Association of TGF-β1 − 509 C/T, 29 C/T and 788 C/T gene polymorphisms with chronic periodontitis: A case–control study

The aim of this study was to investigate the possible association between TGF-β1 − 509 C/T (rs1800469), 29 C/T (Prol10Leu, rs1800470) and 788 C/T (Thr263Ile, rs1800472) gene polymorphisms and chronic periodontitis (CP) in a sample of Iranian population. This case–control study was conducted on 100 CP patients and 100 healthy unrelated, age-, sex-, and ethnicity-matched. Genotyping was performed by tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) technique. Our findings showed that there was a significant difference between the groups regarding TGF-β1 29 C/T (rs1800470) polymorphism (χ2 = 23.23, P < 0.0001). The CT and TT genotypes increased the risk of CP in comparison with the CC genotype (OR = 4.42, 95% CI = 2.16–9.06, P < 0.001 and OR = 5.84, 95% CI = 2.32–14.71, P < 0.001, respectively). The T allele increased the risk of CP (OR = 2.50, 95% CI = 1.66–3.74, P < 0.001) in comparison with C allele. No significant association was found among the groups regarding − 509 C/T and 788 C/T variants of TGF-β1 gene. This study shows that TGF-β1 29 C/T polymorphism, but not − 509 C/T and 788 C/T polymorphisms, may contribute to the development of CP in a sample of Iranian population. Further studies with larger sample sizes and different ethnicities are needed to validate our findings.     

Association of adiponectin (AdipoQ) and sulphonylurea receptor (ABCC8) gene polymorphisms with Type 2 Diabetes in North Indian population of Punjab

In Type 2 Diabetes (T2D), adiponectin (AdipoQ) and sulphonylurea receptor genes (ABCC8) are important targets for candidate gene association studies. The single nucleotide polymorphisms (SNPs) in these genes have been associated with features of the metabolic syndrome across various populations. The present case–control study undertaken in the population of Punjab, evaluates the association of + 45T>G polymorphism in AdipoQ gene; and Exon16-3C>T as well as Exon18C>T polymorphisms in ABCC8 gene with T2D. These SNPs were genotyped in 200 T2D cases and 200 non-diabetic healthy controls using the PCR-RFLP method. The frequency of the minor G-allele for AdipoQ+ 45(T>G) polymorphism was significantly higher in T2D cases (29.0%) than in controls (21.5%) [P = 0.02, OR = 1.49 (1.07–2.04)]. The genetic model analysis revealed that the G-allele cumulatively provides nearly 1.59–1.78 fold increased risk to T2D under the additive (P = 0.009; OR = 1.59, 1.12–2.25 at 95% CI), dominant (TG/GG vs. TT) (P = 0.034, OR = 1.64, 1.04–2.56 at 95% CI) and codominant model (TG vs. TT/GG) (P = 0.014; OR = 1.78, 1.12–2.82 at 95% CI) after adjusting for confounding factors. However, no difference in the distribution of genotype and allele frequencies was observed for both the ABCC8 polymorphisms. The distribution of obesity profiles (BMI, WC and WHR) was also significantly different between cases and controls (P < 0.05). Higher BMI and central obesity were observed to increase the risk of T2D. G-allele of + 45(T>G) polymorphism in the adiponectin gene appears to be associated with increased risk of T2D, but the polymorphisms in sulphonylurea receptor gene do not seem to be associated with T2D in the population of Punjab.     

