Use of biomarkers to characterize functions of polymorphic DNA repair genotypes

Inheritance of variant DNA repair genes is believed to influence individual susceptibility to the development of environmental cancer. However, the validity of the belief is dependent upon understanding the functions of the variant genes. Consequently, a variety of studies have been conducted to investigate the functions of variant DNA repair genes, e.g. using biomarkers. These studies on several representative polymorphic DNA repair genes are reviewed in this report. From a general overview, it appears that the biomarker investigations did not provide consistent observations. However, from a more careful evaluation, it is clear that the inconsistencies are probably caused by the use of populations and biomarkers that are not appropriate for investigating the repair activities of the genes. For example, the use of cigarette smokers and patients may not generate precise information for this type of investigations because these conditions can modify the functions of the investigated genes. Thus, the use of healthy non-smokers would be more appropriate. Other problems with these studies includes the small sample size used and the fact that some of the biomarkers used, such as sister chromatid exchanges, are not appropriate because the mechanisms for formation of the biomarkers and their biological significance are unknown. Nevertheless, the following conclusions can be derived from the review of the various biomarker studies that have been published. XRCC1 194Trp, OGG1 326Cys and APE1 148Glu probably have limited alterations in repair activities compared to the wild-type genotypes. XRCC1 399Gln and XRCC3 241Met are deficient in the repair of X-ray-, but not UV-light-induced chromosome aberrations, therefore the variant genes are defective in base excision repair. XPD 312Asn and XPD 751Gln are deficient in the repair of UV-light- but not X-ray-induced chromosome aberrations, therefore they are defective in nucleotide excision repair.     

氯乙烯致DNA损伤的遗传易感性研究

目的 探讨氯乙烯(VCM)致DNA损伤与DNA修复基因和代谢酶基因多态性的关系.方法 彗星试验检测DNA损伤,并按DNA损伤情况将接触VCM的研究对象分为DNA损伤组(75人),采用病例对照设计方法选择对照组(75人),用聚合酶链反应-限制性酶切片段多态性技术(PCR-RFLP)和PCR测XRCC1(Arg194Trp,Arg280His和Arg399Gln)、XPD(Ile199Met,Asp312Asn和Lys751Gln)和代谢酶(CYP2E1、GSTT1和GSTM1)基因多态性.结果 单因素分析结果表明,CYP2E1c1c2、c2c2和XPD 751 Lys/Gln、Gln/Gln基因犁携带者DNA损伤风险明显增高,而XRCC1 399 Arg/Gln、Gln/Gln基因型携带者DNA损伤风险明显降低,差异均有统计学意义(P<0.05,P<0.01).logistic回归分析发现,XRCC1 194、XRCC1 399、XPD751和CYP2E1多态与DNA损伤有关.累积接触剂量分析表明,具XRCC1 399Arg/Gln、Gln/Gln基因型个体即使在累积接触剂量高的情况下DNA损伤发生率仍明显降低(OR:0.35,95%CI:0.12～1.01);具CYP2E1 c1/c2、c2/c2基因型个体,无论累积接触剂量高低,其DNA损伤发生率均明显高于对照(OR:2.57,95%CI:1.01～6.59和OR:2.57,95%CI:0.99～6.87).结论 VCM累积接触剂量和CYP2E1、XRCC1 194、XRCC1 399及XPD751基因型与VCM诱导的DNA损伤有关.     

Polymorphisms in nucleotide excision repair genes, arsenic exposure, and non-melanoma skin cancer in New Hampshire

BACKGROUND: Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC). OBJECTIVE: We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp312Asn and Lys751Gln) modify the association between arsenic and NMSC. METHODS: Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail clippings. The analysis included 880 cases of BCC, 666 cases of SCC, and 780 controls. RESULTS: There was an increased BCC risk associated with high arsenic exposure among those homozygous variant for XPA [odds ratio (OR) = 1.8; 95% confidence interval (CI), 0.9-3.7]. For XPD, having variation at both loci (312Asn and 751Gln) occurred less frequently among BCC and SCC cases compared with controls (OR = 0.8; 95% CI, 0.6-1.0) for both case groups. In the stratum of subjects who have variant for both XPD polymorphisms, there was a 2-fold increased risk of SCC associated with elevated arsenic (OR = 2.2; 95% CI, 1.0-5.0). The test for interaction between XPD and arsenic in SCC was of borderline significance (p < 0.07, 3 degrees of freedom). CONCLUSIONS: Our findings indicate a reduced NMSC risk in relation to XPD Asp312Asn and Lys751Gln variants. Further, these data support the hypothesis that NER polymorphisms may modify the association between NMSC and arsenic.     

