility: evidence from a meta-analysis

Cytochrome P450 1A1 (CYP1A1), an important phase I xenobiotic metabolizing enzyme, is responsible for metabolizing numerous carcinogens, particularly polycyclic aromatic hydrocarbons. The genetic polymorphism of CYP1A1 at the site of MspI (CYP1A1 MspI) has been implicated in prostate cancer risk, but the results of individual studies remain conflicting and inconclusive. The aim of this meta-analysis was to investigate the association of CYP1A1 MspI polymorphism with prostate cancer risk more precisely. We performed a comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases from their inception up to September 20, 2012 for relevant publications. The pooled odds ratios with the corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the association of CYP1A1 MspI polymorphism with prostate cancer risk. In addition, stratified analyses by ethnicity and sensitivity analyses were conducted for further estimation. Sixteen eligible publications with 6,411 subjects were finally included into the meta-analysis after checking the retrieved papers. Overall, meta-analysis of total studies suggested that individuals carrying the TC genotype and a combined C genotype (CC + TC) were more susceptible to prostate cancer (OR_{TC vs. TT} = 1.33, 95 % CI 1.10–1.61, P _OR = 0.004; OR_{CC+TC vs. TT} = 1.27, 95 % CI 1.05–1.55, P _OR = 0.016). Stratified analysis of high quality studies also confirmed the significant association (OR_{TC vs. TT} = 1.32, 95 % CI 1.04–1.67, P _OR = 0.024; OR_{CC+TC vs. TT} = 1.30, 95 % CI 1.02–1.66, P _OR = 0.035). In subgroup analyses by ethnicity, a significant association between the CYP1A1 MspI polymorphism and risk of prostate cancer was found among Asians (OR_{TC vs. TT} = 1.44, 95 % CI 1.20–1.72, P _OR < 0.001; OR_{CC+TC vs. TT} = 1.33, 95 % CI 1.12–1.58, P _OR = 0.001), but not in Caucasians or mixed populations. The meta-analysis suggests an important role of the CYP1A1 MspI polymorphism in the risk of developing prostate cancer, especially in Asians.     

Association between the NBS1 Glu185Gln polymorphism and lung cancer risk: a systemic review and meta-analysis

Nijmegen Breakage Syndrome protein 1 (NBS1) is one of the most important DNA repair proteins playing important roles in maintaining the genomic stability of NDA. Previous studies regarding the association between NBS1 8360G>C (Glu185Gln) polymorphism and lung cancer reported conflicting results. To derive a more precise estimation of this association, a systemic review and meta-analysis was performed. We performed a meta-analysis using eligible case–control studies to summarize the data on the association between the NBS1 Glu185Gln polymorphism and lung cancer risk. Odds ratios (ORs) with corresponding 95 % confidence intervals (95 %CIs) were pooled to assess the association between NBS1 Glu185Gln polymorphism and lung cancer risk. Six case–control studies with a total of 2,348 lung cancer cases and 2,401 controls without canner were included into the meta-analysis. Overall, there was an association between NBS1 Glu185Gln polymorphism and lung cancer risk under the dominant comparison model (fixed-effects OR _{GluGln/GlnGln vs. GluGlu}  = 1.21, 95 % CI 1.07–1.37, P = 0.002, I ² = 8.1 %). Subgroup analysis by race suggested a significant association between NBS1 Glu185Gln polymorphism and lung cancer risk in Asians (fixed-effects OR _{GluGlnGlnGln vs. GluGlu}  = 1.22, 95 % CI 1.06–1.41, P = 0.005) but not in Caucasians (fixed-effects OR _{GluGlnGlnGln vs. GluGlu}  = 1.17, 95 % CI 0.91–1.50, P = 0.220). This meta-analysis supports that there is an association between NBS1 Glu185Gln polymorphism and lung cancer risk. More studies are needed to further verify this association.     

