CDH1 promoter polymorphism and stomach cancer susceptibility

The relationship of stomach cancer susceptibility and the presence of E-cadherin (CDH1) promoter −160 C/A polymorphism had been reported with conflicting results. To further explore the association of this polymorphism with stomach cancer susceptibility, we performed an extensive search of relevant studies and carried out a meta-analysis to obtain a more precise estimate. A total of 16 studies including 2,611 cases and 3,788 controls were involved in this meta-analysis. When all studies involved, the meta-analysis results suggest no statistically significant association between CDH1 −160 C/A polymorphism and stomach cancer risk (CA vs. CC: OR = 1.01, 95% CI: 0.85–1.19; AA vs. CC: OR = 1.05, 95% CI: 0.75–1.46; dominant model: OR = 1.02, 95% CI: 0.86–1.20; recessive model: OR = 1.04, 95% CI: 0.76–1.41). When subgroup analyses were performed by ethnicity, the A-allele carriers conferred a decreased stomach cancer risk in Asians (AA vs. CC: OR = 0.67, 95% CI: 0.47–0.96; dominant model: OR = 0.85, 95% CI: 0.72–0.99), but no statistically significant association was found in Caucasians. In conclusion, this meta-analysis suggests that CDH1 −160 A-allele may play a protective role of stomach cancer development in Asians but not in Caucasians.     

Quantitative assessment of the effect of MTHFR polymorphisms on the risk of lung carcinoma

Published studies on the relationships between 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and lung cancer risk have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR C677T and A1298C polymorphisms and lung cancer risk. A total of 15 studies including 10,753 cases and 11,275 controls described C677T genotypes, among which 11 articles totalling 6,161 cases and 7,684 controls described A1298C genotypes, were also involved in this meta-analysis. Overall, no significantly elevated lung cancer risk was found in any genetic models when all studies were pooled. For C677T polymorphism: (TT vs. CC: OR = 1.17, 95% CI = 0.97–1.42; TC vs. CC: OR = 1.06, 95% CI = 0.94–1.20; dominant model: OR = 1.09, 95% CI = 0.96–1.24; and recessive model: OR = 1.08, 95% CI = 0.95–1.24); for A1298C polymorphism: (CC vs. AA: OR = 1.04, 95% CI = 0.91–1.19; AC vs. AA: OR = 0.98, 95% CI = 0.91–1.06; dominant model: OR = 0.99, 95% CI = 0.92–1.06; and recessive model: OR = 1.05, 95% CI = 0.92–1.20). In the subgroup analyses, the results showed that 677T varients could decrease lung cancer risk in female (OR = 0.63, 95% CI = 0.41–0.95, P-value = 0.03, 677CC as reference). No evidence of any associations of MTHFR A1298C polymorphism with lung cancer was found in overall or subgroup analyses. Our meta-analysis supports that the common polymorphisms of C677T and A1298C in MTHFR gene are not susceptibility gene for lung cancer from currently available evidence.     

<Emphasis Type="Italic">Complement factor H</Emphasis> Y402H gene polymorphism and coronary heart disease susceptibility: a meta-analysis

The complement factor H (CFH) Y402H (T1277C) gene polymorphism has been reported to be associated with coronary heart disease (CHD), but results were conflicting. To evaluate the role of the variant in CHD, we performed meta-analyses of all available data. Both electronic and manual searches were performed, all relevant studies were identified. ORs with 95% confidential intervals (CI) under codominant (CC versus TT, TC versus TT), dominant (CC + TC versus TT) and recessive (CC versus TT + TC) models were calculated. Publication bias was addressed. Ten studies including 11 cohorts comprising of 29,764 participants were included. No association between the CFH T1227C polymorphism and CHD could be found. (For overall analysis: dominant model, OR = 1.04, 95%CI: 0.97–1.11; recessive model, OR = 1.04, 95%CI: 0.97–1.11; for Caucasian subgroup: OR = 1.08 95%CI: 0.92–1.27; recessive model, OR = 1.03, 95%CI: 0.96–1.11). Two studies reported positive results in separate population (Caucasian study: recessive model, OR = 0.51, 95%CI: 0.30–0.86; Asians study: dominant model, OR = 2.37, 95%CI: 1.13–4.96). Current evidence do not support the association between the CFH T1277C polymorphism and CHD risk among common population. The association, which could be influenced by CHD onset age, CHD risk factors status and genetics backgrounds, might be significant in some population. More studies on different CHD onset ages and risk factor status should be encouraged.     