Further evidence for the contribution of the vascular endothelial growth factor gene in coronary artery disease susceptibility

Coronary artery disease (CAD) receives intensive attentions in the research of cardiovascular diseases, due to its high incidence and severe impact on the quality of life vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, has been strongly implicated in the pathogenesis of CAD. Genetic markers in different regions of the VEGF gene have a plausible role in modulating the risk of CAD. To identify the markers contributing to the genetic susceptibility to CAD, we examined the potential association between CAD and 10 single nucleotide polymorphisms (SNPs, rs699947, rs1570360, rs2010963, rs833068, rs3024997, rs3025000, rs3025010, rs3025020, rs3025030, rs3025039) of the VEGF gene using the MassARRAY system. Participants included 242 CAD patients and 253 healthy controls from a Chinese Han Population (He'nan Province, China). The allelic or genotypic frequencies of the rs699947 (5′ untranslated regions, 5′UTR) and rs2010963 (5′UTR) polymorphisms in the CAD patients were significantly different from those in the healthy controls. The CAD patients had significantly higher frequency of the rs699947 A allele (χ² = 11.141, P = 0.001, OR = 1.665, 95% CI = 1.232–2.250) and rs2010963 C allele (χ² = 13.593, P = 0.0002, OR = 1.611, 95% CI = 1.249–2.077). Strong linkage disequilibrium was observed in the rs699947–rs1570360–rs2010963 haplotype block (D’ > 0.9). Significantly more C–G–C haplotypes (P = 0.040) and significantly fewer C–G–G haplotypes (P = 0.0004) were found in the CAD patients. The possible association of rs699947 and rs2010963 with CAD risks warrant confirmation in independent case–control studies and may be informative for future investigations on the pathogenesis of CAD.     

Effects of polymorphisms in nucleotide excision repair genes on glioma risk in a Chinese population

We performed a case-control study to assess the relationship between six single nucleotide polymorphisms (SNPs) of xeroderma pigmentosum complementation group F (XPF) on glioma risk in a Chinese population. The six SNPs were genotyped in 330 glioma cases and 652 cancer-free controls using a 384-well plate format on the Sequenom MassARRAY platform (Sequenom, San Diego, USA). Rs1800067 did not follow the Hardy–Weinberg equilibrium in the control group, and the genotype distributions differed significantly between the two groups for SNPs rs1800067 and rs2276466. For rs1800067, the variant genotype T/T was strongly associated with an increased risk of glioma when compared with the A/A genotype (OR = 3.77, 95% CI = 2.38–6.01). Individuals with the rs1800067 G allele had a relatively high risk of glioma in a dominant model (OR = 3.47, 95% CI = 2.26–5.37). The rs2276466 G/G genotype was significantly associated with a moderate increased risk of glioma (OR = 1.82, 95% CI = 1.10–3.02) in a codominant model, and variation of rs25489 was associated with a 1.31- and 1.78-fold glioma risk in dominant and recessive models, respectively. Our study is the first to identify polymorphisms in rs1800067 and rs2276466 as correlated with glioma susceptibility.     

Relationship between CCR2-V64I polymorphism and cancer risk: A meta-analysis

Background and objectives

The role of CCR2-V64I polymorphism in various cancers has been reported in many studies. However, results from published studies on the association between CCR2-V64I polymorphism and cancer risk are conflicting. Therefore, we performed a meta-analysis to estimate the overall cancer risk associated with the polymorphism.

Methods

Electronic searches of PubMed and EMBASE were conducted for all publications on the association between this variant and cancer. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association.

Results

Sixteen studies with 2661 cancer patients and 5801 healthy controls were included. Overall, significant association was found between the CCR2-V64I polymorphism and cancer risk (OR = 1.84, 95% CI = 1.35–2.51, AA vs GA/GG, P = 0.37). In the subgroup analysis stratified by cancer types, there was a significant association between this polymorphism and bladder cancer (OR = 2.06, 95% CI = 1.02–4.15, AA vs GA/GG, P = 0.11), cervical cancer (OR = 3.34, 95% CI = 1.48–7.50, AA vs GG, P = 0.56), and oral cancer (OR = 2.04, 95% CI = 1.46–2.84, GA vs GG, P = 0.70). In the subgroup analysis stratified by ethnicities, an increased cancer risk was also found in Europeans (OR = 2.31, 95% CI = 1.45–3.68, AA vs GA/GG, P = 0.16) and Asians (OR = 1.88, 95% CI = 1.12–3.16, AA vs GA/GG, P = 0.92).

