代谢酶基因GSTM1和广西人群胃癌遗传易感性的关系

目的探讨代谢酶基因GSTM1多态性与广西地区人群胃癌遗传易感性之间的相关性。方法采用PCR技术检测广西地区121例胃癌患者和138例健康人的GSTM1基因多态性的分布频率,分析其与广西地区胃癌遗传易感性之间的相关性以及与吸烟、饮酒在胃癌易感性中的交互作用。结果胃癌组GSTM1（-）基因型频率（54．5％）显著高于对照组（39．1％）（X^2=6．140,P=0．013）。携带GSTM1（-）基因型的个体患胃癌的风险是携带GSTM1（＋）基因型个体的2．13倍（95％CI=1．079-1．831,P=0．013）。在吸烟者中,携带GSTM1（-）基因型的个体较携带GSTM1（＋）基因型的个体患胃癌的风险明显增加（OR=3．247,95％CI=1．067—2．328,P=0．015）。其增加程度远远高于总的胃癌风险（OR=2．129）。在饮酒者中,携带GSTM1（-）基因型的个体较携带GSTM1（＋）基因型的个体患胃癌的风险亦明显增加（OR=3．117,95％CI=1．020—2．863,P=0．033）。其增加程度远远高于总的胃癌风险（OR=2．129）。结论GSTM1（-）基因型显著增加广西地区人群患胃癌的风险,且显著增加吸烟、饮酒者患胃癌的风险。     

细胞色素P450基因多态性与肺癌易感性的相关性分析

目的 探讨代谢活化酶细胞色素P4501A1（CYP1A1）、2D6（CYP2D6）、2E1（CYP2E1）和代谢解毒酶谷胱甘肽硫转移酶（GSTM1）与肺癌易感性的关系。方法采用PCR、PCR—RFLP技术检测原发性肺癌组（279例）及对照组（684例）的CYPlAI、CYP2D6、CYP2E1、GSTM1代谢酶基因型，对不同基因型在两组分布频率的差异进行OR值的统计分析。结果CYPlAl突变等位基因（m）、GSTMl功能缺失型（-）分别可使患肺癌的危险性增加1．64（OR=1．64，95％CI为1．21—2．22，P=0．001）和1．58倍（oR=1．58，95％CI为1，19—2．11，P=0．002）。其中CYPlAl与肺鳞癌、小细胞癌，GSTMl与肺鳞癌及肺腺癌明显相关（均P〈0．05）。同时携带GSTMI（-）和CYPlAl（m）可使患肺癌的危险性明显增加（OR=2．75，95％CI为1．73～4．39，P=O．OOO）。在重度吸烟人群携带GSTMl（-）、CYPlAl（m）、CYP2D6（W）或CYP2ElA基因型均可使患肺癌的危险性显著增加5．71—11．67倍（辟O．000）。结论携带GSTMI（-）及CYPlAl（m）等位基因型者患肺癌的危险性上升，二者有协同作用。在重度吸烟人群，CYP及GSTMl的检测有利于发现肺癌的高危人群。     

