Genetic polymorphism of glutathione S-transferase P1 gene and lung cancer risk

Objectives: The human GSTTP1 gene is polymorphic with an A G transition in exon 5 causing a replacement 105 IleVal in the GSTP1 protein. The two isoforms, encoded by the alleles GSTP1*A and GSTP1*B, respectively, show different catalytic efficiencies towards some carcinogenic epoxides. In this study we have addressed the possible role of the Ile105Val GSTP1 polymorphism in lung cancer susceptibility.Methods: The polymorphic site was genotyped by RFLP in a group of lung cancer patients (n=164) and in two control groups (healthy smokers, n=132; general population, n=200). All patients and controls were Northwestern Mediterranean Caucasians of the same ethnic origin.Results and Conclusions: The cancer patients showed frequencies of GSTP1*A/A; GSTP1*A/B and GSTP1*B/B (50%, 38%, 11%, respectively) very similar to those of both control groups (healthy smokers: 48%, 41%, 11%). After adjusting for age, sex and smoking status, no association was found between the GSTP1*B allele and lung cancer risk (OR: 1.18; 95% CI: 0.67–2.07). The Ile105val GSTP1 polymorphism was also analysed in combination with the GSTM1 and GSTT1 genes. The results showed that allelism at GSTP1 did not increase the risk associated with the GSTM1 or GSTT1 deletions.     

肺癌患者GSTP1基因启动子甲基化检测及其临床价值

目的 在肺癌的发生发展过程中,甲基化异常是导致相关基因失活的重要机制.本研究探讨肺癌患者谷胱甘肽S转移酶P1基因(Glutathione S-transferases P1,GSTP1)甲基化水平及其对肺癌诊断的临床价值.方法 收集2015-10-01-2016-01-31郑州大学第一附属医院收治的100例患者的肺泡灌洗液,其中80例肺癌患者(小细胞肺癌和非小细胞肺癌)为肺癌组,20例良性肺疾病患者(肺炎、慢性阻塞性肺疾病和肺结核)为对照组.以PCR联合高分辨率熔解曲线(high resolution melting assay,HRM) (PCR-HRM)方法检测GSTP1基因启动子甲基化水平,并结合肺癌患者临床病理特征进行分析.结果 肺癌组GSTP1基因启动子甲基化率为42.5％(34/80),显著高于对照组的15.0％(3/20),x2 =5.191,P=0.023.不同年龄、性别及病理类型肺癌患者GSTP1基因启动子甲基化率,差异均无统计学意义,P值分别为0.397、0.853和0.751.早期(Ⅰ和Ⅱ期)肺癌患者GSTP1基因启动子甲基化率42.5％(17/40),显著低于晚期(Ⅲ和Ⅳ期)的70.0％(28/40),x2=11.931,P=0.013;但显著高于对照组,x2=4.538,P=0.033.高、中分化肺癌患者GSTP1基因启动子甲基化率为43.9％(18/41),显著低于低分化患者的79.5％(31/39),x2=10.664,P=0.010;但显著高于对照组,x2 =4.974,P=0.026.结论 GSTP1基因启动子甲基化改变与肺癌发生发展及恶性程度有关,GSTP1基因启动子甲基化检测可能有助于肺癌诊断.     

-93G-->A polymorphism of hMLH1 and risk of primary lung cancer

Polymorphisms in DNA repair genes may be associated with differences in the repair capacity of DNA damage and may thereby influence an individual's susceptibility to smoking-related cancer. We investigated the association between the -93G-->A polymorphism in the hMLH1 gene and the risk of lung cancer in a Korean population. The hMLH1 -93G-->A polymorphism was typed in 372 lung cancer patients and 371 healthy controls that were frequency-matched for age and sex. There was no significant association between the hMLH1 -93G-->A genotype and the risk for adenocarcinoma or small cell carcinoma. However, the AA genotype was associated with a significantly increased risk for squamous cell carcinoma compared with both the GG genotype (adjusted OR=2.02; 95% CI=1.15-3.55; p=0.014) and the combined GG and GA genotype (adjusted OR=1.83; 95% CI=1.24-2.71; p=0.003). When the subjects were stratified by smoking exposure, the AA genotype was associated with a significantly increased risk for squamous cell carcinoma in lighter smokers (< or = 39 pack-years; adjusted OR=1.95; 95% CI=1.03-3.66; p=0.039) compared with the combined GG and GA genotype, whereas there was no significant association in heavier smokers (> 39 pack-years; adjusted OR=1.47; 95% CI=0.82-2.61). These results suggest that the hMLH1 -93G-->A polymorphism could be used as a marker of genetic susceptibility to squamous cell carcinoma of the lung.     