Conclusion

This meta-analysis suggested that CCR2-V64I polymorphism may contribute to an increased risk of cancer.     

The effect of XPD/ERCC2 Lys751Gln polymorphism on acute leukemia risk: A systematic review and meta-analysis

Aims

Epidemiological studies have assessed the association between xeroderma pigmentosum group D (XPD) Lys751Gln and acute leukemia risk with conflicting results. We performed this meta-analysis to derive a more precise estimation of the relationship. Pooled odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the strength of the association.

Results

Ten published case–control studies including a total of 1494 cases and 2259 controls were identified. Overall, significant risk effects of Lys751Gln genotype was found under the dominant model (OR = 1.16; 95% CI = 1.01–1.34; P = 0.032). When stratified by clinical types, the variant genotype was associated with the acute myeloid leukemia (AML) risk under the heterozygote comparison (OR = 1.20; 95% CI = 1.00–1.43; P = 0.048), the homozygote comparison (OR = 1.35; 95% CI = 1.05–1.74; P = 0.019) and the dominant model (OR = 1.23; 95% CI = 1.04–1.45; P = 0.015), respectively. Furthermore, significantly increased risks were also pronounced in Caucasian AML patients (the homozygote comparison: OR = 1.38; 95% CI = 1.07–1.78; P = 0.013; the dominant model: OR = 1.23; 95% CI = 1.03–1.46; P = 0.020; and the recessive model: OR = 1.26; 95% CI = 1.00–1.60; P = 0.050). No evident heterogeneities were observed for the overall data under all genetic models. In addition, no statistical evidence for publication bias was found using the method of Begg's and Egger's tests.

Conclusion

This meta-analysis suggested that XPD Lys751Gln polymorphism might be a risk factor for AML and Caucasian acute leukemia patients.     

Association between vaspin rs2236242 gene polymorphism and polycystic ovary syndrome risk

Vaspin, an adipocytokine that has been isolated from the visceral adipose tissue, is a member of the serine protease inhibitor family. In humans, serum vaspin levels are correlated with body mass index (BMI) and obese women with polycystic ovary syndrome (PCOS). The present study is the first investigation to examine the association between vaspin rs2236242 gene polymorphism and risk of PCOS in Iranian patients. This case–control study was performed on 150 patients with PCOS and 150 healthy women. The vaspin genotypes were determined using tetra-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). Our finding showed that there are significant differences in genotype frequencies between case and control group regarding vaspin rs2236242 polymorphism (OR = 0.59, CI = 0.37–0.95, p = 0.03). The A allele decreased the risk of PCOS (OR = 0.67, CI = 0.46–0.96, p = 0.03) as compared to the T allele. There was no significant association between vaspin rs2236242 gene polymorphism and PCOS after adjusting genotypes for BMI. In conclusion, our data suggest a significant association between vaspin rs2236242 polymorphism and the PCOS but this relationship is affected by obesity status.     

Association between the − 786T>C 1polymorphism in the promoter region of endothelial nitric oxide synthase (eNOS) and risk of coronary artery disease: A systematic review and meta-analysis

Background

A variety of studies have evaluated the association between the − 786T>C polymorphism in the promoter region of endothelial nitric oxide synthase (eNOS) and risk of coronary artery disease (CAD). However, the results remain conflicting. To better understand the role of eNOS − 786T>C polymorphism in CAD risk, we conducted a comprehensive systematic review and meta-analysis.

Methods

Case–control, cohort or cross-sectional studies evaluating the association between eNOS − 786T>C polymorphism and CAD risk were searched in electronic databases of PubMed, ISI Web of Knowledge, Medline, Embase and Google Scholar Search (up to January 2013). Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between eNOS − 786T>C polymorphism and CAD risk. Statistical analysis was performed with Review Manager 5.0 and STATA12.0.

