XRCC1、GSTM1基因多态性与肺癌易感性的相关性

目的探讨X射线损伤修复的交叉互补基因(XRCC)1、谷胱甘肽硫转移酶基因(GSTM)1多态性与肺癌易感性的相关性。方法选取150例作为肺癌组,依据病理类型分为75例鳞癌、22例腺癌、20例小细胞癌、33例其他类型癌,同期选取健康体检者150例作为正常组,采用PCR扩增技术检测XRCC1、GSTM1基因型,采用叉生分析法分析二者基因的联合作用与易感性危险度的关系,统计分析所有研究对象的XRCC1、GSTM1基因型表达情况。结果 XRCC1基因分为野生纯合型(Arg/Arg)、杂合型(Arg/His)、突变纯合型(His/His),其中肺癌组Arg/Arg检出率明显低于健康组(P0.05),前者His/His检出率明显高于后者(P0.05),二者Arg/His检出率基本相同(P0.05),鳞癌、腺癌、其他类型癌与正常组比较有显著差异(P0.05),小细胞癌与正常组比较无显著差异(P0.05)。肺癌组GSTM1+检出率明显低于正常组(P0.05),前者GSTM1-检出率明显高于后者(P0.05),鳞癌、腺癌、其他类型癌与正常组比较有显著差异(P0.05),小细胞癌与正常组比较无显著差异(P0.05);叉生分析法显示在患肺癌危险度方面,同时携带XRCC1(Arg/His+His/His52)和GSTM1-XRCC1(Arg/Arg)和GSTM1-XRCC1(Arg/His+His/His52)和GSTM1+XRCC1(Arg/Arg)和GSTM1+(P0.05)。结论 XRCC1(Arg/His+His/His52)和GSTM1-是肺癌的重要易感因素,个体携带者具有较高的患肺癌风险,且二者具有联合作用,可显著增加肺癌发生的风险,提示医师应重点关注和谨慎筛查此类群体。     

NF-κB信号传导通路相关基因不同表型肝癌患者尿8-OHdG水平观察

目的观察NF-κB信号传导通路相关基因不同表型的肝癌患者尿8-羟基脱氧鸟苷（8-OHdG）水平。方法 PCR-RFLP法检测155例肝癌患者（肝癌组）NF-κB信号传导通路中TNF-α、NF-κB、iNOS、COX-2的基因表型。采用ELISA法检测肝癌组及151例健康体检者（对照组）的尿8-OHdG。结果肝癌组尿8-OHdG水平为（9.29±8.04）ng/mg Cr,对照组为（7.27±5.06）ng/mg Cr,两组相比,P〈0.05。肝癌组NF-κB信号传导通路相关基因TNF-α、NF-κB、iNOS、COX-2基因不同表型组尿8-OHdG水平相比,P均〉0.05。结论肝癌患者尿8-OHdG水平高于正常,可能与肝癌发病有关。NF-κB信号传导通路相关基因多态性与肝癌患者尿8-OHdG水平无明显关系。     

汉民族XRCC1基因399位密码子单核苷酸多态性与原发肝癌关系的研究

目的探讨汉民族XRCC1基因399位密码子单核苷酸多态性与原发肝癌之间的关系。方法原发肝癌患者50例,肝炎肝硬化患者61例,健康献血人员92例。针对XRCC1基因的10号外显子设计引物,PCR产物利用MspⅠ限制性酶切进行基因分型,基因型分成XRCC1 399Arg/Arg,399Arg/Gln,399Gln/Gln三种,分析XRCC1多态性与肝癌之间的关系。结果原发肝癌患者中XRCC1 399Arg/Arg 32例(64.0%),Arg/Gln 14例(28.0%),Gln/Gln 4例(8.0%);肝炎肝硬化患者中Arg/Arg 30例(49.2%),Arg/Gln 23例(37.7%),Gln/Gln 8例(13.1%);健康人群Arg/Arg 46例(50.0%),Arg/Gln 41例(44.5%),Gln/Gln 5例(5.5%)。以健康人群为对照组,XRCC1399Gln基因(基因型Arg/Gln和Gln/Gln)并不增加患肝癌的风险性(OR=0.563,95%CI:0.277-1.141,P=0.109);以肝炎肝硬化为对照组,XRCC1 399Gln基因同样与患肝癌的易感性之间没有显著的相关性(OR=0.544,95%CI:0.253-1.170,P=0.118)。结论XRCC1基因密码子399位点的基因多态性与汉民族原发肝癌危险性无统计学相关关系。     