PD-1基因多态位点rs2227982和rs10204525与肺癌关联性分析

目的:PD-1基因是肿瘤免疫调节的关键靶点,本研究探讨PD-1基因的多态性位点（rs2227982 和rs10204525）与肺癌发生的关系。方法:应用病例对照研究的方法,收集肺癌患者302例和健康对照320例,采用Taqman Genotyping方法对收集的样本进行基因分型,并分析其与临床特征关系。结果:发现携带rs2227982 C等位基因,增加肺癌发病风险［OR=1.31,95%CI（1.03~1.64）］（P=0.019）,基因型分析发现在相加性模型(additive model)［OR=1.30,95%CI（1.04~1.62）］和隐性模型(recessive model)［OR=0.62,95%CI（0.42~0.97）］中与肺癌发生具有相关性。进一步通过调整吸烟、年龄和饮酒的影响后,rs2227982基因型仍与肺癌发生显著相关［OR=1.38,95%CI（1.08~1.77）］,P＜0.001。但rs2227982基因型与肺癌的病理类型和临床分期无关联,研究结果未发现rs10204525基因型与肺癌发生相关。结论:PD-1基因多态性与肺癌发生相关,rs2227982-CC基因型人群的肺癌发病率高于rs2227982-CT和rs2227982-TT基因型,通过多中心及大样本的验证,可作为潜在的遗传易感性分子标记。     

Risk modification by CYP1A1 and GSTM1 polymorphisms in the association of environmental tobacco smoke and lung cancer: a case-control study in Japanese nonsmoking women

Genetic backgrounds may modify the association of environmental tobacco smoke (ETS) with lung cancer risk. Polymorphisms of both the activating and detoxifying enzymes, cytochrome P4501A1 (CYP1A1) and glutathione-S-transferase M1 (GSTM1), may be important as genetic factors. We conducted a multicenter case-control study in Japanese nonsmoking women. Cases were women aged 30-89 years and newly diagnosed as having lung cancer from November 1997 to March 2001 in 4 study areas. We also recruited age-matched (5-year strata) and hospital-matched nonsmoking controls. A total of 158 cases and 259 hospital controls supplied blood for genotyping. Detailed information on ETS exposure from husbands and that in other situations and on potential confounders was collected by interview. Odds ratios (ORs) were estimated by using conditional logistic models. We found no increase in the risk of lung cancer for CYP1A1 Msp I genotypes. For the GSTM1 null genotype vs. nonnull genotype, the OR was 1.37 [95% confidence interval (CI) 0.90-2.09], which indicated a somewhat increased risk for the GSTM1 null genotype. A gene-environment interaction was suggested, with combined GSTM1 null genotype and high-dose ETS exposure (>/=40 pack-years by husbands) conferring significantly higher risk (OR = 2.27, 95% CI 1.13-4.57) compared to the GSTM1 nonnull genotype and low-dose ETS exposure (<40 pack-years). Our results do not support a major role of Msp I polymorphism of the CYP1A1 gene as a risk factor for lung cancer among nonsmoking women. In contrast, the GSTM1 null genotype posed an increased, although not significant, risk among them. Additional studies are warranted to confirm the ETS-GSTM1 polymorphism interaction suggested in our present study.     