Meta-analysis of TYK2 gene polymorphisms association with susceptibility to autoimmune and inflammatory diseases

The aim of our meta-analysis was to quantitatively summarize the association of TYK2 gene polymorphisms with autoimmune and inflammatory diseases. 11 studies that included data from 21497 cases and 22647 controls were identified. OR was used as a measure of the effect of the association in a fixed/random effect model. Meta-analysis was performed for six TYK2 gene polymorphisms (rs34536443, rs2304256, rs280523, rs280519, rs12720270 and rs12720356). Significant association was found in rs34536443 (C versus G: OR = 0.76, 95% CI = 0.69–0.84, P < 0.00001; GC + CC versus GG: OR = 0.78, 95% CI = 0.68–0.90, P = 0.0005; CC versus GG + GC: OR = 0.76, 95% CI = 0.28–2.05, P = 0.58; CC versus GG: OR = 0.74, 95% CI = 0.27–2.02, P = 0.56; GC versus GG: OR = 0.78, 95% CI = 0.68–0.90, P = 0.0006) and rs2304256 (A versus C: OR = 0.78, 95% CI = 0.70–0.87, P < 0.0001; CA + AA versus CC: OR = 0.69, 95% CI = 0.59–0.81, P < 0.0001; AA versus CC + CA: OR = 0.75, 95% CI = 0.66–1.00, P = 0.05; AA versus CC: OR = 0.64, 95% CI = 0.47–0.86, P = 0.003; CA versus CC: OR = 0.70, 95% CI = 0.60–0.83, P < 0.0001) in TYK2 gene, but not for the other polymorphisms (rs280523, rs280519, rs12720270, and rs12720356). This meta-analysis demonstrates that autoimmune and inflammatory diseases is associated with TYK2 gene rs34536443 and rs2304256 polymorphisms, but not rs280523, rs280519, rs12720270 and rs12720356.     

XPA A23G polymorphism and susceptibility to cancer: a meta-analysis

Xeroderma pigmentosum group A (XPA) participates in modulating recognition of DNA damage during the DNA nucleotide excision repair process. The XPA A23G polymorphism has been investigated in case–control studies to evaluate the cancer risk attributed to the variant, but the results were conflicting. To clarify the effect of XPA A23G polymorphism in cancer risk, we conducted a meta-analysis that included 30 published case–control studies. Overall, no significant association of XPA A23G variant with cancer susceptibility was observed for any genetic model. However, significant association was observed for colorectal cancer (GG vs. AA: OR = 1.68, 95% CI = 1.15–2.44; dominant genetic model GG + AG vs. AA: OR = 1.54, 95% CI = 1.08–1.17), for breast cancer an increased but non-significant risk was found (GG vs. AA: OR = 1.27, 95% CI = 0.98–1.66; dominant genetic model GG + AG vs. AA: OR = 1.27, 95% CI = 0.99–1.63), and for head and neck cancer an increased risk was observed in recessive model (OR = 1.19, 95% CI = 1.02–1.38), whereas for lung cancer a significant reduced risk was observed (GG vs. AA: OR = 0.77, 95% CI = 0.66–0.90; dominant genetic model GG + AG vs. AA: OR = 0.76, 95% CI = 0.66–0.87), it’s noting that in Asian population the inverse association was more apparent. In addition, in Asian population for esophageal cancer a significant decreased risk was also found in dominant genetic model (OR = 0.55; 95% CI = 0.43–0.70) and for head and neck cancer an increased risk was observed in dominant genetic model (OR = 1.51, 95% CI = 1.03–2.23). The meta-analysis suggested that the XPA A23G G allele is a low-penetrant risk factor for cancer development.     