X线交错互补修复基因1多态性与前列腺癌的遗传易感性

选择华东地区207例前列腺癌（PCa）患者为作为病例组,235例非肿瘤、非前列腺疾病的男性患者作为对照组。用PCR-RFLP方法分析两组X线交错互补修复基因1（XRCC1）Arg194Trp和Arg280His两个位点的多态性,比较不同基因型与PCa易感性的关系。结果显示,XRCC1第194密码子携带194Trp等位基因的个体（Arg/Trp＋Trp/Trp）患PCa的风险较Arg/Arg基因型的个体降低38%（校正OR=0.62,95%CI为0.410.93）;在≤70岁及不吸烟两组人群中,携带194Trp等位基因的个体PCa发病风险比Arg/Arg基因型的个体分别降低45%（OR=0.55,95%CI为0.30-1.00）和52%（校正OR=0.48,95%CI为0.24-0.95）。认为XRCC1 Arg194Trp位点多态性可能对PCa遗传易感性产生影响,并与吸烟在PCa的发病中有一定的协同作用。     

X线损伤交叉互补基因1多态性与结直肠癌易感性研究

目的 探讨DNA修复酶X线损伤交叉互补基因1(XRCC1 )外显子三个位点的基因多态性(Arg194Trp 、Arg280His、Arg399Gln)与结直肠癌(CRC)发病风险的关系.方法 以聚合酶链反应和限制性片段长度多态性(PCR-RFLP)分析方法,采用病例-对照研究,对250例CRC患者(病例组,其中结肠癌128例,直肠癌122例)和213名健康人(对照组)的XRCC1基因三个位点的多态性进行了检测,采用SPSS 11.0软件包统计分析各位点的基因型分布和等位基因频率.结果 XRCC1基因194和399二个位点的各基因型频率在两组间分布差异均无统计学意义(P值均>0.05),但病例组XRCC1基因280 Arg/His基因型频率较对照组显著增高(校正后OR=1.66,95%CI:1.01～2.73,P=0.047).在直肠癌患者组中,280Arg/His基因型频率较对照组显著增高(OR=1.82,95%CI:1.02～3.27),携等位基因280His(Arg280His +His280His)的CRC患者的频率显著高于其在对照组中的频率(校正后OR=1.85,95%CI:1.06～3.22),而在结肠癌患者中风险系数相对较低且差异无统计学意义(校正后OR=1.31,95%CI:0.74～2.35).结论 XRCC1 Arg194Trp和 Arg399Gln基因多态性与结肠癌易感性无关,但280Arg/His基因型能增加CRC易感性,等位基因280His是直肠癌风险因素.

Abstract：

Objective To investigate the correlation between three gene locus polymorphisms of X-ray repair cross-complementary protein 1 (XRCC1) exon (Arg194Trp, Arg280His and Arg399Gln) and the risk of colorectal cancer (CRC). Methods A case-control study was performed in 250 CRC patients (case group, 128 colon cancer patients and 122 rectal cancer patients) and 213 healthy individuals (control group). The three gene locus polymorphism of XRCC1 was tested by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The genotype distribution and allele frequency of each locus was analyzed with SPSS 10.0 software. Results There was no significant difference in allele frequency of XRCC1 at 194 and 399 loci (P > 0.05). However, the 280 Arg/His allele frequency of XRCC1 was higher in case group than that in control group (OR=1.66,95%CI:1.01~2.73,P=0.047). The 280Arg/His allele frequency was higher in rectal cancer group than that in control group (OR =1.82,95%CI:1.02~3.27). The frequency of 280His allele (Arg280His and His280His) was higher in case group than that in control group (OR=1.85,95%CI:1.06~3.22). However, it was a relative low risk factor of colon cancer and there was no significant difference between colon cancer group and control group (OR=1.85, 95%CI:1.06~3.22). Conclusions There was no correlation between XRCC1 Arg194Trp and Arg399Gln polymorpohisms and the risk of CRC. However, 280Arg/His genotype may increase the risk of CRC, and 280His allele is a risk factor of rectal cancer.     