ADAM33基因Met764Thr位点多态性与支气管哮喘发病及患者肺功能的相关性

目的探讨中国华南地区汉族人群ADAM33基因Met764Thr位点多态性与支气管哮喘（简称哮喘）及其患者肺功能的相关性。方法对164例中国华南汉族哮喘患者（哮喘组）及112名汉族健康者（健康对照组），应用聚合酶链反应和限制性片段长度多态性（PCR-RFLP）、DNA测序及肺功能测定的方法。结果（1）不同种族人群ADAM33基因Met764Thr位点等位基因频率的比较差异无统计学意义（χ^2=6．77，P〉0．05）；（2）ADAM33基因Met764Thr位点3种基因型（Met764／Met764、Met764／Thr764、Thr764／Thr764）在哮喘组分布频率分别为78．7％（129／164）、18．3％（30／164）、3．0％（5／164）；健康对照组分布频率分别为91．1％（102／112）、6．3％（7／112）、2．7％（3／112）；各基因型分布频率哮喘组与健康对照组比较差异有统计学意义（χ^2=8．46，P〈0．05）。ADAM33基因Met764Thr位点，Thr764等位基因在哮喘组与健康对照组分布频率分别为0．122、0．058，哮喘组与健康对照组Met764及，Thr764等位基因频率比较差异有统计学意义（χ^2=6．27，P〈0．05）；（3）单变量Logistic回归分析Met764Thr位点基因多态性与哮喘的关系表明，相对Met764／Met764基因型而言，Met764／Thr764杂合型与Met764／Thr764＋Thr764／Thr764基因型均能显著增加哮喘发生的危险性[OR值及95％可信区间（CI）分别为3．389（1．430～8．030）、2．767（1．308～5．854），P均〈0．05]；（4）在哮喘组中3种基因型的用力肺活量（FVC）实测值／预测值％、第一秒用力呼气容积（FEV1）实测值／预测值％水平比较差异有统计学意义（F值分别为0．49、5．17，P均〈0．05）。结论ADAM33基因Met764Thr位点基因多态性与中国华南汉族人群哮喘发病及患者的肺功能相关。     

白细胞介素-6基因多态性对冠心病发病易感性的影响及其机制

目的了解白细胞介素-6（IL-6）基因-597G／A及-572C／G多态性对冠心病（CHD）发病易感性的影响及其影响机制。方法 应用聚合酶链反应．限制性片段长度多态性（PCR-RFLP）分析方法,测定245例CHD患者和260例正常对照者的IL-6基因型,探讨其与CHD的相关关系;观察基因型对血清IL-6水平的影响,并采用logistic回归分析法了解基因型与CHD其他危险因素间的相互作用。结果 两组研究对象中-597位点均仅发现GG基因型。-572C／G基因型和等位基因频率在两组间存在明显统计学差异（P均〈0．01）,CHD组GG基因型和G等位基因频率均显著高于对照组（P均〈0．01）;CG、GG基因型人群患CHD的风险分别为CC基因型人群的1．46倍（95％CI：1．01～2．10,P〈0．05）和5．19倍（95％CI：1．69～15．89,P〈0．01）;不同基因型患者间血清IL-6水平无统计学差异（P〉0．05）;-572C／G基因型与总胆固醇、甘油三酯间存在一定的交互作用,OR值分别为1．76（95％CI：1．05～3．16,P〈0．05）、2．51（95％CI：1．04～6．45,P〈0．05）。结论 IL-6基因-597G／A多态性可能与中国汉族人群CHD发病易感性无关,而-572C／G多态性可能是该人群CHD发病的易感基因之一,其可能通过对组织IL-6水平的影响及与血脂的协同作用参与CHD的发生。     

吸烟者细胞色素P4501A1基因多态性与冠心病的相关性分析

目的 探讨吸烟者细胞色素P4501A1（CYP1A1）基因MspI多态性与冠心病易感性的关系。方法 以病例-对照研究的方法,采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）检测349例冠心病组和404例对照组CYPlAl的基因多态性,并按吸烟指数[smoking index（SI）,吸烟支数／d×吸烟年数]的不同分析患冠心病的风险。结果 CYP1A1 MspI有3种基因型：野生型TT、突变杂合型TC和突变纯合型CC。冠心病组与对照组比较基因型分布差异无统计学意义（X^2=3．224,P=0．200）。在吸烟者中,冠心病组与对照组比较基因型分布差异有统计学意义（X^2=9．403,P=0．009）。冠心病组纯合型CC显著高于对照组,P：0．002,比值比（oddsration,OR）为3．142（95％可信区间1．481～6．668）。在低吸烟量组（I≤SI≤400）和高吸烟量组（SI〉400）中,杂合型TC和纯合型CC合计的OR值分别为2．215（95％可信区间1．087～4．510）及1．407（95％可信区间0．709～2．791）。结论 吸烟者CYP1A1基因MspI多态性与冠心病的发病可能相关。     