修复基因XRCC1和XPD多态性及交互作用对铅毒性易感性的影响

目的 研究XRCC1、XPD基因多态性及交互作用与铅毒性易感性的关系。方法 采集326名某蓄电池企业铅作业工人静脉血和晨尿,检测血铅、血锌原卟啉（ZPP）和尿铅,用PCR RFLP检测XRCC1、XPD的基因多态性,分析不同基因型及交互作用对铅毒性易感性的影响。结果 XRCC1-194CT＋TT基因组平均血铅值较XRCC1-194CC组高;病例组XRCC1-194CT＋TT基因型比例大于对照组,慢性铅中毒发生率风险较XRCC1-194CC组高。结论 在相同职业铅暴露环境下,XRCC1-194CT＋TT基因型工人对铅毒性易感;XPD Asp312Asn和Lys751Gln多态性与铅毒性易感性无关;XRCC1 Arg194Trp、XPD Asp312Asn和Lys751Gln基因对铅毒性的影响不存在交互作用。     

DNA Repair Polymorphisms in B-cell Chronic Lymphocytic Leukemia in Sufferers of Chernobyl Nuclear Power Plant Accident

An association between DNA repair gene polymorphisms, environmental factors, and development of some types of cancer has been suggested by several studies. Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the clean-up workers of the Chernobyl Nuclear Power Plant (NPP) accident and it has some specific features. Therefore, we have studied the possible differences in DNA repair gene polymorphisms in CLL patients depending on ionizing radiation (IR) exposure history and their clinical characterictics. Arg399Gln XRCC1, Thr241Met XRCC3, and Lys751Gln XPD polymorphisms were studied in 64 CLL patients, exposed to IR due to the Chernobyl NPP accident, 114 IR-non-exposed CLL patients, and 103 sex- and age-matched IR-exposed controls using polymerase chain reaction-restriction fragment-length polymorphism analysis. All investigated polymorphisms were equally distributed between two groups of CLL patients and IR-exposed controls, except that that there was a significant reduction of the common homozygous Lys/Lys XPD genotype among IR-exposed CLL patients (23.7%) compared with IR-exposed controls (45.6%), OR = 0.37; 95% CI = 0.18-0.75; (P = 0.005). The number of IR-non-exposed CLL patients (37.4%) with the Lys/Lys XPD genotype was also decreased compared to IR-exposed controls, although this difference was not significant (P = 0.223). These preliminary data suggest a possible modifying role of Lys751Gln XPD polymorphism for the development of CLL, expecially in radiation-exposed persons.     

ERCC2 /XPD gene polymorphisms and lung cancer: a HuGE review

The xeroderma pigmentosum group D (XPD) protein is a well-characterized DNA helicase necessary for the nucleotide excision repair of bulky DNA lesions, such as those induced by cigarette smoking. Polymorphisms in several exons of the XPD gene have been identified; two of them, Asp312Asn and Lys751Gln, are common and result in an amino acid change. Most of the reported data indicate higher levels of DNA adducts in people carrying variant Asn or Gln alleles, which suggests that these persons have lower repair efficiency. These two polymorphisms have been hypothesized to modify the risk of lung cancer. To examine this association, the authors undertook a review and meta-analyses of nine published case-control studies. No clear association between XPD Asp312Asn or XPD Lys751Gln gene polymorphisms and lung cancer was found. However, it may be only the joint effect of multiple polymorphisms within the gene that provides information about an association with lung cancer. Because of advances in high-throughput genotyping techniques, it is likely that future association studies on lung cancer will need to investigate multiple polymorphisms within genes and multiple genes within the same pathway and will need to use recently developed haplotype-based methods to evaluate the haplotypic effects.     

