XPD Lys751Gln polymorphism and esophageal cancer susceptibility: a meta-analysis of case–control studies

The published data on the association between xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism and esophageal cancer (EC) remained controversial. The present meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A comprehensive literature search was conducted to identify all case–control studies of Lys751Gln polymorphism and risk for two main types of EC: esophageal adenocarcinoma (EADC) and esophageal squamous cell carcinoma (ESCC). A total of 12 studies were identified to the meta-analysis, including 2,575 cases (1,294 ESCC and 1,281 EADC) and 4,951 controls (1,891 ESCC and 3,060 EADC). Random-effects or fix-effects model was used according to between-study heterogeneity. The odds ratio (OR) for the variant homozygous genotype Gln/Gln of the Lys751Gln polymorphism, compared with the wild type homozygote Lys/Lys, was 1.26, with 95% confidence interval (95% CI) 1.02–1.56, for EADC risk without between-study heterogeneity. When stratified by ethnicity, statistically significantly elevated risk was found among Chinese (Gln/Gln vs. Lys/Lys: OR 2.45, 95% CI = 1.10–5.44). However, no significant associations were found between XPD Lys751Gln polymorphism and EC risk when all studies pooled into the meta-analysis (Lys/Gln vs. Lys/Lys: OR 1.07, 95% CI = 0.88–1.28; Gln/Gln vs.us Lys/Lys: OR 1.25, 95% CI = 0.92–1.71; dominant model: OR 1.09, 95% CI = 0.90–1.33). In conclusion, this meta-analysis suggests that the Lys751Gln genetic polymorphism may be a potential biomarker of EC susceptibility in Chinese populations. And a study with the larger sample size is needed to further evaluate gene–environment interaction on XPD Lys751Gln polymorphism and EC risk.     

Significant association of XPD Asp312Asn polymorphism with breast cancer in Taiwanese patients

The DNA repair gene XPD, an important caretaker of the overall genome stability, is thought to play a major role in the development of human malignancy. Polymorphic variants of XPD, at Asp312Asn (rs1799793), Lys751Gln (rs13181), and promoter C-114G (rs3810366), were chosen to be studied of their association with breast cancer susceptibility in a central Taiwanese population. In this hospital-based case-control study, the associations of XPD Asp312Asn, Lys751Gln and promoter C-114G polymorphisms with breast cancer risk were investigated. In total, 1232 patients with breast cancer and 1433 healthy controls recruited from the China Medical Hospital in Central Taiwan were genotyped. We found a significant difference in the frequency of the XPD Asp312Asn genotype, but not the XPD Lys751Gln or promoter C-114G genotypes, between the breast cancer and control groups. Those who had G/A or A/A at XPD Asp312Asn showed a 1.78-fold (95% confidence interval = 1.53-2.08) increased risk of breast cancer compared to those with G/G. As for XPD Lys751Gln or promoter C-114G, there was no difference in distribution between the breast cancer and control groups. Our findings suggest that the heterozygous and homozygous A allele of the XPD Asp312Asn may be associated with the development of breast cancer and may be a useful marker for primary prevention and anticancer intervention.     

<Emphasis Type="Italic">MUTYH</Emphasis> Tyr165Cys, <Emphasis Type="Italic">OGG1</Emphasis> Ser326Cys and <Emphasis Type="Italic">XPD</Emphasis> Lys751Gln polymorphisms and head neck cancer susceptibility: a case control study