肿瘤坏死因子α-308基因多态性与慢性阻塞性肺疾病易感性的荟萃分析

目的运用荟萃分析方法综合评价肿瘤坏死因子α基因启动子308位（TNF-α-308）G／A基因型与慢性阻塞性肺疾病（COPD）的相关性。方法检索Medline和中国生物医学光盘数据库，获取TNF-α-308基因多态性与COPD易感性的病例一对照研究，使用统一的表格提取资料，应用RevMan 4．2软件进行统计学处理。结果检索的17篇文献中有18个病例-对照研究，共有1606例COPD患者（亚洲人666例，白种人940例）和2551例对照（亚洲人898例，白种人1653例）被纳入荟萃分析。亚洲人群等位基因TNF2与COPD密切相关（OR=2．62，95％CI为2．00～3．43），基因型TNF1／2及基因型TNF1／2合并TNF2／2者的COPD易感性高于基因型TNF1／1者（OR=2．44，95％CI为1．79-3．33及OR=2．78，95％CI为2．06～3．75），校正吸烟前后的敏感性结果相似。白种人等位基因TNF2与COPD易感性无相关性（OR=0．97，95％CI为0．84～1．14），基因型TNF1／2及基因型TNF1／2合并TNF2／2者的COPD易感性与基因型TNF1／1者相似（OR=0．96，95％CI为0．79～1．16及OR=1．03，95％CI为0．86～1．25），校正吸烟前后的敏感性结果相似。结论在亚洲人群中TNF2等位基因是COPD的危险因素，在白种人群中TNF-α-308的G／A基因多态性与COPD易感性无关。     

ABCA1基因多态性与冠心病易感性的关联研究

目的探讨三磷酸腺苷结合盒转运子A1（ATP binding cassette transporter1,ABCA1）基因R219K及M883I单核苷酸多态性（SNP）位点与脂代谢和冠心病（coronary heart disease,CHD）易感性的关系。方法以医院为基础的病例-对照研究。经冠状动脉造影确诊的冠心病病例224例,同一地区正常对照248例。分别以PCR-RFLP和PIRA-PCR对ABCA1第219密码子G→A（Arg219Lys）和第883G→A（Met883Ile）密码子多态进行检测,比较不同基因型与个体血脂水平和冠心病患病风险的关系。结果吸烟、高血压和高血糖是冠心病的独立危险因素。与携带219RR基因型者比较,携带至少1个219K等位基因者（即RK和KK基因型）冠心病患病风险显著降低59％（OR = 0．41,95％ CI = 0．27～0．61）。而在883位点,II基因型携带者患冠心病率较低（OR = 0．54,95％ CI = 0．26～1．11）。而两位点联合作用分析发现与携带219RR,883MM或883MI基因型者相比较,携带其他组合基因型的个体冠心病患病风险降低61％（OR = 0．39,95％ CI = 0．26～0．60）。另外,对照组中携带219K等位基因者血清HDL-C水平显著高于219K非携带者（P = 0．037）,提示Arg219Lys位点的多态改变主要通过改变HDL-C水平影响个体冠心病的患病风险。结论ABCA1 R219K可能与中国汉族人群冠心病遗传易感性有关,血清高密度脂蛋白可能是其作用靶点。     

基质金属蛋白酶9基因-1562位点C〉T多态性与冠心病关系的Meta分析

目的：评价基质金属蛋白酶-9基因-1562位点C〉T多态性与冠心病的关系。方法：通过PubMed,Elsevier,EMbase,CNKI等数据库搜索2012年11月30日以前发表的基质金属蛋白酶-9基因一1562位点C〉T多态性与冠心病关联性的病例对照研究文章,剔除不符合要求的文献,并根据各入选文献结果的同质性检验结果进行数据合并,计算总OR值,Meta分析采用Revman5．0及Stata11．0统计软件。结果：共有13篇病例对照研究纳入。Meta分析1Tr＋CT基因型比CC基因型OR=1．29（95％CI为1．13～1．47,P〈0．01）;T等位基因比c等位基因OR=1．27（95％CI为1．13-1．42,P〈0．01）;CT基因型比CC＋TT基因型OR=1．29（95％CI：1．13～1．48）,P〈0．01）。结论：基质金属蛋白酶-9基因1562位点C〉T多态性与冠心病发病相关,基质金属蛋白酶-9基因1562位点T等位基因是冠心病易感性的标记基因。     