Genetic diversity of the apolipoprotein E gene and diabetic nephropathy: a meta-analysis

In the past decade, a number of case–control studies have been carried out to investigate the relationship between the ApoE polymorphism and diabetic nephropathy. However, the results have been inconclusive. To investigate this inconsistency, we performed a meta-analysis of all available studies dealing with the relationship between the ApoE polymorphism and DN. The 23 studies in the meta- analysis included 6,012 diabetic patients with (n = 2,979) and without (n = 3,033) DN. The ApoE ε2 allele was significantly associated with DN (OR = 1.64, 95% CI: 1.26–2.13; P(Z) = 0.00027), whereas the ε4 allele was non-significantly associated with DN (OR = 0.93, 95% CI: 0.78–1.11; P(Z) = 0.418). However, significant heterogeneity was detected. In further subgroup analyses, genotyping methods, outcome of cases and duration of diabetes in controls were found to explain some of the heterogeneity. Genotypic analysis also found a strong association between the ε2 carriers and DN (OR = 1.61, 95% CI: 1.22–2.13; P(Z) = 0.001) and indicated that ε4 tended to have a marginally significant protective effect for DN (OR = 0.82, 95% CI: 0.65–1.03; P(Z) = 0.085). The results of our meta-analysis support a genetic association between the ApoE polymorphism and DN. ε2 increases the risk of DN in diabetes patients, while ε4 trends to be protective. These findings may have implications for therapeutic intervention in diabetic nephropathy.     

Association of thrombospondin 1 gene with schizophrenia in Korean population

Thrombospondin 1 (THBS1), a multi-domain glycoprotein, is secreted from astrocytes and promotes synaptogenesis. Increasing evidence has suggested that not only various markers for synaptic pathology, but also astrocytes are affected in schizophrenia. In this study, we investigated whether coding region single nucleotide polymorphisms (cSNPs) of the THBS1 gene were associated with schizophrenia and with the clinical symptoms of schizophrenia patients. We genotyped two cSNPs [rs2228261 (Asn470Asn) and rs2292305 (Thr523Ala)] using direct sequencing in 220 schizophrenia patients and 376 control subjects. In this study, rs2228261 revealed significant association with schizophrenia in both codominant (TT vs. CC, P = 0.009, OR = 2.10, 95% CI = 1.23–3.59) and recessive models (TT vs. CC/CT, P = 0.0012, OR = 2.28, 95% CI = 1.38–3.77). Also, rs2292305 was associated with schizophrenia in the recessive model (GG vs. AA/AG, P = 0.0052, OR = 2.05, 95% CI = 1.24–3.38). Additionally, in the analysis of the haplotype, the CA and TG haplotypes consisting of rs2228261 and rs2292305 were associated with schizophrenia in the dominant (P = 0.019, OR = 1.79, 95% CI = 1.10–2.90) and recessive models, respectively (P = 0.0086, OR = 0.51, 95% CI = 0.31–0.84). In further analysis according to the clinical symptoms, rs2292305 showed a weak association with the poor concentration symptoms of schizophrenia patients in the dominant model (AG/GG vs. AA, P = 0.024, OR = 2.04, 95% CI = 1.09–3.83). The results suggest that the THBS1 gene may contribute to the susceptibility of schizophrenia.     