Risk of lung cancer from environmental exposures to tobacco smoke

Epidemiologic evidence on the relation between environmental tobacco smoke and cancer is reviewed. The labeling of tobacco smoke as an environmental cause of lung cancer has been challenged based on allegations of bias in the epidemiologic data. However, tobacco smoke has been shown to increase the risk of lung cancer down to the lowest exposure levels. Environmental tobacco smoke contains the same carcinogenic compounds as those found in the tobacco smoke inhaled directly by the smoker. Nonsmokers environmentally exposed have elevated levels of tobacco smoke byproducts in biological samples. These observations alone are sufficient to identify tobacco smoke as an environmental carcinogen. The epidemiologic studies showing that environmental exposure to tobacco smoke is associated weakly but consistently with increased risk of lung cancer. While these epidemiologic studies have been challenged, it does not appear that the observed epidemiologic associations are due to misclassification or confounding. Indeed, the epidemiologic results, particularly among the studies with superior data collection methods and better control of bias and confounding, find consistent associations between environmental tobacco smoke and lung cancer. This paper summarizes the evidence that environmental exposure to tobacco smoke increases the risk of lung cancer, and considers the criticisms of the epidemiologic evidence which have been raised.     

晚期非小细胞肺癌ＧＳＴＰ１、ＸＲＣＣ１基因多态性与铂类药物疗效的关系

目的　探讨谷胱甘肽Ｓ转移酶Ｐ１（ＧＳＴＰ１）和Ｘ线修复交叉互补基因１（ＸＲＣＣ１）基因多态性与晚期非小细胞肺癌（ＮＳＣＬＣ）患者化疗疗效的关系。方法　经病理学确诊的晚期ＮＳＣＬＣ患者９４例,化疗前取静脉血采用ＤＮＡ测序法检测ＧＳＴＰ１和ＸＲＣＣ１基因多态性,给予铂类为主方案化疗（顺铂７５ｍｇ／ｍ２,ｄ１）,２～３周期后评价疗效,记录疾病进展时间（ＴＴＰ）,分析ＧＳＴＰ１和ＸＲＣＣ１基因多态性与化疗疗效的关系。结果　在９４例晚期ＮＳＣＬＣ患者中,携带ＧＳＴＰ１Ａ／Ａ基因４９例,Ｇ／Ａ基因３４例,Ｇ／Ｇ基因１１例;携带ＸＲＣＣ１Ｇ／Ｇ基因５２例,Ｇ／Ａ基因３５例,Ａ／Ａ基因７例,均符合Ｈａｒｄｙ Ｗｅｉｎｂｅｒｇ遗传平衡规律。携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ基因型的有效率为４４.４４％,显著高于Ａ／Ａ基因型的２０.４１％（Ｐ＜０.０５）;携带ＸＲＣＣ１Ｇ／Ｇ基因型与Ｇ／Ａ＋Ａ／Ａ基因型的有效率差异无统计学意义（Ｐ＞０.０５）;两基因多态性的联合分析显示,同时携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ和ＸＲＣＣ１Ｇ／Ａ＋Ａ／Ａ基因型的有效率最高,为６６.６７％,但未见统计学意义（Ｐ＞０.０５）。９４例患者中有５例失访,８９例患者的中位ＴＴＰ为６.５个月,携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ基因型的中位ＴＴＰ为８.０个月,Ａ／Ａ基因型为６.０个月,两者差异有统计学意义（Ｐ＜０.０１）;携带ＸＲＣＣ１Ｇ／Ｇ基因型的中位ＴＴＰ为７.０个月,Ｇ／Ａ＋Ａ／Ａ基因型为６.５个月,两者差异无统计学意义（Ｐ＞０.０５）;联合分析显示同时携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ和ＸＲＣＣ１Ｇ／Ａ＋Ａ／Ａ基因型的中位ＴＴＰ最长,为９.５个月,各组间差异有统计学意义（Ｐ＜０.０１）。结论　ＧＳＴＰ１基因多态性与晚期ＮＳＣＬＣ患者接受铂类为主化疗方案的疗效及预后有关,同时携带ＧＳＴＰ１Ｇ／Ａ＋Ｇ／Ｇ和ＸＲＣＣ１Ｇ／Ａ＋Ａ／Ａ基因型患者的化疗有效率高,预后好,但因样本量较小,需要扩大样本进一步验证。     

A European validation study of smoking and environmental tobacco smoke exposure in nonsmoking lung cancer cases and controls