GSTM1基因多态性与肺癌发病的相关性研究

目的探讨谷胱甘肽硫转移酶M1（GSTM1）基因多态性与肺癌易感性的关系，以期用于肺癌的筛检。方法用PCR法分析56例肺癌（简称肺癌组）和42例健康对照组GSTM1基因型，并用Logistic多因素回归法分析可能影响GSTM1的职业环境因素、生活习惯、及宿主个体因素。结果肺癌组GsTM1基因缺失型[GSTM1（-）]发生率达71．43％，显著高于对照组的45．24％，差异有统计学意义，P〈0．05；GSTM1（-）型与肺癌呈高度联系强度，OR=3．09（95％CI=1．32～6．94）；Logistic回归分析表明，职业接触PAHs（OR=6．6939，P=0．009）、吸烟（OR=9．7058，P=0．0010）、既往肺病史（OR=7．5233，P=0．0465）与GST M1（-）型相关。结论GST M1（-）型个体增加了肺癌发生的风险性，可作为宿主肺癌易感性的遗传标志。     

XRCC1和XPD单核苷酸多态性与非小细胞肺癌铂类药物化疗敏感性的关系

目的研究X线修复交叉互补基因1（XRCC1）和着色性干皮病基因（XPD）单核苷酸多态性与老年晚期非小细胞肺癌（NSCLC）铂类药物化疗敏感性关系。方法应用聚合酶链反应结舍限制性片段长度多态性（PCR-RFLP）的方法检测81例以铂类药物为主要化疗方案的NSCLC患者XRCC1 Arg399Gln和XPD Lys751Gin基因型多态性，采用非条件Logistic回归分析不同基因型与化疗疗效的关系。结果81例患者化疗总有效率为35．8％，其中完全缓解（CR）、部分缓解（PR）、稳定（SD）和进展（PD）患者分别为0、29、31、21例。携带至少1个XRCC1 399Arg等位基因的患者化疗敏感性是携带Gln／Gln基因型患者的4.52倍（OR=4．52，95％CI=1.11—18．38）。未发现XPD Lys751Gin遗传多态与化疗敏感性相关。结论XRCC1 Arg399Gln多态可能与晚期NSCLC铂类药物化疗敏感性有关。     

XRCC2 and XRCC3 gene polymorphism and risk of pancreatic cancer

OBJECTIVES: XRCC2 and XRCC3 are key components of the homologous recombination (HR) machinery that repairs DNA double-strand breaks. We hypothesized that the altered HR repair capacity conferred by single nucleotide polymorphisms (SNPs) would modify individual susceptibility to sporadic pancreatic cancer. METHODS: In a hospital-based case-control study, genomic DNA and exposure information was obtained from 468 patients with pathologically confirmed pancreatic adenocarcinoma and 498 frequency-matched healthy controls at M.D. Anderson Cancer Center during January 2000 to September 2006. Genotypes of XRCC2 31479 G>A (Arg188His) and XRCC3 17893 A>G and 18067 C>T (Thr241Met) were determined using the Masscode technology. Unconditional logistic regression models were used to estimate the odds ratio (OR) and its 95% confidence interval (CI) in non-Hispanic whites (408 cases and 449 controls). RESULTS: The distribution of genotype frequencies was not different between cases and controls. We observed a significant effect modification between XRCC2 polymorphism and smoking status and pack-year of smoking in modifying pancreatic cancer risk (P value for interaction 0.02 and 0.05, respectively). Compared with never-smokers carrying the XRCC2 Arg188Arg genotype, the OR (95% CI) for individuals carrying the (188)His allele was 2.32 (1.25-4.31) among ever-smokers, 1.43 (0.59-3.48) among light smokers (< or = 22 pack-years), and 3.42 (1.47-7.96) among heavy smokers (> or =22 pack-years). The two XRCC3 SNPs are in strong linkage disequilibrium, but there was no suggestive association between XRCC3 genotype and the risk of pancreatic cancer. CONCLUSION: XRCC2 Arg188His polymorphism may be one of the genetic modifiers for smoking-related pancreatic cancer.     