Polymorphism in DNA repair genes and oral squamous cell carcinoma in Thailand

DNA repair capacity is essential in maintaining cellular functions and homeostasis. However, the repair capacity can be altered based on DNA sequence variations in DNA repair genes and thus may cause cancer susceptibility. We investigated associations between polymorphisms in DNA repair genes and oral squamous cell carcinoma (OSCC) in a Thai population. Nine known single nucleotide polymorphisms (SNPs) in five common DNA repair genes were investigated: XRCC1 (Arg194Trp and Arg399Gln); XRCC3 (Thr241Met); XPC (PAT and Lys939Gln); XPD (exon 6, and Lys751Gln); and MGMT (Trp65Cys and Leu84Phe). We studied 106 cases and 164 healthy controls that were frequency-matched by age (+/-5 years), gender, and cigarette smoking and alcohol drinking habits. The genotype assays were performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The R version 2.0.1 statistical software was applied for statistical analysis of association. Based on multivariate analyses, we found that the variant genotypes with XRCC3 241Met exhibited a >3-fold elevated risk (OR = 3.3, 95% CI = 1.31-8.36, p = 0.01) for OSCC. There was a marginally significant risk observed in variants with XRCC1 194Trp (OR = 1.81, 95% CI = 0.91-3.63, p = 0.09) and XPD exon 6 (OR = 1.71, 95% CI = 0.93-3.16, p = 0.09). Combination of the variant genotypes of these three susceptibility genes was associated with a highly significant risk for OSCC (OR = 9.43, 95% CI = 1.98-44.9, p < 0.01). From further multivariate analyses, the variants with XRCC1 194Trp and possibly XRCC3 241Met interacted with tobacco and alcohol to further increase the risk (OR = 3.37 95% CI = 1.41-8.02, p < 0.01; OR = 2.92, 95% CI = 0.94-9.04, p = 0.06). On the other hand, increased risk was detected in non-betel chewers (OR = 2.88, 95% CI = 1.31-6.31, p < 0.01; OR = 2.61, 95% CI = 0.97-7.11, p = 0.06) who carry the two variant genotypes, respectively. Males with the variants XRCC1 194Trp or XRCC3 241Met had a higher risk of developing OSCC than males with the corresponding wild-type genotypes (OR = 2.72, 95% CI = 1.34-5.52, p < 0.01; OR = 2.95, 95% CI = 1.12-7.75, p < 0.05). Such association was not detected in females. Interestingly, the risk increased in female carriers of XPD exon 6 (OR = 3.93, 95% CI = 1.14-13.6, p < 0.05). We could not demonstrate a significant interaction of these SNPs with age in this study. Our data indicate that the variant genotypes with XRCC3 241Met and possibly XRCC1 194Trp and XPD exon 6 contribute to OSCC development in a Thai population. In addition, these SNPs influence the repair of DNA damage that is caused by environmental risk factors for oral cancer.     

XPD基因多态性与DNA加合物及肿瘤易感性的研究进展

着色性干皮病互补基团D（XPD）蛋白在核苷酸切除修复和DNA转录过程中起重要作用。研究提示2个常见的XPD多态性（Asp312Asn和Lys751Gln）与DNA损伤修复能力差异有关。而DNA修复能力增强对DNA加合物损伤的修复、铂类药物耐药起关键作用。目前XPD基团多态性与肿瘤的发病风险之间仍存在分歧,但基因-基因、基因-环境交互作用影响较为显著。     

XRCC3 and XPD/ERCC2 single nucleotide polymorphisms and the risk of cancer: a HuGE review

Hundreds of polymorphisms in DNA repair genes have been identified; however, for many of these polymorphisms, the impact on repair phenotype and cancer susceptibility remains uncertain. In this review, the authors focused on the x-ray repair cross-complementing protein group 3 (XRCC3) and xeroderma pigmentosum group D (XPD)/excision repair cross-complementing rodent repair deficiency (ERCC2) genes, because they are among the most extensively studied but no final conclusion has yet been drawn about their role in cancer occurrence. XRCC3 participates in DNA double-strand break/recombinational repair through homologous recombination to maintain chromosome stability. XPD/ERCC2 is a helicase involved in the nucleotide excision repair pathway, which recognizes and repairs many structurally unrelated lesions, such as bulky adducts and thymidine dimers. The authors identified a sufficient number of epidemiologic studies on cancer to perform meta-analyses for XPD/ERCC2 variants in codons 156, 312, and 751 and XRCC3 variants in codon 241. The authors evaluated all cancer sites to investigate whether DNA repair is likely to take place in a rather nonspecific manner for different carcinogens and different cancers. For the most part, the authors found no association between these genes and the cancer sites investigated, except for some statistically significant associations between XPD/ERCC2 single nucleotide polymorphisms and skin, breast, and lung cancers.     