Results

Twenty-four studies were analyzed between 6192 CAD cases and 9281 healthy controls. The combined results of overall analysis showed significant positive associations between CAD risk and eNOS − 786T>C polymorphism in dominant model (OR = 1.45, 95% CI = 1.27–1.65), recessive model (OR = 1.37, 95% CI = 1.20–1.56), homozygote comparison (OR = 1.64, 95% CI = 1.31–2.04), heterozygote comparison (TC vs. TT, OR = 1.39, 95% CI = 1.23–1.57; CC vs. TC, OR = 1.20, 95% CI = 1.04–1.37) and allele comparison (OR = 1.35, 95% CI = 1.21–1.50). On subgroup analysis based on the ethnicity of population (Caucasians, Asians and others), significant differences were found in all genetic models for Caucasians, similar associations existed in Asians except heterozygote comparison (CC vs. TC). However, the associations were only found in dominant model, heterozygote comparison (TC vs. TT) and allele comparison for the populations named others.

Conclusions

Our investigations demonstrate the significant associations between eNOS − 786C>T polymorphism and CAD risk, and this polymorphism might become an early marker for the risk evaluation of CAD.     

Association of interleukin-13 SNP rs20541 with allergic rhinitis risk: A meta-analysis

Studies investigating the association between interleukin-13 (IL-13) single nucleotide polymorphism (SNP) rs20541 and allergic rhinitis (AR) risk have reported conflicting results. The aim of the present study was to conduct a meta-analysis assessing the possible association of IL-13 SNP rs20541 with AR risk. Eight studies were included in the present meta-analysis (2153 cases and 3931 controls). The combined results based on all studies showed that IL-13 SNP rs20541 was associated with increased AR risk (Gln versus Arg: odds ratio (OR) = 1.18, 95% confidence interval (CI) = 1.08–1.30; Gln/Gln versus Arg/Arg: OR = 1.52, 95% CI = 1.20–1.92; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.19, 95% CI = 1.06–1.33; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.42, 95% CI = 1.13–1.79). When stratifying for race, IL-13 SNP rs20541 exhibited increased AR risk in Asians (Gln versus Arg: OR = 1.20, 95% CI = 1.06–1.36; Gln/Gln versus Arg/Arg: OR = 1.57, 95% CI = 1.17–2.12; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.22, 95% CI = 1.04–1.44; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.45, 95% CI = 1.09–1.93), while no significant association was detected in Caucasians (Gln versus Arg: OR = 1.28, 95% CI = 0.93 ~ 1.78; Gln/Gln versus Arg/Arg: OR = 1.42, 95% CI = 0.96–2.11; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.35, 95% CI = 0.89–2.05; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.37, 95% CI = 0.93–2.02). This meta-analysis supported that IL-13 SNP rs20541 was associated with AR, particularly in Asians.     

Myeloperoxidase G-463A polymorphism and susceptibility to coronary artery disease: A meta-analysis

Published data on the association between the myeloperoxidase (MPO) G-463A polymorphism and coronary artery disease (CAD) are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis on this topic was performed. PubMed, EMBASE and Chinese national knowledge infrastructure were searched for studies regarding the association between the MPO G-463A polymorphism and CAD. A logistic regression analysis was used to estimate the genetic effect and the possible genetic model of action. Summary odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were calculated. There was strong evidence for an association between the MPO G-463A polymorphism and CAD. The genetic model of action was most likely to be co-dominant. Overall, the data showed that AA and GA genotypes were significantly associated with reduced risk of CAD (AA vs. GG: OR = 0.37, 95% CI = 0.17–0.78; GA vs. GG: OR = 0.73, 95% CI = 0.57–0.92). In subgroup analyses by study population and sources of controls, statistically significant results were observed in the Chinese population (AA vs. GG: OR = 0.21, 95% CI = 0.10–0.43; GA vs. GG: OR = 0.57, 95% CI =0.44–0.74) and in hospital-based control studies (AA vs. GG: OR = 0.20, 95% CI = 0.10–0.39; GA vs. GG: OR = 0.61, 95% CI = 0.48–0.77). This meta-analysis suggests that the MPO G-463A variant genotypes may be associated with decreased risk of CAD. However, given the limited number of studies and the potential biases, the influence of this polymorphism on CAD risk needs further investigation.     

Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and susceptibility to ischemic stroke: A meta-analysis

Associations between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke have been reported (Ariyaratnam et al., 2007; Banerjee et al., 2007; Casas et al., 2004), but the results of these studies are inconsistent. To investigate the possible associations between the MTHFR gene polymorphism and ischemic stroke, we performed a meta-analysis. Nineteen case–control studies associated with MTHFR gene C667T involving 2223 cases and 2936 controls were included. Heterogeneity among studies was evaluated with I² and Egger's test and an inverted funnel plot was used to assess publication bias. Odds ratio (OR) was observed to identify the associations. Statistically significant association with ischemic stroke was identified for allele T polymorphism of MTHFR [fixed-effects OR = 1.28, 95% confidence interval (95% CI): 1.17–1.40, P < 0.00001] and marginally significant association was detected with genotype CT of MTHFR (fixed-effects OR = 1.13, 95% CI: 1.01–127, P = 0.04) and genotype TT of MTHFR (fixed-effects OR = 1.43, 95% CI: 1.20–1.70, P < 0.001). The results suggested that the MTHFR C667T genetic polymorphism was significantly associated with increased risk of ischemic stroke.     

Association between MDR1 C3435T polymorphism and risk of breast cancer

The C3435T (rs1045642) polymorphism, located in multi-drug resistance gene 1 (MDR1), has demonstrated its role in decreasing the P-gp activity level which is related to the carcinogenesis. Many published studies have evaluated the association between the MDR1 C3435T polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of the association between MDR1 C3435T polymorphism and risk of breast cancer, we performed a meta-analysis comprised of 10 case–control studies, including 5282 breast cancer cases and 7703 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. The overall results indicated that the variant genotypes were associated with a significantly increased risk of breast cancer (TT versus CC: OR = 1.45, 95% CI = 1.14–1.30, TT versus CT/CC: OR = 1.13, 95% CI = 1.04–1.23, TT/CT versus CC: OR = 1.22, 95% CI = 1.02–1.46). Our results suggest that the MDR1 C3435T polymorphism may contribute to individual susceptibility to breast cancer.     

Meta-analysis supports association of a functional SNP (rs1801133) in the MTHFR gene with Parkinson's disease

The MTHFR is a candidate risk gene for Parkinson's disease (PD), and a functional SNP (rs1801133) in the coding region of this gene has been investigated for the associations with the illness extensively among worldwide populations, but overall the results were inconsistent. Here, to assess the relationship between rs1801133 and risk of PD in general populations, we conducted a systematic meta-analysis by combining all available case–control samples in European and Asian populations, with a total of 1820 PD cases and 7530 healthy controls, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for rs1801133 and PD were calculated using the Mantel–Haenszel method with a fixed-effect model. Overall, rs1801133 was significantly associated with the risk of PD (allelic model, pooled OR = 1.212 for T allele, 95% CI = 1.097–1.340, p-value = 0.0002). When stratifying for ethnicity, significant association was also observed in European (allelic model, pooled OR = 1.187 for T allele, 95% CI = 1.058–1.332, p-value = 0.004) and Asian samples (allelic model, pooled OR = 1.293 for T allele, 95% CI = 1.058–1.580, p-value = 0.012) respectively. In addition, rs1801133 was also significantly associated with MTHFR mRNA expression in both CEU (European, p-value = 0.0149) and CHB (Chinese, p-value = 0.0178) HapMap populations. Collectively, our meta-analysis suggests that rs1801133 is significantly associated with susceptibility to PD in European and Asian populations, and MTHFR is likely an authentic risk gene for PD.     

