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

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

Replication study of PLCE1 and C20orf54 polymorphism and risk of esophageal cancer in a Chinese population

Esophageal cancer is one of the most aggressive cancers in the world. Recent large-scale genome-wide association studies (GWAS) reported that functional genetic variations in the phospholipase C epsilon gene (PLCE1) were strongly associated with risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in Chinese population. For C20orf54 rs13042395 genotype and risk of esophageal cancer, the results were inconsistent. We conducted a replication case-control study to evaluate the genetic effects of these two functional single nucleotide polymorphisms (SNPs) on the development of esophageal cancer. A total of 380 cases and 380 controls were recruited for this study. The genotypes were determined by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS). The variant alleles of the functional polymorphism, PLCE1 rs2274223 SNP was associated with the increased risk of esophageal cancer [adjusted odds ratio (OR) = 1.95, 95 % confidence interval (CI) = 1.05-3.59 for PLCE1 rs2274223 GG vs. AA]. However, there was no significant association between the C20orf54 rs13042395 genotype and esophageal cancer risk (adjusted OR = 0.99, 95 % CI = 0.63-1.57 for C20orf54 rs13042395 TT vs. CC). Stratified analyses indicated a significantly increased risk of esophageal cancer associated with the PLCE1 rs2274223 AG genotype was more evident among females, younger patients and never drinkers, compared with the PLCE1 rs2274223 AA genotypes. Stratified analyses also indicated a significantly increased risk of esophageal cancer associated with the PLCE1 rs2274223 GG genotype was more evident among never smokers and never drinkers compared with the PLCE1 rs2274223 AA genotypes. These findings indicated that functional polymorphisms PLCE1 rs2274223 might contribute to esophageal cancer susceptibility.     

Lack of association between pro-inflammatory genotypes of the interleukin-1 (IL-1B -31 C/+ and IL-1RN *2/*2) and gastric cancer/duodenal ulcer in Korean population

IL-1beta is a pro-inflammatory cytokine with multiple biological effects and is a potent inhibitor of gastric acid secretion, and IL-1RN has been shown to be associated with enhanced IL-1beta production in vitro. Recently, it was reported that the pro-inflammatory genotypes, IL-1B -31 C/+ and IL-1RN *2/*2, were associated with an increased risk of gastric cancer in a Caucasian population. We tested the association between the polymorphisms and 190 gastric cancer, 117 duodenal ulcer, and 172 healthy subjects as controls in the Korean population. The allele frequency of IL-1B -31 C was more prevalent in Korean (51%) than in Caucasian (30%), while the frequency of IL-1RN *2 allele was less in Korean (6%) than in Caucasian (27%). Using the IL-1B TT genotype as a reference group, the CC genotype was not associated with an increased risk of gastric cancer or duodenal ulcer in the Korean population (odds ratios (OR)=0.90, 95% confidence interval (CI)=0.50-1.64; OR=0.72, 95% CI=0.36-1.46, respectively). Similarly, IL-1RN*2 was not a risk genotype for either gastric cancer or duodenal ulcer. No association was recognized on the haplotype analysis of the two genes, either. Our results did not support the previous report that IL-1B -31 C/IL-1RN*2 polymorphisms were associated with an increased risk of gastric cancer. The lack of association with duodenal ulcer also suggested that the polymorphisms were not directly related to the acid-secreting capability.     

Effect of CYP17 and PSA gene polymorphisms on prostate cancer risk and circulating PSA levels in the Slovak population

Cytochrome P-450c17α (CYP17) and prostate-specific antigen (PSA) genes, which are involved in the androgen metabolism cascade, have been studied as possible candidates for genetic influences on prostate cancer development. Contradictory results prompted us to evaluate the frequencies of polymorphisms in the CYP17 and PSA genes as well as the association between these genetic variants and serum PSA levels in prostate cancer patients and men routinely screened for prostate cancer with PSA in the Slovak male population. The CYP17 and PSA polymorphisms were determined by the PCR-RFLP analysis in 197 Caucasian prostate cancer patients and 256 Caucasian controls. We did not find any association between the CYP17 and PSA genotypes and prostate cancer risk overall, or by grade. Also the total serum PSA levels in the cases with the AG or AA genotype were not significantly higher than in the men with the GG genotype (P > 0.05). Our study did not provide support for the hypothesized relationship between CYP17 and PSA gene polymorphisms and prostate cancer in the Slovak male population.     