In the present study we investigated the association between three polymorphisms of the MUTYH (Tyr165Cys, rs34612342), the OGG1 (Ser326Cys, rs1052133) and the XPD (Lys751Gln, rs13181) genes with head and neck cancer risk. Genotypes were determined in DNA from peripheral blood lymphocytes of 265 patients with head and neck squamous cell carcinoma (HNSCC) as well as 280 cancer-free controls by PCR-restriction fragment lenght polymorphisms. We found an association between HNSCC and the Ser326Cys (OR 1.69; 95% CI 1.19–2.45) as well as Cys326Cys (OR 4.56; 95% CI 2.07–10.05) variants of the OGG1 gene. The gene–gene interaction between MUTYH and OGG1 as well as OGG1 and XPD polymorphic variants may contribute to higher prevalence of HNSCC. We also found an association between Ser326Cys and Cys326Cys variants of OGG1 gene and smoking status in HNSCC patients (OR 1.97; 95% CI 1.25–3.11), (OR 3.54; 95% CI 1.39–9.04), respectively. Moreover, we also observed a protective association between Tyr165Cys variant of the MUTYH gene and non-smoking status in HNSCC (OR 0.34; 95% CI 0.17–0.66). We also found a link between gene–gene interaction (MUTYH and OGG1 or OGG1 and XPD) and smoking (ORs 2.17–4.20 and 2.18–5.23) or non-smoking status (ORs 0.11 and 7.61) in HNSCC patients, respectively. In conclusion our data showed that the Ser326Cys polymorphism of the OGG1 gene may modify the risk of HNSCC associated with smoking. Finally we suggested that this polymorphism might be used as predictive factor for head and neck cancer in Polish population.     

Susceptibility of XPD and RAD51 genetic variants to carcinoma of urinary bladder in North Indian population

For the present study, two polymorphisms, xeroderma pigmentosum, complementation group D (XPD) Lys751Gln and RAD51 135G/C were studied with regard to bladder cancer. For XPD Lys751Gln polymorphism, an increased risk of bladder cancer was found to be associated with the Gln variant allele (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.27-2.73), on taking AA (Lys/Lys) as the referent genotype. In males, the XPD 751C (Gln) allele was found to be associated with a significantly increased risk (OR=2.33, 95% CI=1.52-3.56). The inhabitants of rural areas showed a significantly increased risk with the XPD Gln allele (OR=2.59, 95% CI=1.46-4.62) when compared with those of urban areas. In smokers (OR=5.30, 95% CI=2.42-11.68), alcohol drinkers (OR=4.33, 95% CI=2.17-8.70), and nonvegetarians (OR=2.21, 95% CI=1.26-3.87), the XPD Gln allele showed a significantly increased risk toward bladder cancer. For RAD51 135G/C polymorphism, no significant difference was observed in the allelic and genotypic frequencies. Even after stratification, no significant association could be seen. After stratifying histopathologically, the RAD51 CC genotype was associted with decreased risk in subjects having superficial stage (OR=0.51, 95% CI=0.27-0.99) and with those having G2 grade (OR=0.24, 95% CI=0.09-0.62) of bladder cancer. XPD polymorphism may be a predisposing factor, but the same cannot be said for RAD51 gene polymorphism.     

Two regions in chromosome 19q13.2-3 are associated with risk of lung cancer

Lung cancer is the most common fatal cancer among Danish men, and the incidence rate is increasing among women. In a case-cohort study, we have investigated the occurrence of lung cancer in relation to a high-risk haplotype, previously identified for breast cancer among post-menopausal women, and in relation to the closely linked polymorphisms XPD Asp312Asn and Lys751Gln. Among 54220 members of a Danish prospective cohort study aged 50-64 at entry, 265 lung cancer cases were identified and a sub-cohort comprising 272 individuals was used for comparison. Among women in the 50-55 year age interval, homozygous carriers of the high-risk haplotype were at increased risk of lung cancer (RR=7.02, 95% CI=1.88-26.18). In the 56-60 year and 61-70 year age intervals, no associations were observed. Among men, no statistically significant associations were found in any age interval. Female homozygous carriers of the variant allele of XPD Lys751Gln were at significantly increased risk of lung cancer in the two younger age-intervals (50-55 years: RR=5.60, 95% CI=1.18-26.45, 56-60 years: RR=10.60, 95% CI=1.50-75.64). Among men, carriers of the variant allele of XPD Lys751Gln had a non-significantly increased risk of lung cancer in the youngest age interval (RR=6.38, 95% CI=0.74-54.90). When the polymorphisms in XPD Asp312Asn and Lys751Gln were mutually adjusted, XPD Asp312Asn was not associated with increased risk of cancer. We found no interaction between genotypes and duration of smoking. In conclusion, two regions of chromosome 19q13.2-3 seem to be associated with risk of lung cancer.     