Association between ATM polymorphisms and cancer risk: a meta-analysis

To date, epidemiological studies have assessed the association between Ataxia-telangiectasia mutated (ATM) gene polymorphisms and cancer risk, including lung cancer, breast cancer, glioma and pancreatic cancer. However, the results of these studies remain controversial. We aimed to examine the associations between two SNPs (rs664143 and rs664677) and cancer risk by conducting a meta-analysis of case–control studies. A total of 12 publications were included in this meta-analysis, 8 for rs664143 and 7 for rs664677. Overall, rs664143 heterozygote carriers turned out to be associated with cancer risk (OR = 1.18, 95% CI 1.02–1.36). In the subgroup analysis by cancer type, we observed that the ATM rs664143 polymorphism was significantly associated with lung cancer risk (GA vs. GG: OR = 1.48, 95% CI 1.18–1.85, AA vs. GG: OR = 1.51, 95% CI 1.18–1.93) and rs664677 polymorphism was associated with decreased lung cancr risk and increased breast cancer risk (for lung cancer: TC vs. TT: OR = 0.76, 95% CI 0.62–0.92, CC vs. TT: OR = 0.80, 95% CI 0.64–0.99 and for breast cancer: TC vs. TT: OR = 1.42, 95% CI 1.17–1.73, CC vs. TT: OR = 1.51, 95% CI 1.21–1.87). In the subgroup analysis by region, we also observed that individuals with ATM rs664143 GA or AA genotype had an obvious increased cancer risk among Asian people (GA vs. GG: OR = 1.40, 95% CI 1.20–1.63, AA vs. GG: OR = 1.37, 95% CI 1.16–1.62). In conclusion, ATM rs664143 polymorphism was associated with cancer susceptibility. ATM rs664143 polymorphism was significantly associated with lung cancer risk. ATM rs664677 polymorphism was associated with decreased lung cancer risk as well as increased breast cancer risk.     

A meta-analysis of three polymorphisms in the endothelial nitric oxide synthase gene (NOS3) and their effect on the risk of diabetic nephropathy

A number of association studies have investigated the role of the nitric oxide synthase 3 (NOS3) gene in the development of diabetic nephropathy (DN). However, results have been inconclusive, largely because the studies have focused on a variety of different polymorphisms and generate inconsistent results. We performed a meta-analysis of 28 association studies focusing on three polymorphisms in the NOS3 gene (G894T (Glu289Asp), 4b/a, and T-786C) and the risk of DN published before July 2009, covering a total of 10,364 subjects. Although significant heterogeneity was initially found in the analysis of G894T, it did not remain when analysis was done by ethnic subgroups. 894T was negatively associated with DN in Caucasian populations of European origin (OR = 0.896, 0.817–0.983, 95% CI), but was positively associated with DN in East Asian (OR = 2.02, 1.20–3.42, 95% CI) and other populations. Association of the 4b/a variant was observed when studies involving microalbuminuria were excluded (OR = 1.19, 1.02–1.39, 95% CI). The T-786C variant showed an overall weak association (OR = 1.16, 1.01–1.34, 95% CI) with little heterogeneity. In summary, our meta-analysis of the effect of NOS3 gene polymorphisms on the risk of DN supports the involvement of the NOS3 gene in the pathogenesis of DN.     

<Emphasis Type="Italic">TP53</Emphasis> codon 72 polymorphism and colorectal cancer susceptibility: a meta-analysis

Colorectal cancer constitutes a significant proportion of the global burden of cancer morbidity and mortality. A number of studies have been conducted to explore whether TP53 codon 72 polymorphism is associated with colorectal cancer susceptibility. However, controversial results were obtained. In order to derive a more precise estimation of the relationship, we systematically searched Medline, Google scholar, and Ovid database for studies reported before May 2010. A total of 3603 colorectal cancer cases and 5524 controls were included. TP53 codon 72 polymorphism was not associated with colorectal cancer risk in all genetic models (for dominant model: OR = 0.99, 95% CI: 0.86–1.15; for recessive model: OR = 1.00, 95% CI: 0.81–1.23; for Arg/Pro vs. Arg/Arg: OR = 1.00, 95% CI: 0.87–1.15; for Pro/Pro vs. Arg/Arg: OR = 0.97, 95% CI: 0.76–1.25). In the subgroup analyses by ethnic groups and sources of controls, no significant associations were found in all models. Taken together, this meta-analysis suggested that the biologically usefulness of TP53 codon 72 polymorphism as a selection marker in colorectal cancer susceptibility may be very limited.     