Association between CASP3 polymorphisms and overall cancer risk: A meta-analysis of case-control studies

Several studies inspected the relationship between caspase-3 (CASP3) polymorphisms and the risk of several human cancers, but the findings remain controversial. We conducted a meta-analysis aiming to inspect the association between CASP3 rs1049216 T>C, rs12108497 C>T, rs4647603 G>A, rs4647602 C>A, rs6948 T>G, rs2705897 A>C, and rs113420705 G>A polymorphisms and cancer risk. Eligible studies were recognized by searching the Web of Science, PubMed, Scopus, and Google Scholar databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to quantitatively evaluate the association between each polymorphism of CASP3 and cancer risk. The rs4647603 variant significantly increased the risk of cancer in an overdominant (OR, 1.44; 95% CI, 1.03-2.01; P = 0.03; AG vs AA+GG) inheritance model. Regarding the rs4647602 variant, the findings revealed that this variant was associated with protection against cancer in homozygous codominant (OR, 0.67; 95% CI, 0.56-0.80; P < 0.00001; AA vs CC), dominant (OR, 0.84; 95% CI, 0.73-0.96; P = 0.009; AC+AA vs CC), recessive (OR, 0.70; 95% CI, 0.61-0.79; P < 0.00001; AA vs AC+CC), and allele (OR, 0.81; 95% CI, 0.75-0.88; P = 0.00001; A vs C) models. The findings suggested that the rs2705897 variant significantly decreased the risk of cancer in heterozygous codominant (OR, 0.80; 95% CI, 0.67-0.94; P = 0.009; AC vs AA), dominant (OR, 0.81; 95% CI, 0.69-0.95; P = 0.009; AC+CC vs AA), overdominant (OR, 0.80; 95% CI, 0.68-0.95; P = 0.01; AC vs CC+AA), and allele (OR, 0.85; 95% CI, 0.74-0.97; P = 0.02; C vs A) models. The results did not support an association between CASP3 rs1049216 and rs6948 polymorphisms and cancer risk. In summary, the findings of this meta-analysis support an association between CASP3 polymorphisms and cancer risk. Larger and well-designed studies are desired to evaluate these associations in detail.     

The Role of the rs1544410 Polymorphism of Vitamin D Receptor Gene in Breast Cancer Susceptibility

This study was devised to investigate the genetic effect modification of the BsmI polymorphism associated with the susceptibility to breast cancer. Case–control studies of the BsmI polymorphism and breast cancer were searched. A total of 17 eligible publications were included in our final analysis. Pooled ORs and 95 % CIs were obtained by means of fixed effects model. The general and stratified analyses according to ethnicity showed that the association between the BsmI polymorphism and the risk of breast cancer was not statistically significant. However, the subgroup of the hospital-based studies was found to confer protection against the disease (OR_BBvs.bb = 0.83, 95 % CI = 0.71–0.97, P _h = 0.571; OR_BBvs.Bb+bb = 0.86, 95 % CI = 0.74–1.00, P _h = 0.903; OR_{allele B vs. allele b} = 0.92, 95 % CI = 0.86–0.99, P _h = 0.337). Our results suggested that the presence of the BsmI polymorphism may contribute to the susceptibility of breast cancer. It is necessary that future large-scale studies should be conducted to further confirm the association between the BsmI polymorphism and breast cancer risk.     

A meta-analysis of the association of glutathione S-transferase P1 gene polymorphism with the susceptibility of breast cancer

Glutathione S-transferase P1 (GSTP1) is one of the important mutant sites for the cancer risk at present. The conclusions of the published reports on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer are still debated. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of breast cancer. The association reports were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. 35 investigations were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and breast cancer susceptibility, consisting of 40,347 subjects (18,665 patients with breast cancer and 21,682 controls). The association between GSTP1 A/G gene polymorphism and breast cancer risk was not found for overall population, Caucasians and Africans. Interestingly, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer in Asians (G allele: OR = 1.10, 95 % CI: 1.04–1.17, P = 0.001; GG genotype: OR = 1.36, 95 % CI: 1.14–1.62, P = 0.0008; AA genotype: OR = 0.92, 95 % CI: 0.85–0.98, P = 0.02). Furthermore, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer for the analysis of the controls from hospital. In conclusion, GSTP1 A/G gene polymorphism is associated with the breast cancer susceptibility in Asians. However, more studies on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer should be performed in further.     