Polymorphisms in the AKT1 and AKT2 genes and oesophageal squamous cell carcinoma risk in an Eastern Chinese population

Ethnic Han Chinese are at high risk of developing oesophageal squamous cell carcinoma (ESCC). Aberrant activation of the AKT signalling pathway is involved in many cancers, including ESCC. Some single nucleotide polymorphisms (SNPs) in genes involved in this pathway may contribute to ESCC susceptibility. We selected five potentially functional SNPs in AKT1 (rs2494750, rs2494752 and rs10138277) and AKT2 (rs7254617 and rs2304186) genes and investigated their associations with ESCC risk in 1117 ESCC cases and 1096 controls in an Eastern Chinese population. None of individual SNPs exhibited an association with ESCC risk. However, the combined analysis of three AKT1 SNPs suggested that individuals carrying one of AKT1 variant genotypes had a decreased ESCC risk [adjusted odds ratio (OR) = 0.60, 95% CI = 0.42–0.87]. Further stratified analysis found that AKT1 rs2294750 SNP was associated with significantly decreased ESCC risk among women (adjusted OR = 0.63, 95% CI = 0.43–0.94) and non‐drinkers (OR = 0.79, 95% CI = 0.64–0.99). Similar protective effects on women (adjusted OR = 0.56, 95% CI = 0.37–0.83) and non‐drinker (adjusted OR = 0.75, 95% CI = 0.60–0.94) were also observed for the combined genotypes of AKT1 SNPs. Consistently, logistic regression analysis indicated significant gene–gene interactions among three AKT1 SNPs (P < 0.015). A three‐AKT1 SNP haplotype (C‐A‐C) showed a significant association with a decreased ESCC risk (adjusted OR = 0.70, 95% CI = 0.52–0.94). Multifactor dimensionality reduction analysis confirmed a high‐order gene–environment interaction in ESCC risk. Overall, we found that three AKT1 SNPs might confer protection against ESCC risk; nevertheless, these effects may be dependent on other risk factors. Our results provided evidence of important gene–environment interplay in ESCC carcinogenesis.     

Genetic polymorphisms of the DNA repair gene and risk of nasopharyngeal carcinoma

Context: X-ray repair cross-complementing groups 1 and 3 (XRCC1 and XRCC3) and xeroderma pigmentosum group D (XPD) are mainly involved in base excision repair, homologous recombination repair, and nucleotide excision repair of DNA repair pathways, respectively. Previous studies have demonstrated that their gene polymorphisms were associated with some cancer susceptibility. Objective and design: To investigate the effect of XPD Lys751Gln, XRCC1 Arg399Gln, Arg194Trp, Arg280His, and XRCC3 Thr241Met polymorphisms on the risk of nasopharyngeal carcinoma (NPC), a population-based case-control study of 153 NPC patients and 168 healthy controls among Sichuan population was conducted. Results: Our results showed that XRCC1 codon 194 Trp allele was associated with an increased risk of NPC (odds ratio [OR] = 1.828, 95% confidence interval [CI]: 1.286-2.598), and XPD codon 751Gln allele was associated with a borderline decrease of NPC (OR = 0.600, 95% CI: 0.361-1.000); combination analysis showed that individuals with both putative genotypes of XPD codon 751 Lys/Lys and XRCC1 codon 194 Arg/Trp or Trp/Trp have a significantly elevated risk of NPC (OR = 2.708, 95% CI: 1.338-5.478). Conclusion: The results indicated that XRCC1 codon 194 Trp allele and XPD codon 751 Lys allele may be contributing factors in the risk of NPC.     