CXCL12 G801A polymorphism and breast cancer risk: a meta-analysis

The G801A polymorphism in the CXCL12 gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Five published case–control studies, including 1,058 breast cancer cases and 1,023 controls were identified. No study had a deviation from the Hardy–Weinberg equilibrium (HWE) in controls. We found that the CXCL12 G801A (rs1801157) polymorphism was associated with a significantly increased risk of breast cancer risk when all studies were pooled into the meta-analysis (codomiant model: AA versus GG, OR = 1.64, 95% CI = 1.16–2.33; GA versus GG, OR = 1.42, 95% CI = 1.18–1.71; dominant model: AA/GA versus GG, OR = 1.44, 95% CI = 1.21–1.72). Furthermore, Egger’s test did not show any evidence of publication bias (P > 0.05 for the dominant model). In conclusion, the results suggest that the CXCL12 G801A polymorphism may be a low-penetrant risk factor for developing breast cancer.     

Association of a LSP1 gene rs3817198T>C polymorphism with breast cancer risk: evidence from 33,920 cases and 35,671 controls

Published data on the association between lymphocyte-specific protein 1 (LSP1) rs3817198T>C polymorphism and breast cancer risk are inconclusive. Hence, we conducted a meta-analysis of the LSP1 gene and risk of breast cancer to obtain the most reliable estimate of the association. PubMed, Embase and Web of Science databases were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the strength of the association between the LSP1 rs3817198T>C polymorphism and risk of breast cancer. A total of seven eligible studies including 33,920 cases and 35,671 controls based on the search criteria were involved in this meta-analysis. The distributions of genotypes in the controls were all in agreement with Hardy–Weinberg equilibrium. We observed that the LSP1 rs3817198T>C polymorphism was significantly correlated with breast cancer risk when all studies were pooled into the meta-analysis (the allele contrast model: OR = 1.06, 95% CI = 1.04–1.08; the homozygote codominant: OR = 1.14, 95% CI = 1.01–1.28). In the stratified analysis by ethnicity, significant association was observed in Caucasians for CC versus TT homozygote codominant model (OR = 1.25; 95% CI = 1.03–1.52) and for the recessive model (OR = 1.22; 95% CI = 1.02–1.47). There was significant association observed in Africans for CC versus TT homozygote codominant model (OR = 0.45; 95% CI = 0.22–0.92) and for the recessive model (OR = 0.43; 95% CI=0.22–0.88). Also, significant association was observed in mixed ethnicities for CC versus TT homozygote codominant model (OR = 1.12; 95% CI = 1.05–1.19). When stratified by study design, statistically significantly elevated risk was found in nested case–control studies (CC vs. TT: OR = 1.12, 95% CI = 1.05–1.19). But no significant association was observed for all comparison models between LSP1 rs3817198T>C polymorphism and breast cancer risk in hospital-based and people-based studies. When stratified by BRCA1 mutation carriers status, statistically significantly elevated risk was found in this meta-analysis (the allele contrast model: OR = 1.07, 95% CI = 1.01–1.14; the dominant model: OR = 1.09, 95% CI = 1.00–1.18). And significant association was found in the BRCA2 mutation carriers in the allele contrast (OR = 1.11, 95% CI = 1.03–1.20), the homozygote codominant (OR = 1.23, 95% CI = 1.04–1.47), the heterozygote codominant (OR = 1.12, 95% CI = 1.00–1.25) and the dominant models (OR = 1.14, 95% CI = 1.03–1.27). There was significant association between LSP1 rs3817198T>C polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort in all comparison models (the allele contrast model: OR = 1.08, 95% CI = 1.03–1.13; CC vs. TT: OR = 1.16, 95% CI = 1.05–1.29; TC vs. TT: OR = 1.09, 95% CI = 1.01–1.16; the dominant model: OR = 1.10, 95% CI = 1.03–1.17; the recessive model: OR = 1.12, 95% CI = 1.01–1.23). In conclusion, this meta-analysis suggests that the LSP1 rs3817198T>C polymorphism is a low-penetrant risk factor for developing breast cancer but may not be in Africans.     