The genetic polymorphisms of intercellular cell adhesion molecules and breast cancer susceptibility: a meta-analysis

Intercellular cell adhesion molecules (ICAMs) genetic polymorphisms have been considered to be implicated in the development of breast cancer. However, the previous reports are conflicting. Therefore, we performed a meta-analysis to assess the association between three polymorphisms, including ICAM1 K469E, ICAM5 V301I, ICAM5 rs281439, and breast cancer risk. The meta-analyses are based on a literature search of PubMed, CNKI and VIP database up until August 2011. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using review manager 5.0.25 package. In total, five populations (2,020 cases and 2,012 controls) on ICAM1 K469E polymorphism, four populations (1,797 cases and 2,244 controls) on ICAM5 V301I polymorphism and five populations (2,744 cases and 3,006 controls) on ICAM5 rs281439 variant were included. Overall, the meta-analysis showed no significant association between ICAM1 K469E polymorphism and breast cancer risk. However, a significant association was observed for ICAM5 V301I polymorphism (VV vs. II: OR = 1.48, 95 % CI 1.04–2.13, P = 0.03; VV/VI vs. II: OR = 1.25, 95 % CI 1.05–1.48, P = 0.01). In addition, there was a significant association between ICAM5 rs281439 variant and breast cancer risk (GG vs. CC: OR = 1.31, 95 % CI 1.03–1.65, P = 0.03). Our meta-analysis suggests that the ICAM5 V301I and rs281439 variants but not ICAM1 K469E polymorphism may contribute to the susceptibility of breast cancer. Given the limited sample sizes, further investigation is needed.     

Ethnic differences in the association of the glutathione S-transferase T1 (GSTT1) null genotype and risk of gastric carcinoma: a systematic review and meta-analysis

We performed a systematic review and meta-analysis of the association between the glutathione S-transferase T1 (GSTT1) deletion polymorphism and gastric cancer risk in populations from different ethnic backgrounds, based on a comprehensive literature search of the MEDLINE, EMBASE, and COCHRANE libraries. Thirty-six individual case–control studies comprising 7,689 gastric cancer cases and 12,445 controls were included in our meta-analysis. Overall, the GSTT1 null genotype appeared to increase gastric cancer risk (OR 1.17, 95 % CI 1.06–1.31, p = 0.003). While Caucasian populations showed an association between the GSTT1 deletion polymorphism and gastric cancer risk (OR 1.27, 95 % CI 1.05–1.52, p = 0.01), Asian populations did not show such an association (p = 0.11). When stratified by quality assessment scores, a significant association between the GSTT1 deletion polymorphism and gastric cancer risk was observed only in the Caucasian high quality subgroup (OR 1.27 95 % CI 1.01–1.60, p = 0.05). Null genotypes for both GSTT1 and GSTM1 deletion polymorphisms also increased gastric cancer risk (OR 1.37, 95 % CI 1.04–1.80, p = 0.03). Our study suggests that the GSTT1 null genotype is associated with a significant increase in gastric cancer risk in Caucasians, but not in Asians. Further well-designed studies are required to confirm the association between GSTT1 polymorphisms and gastric cancer risk in relation to various clinicopathological factors in different ethnic groups, especially Caucasians.     