Association between XPD Lys751Gln polymorphism and risk of head and neck cancer: a meta-analysis

Several studies have investigated the association between Lys751Gln polymorphism in the xeroderma pigmentosum group D (XPD) gene and risk of head and neck cancer; however, the published results are conflicting. We conducted a meta-analysis that comprised 15 published case-control studies examining the association of head and neck cancer risk with XPD Lys751Gln polymorphism in different populations, based on the data identified in Medline up to November 2010. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the strength of the association. Overall, significantly elevated head and neck cancer risk was associated with XPD Lys751Gln polymorphism when all studies were pooled into the meta-analysis [(Gln/Gln + Lys/Gln) vs Lys/Lys: OR = 1.12, 95%CI = 1.03-1.22, P < 0.01, heterogeneity P = 0.11]. In the subgroup analysis by ethnicity, borderline significantly increased risk was found for Europeans [(Gln/Gln + Lys/Gln) vs Lys/Lys: OR = 1.11, 95%CI = 1.00-1.23, P < 0.05]. In conclusion, our meta-analysis demonstrated that XPD Lys751Gln polymorphism could be a prediction marker for risk of head and neck cancer.     

Esophageal Squamous Cell Carcinoma and Gastric Cardia Adenocarcinoma Shared Susceptibility Locus in PLCE1: A Meta-Analysis

Background And Objective

Two recent genome-wide association studies have identified a shared susceptibility variation PLCE1 rs2274223 for esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA). Subsequent case-control studies have reported this association in other populations. However, the findings were controversial and the effect remains undetermined. Our aim is to provide a precise quantification of the association between PLCE1 rs2274223 variation and the risk of ESCC and GCA.

Methods

Studies were identified by a literature search in MEDLINE and EMBASE databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association in allele, dominant, recessive, homozygous, and heterozygous models.

Results

Ten articles were identified, including 22156 ESCC cases and 28803 controls, 5197 GCA cases and 17613 controls. Overall, PLCE1 rs2274223 G allele (G vs. A: OR=1.26, 95% CI: 1.15-1.39 for ESCC; OR=1.51, 95% CI: 1.35–1.69 for GCA) and its carrier (GG +AG vs. AA: OR = 1.23; 95% CI =1.02-1.49 for ESCC; OR =1.62; 95% CI =1.15-2.29 for GCA) were significantly associated with the risk of ESCC and GCA. In stratified analysis by ethnicity, significant association of PLCE1 rs2274223 G allele and the risk of ESCC (OR=1.33, 95% CI 1.21–1.45) and GCA (OR =1.56, 95% CI: 1.47-1.64) was observed in Chinese population.

Conclusions

Our meta-analysis results indicated that PLCE1 rs2274223 G allele significantly contributed to the risk of ESCC and GCA, especially in Chinese population.     