Association of glutathione S-transferase P1 gene polymorphism with the risk of small-cell carcinoma of lung cancer

Abstract

The conclusions of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) gene polymorphism and the risk of small-cell carcinoma of lung cancer are still debated. GSTP1 is one of the important mutant sites reported at present. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of small-cell carcinoma of lung cancer. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Ten reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and small-cell carcinoma of lung cancer. The G allele and GG genotype were not associated with the susceptibility of risk of small-cell carcinoma in overall populations, East-Asians and Turkish population. However, there was an association between GG genotype with the risk of small-cell carcinoma in Caucasians. In conclusion, GG genotype was associated with the risk of small-cell carcinoma in Caucasian patients with lung cancer. However, GSTP1 A/G gene polymorphism is not associated with the susceptibility of small-cell carcinoma in overall populations, East-Asians and Turkish population.     

Meta-analysis of the association of CYP1A1 polymorphisms with gastric cancer susceptibility and interaction with tobacco smoking

The association of two cytochrome P4501A1 (CYP1A1) polymorphisms, m1 (T6235C transition) and m2 (A4889G transition), with gastric cancer risk is inconclusive. We conducted a meta-analysis of all available studies to evaluate the potential role of the polymorphisms and their interactions with tobacco smoking in gastric cancer susceptibility. Published literature from PubMed was retrieved by two investigators independently. Fourteen case-control studies with 2,032 gastric cancer cases and 5,099 controls were selected. A fixed effects model or a random-effects model was used to estimate the odds ratio (OR) for the CYP1A1 polymorphisms and the occurrence of gastric cancer. Significant associations between CYP1A1 m1 and m2 polymorphisms and gastric cancer susceptibility were not observed in all genetic models in the overall analyses. Subgroup analyses by ethnicity and source of controls did not reveal significant associations with gastric cancer risk. Stratification analysis by smoking status found that carriers of the heterozygous and homozygous m1 genotypes decreased the susceptibility of gastric cancer among ever-smokers (pooled OR = 0.56, 95 % CI 0.36-0.89, fixed effects). In contrast, the m2 genotypes (G/G and A/G) did not show any relevance to gastric cancer risk among the smoking population (pooled OR = 1.30, 95 % CI 0.84-2.00, fixed effects). Overall, we found that the CYP1A1 polymorphism itself, either m1 or m2, did not represent an independent genetic risk factor influencing gastric cancer. However, subgroup analyses suggest that carriers of the heterozygous and homozygous m1 genotype who are exposed to tobacco smoke have a significantly lower risk of developing gastric cancer. To explain the observed reduction of gastric cancer risk, we proposed a novel hypothesis of "observation bias". This hypothesis is also applicable to explain the combined effects of other genetic polymorphisms and environmental factors on the risk of developing cancers, and the rationality of the hypothesis needs to be further investigated.     

A meta-analysis of interleukin-10-1082 promoter polymorphism associated with gastric cancer risk

We aimed to explore the role of allele A/G single nucleotide polymorphism (SNP) of gene Interleukin 10 (IL-10) promoter-1082 in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. Twenty studies were ultimately eligible for the meta-analysis of IL-10-1082 A/G SNP. We adopted the most probably appropriate genetic model (dominant model), with the combined group of GG-plus-GA genotypes compared with the AA genotype. Potential sources of heterogeneity were sought out via subgroup analyses and sensitivity analyses, and publication biases were estimated. Between IL-10-1082 GG-plus-GA genotypes with the risk of developing gastric cancer, statistically significant association could be noted with overall gastric cancer, being mainly in Asian subgroup, large sample subgroup, high quality subgroup, intestinal-type subgroup, cardia-type subgroup, and some genotyping method subgroups. Our meta-analysis indicates that IL-10-1082 GG-plus-GA genotypes are associated with the overall risk of developing gastric cancer and seem to be more susceptible to overall gastric cancer in Asian populations. IL-10-1082 GG-plus-GA genotypes are more associated with the pathologically intestinal-type gastric cancer or anatomically cardia-type gastric cancer.     