Quantitative Assessment of the Association Between HDMX Polymorphism and Sarcoma

To investigate the effects of the HDMX polymorphism on sarcoma risk. Relevant studies were identified by searching the PubMed, Embase, and Web of Science databases. Data were extracted by two independent investigators. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using a fixed-effects model to assess the association between the HDMX polymorphism and sarcoma risk. We also conducted heterogeneity test, sensitivity analysis, and publication bias test. A meta-analysis of four published case–control studies involving 1,115 subjects (379 cases and 736 controls) showed no statistical association between the HDMX polymorphism and sarcoma risk (OR_{TT vs. GG}  0.88, 95 % CI  0.68–1.14, P _{heterogeneity}  0.819; OR_{TT + TG vs. GG} 0.95, 95 % CI  0.79–1.15, P _{heterogeneity}  0.937; OR_{TT vs. TG + GG}  0.82, 95 % CI  0.65–1.04, P _{heterogeneity}  0.589; OR_{T allele vs. G allele}  0.91, 95 % CI  0.79–1.05, P _{heterogeneity}  0.727; OR_{TG vs. GG}  0.95, 95 % CI  0.74–1.22, P _{heterogeneity} = 0.869). This null result did not alter when data were stratified according to ethnicity. Our meta-analysis indicates that the HDMX polymorphism is unlikely to contribute to individual susceptibility to sarcoma.     

Association Between a Single Nucleotide Polymorphism in the TP53 Region and Risk of Ovarian Cancer

TP53 is known as a tumor suppressor gene involved in cell cycle regulation. Many previous epidemiological and clinical studies have evaluated the effects of rs1042522 polymorphism on risk of ovarian cancer. But the results are conflicting and heterogeneous. The primary objective of this study was to examine whether rs1042522 polymorphism is associated with ovarian cancer risk. We performed a comprehensive meta-analysis of 19 case–control studies that analyzed rs1042522 polymorphism in ovarian cancer risk. Odds ratios (ORs) were calculated using distinct genetic models. Heterogeneity between studies was detected by the χ²-based Q test. Additional analyses such as sensitivity analyses and publication bias were also performed. The rs1042522 polymorphism was not overall associated with ovarian cancer risk. But there was a borderline association in the heterozygote model (OR = 1.09, 95 % CI 0.99–1.21). Similar effects were observed in the subgroup of Caucasian population (the heterozygote model: OR = 1.11, 95 % CI 1.00–1.24). No significant heterogeneity and publication bias were revealed in this meta-analysis. This study provides statistical evidence that TP53 rs1042522 polymorphism may play a role in modulating risk of ovarian cancer. This observation requires further analysis of a larger study size.     

TNFAIP3 gene polymorphisms confer risk for Behcet’s disease in a Chinese Han population

The tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) gene polymorphisms have recently been reported to be associated with the susceptibility to several immune-related diseases. This study was performed to evaluate the potential association of TNFAIP3 polymorphisms with Behcet’s disease (BD) in a Chinese Han population. Five single-nucleotide polymorphisms (SNPs), rs10499194, rs610604, rs7753873, rs5029928, and rs9494885 of TNFAIP3 were genotyped in 722 BD patients and 1,415 healthy controls using a PCR-restriction fragment length polymorphism assay. Allele and genotype frequencies were compared between patients and controls using the χ ² test. The results showed a significantly increased prevalence of the rs9494885 TC genotype and C allele in BD patients compared with controls (Bonferroni corrected p (p _c) = 1.83 × 10^?10, odds ratio (OR) [95 % CI] 2.03 [1.65–2.49]; p _c = 8.35 × 10^?10, OR [95 % CI] 1.81 [1.51–2.18], respectively).The frequency of the TT genotype and T allele of rs9494885 was markedly lower in BD patients than that in controls (p _c = 1.23 × 10^?10, OR [95 % CI] 0.50 [0.40–0.61]; p _c = 8.35 × 10^?10, OR [95 % CI] 0.55 [0.46–0.66], respectively). For rs10499194, a higher frequency of the CC genotype (p _c = 0.015, OR [95 % CI] 1.96 [1.30–2.97]) and C allele (p _c = 0.005, OR [95 % CI] 1.92 [1.28–2.90]), and a lower frequency of the TC genotype (p _c = 0.015, OR [95 % CI] 0.51 [0.34–0.77]) and T allele (p _c = 0.005, OR [95 % CI] 0.52 [0.35–2.97]) were found in BD patients. Concerning rs7753873, a higher frequency of the AC genotype (p _c = 0.015, OR [95 % CI] 1.49 [1.17–1.91]) and C allele (p _c = 0.025, OR [95 % CI] 1.39 [1.11–1.76]), and a lower frequency of the AA genotype (p _c = 0.03, OR [95 % CI] 0.68 [0.53–0.87]) and A allele (p _c = 0.025, OR [95 % CI] 0.72 [0.57–0.91]) were observed in BD patients. This study identified one strong risk SNP rs9494885 and two weak risk SNPs rs10499194 and rs7753873 of TNFAIP3 in Chinese Han BD patients.     