新疆地区维吾尔族和汉族人群CaSR基因多态性与草酸钙肾结石关系的研究

目的:探讨新疆地区维吾尔族和汉族草酸钙结石与钙敏感受体(calcium sensitive receptor,Ca SR)基因多态性之间的关系。方法:选择398例临床确诊泌尿系草酸钙结石患者(200例维吾尔族,198例汉族)和399例正常对照者(200例维吾尔族,199例汉族),应用Sna Pshot方法对Ca SR基因两位点(rs1042636,rs1801726)的基因型及等位基因频率进行检测,并分析其与草酸钙结石发病的相关性以及对血钙、24 h尿钙水平的影响。结果:各组2个位点的基因型分布均符合Hardy-Weinberg平衡。汉族结石组与汉族对照组及维吾尔族结石族与维吾尔族对照组rs1042636、rs1801726位点基因型分布及基因频率差异均无统计学意义(P0.05)。维吾尔和汉族rs1042636基因型及等位基因频率比较差异有统计学意义(P0.05),且维吾尔族人群携带rs1042636等位基因A的风险高于汉族人群(病例组中OR值=2.145,%95CI=[1.602~2.866],P0.01;对照组中OR值=1.773,%95CI=[1.332~2.359],P0.01),其中维/汉病例组中等位基因频率分别为A=278(69.5%)/204(51.5%),G=122(30.5%)/192(48.5%);维/汉对照组中等位基因频率分别为A=264(66.0%)/208(52.3%),G=136(34.0%)/190(47.7%)。而病例组和对照组rs1801726基因型频率差异无统计学意义(P0.05);汉族病例组、对照组发现GG+AG基因型较AA基因型有较高的尿钙水平(病例组:P=0.007和对照组:P=0.006),维吾尔族人群该位点与两项指标无相关性。结论:Ca SR基因2个基因位点rs1042636、rs1801726可能不是新疆地区维吾尔族和汉族草酸钙结石发病的危险因子,两族rs1042636基因多态性分布存在差异,rs1042636位点基因多态性能影响汉族人群尿钙排泄,可能汉族调节钙排泄的遗传因素之一。     

Association between the PNPLA3 I148M Polymorphism and Non-Alcoholic Fatty Liver Disease in the Uygur and Han Ethnic Groups of Northwestern China

Objective

Multiple common gene variants play a role in non-alcoholic fatty liver disease (NAFLD) susceptibility. Our goal was to investigate the association between variants polymorphisms and NAFLD in the Uygur and Han from Northwestern China.

Methods

Eight tag single nucleotide polymorphisms (tSNPs) previously reported to be associated with NAFLD were characterized in 396 NAFLD individuals and 399 controls. The association of variants with NAFLD in the Uygur and Han was assessed using the chi-squared (χ²) test in different gene models. Unconditional logistic regression analysis was performed to obtain the odds ratios (ORs) for risk of NAFLD and their 95% confidence intervals (CI), adjusted for confounding factors. Finally, stratified analysis was used to explore the potential gene-environment interactions on the risk of NAFLD.

Results

In a recessive model, we found a potential association between rs738409 and NAFLD in both ethnic groups: Chinese Han (OR = 1.84, 95% CI: 1.03–3.27, p = 0.036), Uygur (OR = 2.25, 95% CI: 1.23–4.09, p = 0.006). The multiple logistic regression revealed that PNPLA3 rs738409 GG genotype may increase the risk of NAFLD by adjusting some confounding factors: Han (OR = 5.22, 95% CI: 1.94–14.04, p = 0.001), Uygur (OR = 4.29, 95% CI: 1.60–11.48, p = 0.004). Stratified analysis found that rs738409 polymorphism appeared to have interaction with sex, smoking status in Uygur, and have interaction with sex, age, BMI stage, lifestyle in Han.

Conclusion

Our data suggest the PNPLA3 I148M polymorphism influences susceptibility to NAFLD in the Han and Uygur of Northwestern China.     

Impact of Two Common Xeroderma Pigmentosum Group D (XPD) Gene Polymorphisms on Risk of Prostate Cancer

Background

DNA repair genes (eg: xeroderma pigmentosum group D, XPD) may affect the capacity of encoded DNA repair enzymes to effectively remove DNA adducts or lesions, which may result in enhanced cancer risk. The association between XPD gene polymorphisms and the susceptibility of prostate cancer (PCa) was inconsistent in previous studies.