Objectives: The purpose of this study was to validate, in a case-control study, the reporting by lung cancer cases and controls of their own lifetime smoking habits and of the smoking habit of the spouse. Methods: In a multicenter (Sweden, Spain, Italy) case-control study of environmental tobacco smoke (ETS) and lung cancer, subjects were screened by repeated probing to exclude regular smokers of one cigarette/day or more for one year or more, and to quantify any occasional smoking. We then performed a short validation interview with next-of-kin in three centers. Results: Only five of 408 index subjects who had never smoked regularly (1.7 percent) were reported by next-of-kin to be former regular smokers. These subjects had a cumulative lifetime consumption of cigarettes below 1.1 pack years. Among 351 subjects with quantitative smoking information from both sources who reported ever smoking 400 cigarettes or less (the definition of never-smoker used in the multicenter ETS study), nine subjects (2.6 percent) had smoked more than this amount occasionally according to next-of-kin. Misclassification was not higher for cases than controls. Relative risks for lung cancer associated with indicators of ETS exposure were not substantially altered by excluding the nine possibly misclassified subjects. The reports from 223 pairs of index subjects and next-of kin regarding the cumulative amount smoked by the spouse agreed quite well (Spearman's rank correlation 0.75 for reported smokers, 0.92 for all subjects). Only one index subject failed to report a spouse who had smoked regularly (99 percent sensitivity). Conclusions: Smoking status and exposure to spousal ETS as reported by lung cancer cases and controls agreed strongly with reports by next-of-kin. Overall, our results suggest that bias from smoker misclassification is likely to be insignificant, and they contribute to the evidence linking exposure to ETS with an increased risk of lung cancer.     

Association of a common AGO1 variant with lung cancer risk: A two‐stage case–control study

Based on the important role of microRNA (miRNA) biosynthesis genes in carcinogenesis, we hypothesized that polymorphisms in the miRNA biosynthesis genes may modulate susceptibility to lung cancer. To test this hypothesis, we conducted a two‐stage study to evaluate the associations between single nucleotide polymorphisms (SNPs) in the miRNA biosynthesis genes and the risk of lung cancer. In stage 1 of the study, 24 SNPs in the 11 miRNA biosynthesis genes (DROSHA, DGCR8, RAN, XPO5, DICER, AGO1, AGO2, HIWI, GEMIN3, GEMIN4, and TRBP) were genotyped in 100 lung cancer patients and 100 healthy controls using a sequenome mass spectrometry‐based genotyping assay. One promising SNP (AGO1 rs636832A > G) was selected for stage 2 of the study, and genotyped by a melting‐curve analysis using fluorescence‐labeled hybridization probes in an independent set of 552 cases and 552 controls. The AGO1 rs636832A > G exhibited highly consistent results between the two stages of the study. In combined analysis, the 636832A > G was associated with a significantly decreased risk of lung cancer in a dose‐dependent manner (P_trend = 6.0 × 10^?4). Individuals with at least one rs636832G allele were at a significantly decreased risk of lung cancer compared with those with the AA genotype (adjusted odds ratio = 0.67, 95% confidence interval = 0.53–0.84, P = 4.0 × 10^?4). This finding suggests that the AGO1 rs636832A > G might be a useful marker for determining the susceptibility to lung cancer and that the AGO1 gene might be involved in the development of lung cancer. © 2010 Wiley‐Liss, Inc.     

GSTP1 polymorphisms and gastric cancer in a high-risk Chinese population

Objectives: In a population-based case–control study in Yangzhong, China, we investigated the relationship between genetic polymorphisms of GSTP1 and susceptibility to gastric cancer and its premalignant lesion, chronic gastritis. The possible gene–gene interactions between GSTP1 polymorphisms and GSTM1, GSTT1 genes were explored. Methods: Epidemiologic data were collected by standard questionnaire from 133 gastric cancer cases, 166 chronic gastritis cases, and 433 cancer-free population controls. Blood samples for Helicobacter pylori and molecular marker assays were collected from 84 gastric cancer cases, 146 chronic gastritis, and 429 population controls. GSTP1 polymorphisms were determined by the PCR-RFLP method and H. pylori infection was measured by the ELISA method. Associations between certain GSTP1 genotypes and both gastric cancer and chronic gastritis were assessed by odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression. Results: The distributions of three GSTP1 genotypes, Ile/Ile, Ile/Val, and Val/Val, were similar in gastric cancer cases, chronic gastritis, and controls. After adjusting for age, gender, education, body mass index, pack-year of smoking, alcohol drinking, H. pylori infection, salt and fruit intakes, the adjusted ORs of Val/Val were 1.3 (95% CI: 0.1–11.2) for gastric cancer and 0.9 (95% CI: 0.2–4.8) for chronic gastritis. Combining the Val alleles (Val/Val and Ile/Val) into one group, no association was observed between GSTP1 and both gastric cancer and chronic gastritis. In addition, the allelism at the GSTP1 locus did not increase gastric cancer and chronic gastritis risks associated with the GSTM1 or GSTT1 genotypes. Conclusion: Our data suggest that the GSTP1 genotype seems not to be associated with the risk of gastric cancer and chronic gastritis in a high-risk Chinese population.     