CYP1A1 Ile462Val Polymorphism Contributes to Lung Cancer Susceptibility among Lung Squamous Carcinoma and Smokers: A Meta-Analysis

Many studies have examined the association between the CYP1A1 Ile462Val gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. Ultimately, 43 case-control studies, comprising 19,228 subjects were included. A significantly elevated lung cancer risk was associated with 2 Ile462Val genotype variants (for Val/Val vs Ile/Ile: OR = 1.22, 95% CI = 1.08–1.40; for (Ile/Val +Val/Val) vs Ile/Ile: OR = 1.15, 95% CI = 1.07–1.23) in overall population. In the stratified analysis, a significant association was found in Asians, Caucasians and lung SCC, not lung AC and lung SCLC. Additionally, a significant association was found in smoker population and not found in non-smoker populations. This meta-analysis suggests that the Ile462Val polymorphisms of CYP1A1 correlate with increased lung cancer susceptibility in Asian and Caucasian populations and there is an interaction with smoking status, but these associations vary in different histological types of lung caner.     

粘蛋白MUC1 568A/G SNP与辽宁地区人群胃癌遗传易感性的关系

为了探讨粘蛋白(MUC1)基因568位点A/G单核苷酸多态性与胃癌遗传易感性的关系, 采用序列特异性引物-聚合酶链反应(Sequence specific primers PCR, PCR-SSPs)检测来自辽宁地区人群138例胃癌患者及与其配比的131例对照个体MUC1 568 位点A/G多态性, 以ELISA法检测血清H. pylori IgG抗体。结果显示:(1)对照人群MUC1基因568位点AA、AG、GG 3种基因型分布频率分别为73.3%、22.1%、4.6%; (2)胃癌组MUC1 AA基因型携带频率显著高于正常对照组(P=0.03), 携带MUC1 AA基因型个体胃癌的发病风险增高到1.92倍; (3)以MUC1 AG+GG基因型并血清幽门螺杆菌(H. pylori)IgG抗体阴性的个体为对照, AG+GG基因型并H. pylori IgG抗体阳性个体、AA基因型并H. pylori IgG抗体阴性个体、AA基因型并H. pylori IgG抗体阳性个体胃癌患病风险增高, 但3组各组间差异均无统计学意义(P>0.05)。说明MUC1基因568位点A/G多态与胃癌的遗传易感性相关; MUC1 A/G基因多态性和H. pylori感染在胃癌发生发展过程未见交互作用。     

Current evidence on the relationship between CYP1B1 polymorphisms and lung cancer risk: a meta-analysis

The association between single-nucleotide polymorphisms (SNPs) of the CYP1B1 gene and lung cancer risk is still ambiguous. In this meta analysis, we assessed 10 case–control studies included 7,067 cases and 9,374 controls of the association between CYP1B1 SNPs of Leu432Val (rs1056836, 432C>G), Asn453Ser (rs1800440, 453A>G), Ala119Ser (rs1056827, 119G>T), Arg48Gly (rs10012, 48C>G) and the risk of lung cancer. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of association between the polymorphism and lung cancer risk under codominant model, dominant model and additive model respectively. Although there were limitations, this meta analysis indicated that individuals with 432GG genotype had a 39.7% higher risk of having lung cancer than those with the 432CC genotype, and individuals with the 432G allele had a 26.3% increased risk as well. An increased risk of lung cancer of 2.13 fold was observed in individuals with 119TT genotype. For Arg48Gly, individuals with 48GG genotype had a significantly increased risk of lung cancer compared with individuals with 48CC (OR 3.859; 95% CI 2.536–5.87). Elevated risk of lung cancer were observed in dominant model (OR 2.115; 95% CI 1.653–2.705) as well. The risk of lung cancer was elevated as the frequency of G allele increased in additive model (P = 0.000). For individuals with the polymorphism at codon 453, no evidence of such association was observed. Furthermore, a possible association between the CYP1B1 polymorphism at codon 432 and the lung cancer could be detected in individuals of Caucasian origin, while a negative association was suggested in Asians and African-Americans. An increased lung cancer risk was also found in women with polymorphism at codon 453. These results are supportive for the hypothesis that the CYP1B1 432GG, 119TT and 48GG genotypes are low-penetrance risk factors for developing lung cancer, and further studies are needed to validate these associations.     

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.     