Methodology/Principal Findings

A meta-analysis based on 9 independent case-control studies involving 3165 PCa patients and 3539 healthy controls for XPD Gln751Lys SNP (single nucleotide polymorphism) and 2555 cases and 3182 controls for Asn312Asp SNP was performed to address this association. Meanwhile, odds ratio (OR) and 95% confidence intervals (CIs) were used to evaluate this relationship. Statistical analysis was performed with STATA10.0. No significant association was found between XPD Gln751Lys SNP and PCa risk. On the other hand, in subgroup analysis based on ethnicity, associations were observed in Asian (eg. Asn vs. Asp: OR = 1.34, 95%CI = 1.16–1.55; Asn/Asn+Asn/Asp vs. Asp/Asp: OR = 1.23, 95%CI = 1.07–1.42) and African (eg. Asn vs. Asp: OR = 1.31, 95%CI = 1.01–1.70; Asn/Asn vs. Asp/Asp: OR = 1.71, 95%CI = 1.03–7.10) populations for Asn312Asp SNP. Moreover, similar associations were detected in hospital-based controls studies; the frequency of Asn/Asn genotype in early stage of PCa men was poorly higher than those in advanced stage of PCa men (OR = 1.45, 95%CI = 1.00–2.11).

Conclusion/Significance

Our investigations demonstrate that XPD Asn312Asp SNP not the Gln751Lys SNP, might poorly increase PCa risk in Asians and Africans, moreover, this SNPs may associate with the tumor stage of PCa. Further studies based on larger sample size and gene-environment interactions should be conducted to determine the role of XPD gene polymorphisms in PCa risk.     

Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk

Polymorphisms in DNA repair genes may be associated with differences in DNA repair capacity, thereby influencing the individual susceptibility to smoking-related cancer. We investigated the association of 10 base-excision and nucleotide-excision repair gene polymorphisms (XRCC1 -77 T/C, Arg194Trp, Arg280His and Arg399Gln; APE1 Asp148Glu; OGG1 Ser326Cys; XPA -4 G/A; XPC PAT; XPD Asp312Asn and Lys751Gln) with lung cancer risk in Caucasians. Genotypes were determined by PCR-RFLP and PCR-single base extension assays in 110 lung cancer patients and 110 age- and sex-matched controls, and the results were analyzed using logistic regression adjusted for relevant covariates. A significant association between the APE1 Asp148Glu polymorphism and lung cancer risk was found, with adjusted odds ratios (OR) of 3.38 (p=0.001) for the Asp/Glu genotype and 2.39 (p=0.038) for the Glu/Glu genotype. Gene-smoking interaction analyses revealed a statistically significant interaction between cumulative cigarette smoking and the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms: these polymorphisms were significantly associated with lung cancer in nonsmokers and light smokers (<25 PY; OR=4.92, p=0.021 for XRCC1 399 Gln/Gln; OR=3.62, p=0.049 for XPD 751 Gln/Gln), but not in heavy smokers (> or =25 PY; OR=0.68, p=0.566 for XRCC1 399 Gln/Gln; OR=0.46, p=0.295 for XPD 751 Gln/Gln). Both the XRCC1 Arg194Trp and Arg280His as well as the OGG1 Ser326Cys heterozygous genotypes were associated with a significantly reduced risk for lung cancer (OR=0.32, p=0.024; OR=0.25, p=0.028; OR=0.51, p=0.033, respectively). No associations with lung cancer risk were found for the XRCC1 -77 T/C, the XPA -4 G/A and the XPC PAT polymorphisms. In conclusion, the APE1 Asp148Glu polymorphism is highly predictive for lung cancer, and cumulative cigarette smoking modifies the associations between the XRCC1 Arg399Gln and the XPD Lys751Gln polymorphisms and lung cancer risk.     