Influence of interleukin-6 gene − 174G>C polymorphism on development of atherosclerosis: A meta-analysis of 50 studies involving 33,514 subjects

Increasing epidemiological studies have focused on the associations between interleukin-6 (IL-6) gene − 174G>C polymorphism and atherosclerotic diseases, but the results are still controversial. This meta-analysis was designed to identify whether this association exists. PubMed, Embase, Web of Science, Cochrane database, Clinicaltrials.gov and Current Controlled Trials, Chinese Clinical Trial Registry, CBMdisc, CNKI and Google Scholar were searched to get the genetic association studies. The crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the IL-6 gene − 174G>C polymorphism and atherosclerosis ( AS ) risk. The subgroup analyses were made on the following: ethnicity, atherosclerotic diseases and source of controls. Finally, 50 studies (15,029 cases and 18,485 controls) were included in this meta-analysis. Overall, no significant association was found between the IL-6 gene − 174G>C polymorphism and AS risk (for C allele vs. G allele: OR = 1.02, 95% CI = 0.94–1.11, p = 0.64; for C/C vs. G/G: OR = 1.01, 95% CI = 0.85–1.21, p = 0.88; for C/C vs. C/G + G/G: OR = 0.97, 95% CI = 0.84–1.12, p = 0.68; for C/C + C/G vs. G/G: OR = 1.07, 95% CI = 0.97–1.17, p = 0.18). In the subgroup analyses, significant associations were found between the IL-6 gene − 174G>C polymorphism and AS in non-Caucasian group (for CC + CG vs. GG: OR = 1.22, 95% CI = 1.06–1.41, p = 0.005), other atherosclerotic diseases group (for C allele vs. G allele: OR = 0.75, 95% CI = 0.61–0.93, p = 0.008; for C/C vs. G/G: OR = 0.56, 95% CI = 0.38–0.81, p = 0.002; for C/C vs. C/G + G/G: OR = 0.60, 95% CI = 0.45–0.79, p = 0.0004) and population-based group (for C allele vs. G allele: OR = 1.09, 95% CI = 1.00–1.18, p = 0.04; for CC + CG vs. GG: OR = 1.15, 95% CI = 1.04–1.27, p = 0.005). In summary, the present meta-analysis suggests that the IL-6 gene − 174G C polymorphism is associated with the susceptibility to AS. However, due to the high heterogeneity in the meta-analysis, the results should be interpreted with caution.     

Association between two genetic variants of CD226 gene and Cervical Squamous Cell Carcinoma: A case–control study

Cervical carcinoma is a common gynecologic tumor severely influencing the health and life quality of women worldwide. CD226, a costimulatory molecule, is mainly participated in the activation and differentiation of T cells. Recent studies have investigated the association between two genetic variants (rs763361 and rs727088) of CD226 gene and many diseases. In order to evaluate whether these two variants are associated with Cervical Squamous Cell Carcinoma (CSCC), a case–control study including 349 CSCC patients and 380 unrelated healthy controls was carried out to determine the genotypes of these two variants by using the methods of polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and DNA sequencing methods. Significantly increased CSCC risk was observed to be associated with G allele of rs727088 locus (OR = 1.422, 95% CI = 1.129–1.792). We have also observed that increased CSCC risk was statistically associated with rs727088 polymorphism in a dominant model (OR = 1.41, 95% CI = 1.05–1.89). Results of stratified analysis revealed that both rs763361 and rs727088 polymorphisms were not associated with clinical characters. Collectively, this study supports that rs727088 polymorphism may contribute to increased CSCC susceptibility.     