The relationship between lung cancer and genetic polymorphism of XRCC1

目的 探讨X线交叉互补修复基因1(XRCC1)多态性与肺癌之间的关系,研究吸烟与易感基因的交互作用.方法 采用病例对照研究,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测XRCC1-194、XRCC1-399基因型频率.结果 XRCC1-194突变型基因频率在肺癌组及对照组中分别为30.5％和20％,两者比较差异有统计学意义(P＜0.05);XRCC 1-399突变型基因频率在两组中分别为20.5％和15％,两者比较差异无统计学意义(P＞0.05);但XRCC1-194突变型基因频率在小细胞肺癌患者及非小细胞肺癌患者中分别为18.18％和33.97％,两者比较差异有统计学意义(P＜0.05).有吸烟史而无XRCC1-194单核苷酸多态性时的相对危险度为1.851,无吸烟史而有XRCC1 - 194单核苷酸多态性时的相对危险度为2.336,有吸烟史且XRCC1-194单核苷酸多态性均存在时的相对危险度为8.01.结论 XRCC1-194基因多态性与肺癌的发生相关,主要与非小细胞肺癌的发生密切相关;吸烟史及XRCC1-194单核苷酸多态性在肺癌的发生中有交互作用.     

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。     

xpc 基因多态性与胃癌发生风险的关系

目的：探讨xpc基因多态性与胃癌发生风险的关系。方法提取202例胃癌患者（胃癌组）及327例健康体检者（正常对照组）外周血基因组 DNA,分别用 PCR-PFLP、PCR 方法检测 xpc exon8 Ala499Val、exon15 Lys939 Gln和intron9 PAT位点的基因型,以非条件Logistic回归分析其多态性及相关单倍型与胃癌发生风险的关系。结果 xpc exon8 Ala499 Val、exon15 Lys939 Gln和intron9 PAT多态性位点基因型频率在胃癌组与正常对照组间比较差异无统计学意义（P均＞0．05）。这3个多态性位点所构建的8个单倍型在胃癌组与正常对照组间比较差异亦无统计学意义（ P均＞0．05）。结论 xpc基因多态性与胃癌发生风险无关。     

脑梗死患者血小板膜糖蛋白Ⅰ bα基因HPA-2、Kozak位点多态性分析

目的观察脑梗死患者血小板膜糖蛋白（GP）Ⅰbα基因HPA-2、Kozak位点多态性,探讨其与脑梗死的关系。方法选取316例经CT或MR I证实的脑梗塞患者（观察组）及209例无脑血管疾病者（对照组）,采用聚合酶链反应—限制性片断长度多态性（PCR-RFLP）法检测GPⅠbα基因HPA-2、Kozak位点多态性,用流式细胞术（FCM）测定血小板活化标志物CD62P、CD63的表达。结果观察组血小板GPⅠbα基因HPA-2位点基因型分布及等位基因频率与对照组相比P均〉0.05;观察组Kozak位点观察组基因型为CC者20例、CT者113例、TT者169例,等位基因C频率为25.33%、T频率为74.67%;对照组分别为6、28、162例和10.20%、89.80%。两组基因型分布和等位基因C、T频率相比,P均〈0.05。观察组表达等位基因C者（基因型CC＋CT）CD62P表达量为20.94±7.35、CD63表达量为28.62±9.47,不表达等位基因C者（基因型为TT）分别为13.36±6.27、20.27±5.45,二者CD62P、CD63表达量相比P均〈0.05。结论 脑梗死患者血小板GPⅠbα基因Kozak位点存在多态性,HPA-2位点未发现多态性。GPⅠbα基因Kozak位点多态性可能通过影响血小板的活化参与脑梗死的发生过程。     