Meta analysis of XRCC3 Thr241Met polymorphism and lung cancer susceptibility of populations in East Asia

Objective:To assess the relation between XRCC3 Thr241Met polymorphism and lung cancer susceptibility of populations in East Asia.Methods:Related studies of XRCC3 Thr24lMet polymorphism and lung cancer susceptibility of populations in East Asia were collected through searching the Pubmed,Embase Library,SPRINGER.CNKI and CSSCI.Results:According to the entry criteria,there were 8 case-control studies in the assessing system and there were 6 321study cases,including 3 215 patients with lung cancer and 3 106 cases without cancers.Meta analysis results showed the combined OR value of the ratio of genotype Thr/Met+Met/Met and Thr/Thr was 1.03(95%CI:0.89-1.20)(P0.05).Conclusions:XRCC3 Thr241Met polymorphism may not related to lung cancer susceptibility of populations in East Asia.Allele 241Met did not increase the risk of lung cancer.     

Polymorphisms of DNA repair genes XRCC1 and XRCC3, interaction with environmental exposure and risk of chronic gastritis and gastric cancer

AIM: To evaluate the association between polymorphisms XRCC1 Arg194Trp and Arg399Gln and XRCC3 Thr241Met and the risk for chronic gastritis and gastric cancer, in a Southeastern Brazilian population. METHODS: Genotyping by PCR-RFLP was carried out on 202 patients with chronic gastritis (CG) and 160 patients with gastric cancer (GC), matched to 202 (CI) and 150 (C2) controls, respectively. RESULTS: No differences were observed among the studied groups with regard to the genotype distribution of XRCCl codons 194 and 399 and of XRCC3 codon 241. However, the combined analyses of the three variant alleles (194Trp, 399Gln and 241Met) showed an increased risk for chronic gastritis when compared to the GC group. Moreover, an interaction between the polymorphic alleles and demographic and environmental factors was observed in the CG and GC groups. XRCC1 194Trp was associated with smoking in the CG group, while the variant alleles XRCC1 399Gln and XRCC3 241Met were related with gender, smoking, drinking and H pylori infection in the CG and GC groups. CONCLUSION: Our results showed no evidence of a rela-tionship between the polymorphisms XRCCl Argl94Trp and Arg399Gln and XRCC3 Thr241Met and the risk of chronic gastritis and gastric cancer in the Brazilian population, but the combined effect of these variants may interact to increase the risk for chronic gastritis, considered a premalignant lesion. Our data also indicate a gene-environment interaction in the susceptibility to chronic gastritis and gastric cancer.     

Prognostic importance of DNA repair gene polymorphisms of <Emphasis Type="Italic">XRCC1</Emphasis> Arg399Gln and <Emphasis Type="Italic">XPD</Emphasis> Lys751Gln in lung cancer patients from India