Effects of selected genetic polymorphisms in xeroderma pigmentosum complementary group D on gastric cancer

DNA repair capacity (DRC) can be altered based on sequence variations in DNA repair genes, which may result in cancer susceptibility. The current study was to evaluate the association between genetic polymorphisms, including associated haplotypes of xeroderma pigmentosum complementary group D (XPD), and individual susceptibility to gastric cancer. Two-hundred-eight patients with gastric cancer and 339 healthy controls were enrolled in this study. Their genomic DNA was extracted from peripheral blood leukocytes. The genotypes at exon 6, 10 and 23 were identified by polymerase chain reaction (PCR). Unconditional logistic regression model was used to analyze the effects of the polymorphisms, including the corresponding haplotypes, on the susceptibility to develop gastric cancer. The proportion of genotypes GA or AA at exon 10 in cases was showed to be significantly higher than that in controls (P < 0.01, P < 0.01, respectively). The risk of genotype GA or AA carriers to develop gastric cancer was simultaneously much higher (OR = 3.38, 95% CI 2.30–4.95; OR = 6.13, 95% CI 2.45–15.31, respectively). The allele A at exon 10 was also observed to manifest a substantially higher frequency in cases compared to controls (P < 0.01), which might indicate an increased tendency to gastric cancer (OR = 2.40, 95% CI 1.81–3.17). No significant differences were found in the distribution of genotypes at exon 6 or 23 between the two groups (P = 0.23, P = 0.52; P = 0.44, P = 0.56, respectively). By haplotype analysis, haplotype AAA could individually increase incidence of gastric cancer (P < 0.01, OR = 3.39, 95% CI 2.21–5.21). In contrast, haplotypes CGA and AGA were showed a decline in gastric cancer susceptibility (OR = 0.67, 95% CI 0.46–0.97; OR = 0.58, 95% CI 0.41–0.83, respectively). The rest of haplotypes made no statistically significant difference between cases and controls. Taken together, this study demonstrates that the genetic variation at exon 10 and haplotype AAA may be contributing factors in developing gastric cancer.     

Association of p53 codon 72 polymorphism with prostate cancer: a meta-analysis

Relationship of prostate cancer with the polymorphism of p53 codon 72 was reported with inconsistent results. The purpose of this study was to quantitatively evaluate the association between p53 codon 72 polymorphism and prostate cancer susceptibility. We performed an extensive search of relevant studies and made a meta-analysis, including 8 studies with 815 prostate cancer cases and 1047 controls. The combined results showed that there were no significant differences in genotype distribution between prostate cancer cases and control on the basis of all studies, CC/GC versus GG (OR = 1.24, 95% CI: 0.93–1.65), GG/GC versus CC (OR = 0.96, 95% CI: 0.60–1.55), GC versus GG (OR = 1.27, 95% CI: 0.91–1.77), CC versus GG (OR = 1.25, 95% CI:0.74–2.12), GC versus CC (OR = 1.09, 95% CI: 0.63–1.87). When stratifying for the race, there were also no statistically significant differences in genotype distribution between prostate cancer cases and controls. This meta-analysis did not provide an evidence of confirming association between p53 codon 72 polymorphism and prostate cancer.     

MTHFR 677C>T and 1298A>C polymorphisms and male infertility risk: a meta-analysis

Epidemiological studies have evaluated the association between MTHFR 677C>T and 1298A>C polymorphisms and risk of male infertility. However, the results from the published studies on the association between these two MTHFR polymorphisms and male infertility risk are conflicting. To derive a more precise estimation of association between the MTHFR polymorphisms and risk of male infertility, we performed a meta-analysis. A comprehensive search was conducted to identify all case–control studies of MTHFR polymorphisms and male infertility risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that both 677C>T and 1298A>C polymorphisms were not significantly associated with male infertility risk. However, in stratified analysis by ethnicity, we found that the 677C>T polymorphism was significantly associated with the risk of male infertility in Asian population (TT vs. CC: OR = 1.57, 95% CI: 1.05–2.37, P = 0.03; TT vs. TC + CC: OR = 1.40, 95% CI: 1.05–1.86, P = 0.02; TT + TC vs. CC: OR = 1.34, 95% CI: 1.01–1.77, P = 0.04). Although some modest bias could not be eliminated, this meta-analysis suggested that the MTHFR 677T allele might be a low-penetrant risk factor for male infertility, especially in Asian population.     