Genetic Association of rs1800780 (A→G) Polymorphism of the eNOS Gene with Susceptibility to Essential Hypertension in a Chinese Han Population

To investigate the association of eNOS gene polymorphism with essential hypertension in the Chinese Han population, we examined polymorphisms of the rs2070744 (T→C), rs1800780 (A→G), and rs3918181 (A→G) loci. The results demonstrated that the genotypic frequency at the rs1800780 (A→G) locus was significantly different between patients with essential hypertension and the control cohorts (P < 0.05); while genotypic frequencies and allelic frequencies at rs2070744 (T→C) and rs3918181 (A→G) loci had no statistical difference between the patient group and controls (P > 0.05). In addition, haplotype analysis found a statistically significant difference for haplotype TGA, with OR (95% CI) of 1.549 (1.116–2.150) (P < 0.05). These findings suggest that polymorphism of rs1800780 (A→G) in the eNOS gene may be one of the most important genetic factors associated with essential hypertension susceptibility, and those who have haplotype TGA may be at risk to develop essential hypertension.     

Common genetic variants (rs4779584 and rs10318) at 15q13.3 contributes to colorectal adenoma and colorectal cancer susceptibility: evidence based on 22 studies

Several genome-wide association studies on colorectal cancer (CRC) have reported similar findings of a new susceptibility locus, 15q13.3. After that, a number of studies have reported that the rs4779584 and rs10318 polymorphisms at chromosome 15q13.3 have been implicated in CRC and colorectal adenoma (CRA) risk; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 22 studies involving a total of 48,468 CRC cases, 4,189 CRA cases, and 85,105 controls for the two polymorphisms to evaluate its effect on genetic susceptibility for CRC/CRA. Potential sources of heterogeneity and publication bias were also systematically explored. Overall, the summary odds ratio (OR) of rs4779584-T variant for CRC was 1.13 (95 % CI 1.09–1.16, P < 10^?5) and 1.15 (95 % CI 1.04–1.28, P = 0.006) for CRA. After stratified by ethnicity, significantly increased CRC risks were found for rs4779584 polymorphism among East Asians and Caucasians, while no significant associations were detected among African American and other ethnic populations. A meta-analysis of studies on the rs10318 polymorphism also showed significant overall association with CRC, yielding a per-allele OR of 1.13 (95 % CI 1.02–1.24, P = 0.02). In the subgroup analysis by ethnicity, significantly increased CRC risks were found in Caucasians; whereas no significant associations were found among East Asians and African Americans. This meta-analysis demonstrated that the rs4779584 and rs10318 polymorphism at 15q13.3 is a risk factor associated with increased CRC/CRA susceptibility, but these associations vary in different ethnic populations.     