Purpose Inter individual variation in lung cancer susceptibility may be modulated in part through genetic polymorphisms in the DNA repair genes, especially the genes involved in the Base Excision Repair (BER) and nucleotide excision repair (NER) pathway. Two of the genetic polymorphisms, XRCC1Arg399Gln and XPD Lys751Gln have been extensively studied in the association with lung cancer risk, although published studies have been inconclusive. Methods In order to verify the role of the common variant alleles in the XPD gene, we have genotyped 211 lung cancer patients and 211 healthy controls using PCR-RFLP assays in a hospital based, case-control study in an Indian population. Logistic regression models were fit to examine the relationship between the log odds of lung cancer and each covariate. Overall Survival in relation to various genotypes and clinicopathological factors were analyzed using Kaplan Meier estimates and hazard ratios were calculated using Cox Regression analysis. Results The carriers of XRCC1 399 AA genotypes were at higher risk of lung cancer (OR = 2.1, 95% CI:1.224–3.669, P = 0.007) than carriers of GG genotype. Subjects carrying 751 AC genotype were at an increased risk of carcinoma of the lung (OR = 1.8; 95% CI:1.233–2.807, P = 0.003) than subjects with AA genotypes. Compared to the XRCC1 399 GG/ XPD 751 AA reference genotype, the combined variants, XRCC1 399 GG/ XPD 751 AC+CC (OR = 1.9, 95% CI: 1.037–3.481), P = 0.03), XRCC1 399 GA+AA/ XPD 751 AA (OR = 1.7, 95% CI: 1.020–2.833, P = 0.04), XRCC1 399 GA+AA/XPD 751 AC+CC (OR = 2.7, 95% CI: 1.582–4.864, P = 0.01), had significantly higher odds ratios. Increasing numbers of either XPD or XRCC1 variant alleles were associated with shorter overall survival, the risk being significant for the XRCC1 gene polymorphism (P = 0.01 by log-rank test). The hazard of dying was significant for the XRCC1 399 AA genotype (HR = 3.04, 95%CI: 1.393–6.670, P = 0.005). Higher tumour stage also came out as significant predictors of patient death. Conclusions These findings suggest that genetic polymorphisms in the DNA repair genes may modulate overall lung cancer susceptibility and that pathological stage and XRCC1 Arg399Gln independently predicted overall survival among Indian lung cancer patients.     

Polymorphisms in DNA repair genes XRCC1, XRCC3 and XPD, and colorectal cancer risk: a case–control study in an Indian population

Purpose

Genetic polymorphisms in DNA repair genes may influence variations in individual DNA repair capacity, which could be associated with the development of cancer. We detected the distributions of three single-nucleotide polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln) in DNA repair genes, and assessed the associations of these genetic polymorphisms with colon and rectal cancer susceptibility as well as evaluated the interactions of gene–gene and gene–environment in a case–control study of an Indian population.

Methods

This case–control study was conducted with 302 cases (including 59 colon and 243 rectal cancer patients) and 291 cancer-free healthy controls. Genotypes were determined by PCR–RLFP assays. The effects [odds ratios (ORs) and 95% confidence intervals (95% CIs)] of genetic polymorphisms on colorectal cancer were estimated using unconditional logistic regression.

Results

The XRCC1 399Gln allele was found to be associated with a significantly increased rectal cancer risk among men (OR = 1.65, 95% CI 1.04–2.64). Whereas the XRCC3 241Met allele showed a protective tendency against rectal cancer (OR = 0.68, 95% CI 0.46–1.02) for both men and women. Furthermore, a combination of the XRCC1 399Gln allele with XRCC3 Thr/Thr genotype and the XPD 751Gln allele demonstrated the highest rectal cancer risk (OR = 3.52, 95% CI 1.43–9.44).

Conclusions

The combined effects of putative risk alleles/genotypes for different DNA repair pathways may strengthen the susceptibility to rectal cancer.     

A prospective study of genetic polymorphisms in the cytochrome P-450 2C9 enzyme and the risk for distal colorectal adenoma.