Association Between the GSTP1 Codon 105 Polymorphism and Gastric Cancer Risk: an Updated Meta-analysis

Objective: The current meta-analysis was performed to address a more accurate estimation of the associationbetween glutathione S-transferase P1 (GSTP1) codon 105 polymorphism and risk of gastric cancer (GC), whichhas been widely reported with conflicting results. Methods: A comprehensive literature search was conductedto identify all the relevant studies. Fixed or random effect models were selected based on the heterogeneitytest. Publication bias was estimated using Begg’s funnel plots and Egger’s regression test. Results: A total of 20studies containing 2,821 GC cases and 6,240 controls were finally included in the analyses. Overall, no significantassociation between GSTP1 polymorphism and GC risk was observed in worldwide populations. However,subgroup analysis stratified by ethnicity showed that GSTP1 polymorphism was significantly associated withincreased risk of GC in Asians (G vs. A, OR = 1.273, 95%CI=1.011-1.605; GG vs. AA, OR=2.103, 95%CI=1.197-3.387; GG vs. AA+AG, OR =2.103, 95%CI=1.186-3.414). In contrast, no significant association was found inCaucasians in any genetic models, except for with AG vs. AA (OR=0.791, 95%CI=0.669-0.936). Furthermore, theGSTP1 polymorphism was found to be significantly associated with GC in patients with H. pylori infection andin those with a cardiac GC. Subgroup analysis stratified by Lauren’s classification and smoking status showedno significant association with any genetic model. No studies were found to significantly influence the pooledeffects in each genetic mode, and no potential publication bias was detected. Conclusions: This meta-analysissuggested that the GSTP1 polymorphism might be associated with increased risk of GC in Asians, while GSTP1heterozygote genotype seemed to be associated with reduced risk of GC. Since potential confounders could notbe ruled out completely, further studies are needed to confirm these results.     

Association between GSTP1 Genotypes and Hormone Receptor Phenotype in Invasive Ductal Carcinomas of Breast

Eighty six cases of invasive ductal breast carcinomas were utilized to investigate GSTP1 polymorphisms incertain immunohistochemistry (IHC) subtypes of breast cancer with respect to ER, PR and HER2 expression.The frequency of wild allele homozygote, heterozygote and variant allele homozygote genotypes were 46.5%,52.3% and 1.16% respectively; Whereas 54.3% of the control subjects were GSTP1 wild type allele homozygous,40.0% were heterozygous and 5.71% mutant allele homozygous. There was dramatic inverted relation betweenpositive IHC ER staining and increasing grade of tumors in general (100%, 88.6%, 40.4%) and especially amongtumors with heterozygote genotype of GSTP1 (70%, 35.4%, 22.7). There was increase in positive IHC HER2staining consistent with higher grades in general (20%, 29.6%, 50.0%), especially among tumors with GSTP1wild allele homozygote genotype (5.0%, 9.1%, 31.8%). A remarkable reverse relation was also observed betweenthe fraction of IHC hormone receptor phenotype ER+/PR+/ HER2- and increased grade of tumors (60.0%,45.5%, and 27.3%) especially among tumors with GSTP1 heterozygote genotype, and a similar link was notedregarding ER+/PR-/ HER2- and tumor grade. There was increase in frequency of ER-/PR-/ HER2- (0.0%, 6.8%,and 18.2%) and ER-/PR-/ HER2+ (0.0%, 4.54%, and 40.9%) consistent with the higher grades of tumors ingeneral and especially GSTP1 heterozygote genotype tumors. As a conclusion, there is no correlation betweenGSTP1 polymorphism and increased risk of breast cancer i.e. the mutant allele is randomly distributed in cancerand control cases. However, there is a link between GSTP1 genotypes and hormone receptor expression statusand certain phenotypes of breast cancer, which may have clinical importance.     