Effects of polymorphisms in translesion DNA synthesis genes on lung cancer risk and prognosis in Chinese men

PurposeTranslesion DNA synthesis (TLS) plays an important role in promoting replication through DNA lesions. Genetic polymorphisms in TLS genes may have potential roles in lung cancer development in humans.MethodsWe evaluated the association between genetic variants in six TLS genes and the risk and survival of lung cancer in a case–control study in China. Included in the study are 224 lung cancer patients and 448 healthy controls.ResultsCarriers of the G allele of POLκ rs5744724 had significantly reduced risk of lung cancer (odds ratio (OR) = 0.62, 95% confidence interval (CI): 0.44–0.89), comparing with those carrying the C allele, and the AA genotype of PCNA rs25406 was also associated with significantly decreased cancer risk compared with the major homozygote alleles (OR = 0.47, 95% CI: 0.25–0.86). Haplotype analysis showed that subjects with the POLκ C-G (rs5744533–rs5744724) haplotype had decreased risk of lung cancer (OR = 0.69, 95% CI: 0.49–0.98), comparing with those carrying the C-C haplotype. Besides, the heterozygote of REV1 rs3087386 and rs3792136 were independent prognostic factors for lung cancer survival with hazard radio (HR) 1.54 (95% CI: 1.12–2.12) and 1.44 (95% CI: 1.06–1.97) respectively.ConclusionsOur findings suggested that genetic variants in POLκ and PCNA genes may play roles in the susceptibility of lung cancer, and REV1 gene may have roles in lung cancer survival in Chinese men.     

Genetic polymorphisms in the ITPKC gene and cervical squamous cell carcinoma risk

Cervical cancer is caused primarily by infection with oncogenic types of human papillomavirus (HPV). However, HPV infection alone is not sufficient for the progression to cervical cancer. Host immunogenetic factors may involve in the development of this disease. Inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) is recently shown to act as a negative regulator of T-cell activation. We aim to study if polymorphisms in the ITPKC gene are associated with the risk of cervical cancer in Taiwanese women. ITPKC rs28493229 C/G, rs890934 G/T, rs2303723 C/T, and rs10420685 A/G polymorphisms were genotyped in a hospital-based study of 465 women with cervical squamous cell carcinoma (CSCC) and 800 age-matched healthy control women. The presence and genotypes of HPV in CSCC were determined. The frequency of G/G genotype and G allele of the ITPKC rs28493229 polymorphism was significantly higher in patients with CSCC compared with controls (OR = 1.81, 95 % CI 1.20–2.73, P = 0.005, P _c = 0.02; OR = 1.70, 95 % CI 1.14–2.54, P = 0.008, P _c = 0.03, respectively). No significant associations were found for other 3 polymorphisms. Haplotype analysis revealed the distribution of haplotype CGTA was significantly reduced in women with CSCC (OR = 0.59, 95 % CI 0.40–0.89, P = 0.01, P _c = 0.04). In conclusion, we found the G/G genotype and G allele of the ITPKC rs28493229 polymorphism may contribute to the risk of CSCC in Taiwanese women. This finding provides new insights into the mechanisms of immune activation in cervical cancer.     

Novel functional variants locus in PLCE1 and susceptibility to esophageal squamous cell carcinoma: Based on published genome-wide association studies in a central Chinese population

A novel functional single nucleotide polymorphism (SNP) rs2274223 located in the phospholipase C epsilon 1 (PLCE1) gene was found to be associated with the risk of esophageal squamous cell carcinoma (ESCC) by three large-scale genome-wide association studies (GWAS) in Chinese populations. In the present study, we validated this finding and also explored the risk of ESCC associated with other two unreported potentially functional SNPs (rs17417407 G > T and rs2274224 C > G) of PLCE1 in a population-based case–control study to investigate the association between these three potentially functional SNPs in PLCE1 and susceptibility to ESCC. A total of 381 ESCC cases and 420 controls matched by age and sex were recruited and successfully genotyped for three SNPs (rs17417407, rs2274223 and rs2274224) of the PLCE1 in a central Chinese population. SNP rs2274223 was independently associated with increased risk of ESCC (adjusted odds ratio [OR], 2.80; 95% confidence interval [95% CI], 1.45–5.39 for GG vs. AA), and SNP rs2274224 was found to be associated with decreased risk of ESCC (adjusted OR, 0.65; 95% CI, 0.46–0.91 for CG vs. CC). The combined effects of risk alleles for three SNPs (rs17417407T, rs2274223G and rs2274224G) were found to be associated with elevated risk of ESCC in a dose-dependent effect manner (P_trend = 0.005). The G_rs17417407A_rs2274223C_rs2274224 haplotype decreased the risk of ESCC (adjusted OR, 0.76; 95% CI, 0.62–0.93), meanwhile the G_rs17417407G_rs2274223C_rs2274224 and T_rs17417407G_rs2274223C_rs2274224 haplotypes could increase the risk of ESCC (adjusted OR, 1.75; 95% CI, 1.33–2.18 and OR, 2.51; 95% CI, 1.15–2.49). Gene–environment interaction analysis presented a best model consisted of four factors (rs2274223, rs2274224, family history, and smoking) with testing balance accuracy (TBA): 0.66 and cross validation consistency (CVC): 7/10, which could increase the esophageal cancer risk in the “high risk group” with 3.67-fold (OR: 3.67, 95% CI: 2.74–4.92), compared to the “low risk group”. Our results further confirmed that genetic variations in PLCE1 may contribute to ESCC risk associated with tobacco exposure in a central Chinese population. Further functional studies are needed to validate our results.     