砷中毒患者皮肤组织中DNA修复基因的表达变化

目的检测DNA修复基因MGMT、XRCC1、hMSH2mRNA在燃煤型砷中毒患者皮肤组织中的表达变化,探讨其表达与砷性皮肤癌发生发展及临床病理特征之间的关系。方法应用原位杂交技术检测了61例砷中毒患者皮肤组织中MGMT、XRCC1、hMSH2mRNA的表达变化。结果随着砷中毒患者皮肤病变的发展,MGMT、XRCC1、hMSH2mRNA的表达逐渐降低,癌变组MGMT和XRCC1mRNA阳性表达率与一般病变组比较差异有统计学意义(P<0.05、P<0.01)。结论MGMT、XRCC1、hMSH2作为DNA损伤修复基因,在砷性皮肤病变过程中起重要作用;砷可能通过抑制砷中毒患者皮肤组织中MGMT、XRCC1等DNA修复基因的表达,影响基因组DNA稳定性和DNA修复功能而导致对皮肤的致癌作用。     

DNA polymorphism and risk of esophageal squamous cell carcinoma in a population of North Xinjiang,China

AIM:To investigate the role of metabolic enzyme and DNA repair genes in susceptibility of esophageal squamous cell carcinoma(ESCC). METHODS:A case-control study was designed with 454 samples from 128 ESCC patients and 326 gender, age and ethnicity-matched control subjects.Genotypes of 69 single nucleotide polymorphisms(SNPs)of metabolic enzyme(aldehyde dehydrogenase-2,ALDH2; alcohol dehydrogenase-1 B,ADHB1;Cytochrome P450 2A6,CYP2A6)and DNA repair capacity genes(excision repair cross complementing group 1,E...     

Correlation between polymorphisms in DNA mismatch repair genes and the risk of primary hepatocellular carcinoma for the Han population in northern China

Abstract

Purpose: This study investigated correlations between polymorphisms in DNA mismatch repair (MMR) genes and the risk of primary hepatocellular carcinoma (PHC). Methods. Single nucleotide polymorphisms (SNPs) in the DNA MMR genes MLH3 (rs175080), PMS1 (rs5742933), PMS2 (rs1059060), MSH3 (rs26279), MSH5 (rs1150793, rs2075789) and MSH6 (rs1042821) were detected using the SNaPshot method in 250 PHC cases and in 308 patients without PHC in the Han population in northern China. Results. The AA genotype in MLH3 (rs175080) increased the risk of PHC (odds ratio [OR] = 3.424; 95% confidence interval [CI]: 1.097–10.689). The AG and GG genotypes in MSH3 (rs26279) increased the risk of PHC (OR: 1.644 and 3.300; 95% CI: 1.112–2.428 and 1.765–6.168, respectively). The AA genotype in MSH5 (rs2075789) increased the risk of PHC (OR: 9.229; 95% CI: 1.174–72.535). The CT genotype in MSH6 (rs1042821) reduced the risk of PHC (OR: 0.629; 95% CI: 0.428–0.924). Conclusions. Our study suggests that polymorphisms in MLH3 (rs175080), MSH3 (rs26279), MSH5 (rs2075789) and MSH6 (rs1042821) may be independent risk factors for PHC.     