Polymorphisms in DNA Repair Gene and Susceptibility to Glioma: A Systematic Review and Meta-Analysis Based on 33 Studies with 15 SNPs in 9 Genes

At present, many publications have evaluated the correlation between the DNA repair gene polymorphisms and glioma susceptibility. However, the results remain inconclusive. The aim of this research is to exhaustively assess the association of genetic polymorphisms in DNA repair genes with glioma risk in human. Meta-analysis method was conducted, and 33 studies with 15 SNPs in 9 genes were included (12553 glioma cases and 17178 controls). Correlation strength was evaluated by odds ratio with a 95 % confidence interval. Rs1799782 T allele and rs25487A allele might bring about higher risk of glioma in Asian population. Rs1805377 G allele was an increased risk genetic factor of glioma. Asian carried with rs3212986 A allele was more likely to have glioma. Rs1800067 G allele was a risk factor of developing glioma. Carriers with rs12917 CC genotype in MGMT gene had higher risk of glioma in Caucasian than other non-CC genotype carriers. Carriers with rs1136410 T allele in PARP1 gene could more likely to develop glioma in Caucasian. This meta-analysis suggests that glioma susceptibility is associated with rs1799782 and rs25487 of X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1), rs1805377 of XRCC4, rs1800067 of excision repair cross-complementing rodent repair deficiency complementation group 4 (ERCC4) and rs3212986 of ERCC1 in Asian population, and rs12917 of O-6-methylguanine-DNA methyltransferase (MGMT) and rs1136410 of poly(ADP-ribose) polymerase 1 (PARP1) in Caucasian population.     

Association of interleukin‐17 gene polymorphisms and susceptibility to brucellosis in Hamadan,western Iran

IL‐17is one of the most important inflammatory cytokines that stimulate immunity responses in humans infected with Brucella species, acting as a regulator that reduces release of γ‐IFN, thus increasing resistance to brucellosis. Gene polymorphisms in the regulatory regions of cytokine‐encoding genes affect the amountsof cytokines produced and play a fundamental role in infectious diseases. The aim of this study was to determine the association between IL‐17 gene polymorphisms and susceptibility to brucellosis. In this case‐control study, 86 patients with brucellosis and 86 healthy persons in Hamadan, western Iran, from September 2014 to September 2016, were included. IL‐17 genetic variants at positions rs4711998 A/G, rs8193036 C/T, rs3819024 A/G, rs2275913 A/G, rs3819025 A/G, rs8193038 A/G, rs3804513 A/T, rs1974226 A/G and rs3748067 A/G were analyzed by restriction fragment length polymorphism‐PCR. Serum IL‐17 titers were measured by sandwich ELISA. GG genotypes at positions rs4711998 and rs3748067 were present significantly more frequently in patients with brucellosis than in controls (P < 0.05). The AA genotype at positions rs4711998, rs2275913 and rs3748067 and GG genotype at position rs19744226 were present significantly more frequently in controls than in the patient group. These results suggest that the AA genotype at positions rs3748067, rs3819025 and rs4711998 and GG genotype at position rs3819024 are likely protective factors against brucellosis, whereas the GG genotype at positions rs3748067, rs3819025 and rs4711998 and AA genotype at position rs3819024 may be risk factors against the disease. No significant relationships were found between serum IL‐17 titers and genotypes of the single‐nucleotide polymorphisms.     

Single nucleotide polymorphism of CACNA2D1 gene and its association with milk somatic cell score in cattle

The objective of the present study was to identify polymorphisms of the CACNA2D1 gene, and to analyze associations between these polymorphisms and mastitis in several cattle breeds. Through PCR-RFLP methods and DNA sequencing, an allelic variant corresponding to the A→G mutations and Aspartic (Asp) to Glycine (Gly) amino acid replacement at positions 526745 in the exon 25 of bovine CACNA2D1 gene could be detected. Two alleles, A and G, and three genotypes, AA, AG and GG were defined. Genetic character in the studied populations indicated that the A526745G loci of CACNA2D1 gene was moderate polymorphism and fitted with Hardy-Weinberg equilibrium (P > 0.05). The effects of CACNA2D1 polymorphisms on somatic cell score (SCS) were analyzed and significant association was found between A526745G and SCS. The mean of genotype GG was significantly lower than those of genotype AG and AA (P = 0.0469). Information provided in this research could be useful in further studies to determine the role of CACNA2D1 gene in the mastitis resistance.     