GSTM1, GSTT1 and GSTP1 polymorphisms, environmental tobacco smoke exposure and risk of lung cancer among never smokers: a population-based study

Carcinogenesis, 26, 395–401, 2005. The     

GSTM1, GSTT1 and GSTP1 polymorphisms, environmental tobacco smoke exposure and risk of lung cancer among never smokers: a population-based study

Glutathione S-transferases detoxify polycyclic aromatic hydrocarbons found in tobacco smoke by glutathione conjugation. Polymorphisms within the GSTM1, GSTT1 and GSTP1 genes, coding for enzymes with deficient or reduced activity, have been studied as potential modifiers of lung cancer risk. It is hypothesized that risk associated with potential susceptibility gene polymorphisms might be most evident at low levels of exposure. Never smokers developing lung cancer represent a highly susceptible subset of the population, exposed to tobacco carcinogens only through environmental tobacco smoke. This population-based case-control study examines the association between GSTM1, GSTT1 and GSTP1 genotypes and lung cancer in one of the largest samples of never smokers to date. Cases (n = 166) were identified through the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program and age- and race-matched population-based controls (n = 181) were identified using random digit dialing. Overall, there was no significant association between single or combinations of genotypes at GSTM1, GSTT1 or GSTP1 and lung cancer risk after adjustment for age, race, sex and household ETS exposure in years. However, in never smokers exposed to 20 or more years of household ETS, carrying the GSTM1 null genotype was associated with a 2.3-fold increase in risk [95% confidence interval (CI) 1.05-5.13]. Individuals in this high ETS exposure category carrying the GSTM1 null and the GSTP1 Val allele were at over 4-fold increased risk of developing lung cancer (OR = 4.56, 95% CI: 1.21-17.21). These findings suggest that in the presence of ETS, the GSTM1 genotype both alone and in combination with the GSTP1 genotype alters the risk of developing lung cancer among never smokers.     

GSTP1基因多态性与新疆维、汉肺癌易感性的关系

目的探讨谷胱甘肽S转移酶P1基因（glutathione S-transferase P1,GSTP1）rs1695位点多态性与新疆地区维吾尔族（维族）和汉族肺癌患者的相关性。方法采用病例—对照研究方法,选取维族、汉族肺癌患者各80例作为病例组,另以维族、汉族健康人群各80例为对照组,运用限制性片段长度多态性聚合酶链反应（PCRrestriction fragment length polymorphism,PCR-RFLP）技术检测GSTP1基因Ile105Val多态性,分析其基因型频率在2个民族间分布的差异。结果 （1）GSTP1基因rs1695位点多态性在对照组与病例组中的分布均符合HardyWeinberg平衡;（2）在维族人群中,GSTP1基因rs1695位点基因型在病例组与对照组中的分布频率差异无统计学意义（P〉0.05）。在汉族人群中,携带G等位基因者发生肺癌的风险增加（OR=2.170,95%CI：1.146~4.107,P〈0.05）;（3）维族人群突变型杂合子AG和纯合子GG基因型频率均高于汉族,其中在对照组中维族GSTP1（GG）基因型频率较汉族高1.3倍（8.8%vs 3.8%）,但差异均无统计学意义（均P〉0.05）。结论 GSTP1基因rs1695多态性与汉族人群肺癌发病风险相关,与维吾尔族人群无关,其相关性具有民族差异。     