Glutathione S-transferases gene polymorphisms and risk of male idiopathic infertility: a systematic review and meta-analysis

The Glutathione S-transferases (GSTs) polymorphisms have been implicated in susceptibility to male idiopathic infertility, but study results are still controversial. To investigate the genetic associations between GSTs polymorphisms and risk of male idiopathic infertility, a systematic review and meta-analysis were performed. Meta-analysis was performed by pooling odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) form studies in electronic databases up to March 16, 2012. Glutathione S-transferase M 1 (GSTM1) null genotype, Glutathione S-transferase T 1 (GSTT1) null genotype, and dual null genotype of GSTM1/GSTT1 were analyzed independently. 14 eligible studies with a total of 1,845 idiopathic infertility males and 1,729 controls were included. There were 13 studies on GSTM1 polymorphism, 10 ones on GSTT1 polymorphism and 5 ones on GSTM1-GSTT1 interaction analysis. Meta-analyses of total relevant studies showed GSTM1 null genotype was significantly associated with an increased risk of male idiopathic infertility (OR = 1.40, 95 % CI 1.07–1.84, P _OR = 0.015). The GSTM1-GSTT1 interaction analysis showed dual null genotype of GSTM1/GSTT1 was also significantly associated with increased risk of male idiopathic infertility (OR = 1.85, 95 % CI 1.07–3.21, P _OR = 0.028). Subgroup analyses by ethnicity showed the associations above were still statistically significant in Caucasians (For GSTM1, OR = 1.51, 95 % CI 1.11–2.05, P _OR = 0.009; For GSTM1/GSTT1, OR = 2.10, 95 % CI 1.51–2.91, P _OR < 0.001). This meta-analysis suggests GSTM1 null genotype contributes to increased risk of male idiopathic infertility in Caucasians, and males with dual null genotype of GSTM1/GSTT1 are particularly susceptible to developing idiopathic infertility.     

The association between common genetic variant of microRNA-499 and cancer susceptibility: a meta-analysis

Published data on the association between microRNA-499 (miR-499) rs3746444 T>C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of this relationship, a comprehensive meta-analysis was performed on nine published studies, with a total sample of 4,794 cases and 5,971 controls. Overall, no significant association was found between miR-499 polymorphism and cancer risk after all studies were pooled into the meta-analysis. However, in the subgroup analysis by ethnicity, significant association with an increased risk was found in Asian (CC vs. TT: OR = 1.439, 95 % CI = 1.118–1.852, P = 0.005, p-heterogeneity = 0.116). Moreover, in the the subgroup analysis by cancer type, this SNP was associated with an increased risk of breast cancer in the recessive model (OR = 1.077, 95 % CI = 1.008–1.151, P = 0.028, p-heterogeneity = 0.125). Our findings support the view that miR-499 rs3746444 T>C polymorphism is associated with breast cancer and the C allele can increase cancer susceptibility in Asian.     