广西人群DNA修复途径部分基因多态性与肝癌临床病理特征的关联研究

目的探讨广西地区人群DNA修复途径基因XRCC1、APE1、hOGG1、XPC、XPD、XPG、XRCC3多态性与肝癌临床病理特征的关系。方法收集2007年2月～2008年10月在广西医科大学第一附属医院就诊和治疗的共257例广西肝癌新发病例临床病理资料、血液DNA,应用荧光定量聚合酶链式反应（real-time fluorescent quantita-tive polymerase chain reaction,RT-PCR）技术对XPC499、XPC939、XPD312、XPG1104、XRCC1-194、XRCC1-280、XRCC1-399、APE1-148、hOGG1-326、XRCC3-241 10个位点进行基因分型。基因多态性与临床病理特征的关系采用2检验和非条件Logistic回归模型进行分析。结果 XRCC1-399多态与肝癌门静脉癌栓相关（P=0.036）,hOOG1-326多态与包膜侵犯相关（P=0.036）,XPC499多态与大体分型相关（P=0.047）。分层分析显示,在发病年龄〈47岁组,XPD312基因多态与肿瘤个数有关（P=0.025）。在发病年龄≥47岁组,XPD312多态与肿瘤直径大小相关（P=0.009）,XRCC1-280多态与门静脉癌栓（P=0.024）、病理分期（P=0.050）相关;不同修复途径基因多态联合作用基因型分布频率与肝癌子灶差异有统计学意义（P=0.037）。APE1-148、XPC939、XPG1104、XRCC3-241位点多态性与原发性肝癌（primary liver cancer,PLC）临床病理特征差异均无统计学意义（均有P〉0.05）。结论 XRCC1-280、XRCC1-399、hOGG1-326和XPC499、XPD312基因多态性可能与肝癌相关生物学行为相关。     

联合分析XRCC1、XPD和GSTP1基因单核苷酸多态性在铂类药物化疗敏感性中的预测作用

目的 联合分析X线修复交叉互补基因1（X-rayCOrSS—complementing1,XRCCl）第194和399位点,着色性干皮病基因D（XerodermapigmentosumgroupD,XPD）第312位点及谷胱甘肽-s-转移酶P1基因（GlutathioneS-Transferasepl,GSTPl）第105位点的单核苷酸多态性（singlenucleotidepolymorphisms,SNPs）在预测铂类药物化疗敏感性中的作用。方法采用基因测序法对50例恶性肿瘤患者的外周血进行XRCCl、XPD和GSTPl基因单核苷酸多态性（SNPs）检测,分析各基因型与铂类药物化疗敏感性的关系。结果有效率高的基因型为：XRCC1194位点的Arg／Trp和Trp／Trp,XRCC1399位点的Arg／Arg,XPD312位点的Asn／Asn,GSTPl105位点的Val／Val,它们的化疗有效率分别为57．1％、75．0％、60．9％、85．7％、87．5％。有两个以上和有1个或0个高效基因型患者的化疗有效率分别是78．9％、36．4％和0,有两个以上高效基因型的患者的敏感性明显高于有1个或0个高效基因型的患者,其差异有统计学意义（x2=25．79,P〈0．01）。结论对XRCC1、XPD和GSTP1基因的单核苷酸多态性进行联合检测,可能预测患者对铂类药物的敏感性。     