A risk-associated single nucleotide polymorphism of <Emphasis Type="Italic">SMAD7</Emphasis> is common to colorectal,gastric, and lung cancers in a Han Chinese population

SMAD7 has been demonstrated to antagonize TGF-β-mediated fibrosis, carcinogenesis, and inflammation. Two previous genome-wide association studies identified three single nucleotide polymorphisms (SNPs) (rs4939827, rs12953717 and rs4464148) in SMAD7 to be associated with colorectal cancer in a Western population. We conducted the first case–control study in a Han Chinese population to explore the associations between these three SNPs and colorectal, gastric, and lung cancers. Of the three SNPs, only rs12953717 was strongly associated with the three types of cancer, fitting the overdominant model. Compared with the CC/TT (CC combined with TT) genotype, the adjusted odds ratios for the CT genotype were 2.002 (95% CI, 1.250–3.207, P = 0.004), 1.678 (95% CI, 1.048–2.689, P = 0.031), 3.825 (95% CI, 2.310–6.335, P < 1 × 10⁻⁴), and 2.294 (95% CI, 1.537–3.343, P < 1 × 10⁻⁴), respectively, for colorectal, gastric, lung, and combined cancers. These outcomes suggest that rs12953717 is a common risk marker of these three types of cancer in the Han Chinese.     

The Effect of XPD/ERCC2 Polymorphisms on Gastric Cancer Risk among Different Ethnicities: A Systematic Review and Meta-Analysis

Background

Potential xeroderma pigmentosum group D (XPD), also called excision repair cross-complimentary group two (ERCC2), Lys751Gln and Asp312Asn polymorphisms have been implicated in gastric cancer risk among different ethnicities.

Methods

We aimed to explore the effect of XPD Lys751Gln and Asp312Asn polymorphisms on the susceptibility to gastric cancer among different ethnicities through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. 13 studies were ultimately eligible for the meta-analysis of Lys751Gln polymorphism and 9 studies for the meta-analysis of Asp312Asn polymorphism. We adopted the most probably appropriate genetic model (recessive model) for both Lys751Gln and Asp312Asn polymorphisms. Potential sources of heterogeneity were sought out via subgroup and sensitivity analyses, and publication biases were estimated.

Results

Statistically significant findings were apparently noted in Asians but not in Caucasians for both XPD Lys751Gln and XPD Asp312Asn polymorphisms. A statistically significant finding could be seen in noncardia-type gastric cancer for XPD Lys751Gln polymorphism. A statistically significant finding could also be seen in high quality subgroup, small-and-moderate sample size subgroup, articles published after 2007, or PCR-RFLP genotyping subgroup for XPD Asp312Asn polymorphism.

Conclusions

Our meta-analysis indicates that XPD Gln751Gln (CC) genotype and Asn312Asn (AA) genotype may seem to be more susceptible to gastric cancer in Asian populations but not in Caucasian populations, suggesting that the two genotypes may be important biomarkers of gastric cancer susceptibility for Asian populations, the assumption that needs to be further confirmed in well-designed studies among different ethnicities. Gln751Gln (CC) genotype may also be associated with noncardia-type gastric cancer risk, which should also be confirmed among different ethnicities in the future.     

Effect of SNP Polymorphisms of EDN1, EDNRA,and EDNRB Gene on Ischemic Stroke

The objective of this study is to investigate the association between SNP polymorphisms of endothelin-1 (EDN1) and endothelin receptor (EDNRA and EDNRB) gene and ischemic stroke (IS) in the Chinese Han population in northern. A case–control study was introduced. We genotyped eight SNPs (rs1800541, rs2070699, and rs5370 in EDN1 gene; rs1801708, rs5333, and rs5335 in EDNRA gene; and rs3818416 and rs5351 in EDNRB gene) and calculated their polymorphic distribution in control group, IS group, and the IS subgroups. In male population, EDN1 gene rs2070699 G allele increased the incidence risk to 1.78 times (P = 0.009; OR 1.78; 95 % CI 1.15–2.75) and the risk of morbidity of rs5370 T allele carrying increased to 1.49 times (P = 0.048; OR 1.49; 95 % CI 1.00–2.21). EDNRA gene mutation rs5335 homozygous CC morbidity risk was significantly lower (P = 0.016; OR 0.52; 95 % CI 0.31–0.88). In the female population, the mutant homozygous AA cancer risk was significantly higher than G allele carriers (P = 0.019; OR 2.65; 95 % CI 1.18–6.00) on EDNRA gene rs1801708. In EDN1 gene, T allele of rs5370 and G allele of rs2070699 may be IS incidence risk factors in Northern Han male population. A allele of rs1801708 in EDNRA gene can increase the risk of IS in Northern Han women population.     