Meta-analysis on the association of nucleotide excision repair gene XPD A751C variant and cancer susceptibility among Indian population

Polymorphism A751C (A>C) in XPD gene has shown susceptibility to many cancers in Indian population; however the results of these studies are inconclusive. Thus, we performed this meta-analysis to estimate the association between XPD A751C polymorphism and overall cancer susceptibility. We quantitavely synthesized all published studies of the association between XPD A751C polymorphism and cancer risk. Pooled odds ratios (ORs) and 95 % CI were estimated for allele contrast, homozygous, heterozygous, dominant and recessive genetic model. A total of thirteen studies including 3,599 controls and 3,087 cancer cases were identified and analyzed. Overall significant results were observed for C allele carrier (C vs. A: p = 0.001; OR 1.372, 95 % CI 1.172–1.605) variant homozygous (CC vs. AA: p = 0.001; OR 1.691, 95 % CI 1.280–2.233) and heterozygous (AC vs. AA: p = 0.001; OR 1.453, 95 % CI 1.215–1.737) genotypes. Similarly dominant (CC+AC vs. AA: p = 0.001; OR 1.512, 95 % CI 1.244–1.839) and recessive (CC vs. AA+AC: p = 0.001; OR 1.429, 95 % CI 1.151–1.774) genetic models also demonstrated risk of developing cancer. This meta-analysis suggested that XPD A751C polymorphism likely contribute to cancer susceptibility in Indian population. Further studies about gene–gene and gene–environment interactions are required.     

ATG16L1 T300A polymorphism and Crohn’s disease susceptibility: evidence from 13,022 cases and 17,532 controls

Many studies have reported the association between the autophagy-related 16-like 1 gene (ATG16L1) T300A polymorphism (rs2241880) and Crohn’s disease (CD) susceptibility, but the results were inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 24 studies including 13,022 cases and 17,532 controls were included in this meta-analysis. Logistic regression analysis indicated that the ATG16L1 T300A polymorphism was associated with CD risk in Caucasians (P < 0.01). The pooled estimations of OR₁ (GG vs. AA) and OR₂ (GA vs. AA) in Caucasian studies by Bayesian meta-analysis method was [1.87, 95% confidence interval (CI) 1.69–2.05] and (1.39, 95% CI 1.27–1.51), respectively. The mode of heritance of the G allele was most likely to be co-dominant in Caucasians. However, no significant association was found in Asians. This meta-analysis suggests that the G allele of ATG16L1 T300A is a low-penetrant gene for developing CD in Caucasians.     

The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and tumor risk: evidence from 134 case–control studies

Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism, which is essential for DNA synthesis and methylation. Genetic variations in the MTHFR gene seem to contribute to a decreased activity of MTHFR, ultimately confer increased susceptibility to cancer. As the most extensively studied polymorphism, MTHFR C677T polymorphism was shown to contribute to cancer susceptibility but the results were inconsistent. The authors performed a meta-analysis including 134 studies (46,207 cases and 69,160 controls) to address the issue. Odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were used to assess the association. Overall, a significant elevated risk of cancer was associated with the MTHFR C677T polymorphism in T-allele versus C-allele comparison (OR = 1.06, 95 % CI 1.02–1.11, P _{heterogeneity}  < 0.001), homozygote model (OR = 1.08, 95 % CI 1.01–1.17, P _{heterogeneity}  < 0.001) and dominant model (OR = 1.05, 95 % CI 1.00–1.10, P _{heterogeneity}  < 0.001). In the stratified analyses, significantly increased cancer risks were indicated among Asians in all genetic models except for heterozygote model. Further analysis revealed that C677T was significantly associated with an increased risk of esophageal and stomach cancer. This meta-analysis supports an association between the MTHFR C677T polymorphism and increased risk of esophageal and stomach cancer, especially among Asians. Additionally, more high-quality studies and that the covariates responsible for heterogeneity should be controlled to obtain a more conclusive response about the function of MTHFR C677T in cancer.