Genotype frequencies of 50 polymorphisms for 241 Japanese non-cancer patients

This paper lists the genotype frequencies of 50 polymorphisms of 37 genes (ALDH2, ADRB2, ADRB3, COMT, CD36, CXCR2, CCND1, COX2, CYP2A6, CYP17, CYP19, IGF1, IL-1A, IL-1B, IL-1RN, IL-1R1, IL-6, IL-8, IL-10, LEP, Le, L-myc, MPO, MTR, MTHFR, MAO-A, NQO1, OGG1, p53, p73, Se, SRD5A2, TGF-B, TNF-A, TNF-B, XPD, and XRCC1) and 6 sets of combined genotype frequencies for 241 non-cancer Japanese outpatients. Though the genotype frequencies of 25 polymorphisms have already been reported in our previous papers, 15 polymorphisms (CD36 A52C, CXCR2 C785T, CCND1 G870A, IGF1 C/T at intron 2 and G2502T, IL-1A 46-bp VNTR, IL-1R1 C-116T, IL-6 Ins/Del 17C, IL-8 A-278T and C74T, IL- 10 T-819C, LEP A-2548G, SRD5A2 2-bp VNTR, XPD Lys751Gln, and XRCC1 Arg399Gln) and six sets of combined genotype frequencies (IL-1B C-31T and IL-1A C-889T, IL-1B C-31T and IL-1RN 86-bp VNTR, IL-1B C-31T and IL-1R1 C-116T, TNF-A G-308A and TNF-B A252G, SRD5A2 Val89Leu and 2-bp VNTR, and XRCC1 Arg399Gln and XPD Lys751Gln) were reported in this paper for the first time for Japanese. Although microarray technology will produce this kind of information in near future, this is the first document that reports the genotype/allele frequencies among Japanese for an archival purpose.     

Correlations between DNA polymorphism and frequencies of gamma-radiation induced and spontaneous cytogenetic damage

With the aim of developing genetic tests for elevated and reduced radiation sensitivity, the authors studied the correlations between various genotypes and frequencies of spontaneous and radiation-induced chromosome aberrations in human lymphocytes. Cytogenetic analysis and genotyping (19 sites of detoxification and DNA repair genes) were carried out for a group of cleanup workers of the Chernobyl nuclear power plant accident (83 people) and for a uniform control group of volunteers (97 people). In both cases, the frequencies of chromosome type aberrations were higher in carriers of minor alleles of gene XPD [sites T2251G (Lys751Gln) and G862A (Asp312Asn)] and the "positive" genotypes GSTM1/GSTT1. The polymorphism of these genes did not affect the frequency of aberrations induced by gamma radiation in the control group (1 Gy in vitro), which was associated with genotypes by loci OGG1, XRCC1, and CYP1A1. Thus, in the control group, spontaneous and in vitro induced cytogenetic effects are associated with different groups of polymorphic genes. In the cleanup workers group (irradiated in vivo), the elevated frequency of aberrations was observed in the carriers of those genotypes that typically have a higher level of spontaneous (but not in vitro induced) cytogenetic damage in the control. The genotype "minor XPD + insertion GST," having an estimated incidence of 64% in central Russia, was characterized and found to be strongly associated with an elevated frequency of chromosome type aberrations following irradiation in vivo (OR = 6.9; p = 0.008).     

ERCC2/XPD单核苷酸多态与苯并芘体外诱导DNA加合物损伤的关联性研究

目的评价环境致癌因子苯并芘(B[a]P)所致DNA损伤修复与ERCC2/XPD单核苷酸多态(SNP)的关联。方法收集282例辽宁地区汉族健康人群外周血8ml,常规提取淋巴细胞及DNA,采用Taqman实时定量PCR检测ERCC2/XPDLys751Gln(rs13181),Asp312Asn(rs1799793)和Arg156Arg(rs238406)的基因型;体外培养淋巴细胞,应用B[a]P及S9活化系统,诱导BPDE-DNA加合物的形成;高效液相色谱法检测BPDE-DNA加合物含量;分析BPDE-DNA加合物水平与ERCC2/XPD SNP位点的关联。结果携带ERCC2/XPD Arg156Arg位点AA基因型个体BPDE-DNA加合物水平显著高于CC基因型携带者;50～70岁和≥70岁年龄组人群的加合物水平高于≤30岁年龄组(P<0.05);多元线性回归分析同样显示,ERCC2/XPD Arg156Arg位点SNP及年龄对BPDE-DNA加合物含量的影响有统计学意义(P<0.05)。结论 ERCC2/XPD Arg156Arg位点A等位基因可能与BPDE-DNA加合物的DNA修复能力降低相关联,可能会增加肿瘤易感风险。     

Candidate gene association study of the radiosensitivity of human chromosomes with candidate gene polymorphisms upon exposure to gamma-irradiation in vitro and in vitro