DNA repair gene XRCC7 polymorphisms (rs#7003908 and rs#10109984) and hepatocellular carcinoma related to AFB1 exposure among Guangxi population, China

Aim: The X‐ray repair cross‐complementing group 7 (XRCC7) plays an important role in the repair of DNA double‐strand breaks by nonhomologous end‐joining repair (NEJR) pathway. However, the role of XRCC7 polymorphisms (rs#7003908 and rs#10109984) possibly influencing NEJR capacity in hepatocellular carcinoma (HCC) induced by aflatoxin B1 (AFB1) has not been well elaborated. Methods: This hospital‐based case‐control study, including 348 patients with newly diagnosed HCC and 597 controls without any evidence of liver diseases, was conducted to elucidate the association between these two polymorphisms and the risk of HCC related to AFB1 exposure among a Guangxi population from a high AFB1‐exposure area by means of TaqMAN‐polymerase chain reaction technique. Results: We observed that HCC patients featured higher AFB1 exposure than control group (odds ratios [OR] = 6.49 and 6.75 for exposure years and exposure levels, respectively). Furthermore, these individuals with the genotypes of XRCC7 rs#7003908 G alleles (namely XRCC7‐TG or ‐GG), compared the homozygote of XRCC7 rs#7003908 T alleles (XRCC7‐TT), faced increasing risk of HCC (OR, 3.45 and 5.04; 95% confidence intervals [CIs], 2.40–4.94 and 3.28–7.76, respectively). We also found some evidence that this polymorphism interacted with AFB1‐expousure years or levels in the process of HCC carcinogenesis. Additionally, XRCC7 rs#7003908 polymorphism was correlated with the levels of AFB1‐DNA adducts (r = 0.142, P < 0.001). XRCC7 rs#10109984 polymorphism, however, did not modify the risk of HCC related to AFB1 exposure (P > 0.05). Conclusion: These data suggest that XRCC7 rs#7003908 polymorphism may be one of the genetic modifiers for AFB1‐related HCC among Guangxi population.     

Polymorphisms in DNA repair genes and risk of non‐Hodgkin lymphoma in a pooled analysis of three studies

Genetic variations in DNA repair genes are thought to play an important role in the pathogenesis and development of non‐Hodgkin lymphoma (NHL). To further explore this hypothesis, we genotyped 319 tag single nucleotide polymorphisms (SNPs) in 27 DNA repair gene regions in 1946 cases and 1808 controls pooled from three population‐based case‐control studies of NHL in the US and Australia. Relative risks of NHL and NHL subtypes in relation to SNP genotypes were assessed using logistic regression. Associations of gene regions and pathways with NHL or NHL subtypes were explored using the minP and tail‐strength statistics, respectively. Overall, genetic polymorphisms within the DNA repair pathway were associated with NHL (P = 0·005). Similar associations were seen with the double‐strand break repair (P = 0·02) and nucleotide excision repair (P = 0·04) pathways. Five SNPs (BLM rs441399, RAD50 rs2237060, FAM82A2 rs2304583, ERCC3 rs4150506, and XRCC4 rs13178127) were particularly noteworthy because their gene regions were significantly associated with NHL or NHL subtypes (minP ≤ 0·05), or because of high level of statistical significance (P ≤ 0·005) and consistent findings across the three studies. These results support the hypothesis that common genetic polymorphisms in human DNA repair genes may modify the risk of NHL.     

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.     

Polymorphism of glutathione S-transferase mu 1 and theta 1 genes and hepatocellular carcinoma in southern Guangxi, China

AIM: Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism of a wide range of carcinogens, but deletions of the genes are commonly found in the population. The present study was undertaken to evaluate the association between GSTM1 and GSTT1 gene polymorphisms and hepatocellular carcinoma (HCC) risk. METHODS: The genetic polymorphisms were studied at an aflatoxin highly contaminated region in Guangxi, China. Pdymerase chain reaction (PCR) technique was used to detect the presence or absence of the GSTM1 and GSTT1 genes in blood samples. The case group was composed of 181 patients of HCC identified by the pathologists and the control group was composed of 360 adults without any tumor. RESULTS: The frequencies of GSTM1 and GSTT1 null genotypes in the control were 47.8% and 42.7%, while those in the HCC group were 64.6% and 59.7%, respectively. The differences between HCC group and control group were very significant (P<0.01). GSTM1 and GSTT1 combined null genotypes in HCC group and control group were 38.2% and 18.5% respectively, and the difference was significant (P<0.05). CONCLUSION: The GSTM1 and GSTT1 null genotypes are associated with an increased risk of HCC in a special geographic environment. Combination of the two null genotypes in an individual is substantially increased twice the risk of HCC.     