BACKGROUND & AIMS: Regular aspirin use is associated with a reduced risk for colorectal adenoma, whereas smoking increases risk. The cytochrome P-450 (CYP) 2C9 (CYP2C9) enzyme is involved in the metabolism of several drugs, including possibly aspirin, and such carcinogens as smoking-related polycyclic aromatic hydrocarbons. Genetic variation in this enzyme may modulate the influence of aspirin and smoking on adenoma risk. METHODS: We examined the risk for incident distal colorectal adenoma according to CYP2C9 genotype, aspirin use, and smoking in a prospective nested case-control study of women. RESULTS: Among 394 cases and 396 controls, women with at least 1 variant CYP2C9 allele had a significantly greater risk for adenoma (multivariate odds ratio [OR], 1.56; 95% confidence interval [CI], 1.13-2.15; P = 0.007). Although women who used aspirin regularly (>/=2 standard tablets/wk) experienced a lower risk for adenoma compared with non-regular users, the effect was similar irrespective of genotype. Women who smoked >20 pack-years had an OR of adenoma of 1.50 (95% CI, 1.07-2.12; P = 0.02) compared with those who smoked 20 pack-years, the OR of adenoma was 2.50 (95% CI, 1.44-4.38; P = 0.001) compared with women with no variant alleles who smoked 相似文献   

Genetic polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase and risk of pancreatic cancer.

BACKGROUND & AIMS: Human pancreatic cancer might be associated with folate deficiency and impaired metabolism. We tested this hypothesis by examining the contribution of functional polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) to risk of cancer. METHODS: DNA from 163 pancreatic cancer patients and 337 control subjects was genotyped for MTHFR (677C > T and 1298A > C) and TS (5'-untranslated region tandem repeat and G/C). Association with risk of pancreatic cancer was estimated by logistic regression. All statistical tests were two-sided. RESULTS: We observed an increased risk of pancreatic cancer associated with the MTHFR 677CT (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.61-4.29; P = .0005) or 677TT (OR, 5.12; 95% CI, 2.94-9.10; P < .0001) genotype compared with the MTHFR CC genotype. An increased risk of pancreatic cancer was also associated with the TS 3Rc/3Rc genotype (OR, 2.19, 95% CI, 1.13-4.31; P = .022) compared with the TS 3Rg/3Rg genotype. Joint effect between MTHFR C677T polymorphism and smoking or drinking increased risk of pancreatic cancer in a super-multiplicative manner. The ORs for smoking, the polymorphism, and both factors combined were 0.70 (95% CI, 0.30-1.63), 2.17 (95% CI, 1.17-4.21), and 3.10 (95% CI, 1.54-6.51), respectively. This joint effect was much stronger in heavy smokers (OR, 6.69; 95% CI, 3.39-13.63; P < .0001). The ORs for drinking, the polymorphism, and both factors combined were 0.98 (95% CI, 0.40-2.30), 2.81 (95% CI, 1.65-4.98), and 4.39 (95% CI, 2.25-8.78), respectively. CONCLUSION: The MTHFR and TS polymorphisms are genetic determinants for developing pancreatic cancer.     

DNA修复基因XRCC1 Arg194Trp Arg280His和Arg399Gln多态性与前列腺癌相关性的Meta分析

目的探讨DNA修复基因X线修复交叉互补因子1（XRCC1）主要单核苷酸多态性与前列腺癌易感性的关系。方法在MEDLINE、EMBASE和OVID数据库上检索文献,收集及提取符合纳入标准的以XRCC1密码子194、280、399多态性与前列腺癌易感性为内容的病例对照研究文献,应用Stata统计软件进行Meta分析,比值比（ORs）及其95%可信区间（95%CI）评价关联强度;应用SPSS软件分析吸烟与前列腺癌关系,OR？评价其相对危险度。结果 XRCC1 399 Gln/Gln和XRCC1 280 Arg/His与前列腺癌的发病风险有关（Gln/Gln vs Arg/Arg：OR？=1.27,95%CI=1.02～1.59;Arg/His vs Arg/Arg：OR？=1.66,95%CI=1.09～2.52）,尤其在亚组分析中亚洲人的Gln/Gln明显增加了前列腺癌的发病风险（OR？=1.52,95%CI=1.18～1.96）;Arg194Trp与前列腺癌的发病风险无明显关联。吸烟是前列腺癌的危险因素（χ2=13.974,P=0.000,OR？=1.22）。结论 XRCC1 399 Gln/Gln和280 Arg/His可能与前列腺癌的易感性相关。     

Adenosine diphosphate ribosyl transferase and x-ray repair cross-complementing 1 polymorphisms in gastric cardia cancer