The genotypic associations of the frequencies of spontaneous and radiation-induced chromosome aberrations in human lymphocytes were studied to develop genetic tests for elevated and reduced radiosensitivity. Cytogenetic analysis and genotyping (19 sites of detoxification and DNA repair genes) were carried out for a sample of Chernobyl cleanup workers (n = 83) and for a homogenous control sample of volunteers (n = 99). In both groups, the frequency of chromosome-type aberrations proved to be elevated in carriers of minor alleles in the XPD gene (sites T2251G (Lys751Gln) and G862A (Asp312Asn)) and a combination of GSTM1-GSTT1-positive genotypes. The polymorphism of these gene did not affect the frequency of gamma-radiation-induced aberrations in the controls (1 Gy in vitro), which was associated with the alleles of the OGG1, XRCC1, and CYP1A1 genes. Thus, the frequencies of spontaneous and in vitro induced chromosome-type aberrations are associated with the alleles of different xenobiotic detoxification and DNA repair genes. At the same time, among the cleanup workers (irradiated in vivo), the elevated frequency of aberrations was observed in the carriers of the genotypes associated with the higher rate of spontaneous (but not induced in vitro) cytogenetic damages in the controls.     

DNA修复基因XPD单核苷酸多态性和环境因素的交互作用与肝细胞癌的关联研究

目的 探讨XPD基因751、312位点单核苷酸多态性和环境因素的交互作用与肝细胞癌的关系.方法 采用以医院为基础的病例对照研究方法,运用TaqMan MGB荧光定昔实时PCR分析方法对病例组300例肝细胞癌患者和对照组312例非肿瘤患者进行XPD基因751和312位点的基因型分析.以非条件logistic回归模型分析比较各基因型在两组中分布频率的差异,以及基因多态性和环境因素的交互作用.结果 XPD基因751位点3种基因型AA、AC、CC在病例组和对照组中的分布差异无统计学意义(P>0.05),与携带XPD751野生纯合子AA基因型者比较,携带XPD751AC或CC基因型者患肝细胞癌风险无显著增加(P>0.05).XPD基因312位点3种基因型GG、GA、AA在病例组和对照组中的分布差异有统计学意义(P<0.01).与携带XPD312野生纯合子GG基因型者比较,携带XPD312 AA基因型个体罹患HCC的风险是携带XPD312 GG基因型的2.67倍(OR=2.67,95%CI:0.431～16.537),但差异无统计学意义;携带至少一个XPD312A等位基因的个体罹患肝细胞癌的风险是GG基因型的2.62倍(95%CI:1.626～4.222),且差异有统计学意义.交互作用分析结果表明XPD基因751位点多态性与吸烟、XPD基因312位点多态性与吸烟、XPD基因312位点多态性与HBsAg阳性之间在肝细胞癌发生中存在交瓦作用,交互作用的OR值分别为4.291、5.341、7.348.结论 DNA修复基因XPD312A等位基因可能是广西南部地区人群肝细胞癌的危险等位基因,XPD基因多态性与吸烟、HBsAg阳性之间在肝细胞癌发生中存在交互作用,能增加罹患肝细胞癌的风险.     

DNA修复基因XPD单核苷酸多态性和环境因素的交互作用与肝细胞癌的关联研究

目的 探讨XPD基因751、312位点单核苷酸多态性和环境因素的交互作用与肝细胞癌的关系.方法 采用以医院为基础的病例对照研究方法,运用TaqMan MGB荧光定昔实时PCR分析方法对病例组300例肝细胞癌患者和对照组312例非肿瘤患者进行XPD基因751和312位点的基因型分析.以非条件logistic回归模型分析比较各基因型在两组中分布频率的差异,以及基因多态性和环境因素的交互作用.结果 XPD基因751位点3种基因型AA、AC、CC在病例组和对照组中的分布差异无统计学意义(P>0.05),与携带XPD751野生纯合子AA基因型者比较,携带XPD751AC或CC基因型者患肝细胞癌风险无显著增加(P>0.05).XPD基因312位点3种基因型GG、GA、AA在病例组和对照组中的分布差异有统计学意义(P<0.01).与携带XPD312野生纯合子GG基因型者比较,携带XPD312 AA基因型个体罹患HCC的风险是携带XPD312 GG基因型的2.67倍(OR=2.67,95%CI:0.431～16.537),但差异无统计学意义;携带至少一个XPD312A等位基因的个体罹患肝细胞癌的风险是GG基因型的2.62倍(95%CI:1.626～4.222),且差异有统计学意义.交互作用分析结果表明XPD基因751位点多态性与吸烟、XPD基因312位点多态性与吸烟、XPD基因312位点多态性与HBsAg阳性之间在肝细胞癌发生中存在交瓦作用,交互作用的OR值分别为4.291、5.341、7.348.结论 DNA修复基因XPD312A等位基因可能是广西南部地区人群肝细胞癌的危险等位基因,XPD基因多态性与吸烟、HBsAg阳性之间在肝细胞癌发生中存在交互作用,能增加罹患肝细胞癌的风险.     