Polymorphisms in GSTT1 and p53 and urinary transitional cell carcinoma in south-western Taiwan: a preliminary study.

Little is known about the relevance of genetic polymorphisms to arsenic-related bladder cancer. A preliminary case-control study was conducted to explore the association between genetic polymorphisms of GSTT1, p53 codon 72 and bladder cancer in southern Taiwan, a former high arsenic exposure area. Fifty-nine urinary transitional cell carcinoma (TCC) patients from a referral centre in south-western Taiwan and 81 community controls matched on residence were recruited from 1996 to 1999. A questionnaire was administered to obtain arsenic exposure and general health information. Genotypes of p53 codon 72 and GSTT1 were analysed by polymerase chain reaction-restriction fragment length polymerase. The combined variant genotypes (heterozygous or homozygous variant) of p53 codon 72 and GSTT1 null were observed in 29% of cases and in 44% of controls, respectively. In this preliminary study, bladder cancer risk was slightly elevated for subjects carrying the variant genotype of p53 codon 72 or in subjects carrying the GSTT1 null genotype. Variants in p53 codon 72 increased the risk of bladder cancer among smokers. However, the results were not statistically significant and larger confirmatory studies are needed to clarify the role of candidate gene polymorphisms and bladder cancer risk in arsenic exposed populations.     

Association of polymorphisms in the interleukin-4 gene with response to hepatitis B vaccine and susceptibility to hepatitis B virus infection: A meta-analysis

Objective

The aim of this meta-analysis is to evaluate the associations between functional polymorphisms in the interleukin-4 (IL4) gene and individuals' responses to hepatitis B vaccine and their susceptibility to hepatitis B virus (HBV) infection.

Methods

A literature search on articles published before December 1st, 2012 was conducted in PubMed, Embase, Web of Science and China BioMedicine (CBM) databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical analyses were performed using the STATA 12.0 software.

Results

Eight studies were eligible for inclusion in this meta-analysis, including five cross-sectional studies on individual's response to hepatitis B vaccine and three case–control studies on HBV infection risk. The meta-analysis results showed that the T allele of rs2243250, the T allele of rs2070874, and the C allele of rs2227284 in IL4 gene were associated with high responses to hepatitis B vaccine. Further subgroup analysis by ethnicity showed that there was a significant association between IL4 genetic polymorphisms and an individual's responses to hepatitis B vaccine among Asian populations, but similar association was not found among Caucasian populations. However, there was no evidence indicating a correlation between IL4 genetic polymorphism and susceptibility to HBV infection.

Conclusion

Our current meta-analysis suggests that rs2243250, rs2070874 and rs2227284 polymorphisms in IL4 gene may play an important role in determining the response to hepatitis B vaccine, especially among Asian populations. However, further studies are still needed to evaluate the associations between IL4 genetic polymorphisms and HBV infection risk.     

Role of NQO1 609C>T and NQO2-3423G>A polymorphisms in susceptibility to gastric cancer in Kashmir valley

NADPH: quinone oxidoreductase 1 (NQO1) and dihydronicotinamide riboside: quinone oxidoreductase 2 (NQO2) are cytosolic enzymes that catalyze reductive activation of carcinogens from cigarette smoke, such as nitrosamines and heterocyclic amines. These enzymes also protect cells against oxidative damage from reactive oxygen species. The present study investigated the associations of genetic variants of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility to gastric cancer (GC) as well as their interactions with known risk factors in Kashmir valley. A case control study was performed in 303 subjects (108 GC and 195 healthy controls). All subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Data were statistically analyzed by chi-square test and logistic regression model. The NQO1 609C>T TT genotype and T allele were significantly associated with increased risk for GC, whereas NQO2 -3423G>A polymorphism did not show any association with GC. Also, NQO1 609C>T TT genotype showed significant association with gastric adenocarcinoma. The interaction of NQO1/NQO2 genotypes with high consumption of salted tea, a known risk factor, did not further modulate the risk of GC. In conclusion, NQO1 609C>T polymorphism shows association with GC risk in Kashmir valley.     