BACKGROUND & AIMS: Adenosine diphosphate ribosyl transferase (ADPRT) and x-ray repair cross-complementing 1 (XRCC1) are major DNA base excision repair proteins acting interactively in repair processes. This study examined the effects of ADPRT Val762Ala and XRCC1 Arg399Gln polymorphisms on ADPRT-XRCC1 interaction in vitro in cells and their contributions to gastric cardia adenocarcinoma (GCA) risk. METHODS: The ADPRT-XRCC1 interaction in cells transfected with ADPRT and XRCC1 variant complementary DNA (cDNA) constructs were examined by immunoprecipitation and immunoblotting analysis. Genotypes were analyzed in 500 patients and 1000 controls, and odds ratios (ORs) were estimated by logistic regression. RESULTS: Interactions between ADPRT-762Val and XRCC1-399Arg or XRCC1-399Gln were robust, but interactions between ADPRT-762Ala and either XRCC1-399Arg or XRCC1-399Gln were very weak. A case-control analysis showed ORs of 2.17 (95% CI, 1.55-3.04) and 1.61 (95% CI, 1.06-2.44) for GCA in the ADPRT Ala/Ala or XRCC1 Gln/Gln genotype carriers, respectively, compared with noncarriers. Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased the OR of GCA in a multiplicative manner (OR for the presence of both ADPRT Ala/Ala and XRCC1 Gln/Gln genotypes, 6.43; 95% CI, 1.80-22.97). A supermultiplicative joint effect between the ADPRT polymorphism and smoking was observed. The ORs (95% CIs) of the Ala/Ala genotype for nonsmokers and smokers who smoked < or = 24 or > 24 pack-years were 1.44 (0.89-2.32), 2.00 (1.09-3.67), or 3.19 (1.59-6.42), respectively (Ptrend test = .008). CONCLUSIONS: The ADPRT and XRCC1 polymorphisms confer host susceptibility to GCA, which might result from reduced ADPRT-XRCC1 interaction and attenuated base excision repair capacity.     

Angiotensinogen Met235Thr polymorphism, angiotensin-converting enzyme inhibitor therapy, and the risk of nonfatal stroke or myocardial infarction in hypertensive patients

The ThrThr genotype of the angiotensinogen (AGT) Met235Thr polymorphism has been associated with elevated AGT levels, hypertension, increased heart disease risk, and improved blood pressure (BP) response to angiotensin-converting enzyme (ACE) inhibitors. We hypothesized that risk of stroke or myocardial infarction (MI) associated with ACE inhibitor use varies by AGT genotype, with a larger protective effect of ACE inhibitors in individuals with the ThrThr genotype than individuals who are carriers of the Met allele. METHODS: We conducted a population-based case-control study. Participants were health maintenance organization members aged 30 to 79 years with treated hypertension. Those who survived incident stroke (n = 116) or MI (n = 208) during the study period were designated as cases. Control subjects (n = 717) were randomly sampled and frequency-matched to MI cases on age, sex, and calendar year. Health history, medication use, and AGT genotype were assessed. RESULTS: ThrThr genotype was present in 21% of stroke cases, 26% of MI cases, and 19% of control subjects. Compared with nonuse, ACE inhibitor use was associated with lower stroke risk among Thr homozygotes (odds ratio [OR] = 0.37, 95% CI = 0.14 to 0.99) than among Met carriers (OR = 1.4, 95% CI = 0.88 to 2.4; P for interaction =.02). Compared with nonuse, ACE inhibitor use was associated with similar MI risk among Thr homozygotes (OR = 0.90, 95% CI = 0.62 to 1.3) and among Met carriers (OR = 1.2, 95% CI = 0.60 to 2.5; P for interaction = 0.5). CONCLUSIONS: In this hypertensive population, the association of ACE inhibitor use with risk of nonfatal stroke varied by genotype. The protective association between ACE inhibitor use and nonfatal stroke risk among individuals with ThrThr genotype was not observed for nonfatal MI.