DNA修复基因XPD单核苷酸多态性和环境因素的交互作用与肝细胞癌的关联研究

目的 探讨XPD基因751、312位点单核苷酸多态性和环境因素的交互作用与肝细胞癌的关系.方法 采用以医院为基础的病例对照研究方法,运用TaqMan MGB荧光定昔实时PCR分析方法对病例组300例肝细胞癌患者和对照组312例非肿瘤患者进行XPD基因751和312位点的基因型分析.以非条件logistic回归模型分析比较各基因型在两组中分布频率的差异,以及基因多态性和环境因素的交互作用.结果 XPD基因751位点3种基因型AA、AC、CC在病例组和对照组中的分布差异无统计学意义(P>0.05),与携带XPD751野生纯合子AA基因型者比较,携带XPD751AC或CC基因型者患肝细胞癌风险无显著增加(P>0.05).XPD基因312位点3种基因型GG、GA、AA在病例组和对照组中的分布差异有统计学意义(P<0.01).与携带XPD312野生纯合子GG基因型者比较,携带XPD312 AA基因型个体罹患HCC的风险是携带XPD312 GG基因型的2.67倍(OR=2.67,95%CI:0.431～16.537),但差异无统计学意义;携带至少一个XPD312A等位基因的个体罹患肝细胞癌的风险是GG基因型的2.62倍(95%CI:1.626～4.222),且差异有统计学意义.交互作用分析结果表明XPD基因751位点多态性与吸烟、XPD基因312位点多态性与吸烟、XPD基因312位点多态性与HBsAg阳性之间在肝细胞癌发生中存在交瓦作用,交互作用的OR值分别为4.291、5.341、7.348.结论 DNA修复基因XPD312A等位基因可能是广西南部地区人群肝细胞癌的危险等位基因,XPD基因多态性与吸烟、HBsAg阳性之间在肝细胞癌发生中存在交互作用,能增加罹患肝细胞癌的风险.     

DNA修复基因XPD单核苷酸多态性和环境因素的交互作用与肝细胞癌的关联研究

目的 探讨XPD基因751、312位点单核苷酸多态性和环境因素的交互作用与肝细胞癌的关系.方法 采用以医院为基础的病例对照研究方法,运用TaqMan MGB荧光定昔实时PCR分析方法对病例组300例肝细胞癌患者和对照组312例非肿瘤患者进行XPD基因751和312位点的基因型分析.以非条件logistic回归模型分析比较各基因型在两组中分布频率的差异,以及基因多态性和环境因素的交互作用.结果 XPD基因751位点3种基因型AA、AC、CC在病例组和对照组中的分布差异无统计学意义(P>0.05),与携带XPD751野生纯合子AA基因型者比较,携带XPD751AC或CC基因型者患肝细胞癌风险无显著增加(P>0.05).XPD基因312位点3种基因型GG、GA、AA在病例组和对照组中的分布差异有统计学意义(P<0.01).与携带XPD312野生纯合子GG基因型者比较,携带XPD312 AA基因型个体罹患HCC的风险是携带XPD312 GG基因型的2.67倍(OR=2.67,95%CI:0.431～16.537),但差异无统计学意义;携带至少一个XPD312A等位基因的个体罹患肝细胞癌的风险是GG基因型的2.62倍(95%CI:1.626～4.222),且差异有统计学意义.交互作用分析结果表明XPD基因751位点多态性与吸烟、XPD基因312位点多态性与吸烟、XPD基因312位点多态性与HBsAg阳性之间在肝细胞癌发生中存在交瓦作用,交互作用的OR值分别为4.291、5.341、7.348.结论 DNA修复基因XPD312A等位基因可能是广西南部地区人群肝细胞癌的危险等位基因,XPD基因多态性与吸烟、HBsAg阳性之间在肝细胞癌发生中存在交互作用,能增加罹患肝细胞癌的风险.