白介素-10-819 C/C和肿瘤坏死因子-α-1031 C/C/基因型与胃十二指肠疾病易感性的关系

目的分析人群中IL-10-819 C/C和TNF-α-1031 C/C基因型与胃十二指肠疾病的关系,确定携带以上该基因型的的人群罹患胃十二指肠疾病易感性的风险性。为临床诊断和预防这些疾病提供新的思路和方法。方法选取H.pylori阳性的48例慢性胃炎患者,46例十二指肠溃疡患者,51例胃溃疡患者,43例胃癌患者和100例健康对照者,2种基因型分别采用普通PCR和多重引物特异PCR法检测。结果在胃炎组中TNF-A-1031各基因型的频率(T/T,50%;T/C,40%;C/C,10%)与对照组(T/T,73%;T/C,25%;C/C,2%)比较,分布差异有统计学意义(χ2=9.975,P0.05)。在胃溃疡组中TNF-A-1031各基因型的频率(T/T,49%;T/C,43%;C/C,8%)与对照组(T/T,73%;T/C,25%;C/C,2%)比较,分布差异有统计学意义(χ2=9.464,P0.001)。在十二指肠溃疡组中TNF-A-1031各基因型的频率(T/T,72%;T/C,26%;C/C,2%)与对照组(T/T,73%;T/C,25%;C/C,2%)比较,分布差异有统计学意义(χ2=9.840,P0.05)。在胃癌组中TNF-A-1031各基因型的频率(T/T,50%;T/C,41%;C/C,9%)与对照组(T/T,73%;T/C,25%;C/C,2%)比较,分布差异有统计学意义(χ2=9.335,P0.001);Logistic回归分析与携带TNF-A-1031 T/T者比较,携带TNF-A-1031 C/C者发生胃炎的危险性为OR=7.60(95%CI:1.38-41.77);与携带TNF-A-1031 T/T者比较,携带TNF-A-1031 C/C者发生胃溃疡的危险性为OR=5.84(95%CI:1.00-33.84);与携带TNF-A-1031 T/T者比较,携带TNF-A-1031 C/C者发生十二指肠溃疡的危险性为OR=7.94(95%CI:1.44-43.67);与携带TNF-A-1031 T/T者比较,携带TNF-A-1031 C/C者发生胃癌的危险性为OR=6.95(95%CI:1.19-40.63)。在疾病组和对照组中IL-10-819的各基因型频率的分布差异无统计学意义(P0.05)。结论 TNF-α-1031基因多态性与胃炎、胃溃疡、十二指肠、胃癌的易感性相关。     

DNMT3A rs36012910 A>G polymorphism and gastric cancer susceptibility in a Chinese population

DNA-methyltransferase (DNMT)-3A plays a crucial role in embryonic development and aberrant DNA methylation in carcinogenesis. Polymorphisms of the DNMT3A gene may influence its enzymatic activity and its contribution to susceptibility to cancer. This study evaluated the association of DNMT3A rs36012910 A>G with susceptibility to gastric cancer (GC) in a Chinese population. Genomic DNA was extracted from samples taken from 340 patients with GC and 251 healthy control subjects. The genotype frequency of DNMT3A rs36012910 A>G in all subjects was detected by polymerase chain reaction–restriction fragment length polymorphism and confirmed by sequencing. Stratification analyses were used to study subgroups by age and gender and to evaluate the association of rs36012910 A>G polymorphism with genetic susceptibility to GC. All patients and control individuals were successfully genotyped for the DNMT3A rs36012910 A>G polymorphism. The frequency of DNMT3A rs36012910 allele G is 3.39?% in healthy individuals and 7.78?% in GC patients, respectively. The rs36012910 AG genotype was significantly more common in the GC group than in the controls, although the rs36012910 GG genotype was only one case in GC patients. Further stratification indicated that AG+GG genotypes were associated with susceptibility to GC in males older than 60, but this polymorphism has no significant association with GC susceptibility in females. Male individuals who carried AG+GG genotypes had a 2.362-fold increased risk of GC compared to those who carried the AA genotype. The rs36012910 allele G was associated with an increased risk of GC compared to the rs36012910 allele A. This is the first report to investigate the distribution and evaluate the association of a rare SNP in DNMT3A with genetic susceptibility to GC. DNMT3A rs36012910 A>G might become a potential biomarker for use in GC prediction, although further studies in larger groups and different populations are needed for confirmation.