Glucagon gene polymorphism modifies the effects of smoking and physical activity on risk of type 2 diabetes mellitus in Han Chinese

Few genome-wide association studies have considered interactions between multiple genetic variants and environmental factors associated with disease. The interaction was examined between a glucagon gene (GCG) polymorphism and smoking, alcohol consumption and physical activity and the association with risk of type 2 diabetes mellitus (T2DM) in a case–control study of Chinese Han subjects. The rs12104705 polymorphism of GCG and interactions with environmental variables were analyzed for 9619 participants by binary multiple logistic regression. Smoking with the C-C haplotype of rs12104705 was associated with increased risk of T2DM (OR = 1.174, 95% CI = 1.013–1.361). Moderate and high physical activity with the C-C genotype was associated with decreased risk of T2DM as compared with low physical activity with the genotype (OR = 0.251, 95% CI = 0.206–0.306 and OR = 0.190, 95% CI = 0.164–0.220). However, the interaction of drinking and genotype was not associated with risk of T2DM. Genetic polymorphism in rs12104705 of GCG may interact with smoking and physical activity to modify the risk of T2DM.     

Poly (AT) deletion/insertion polymorphism of the XPC gene contributes to urinary system cancer susceptibility: A meta-analysis

Numerous studies have investigated the association between xeroderma pigmentosum complementation group C (XPC) poly (AT) deletion/insertion (PAT −/+) polymorphism and cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis based on 32 publications including 10,214 cases and 11,302 controls to acquire a more robust estimation of the relationship. We searched publications from MEDLINE, EMBASE and CBM which assessed the associations between XPC PAT −/+ polymorphism and cancer risk. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model. We found that individuals carrying the PAT +/+ genotype have significantly increased cancer risk (PAT +/+ vs. PAT −/−: OR = 1.18, 95% CI = 1.03–1.35 and recessive model: OR = 1.19, 95% CI = 1.06–1.33). Further stratification analysis showed a significantly increased risk for prostate cancer (PAT +/+ vs. PAT −/−: OR = 2.20, 95% CI = 1.39–3.48, recessive model: OR = 2.07, 95% CI = 1.33–3.23 and PAT + vs. PAT −: OR = 1.39, 95% CI = 1.12–1.71), bladder cancer (recessive model: OR = 1.33, 95% CI = 1.03–1.72), Caucasian ethnicity (recessive model: OR = 1.21, 95% CI = 1.02–1.43), population-based studies (recessive model: OR = 1.23, 95% CI = 1.05–1.43) and studies with relatively large sample size (PAT +/+ vs. PAT −/−: OR = 1.18, 95% CI = 1.04–1.35 and recessive model: OR = 1.20, 95% CI = 1.08–1.33). Despite some limitations, this meta-analysis established solid statistical evidence for the association between the XPC PAT +/+ genotype and cancer risk, especially for urinary system cancer, but this association warrants further validation in single large studies.     

Genetic association of interleukin-10 promoter polymorphisms and susceptibility to diffuse large B-cell lymphoma: A meta-analysis