miR-146a 多态性与非小细胞肺癌易感性的研究

目的：研究汉族人群miR-146a rs2910164 G/C基因多态性与非小细胞肺癌易感性的关系。方法：通过病例-对照研究,应用PCR-限制性片段长度多态性（PCR-RFLP）检测技术对198例非小细胞肺癌患者与218例对照组人群进行rs2910164基因型的检测,并随机抽取10%的样本进行DNA测序,进行遗传平衡检测。进一步采用Logistic回归分析该位点与非小细胞肺癌的相关性。结果：rs2910164被酶切成GG、GC、CC基因型,GG、GC、CC分型在对照组分别为103例（47.25%）、85例（38.99%）、30例（13.76%）;在病例组分别为31例（15.66%）、99例（50.00%）、68例（34.34%）。随机抽取10%的样本进行DNA测序,其结果与PCRRFLP分型结果一致,基因分型频率满足Hardy-Weinberg遗传平衡（P>0.05）。与对照组相比,Logistic回归分析发现携带C等位基因的基因型可明显增加非小细胞肺癌的发病风险[显性模型OR=5.04,95%CI为（4.72,5.39）,P<0.01;隐性模型OR=2.75,95%CI为（2.57,2.94）,P<0.01];而rs2910164基因多态性与非小细胞肺癌的临床病理特征（分级、分期、转移）之间无明显相关关系（P>0.05）,rs2910164基因多态性与吸烟之间无交互作用（P>0.05）。结论：携带miR-146a rs2910164 C等位基因的基因型可能与非小细胞肺癌的遗传易感性相关。     

Glu346Lys polymorphism in the methyl-CpG binding domain 4 gene and the risk of primary lung cancer

BACKGROUND: Methyl-CpG binding domain 4 (MBD4) protein functions as a DNA repair enzyme and minimizes mutations at 5-methylcytosine. Polymorphisms in the DNA repair gene MBD4 may be associated with differences in DNA repair capacity and thereby influence an individual's susceptibility to lung cancer. To test this hypothesis, we examined the potential association between the MBD4 Glu346Lys polymorphism and the risk of lung cancer in a Korean population. METHODS: The MBD4 Glu346Lys genotypes were determined in 432 lung cancer patients and 432 healthy age- and gender-matched control subjects. RESULTS: The distribution of the MBD4 Glu346Lys genotypes was not significantly different between the overall lung cancer cases and the controls. However, when the cases were categorized by tumor histology, the Lys346Lys genotype was associated with a significantly decreased risk of adenocarcinoma (AC) as compared with the Glu346Glu genotype [adjusted odds ratio (OR) = 0.50, 95% confidence interval (CI) = 0.26-0.97, P = 0.04]. On the stratification analysis, the protective effect of the Lys346Lys genotype against AC was statistically significant in older individuals and heavier smokers (adjusted OR = 0.08, 95% CI = 0.01-0.64, P = 0.02; and adjusted OR = 0.09, 95% CI = 0.01-0.72, P = 0.02, respectively). CONCLUSIONS: Our findings suggest that the MBD4 Glu346Lys polymorphism could be used as a marker for genetic susceptibility to AC of the lung.     

Association between polymorphisms in the GSTA4 gene and risk of lung cancer: a case-control study in a Southeastern Chinese population

GST Alpha 4 (GSTA4) has an important role in the protection against oxidative stress induced by carcinogens such as tobacco smoke. However, few studies investigated the association between GSTA4 polymorphisms and lung cancer risk. We genotyped three selected GSTA4 SNPs (rs182623 - 1718:T > A, rs3798804 + 5034:G > A and rs316141 + 13984:C > T) in a case-control study of 500 lung cancer patients and 517 cancer-free controls and evaluated the association between these SNPs and risk of lung cancer in this Han Chinese population. We found that there was a significant difference in genotype and allele frequency distributions of GSTA4 -1718 between the cases and the controls (P = 0.006 and P = 0.003, respectively). Compared with the GSTA4 -1718TT genotype, individuals with the TA + AA genotypes had a significantly decreased risk of lung cancer (adjusted OR, 0.63; 95% CI, 0.47-0.84; P = 0.006). Although there were no such statistical differences between the cases and controls at the loci +5034 and +13984, nor for histological types, individuals carrying the genotypes of -1718TA, +5034GG and +13984CT had a significantly decreased lung cancer risk (OR, 0.37; 95% CI, 0.23-0.61; P < 0.0001), especially for those smokers who smoked 相似文献