<Emphasis Type="Italic">FAS</Emphasis> −1,377 G/A polymorphism is associated with cancer susceptibility: evidence from 10,564 cases and 12,075 controls

Published data on the association between FAS −1,377 G/A polymorphism and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 17 studies including 10,564 cases and 12,075 controls were involved in this meta-analysis. Overall, significantly elevated cancer risk was associated with AA variant genotype when all the eligible studies were pooled into the meta-analysis (for AA vs GG: OR = 1.19; 95% CI = 1.01–1.40; P _{heterogeneity} = 0.05; for recessive model: OR = 1.21; 95% CI = 1.04–1.41; P _{heterogeneity} = 0.05). In the subgroup analysis by ethnicity, borderline statistically significantly increased risks were found among Asians for recessive model (OR = 1.20; 95% CI = 1.00–1.45; P _{heterogeneity} = 0.01). In the subgroup analysis by population-based controls or hospital-based controls, statistically significantly increased risks were found among groups with population-based controls for AA versus GG (OR = 1.27; 95% CI = 1.02–1.58; P _{heterogeneity} = 0.05) and recessive model (OR = 1.25; 95% CI = 1.00–1.59; P _{heterogeneity} = 0.01). For breast cancer, borderline statistically significantly increased risks were found for AA versus GG (OR = 1.29; 95% CI = 1.00–1.67; P _{heterogeneity} = 0.41). In summary, this meta-analysis suggests that the FAS −1,377 G/A polymorphism is associated with cancer susceptibility. L. X. Qiu, J. Shi and H. Yuan contributed equally to this work and should be considered as co-first authors.     

Association between TNF-α polymorphisms and cervical cancer risk: a meta-analysis

Tumor necrosis factor alpha (TNF-α) is a vital cytokine involved in inflammation, immunity, and cellular organization. The TNFA-308G/A (rs1800629) and -238G/A (rs361525) polymorphisms are two widely investigated variants for their associations with risk of cervical cancer, but the results are conflicting. Here, we performed a meta-analysis to pool the data and evaluate the between-studies heterogeneity. All the case–control studies published from January 1989 to October 2010 on the association between the two polymorphisms of TNFA and cervical cancer risk were identified by searching the electronic literature Medline. The cervical cancer risk associated with the two polymorphisms of TNFA gene was estimated for each study by OR together with its 95% CI, respectively, by using the Review Manager 4.2 software. It was showed that the variant homozygote -308AA was associated with a significantly increased risk of cervical cancer (AA vs. GG: OR = 1.41, 95% CI = 1.03–1.92, P = 0.033; AA vs. GA/GG: OR = 1.39, 95% CI = 1.02–1.90, P = 0.036), and the effect was more evident among Asians (AA vs. GA/GG: OR = 3.67, 95% CI = 1.25–10.81, P = 0.018). We also found that the variant genotypes -238GA/AA was associated with a significantly decreased risk of cervical cancer (GA/AA vs. GG: OR = 0.55, 95% CI = 0.41–0.74, P < 0.001). The results suggested that TNFA-308G/A and -238G/A may contribute to cervical cancer susceptibility.     

Association between paraoxonase-1 gene polymorphisms and risk of metabolic syndrome