Mismatch repair-dependent mutagenesis in nondividing cells

Mismatch repair (MMR) is a major DNA repair pathway in cells from all branches of life that removes replication errors in a strand-specific manner, such that mismatched nucleotides are preferentially removed from the newly replicated strand of DNA. Here we demonstrate a role for MMR in helping create new phenotypes in nondividing cells. We show that mispairs in yeast that escape MMR during replication can later be subject to MMR activity in a replication strand-independent manner in nondividing cells, resulting in either fully wild-type or mutant DNA sequence. In one case, this activity is responsible for what appears to be adaptive mutation. This replication strand-independent MMR activity could contribute to the formation of tumors arising in nondividing cells and could also contribute to mutagenesis observed during somatic hypermutation of Ig genes.     

去氢骆驼蓬碱致细粒棘球蚴DNA损伤修复相关基因表达量的检测

目的观察去氢骆驼蓬碱(HM)对细粒棘球蚴不同类型DNA损伤修复基因表达量的影响。方法以细粒棘球蚴为实验材料,以HM为药物,以虫体不同类型DNA损伤修复方式(同源重组修复、非同源末端连接修复、碱基切除修复)及核苷酸切除修复通路的关键修复基因为目的基因设计引物,筛选确定qRT-PCR反应体系,采用该体系检测基因的差异表达水平,分析HM对细粒棘球蚴不同类型DNA损伤修复相关基因的影响。结果筛选的细粒棘球蚴DNA损伤修复类型代表基因BRCA1引物F:5’-TGATTGCGACCTAAGAGAC-3’,R:5’-TTCCATACACAAGCCATCC-3’);KU70引物F:5’-TGATTGCGACCTAAGA GAC-3’,R:5’-GTCGCCATCTCAACTTCA-3’);OGG1引物5’-CGCTATGGTAAGAAGATGTG-3’,R:5’-CGTGAAGATGGATGGAGAA-3’);ERCC1引物F:5’-TCGTGCTCATTGTGTTAGT-3’,R:5’-CTCCTCTGGTGGCTTATTC-3’)。各基因扩增曲线Ct值可用,溶解曲线特异性良好。qRT-PCR检测各样品组BRCA1,KU70,OGG1基因表达均有不同程度上调,DOX组分别为26.05倍,323.44倍,29.63倍,HM组分别为7.24倍,55.65倍,3.22倍,以KU70和BRCA1基因上调尤为明显。ERCC1基因表达量DOX组显著上调(上调倍数25.24),HM组无显著变化。结论 HM对DNA双链断裂修复类型代表基因BRCA1,KU70,OGG1表达量有较大影响,而对ERCC1基因表达无显著影响。     

DNA损伤修复基因hOGG1的遗传多态与乙肝相关性HCC的风险

目的:探讨DNA损伤修复基因hOGGI的遗传多态Ser326Cys与肝细胞癌(HCC)易感性的关系．方法:应用基因测序分型方法,分析96例HCC患者和96例健康对照hOGG1的遗传多态及与HBV感染的交互作用．结果:HCC病例组的Cys／Cys,Cys／Ser和Ser／Ser基因型分别为20．9％,44．2％和34．9％．Ser／Cys杂合子个体的OR值为1．5,Cys／Cys纯合子个体的OR值为1．9,明显高于Ser/Ser个体,表现出剂量效应．HBV感染者发生HCC的相对风险度是非HBV感染者的9倍(OR=9．2;95％CI 0．99-5．9)．对于HCC,hOGG1-Ser326Cys变异或HBV感染单一因素的OR值分别为5．5 (95％CI 0．7-240．1)和10．9(95％CI1．6-453．3),但携带变异基因者如果感染HB V,OR值则高达27．8(95％CI4．7-970．2)．结论:DNA修复基因hOGG1的Cys等位基因可能增加HCC的遗传易感性,他与HBV协同在乙肝相关性HCC的发生中起着重要作用．