Published data on the association between interleukin-10 (IL-10) gene polymorphisms and diffuse large B-cell lymphoma (DLBCL) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed, focusing on four major IL-10 gene variants in the promoter region: –3575T/A, –1082A/G, –819C/T and –592C/A. We applied the false discovery rate (FDR) method to adjust for multiple testing. A significant association between IL-10 –3575T/A polymorphism and the risk of DLBCL was observed in the pooled 10 case–control studies (A vs. T: OR = 1.16, 95% CI = 1.08–1.25, P < 0.0001; AA + TA vs. TT: OR = 1.20, 95% CI = 1.08–1.33, P = 0.0009; AA vs. TA + TT: OR = 1.25, 95% CI = 1.09–1.44, P = 0.001). The results indicated that carriers of –1082G allele (–1082GG/GA genotypes) had a nearly 30% increased risk of DLBCL, as compared with carriers of –1082AA genotype (GG + GA vs. AA: OR = 1.30, 95% CI = 1.08–1.57, P = 0.005). When P-values were not adjusted for multiple testing, the risk was significantly decreased among people with –592AA genotype (AA vs. AC + CC: OR = 0.63, 95% CI = 0.43–0.94, P = 0.02), while carriers with –819TT genotype also modestly weakened the DLBCL susceptibility at a marginal level of significance (TT vs. CT + CC: OR = 0.59, 95% CI = 0.35–0.99, P = 0.05). However, these associations were not significant after correction for multiple testing. This meta-analysis suggests that IL-10 –3575A allele confers a greater risk to DLBCL susceptibility, while –1082A/G polymorphism also has significant association with DLBCL risk. These results may help to further clarify the malignancy-risk gene signature of DLBCL, and thus have prognostic and predictive value especially for early-stage DLBCL.     

Tagging SNPs in the ERCC4 gene are associated with gastric cancer risk

ERCC4 plays an essential role in the nucleotide excision repair (NER) pathway, which is involved in the removal of a wide variety of DNA lesions. To determine whether the ERCC4 tagging SNPs (tSNPs) are associated with risk of gastric cancer, we conducted a hospital-based case-control study of 350 cases and 468 cancer-free controls. In the logistic regression (LR) analysis, we found a significantly decreased risk of gastric cancer associated with the rs744154 GC/CC genotypes [adjusted odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.42–0.75, false discovery rate (FDR) P = 0.003] compared with the wild-type GG genotype. Haplotype-based association study revealed that the CGC haplotype that containing the rs744154 C allele can decrease the risk of gastric cancer compared with the most common haplotype GGT (adjusted OR = 0.61, 95% CI = 0.46–0.81). Using the multifactor dimensionality reduction (MDR) analysis, we identified that the SNP rs744154 and smoking status were the best two predictive factors for gastric cancer with a testing accuracy of 55.76% and a perfect cross-validation consistency (CVC) of 10 (P = 0.001). Furthermore, the smokers with the rs744154 GC/CC genotypes showed a decreased risk of gastric cancer (adjusted OR = 0.55, 95% CI = 0.35–0.85) compared with the smokers with the GG genotype using multivariate LR analysis. The above findings consistently suggested that genetic variants in the ERCC4 gene may play a protective role in the etiology of gastric cancer, even in the smokers.     

Single nucleotide polymorphism in hMLH1 promoter and risk of tobacco-related oral carcinoma in high-risk Asian Indians

hMLH1 is a member of mismatch repair genes (MMR) that plays a crucial role in correcting replication errors, cell cycle arrest, apoptosis and oxidative stress. We explored the risk associated with hMLH1 − 93 A>G (rs 1800734) single nucleotide polymorphism (SNP) with the oral squamous cell carcinoma (OSCC) in Asian Indians. We genotyped 242 patients with tobacco-related OSCC and 205 healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The frequency of AA genotype was found to be significantly (P_c < 0.0006) lower in patients as compared to the controls (21.49% vs. 47.8%) while GG genotype showed significantly higher (P_c < 0.0006) prevalence in patients as compared to the healthy controls (41.32% vs. 13.66%). In logistic regression analysis AG (adjusted OR = 1.95, 95% CI = 0.72–5.26) and GG genotype (adjusted OR = 4.5, 95% CI = 1.54–13.16, P = 0.006) appeared susceptible when compared with the wild-type AA genotype. The allelic distribution showed that variant G allele is significantly higher (P_c < 0.0004) in patients and associated with increased risk (adjusted OR = 2.36, 95% CI = 1.33–4.19, P = 0.003) as compared to the wild-type A allele. Altogether, our results suggest that the hMLH1 − 93 A>G polymorphism is associated with the higher risk of tobacco-related OSCC in Asian Indians and could be useful in screening population at a higher risk.