A globally occurring indel polymorphism in the promoter of the IFNA2 gene is not associated with severity of malaria but with the positivity rate of HCV

Background

Glutathione S-transferases (GSTs) is a genetic factor for many diseases and exhibits great diversities among various populations. We assessed association of the genotypes of Glutathione S-transferases Omega-1 (GSTO1) A140D with ethnicity in China.

Results

Peripheral blood samples were obtained from 1314 individuals from 14 ethnic groups. Polymorphisms of GSTO1 A140D were measured using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression was employed to adjustment for regional factor. The frequency of GSTO1 140A allele was 15.49% in the total 14 ethnic populations. Compared to Han ethnic group, two ethnic populations were more likely to have AA or CA genotype [odds ratio (OR): 1.77, 95% confidence interval (95% CI): 1.05–2.98 for Uygur and OR: 1.78, 95% CI: 1.18–2.69 for Hui]. However, there were no statistically significant differences across 14 ethnic groups when region factor was adjusted. In Han ethnicity, region was significantly associated with AA or CA genotype. Han individuals who resided in North-west of China were more likely to have these genotypes than those in South of China (OR: 1.63, 95% CI: 1.21–2.20).

Conclusion

The prevalence of the GSTO1 140A varied significantly among different regional populations in China, which showed that geography played a more important role in the population differentiation for this allele than the ethnicity/race.     

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.     

Associations of Genetic Variants in the PSCA,MUC1 and PLCE1 Genes with Stomach Cancer Susceptibility in a Chinese Population

BackgroundSeveral genetic variants including PSCA rs2294008 C>T and rs2976392 G>A, MUC1 rs4072037 T>C, and PLCE1 rs2274223 A>G have shown significant association with stomach cancer risk in the previous genome-wide association studies (GWASs).MethodsTo evaluate associations of these SNPs in the Han Chinese, an independent hospital based case-control study was performed by genotyping these four polymorphisms in a total of 692 stomach cancer cases and 774 healthy controls acquired by using frequency matching for age and gender. False-positive report probability (FPRP) analysis was also performed to validate all statistically significant findings.ResultsIn the current study, significant association with stomach cancer susceptibility was observed for all the four polymorphisms of interest. Specifically, a significant increased stomach cancer risk was associated with PSCA rs2294008 (CT vs. CC: adjusted OR = 1.37, 95% CI = 1.07–1.74, and CT/TT vs.CC: adjusted OR = 1.30, 95% CI = 1.03–1.63), PSCA rs2976392 (AG vs. GG: adjusted OR = 1.30, 95% CI = 1.02–1.65, and AG/AA vs. GG: adjusted OR = 1.26, 95% CI = 1.00–1.59), or PLCE1 rs2274223 (AG vs. AA: adjusted OR = 1.48, 95% CI = 1.15–1.90, and AG/GG vs. AA: adjusted OR = 1.45, 95% CI = 1.14–1.84), respectively. In contrast, MUC1 rs4072037 was shown to decrease the cancer risk (CT vs. TT: adjusted OR = 0.77, 95% CI = 0.60–0.98). Patients with more than one risk genotypes had significant increased risk to develop stomach cancer (adjusted OR = 1.30, 95% CI = 1.03–1.64), when compared with those having 0–1 risk genotypes. Stratified analysis indicated that the increased risk was more pronounced in younger subjects, men, ever smokers, smokers with pack years ≤ 27, patients with high BMI, or non-cardia stomach cancer.ConclusionsThis study substantiated the associations between four previous reported genetic variants and stomach cancer susceptibility in an independent Han Chinese population. Further studies with larger sample size and different ethnicities are warranted to validate our findings.