Paraoxonase-1 (PON1), a high-density lipoprotein (HDL) associated enzyme, is involved in the metabolism and detoxification of insecticides and pesticides. Three polymorphisms within the PON1 gene affect the enzyme activity. Two of these (L55M and Q192R) are located at the coding region and the third (–107C/T) is in promoter region. We performed a case–control study in order to elucidate the possible contribution of variability within PON1 at three mentioned positions to the risk of MS in a South-East Iranian population. DNA was isolated from peripheral blood of patients (N = 119) with MS and healthy controls (N = 201). Allelic polymorphisms at positions Q192R, L55M and –107C/T in the PON1 gene were studied by Amplification Refractory Mutation System (ARMS)-PCR. It was observed that genotypes RR and QR + RR of Q192R locus significantly increased the risk of MS (OR = 2; 95% CI: 1.17–3.40, P = 0.0001 and OR = 1.62; 95% CI: 1.0–2.63; P = 0.05, respectively). The risk in patients with MM and LM + MM genotypes at the L55M locus was marginal (OR = 1.33; 95% CI: 0.68–1.85; P = 0.34 and OR = 1.12; 95% CI: 0.68–1.85; P = 0.73 respectively). The CC genotype at –107C/T locus also increased the risk of metabolic syndrome, but was not significant. This association was somewhat stronger when combined genotypes at Q192R and L55M loci were analyzed (OR = 3.30; 95% CI: 1.34–8.24; P = 0.007). Our results, in this first study, provide evidence for association of PON1 gene polymorphisms with the risk for metabolic syndrome.     

A genetic variant in microRNA-196a2 is associated with increased cancer risk: a meta-analysis

MicroRNAs (miRNAs) are small non-coding RNA molecules that function as negative regulators of gene expression. Common genetic variants (single nucleotide polymorphisms, SNPs) in miRNA genes may alter their expression or maturation resulting in varied functional consequences. Until now, several studies had evaluated the association between the polymorphisms in the hsa-miR-196a2 rs11614913 and cancer risk in diverse populations and in multiple types of cancer, with contradictory outcomes. Therefore, here we performed a meta-analysis to address the association between this polymorphism and cancer risk. A total of nine studies involving 6,540 cases and 7,562 controls were retrieved based on PubMed. Our analysis demonstrated that hsa-miR-196a2 rs11614913 CC genotype significantly increased the cancer risk in homozygote comparison model compared to TT genotype (OR = 1.18; 95% CI, 1.01–1.68). Moreover, significant association of this polymorphism with breast cancer was found based on homozygote comparison model (OR = 1.30; 95% CI, 1.01–1.26) and dominant model (OR = 1.11; 95% CI, 1.01–1.23). In addition, hsa-miR-196a2 rs11614913 CC genotype was significantly associated with cancer risk in Chinese and Indian (OR = 1.21; 95% CI, 1.05–1.40), but not in Caucasians (OR = 1.03; 95% CI, 0.89–1.19). Taken together, our results indicate that the polymorphism of hsa-miR-196a2 rs11614913 is associated with cancer susceptibility, especially with breast cancer and in Chinese and Indian populations.     

Association of IL-10-1082 promoter polymorphism with susceptibility to gastric cancer: evidence from 22 case–control studies

Evidence suggested that interleukin-10 (IL-10) may be involved in the etiology of gastric cancer (GC). However, epidemiological studies on the association between IL-10-1082 promoter polymorphism and GC risk are still ambiguous. To quantitatively summarize the evidence for such a relationship, we performed a meta-analysis. Systemic searches of the PubMed and Medline databases were performed, with the last report up to July 2011. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. 22 independent studies including 4,289 cases and 5,965 controls were involved in this meta-analysis. Obvious association was found when all studies were pooled into the meta-analysis (A vs. G: OR = 0.489, 95% CI = 0.335–0.713, P < 0.001). In the subgroup analysis by ethnicity, we observed significant associations in Asians (A vs. G: OR = 0.651, 95% CI = 0.506–0.838, P = 0.001; AA vs. GG: OR = 0.482, 95% CI = 0.328–0.709, P < 0.001; AA/AG vs. GG: OR = 0.711, 95% CI = 0.527–0.959, P = 0.025; AA vs. AG/GG: OR = 0.701, 95% CI = 0.520–0.944, P = 0.019) and Caucasians (A vs. G: OR = 0.365, 95% CI = 0.140–0.949, P = 0.039), but not in Latino population. When stratified analysis by control sources, our results indicated that A allele decreased approximately 48% risk among population-based studies (A vs. G: OR = 0.524, 95% CI = 0.374–0.733, P < 0.001). Taken together, this meta-analysis suggests that IL-10-1082 polymorphism is associated with GC risk.