DNA Repair Gene XRCC1 and XPD Polymorphisms and Risk of Prostate Cancer

The X-ray repair cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XPD) genes are involved in base excision repair and nucleotide excision repair of DNA repair pathways, respectively. A growing body of evidence suggests that XRCC1 and XPD are important in environmentally induced cancers, and polymorphisms in both genes have been identified. To determine whether the XRCC1 (codon Arg399Gln) and XPD (codon Asp312Asn and codon Lys751Gln) polymorphisms are associated with prostate cancer susceptibility, we genotyped these polymorphisms in a primarily Caucasian sample of 506 sibships (n = 1,117) ascertained through a brother with prostate cancer. Sibships were analyzed with a Cox proportional hazards model with age at prostate cancer diagnosis as the outcome. Of the three polymorphisms investigated, only the XPD codon 312 Asn/Asn genotype had an odds ratio (OR) significantly different from one (OR, 1.61; 95% CI, 1.03–2.53). Analyses stratified by the clinical characteristics of affected brothers in the sibship did not reveal any significant heterogeneity in risk. In exploring two-way gene interactions, we found a markedly elevated risk for the combination of the XPD codon 312 Asn/Asn and XRCC1 codon 399 Gln/Gln genotypes (OR, 4.81; 95% CI, 1.66–13.97). In summary, our results suggest that the XPD codon 312 Asn allele may exert a modest positive effect on prostate cancer risk when two copies of the allele are present, and this effect is enhanced by the XRCC codon 399 Gln allele in its recessive state.

[1]  J. Witte,et al.  CYP3A4 and CYP3A5 genotypes, haplotypes, and risk of prostate cancer. , 2003, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[2]  E. Friedberg,et al.  DNA damage and repair , 2003, Nature.

[3]  Jack A. Taylor,et al.  Differences in base excision repair capacity may modulate the effect of dietary antioxidant intake on prostate cancer risk: an example of polymorphisms in the XRCC1 gene. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[4]  M. Kulldorff,et al.  A geographic analysis of prostate cancer mortality in the United States, 1970–89 , 2002, International journal of cancer.

[5]  F. Perera,et al.  Polymorphisms in the DNA Repair Enzyme XPD are Associated with Increased Levels of PAH–DNA Adducts in a Case-Control Study of Breast Cancer , 2002, Breast Cancer Research and Treatment.

[6]  D. Tang,et al.  DNA repair gene XRCC1 and XPD polymorphisms and risk of lung cancer in a Chinese population. , 2002, Carcinogenesis.

[7]  A. Olshan,et al.  XRCC1 polymorphisms and head and neck cancer. , 2002, Cancer letters.

[8]  E. Bleecker,et al.  Associations between hOGG1 sequence variants and prostate cancer susceptibility. , 2002, Cancer research.

[9]  S. Coughlin,et al.  A review of genetic polymorphisms and prostate cancer risk. , 2002, Annals of epidemiology.

[10]  J M Trent,et al.  Heterogeneity of genetic alterations in prostate cancer: evidence of the complex nature of the disease. , 2001, Human molecular genetics.

[11]  S. Cichon,et al.  Caught in the trio trap? Potential selection bias inherent to association studies using parent-offspring trios. , 2001, American journal of medical genetics.

[12]  N. Fleshner,et al.  Antioxidant dietary supplements: Rationale and current status as chemopreventive agents for prostate cancer. , 2001, Urology.

[13]  E J Duell,et al.  Polymorphisms in the DNA repair gene XRCC1 and breast cancer. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[14]  Richard D. Wood,et al.  Human DNA Repair Genes , 2001, Science.

[15]  M. Tockman,et al.  Polymorphisms of the DNA repair gene XRCC1 and lung cancer risk. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[16]  M. Spitz,et al.  XPD/ERCC2 polymorphisms and risk of head and neck cancer: a case-control analysis. , 2000, Carcinogenesis.

[17]  S. Z. Abdel‐Rahman,et al.  The 399Gln polymorphism in the DNA repair gene XRCC1 modulates the genotoxic response induced in human lymphocytes by the tobacco-specific nitrosamine NNK. , 2000, Cancer letters.

[18]  B. Levin,et al.  Inheritance of the 194Trp and the 399Gln variant alleles of the DNA repair gene XRCC1 are associated with increased risk of early-onset colorectal carcinoma in Egypt. , 2000, Cancer letters.

[19]  A. Harris,et al.  A variant within the DNA repair gene XRCC3 is associated with the development of melanoma skin cancer. , 2000, Cancer research.

[20]  B Langholz,et al.  Testing linkage disequilibrium in sibships. , 2000, American journal of human genetics.

[21]  E. Mark,et al.  Polymorphisms in the Dna Repair Genes Xrcc1 and Ercc2 and Biomarkers of Dna Damage in Human Blood Mononuclear Cells Cross-complementing Group 1) than in 399arg/arg Carriers of Breaks following Base Excision Repair (ber) Resulting From , 2022 .

[22]  R. Parshad,et al.  XPD polymorphisms: effects on DNA repair proficiency. , 2000, Carcinogenesis.

[23]  M. West,et al.  XRCC1 keeps DNA from getting stranded. , 2000, Mutation research.

[24]  M. Spitz,et al.  Polymorphisms of DNA repair gene XRCC1 in squamous cell carcinoma of the head and neck. , 1999, Carcinogenesis.

[25]  C. Poole.  Controls who experienced hypothetical causal intermediates should not be excluded from case-control studies. , 1999, American journal of epidemiology.

[26]  G. Haas,et al.  N-Acetyltransferase expression and DNA binding of N-hydroxyheterocyclic amines in human prostate epithelium. , 1999, Carcinogenesis.

[27]  D. Bell,et al.  XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. , 1999, Cancer research.

[28]  R. V. Prasad,et al.  Role of DNA Polymerase β in the Excision Step of Long Patch Mammalian Base Excision Repair* , 1999, The Journal of Biological Chemistry.

[29]  J. Witte,et al.  Asymptotic bias and efficiency in case-control studies of candidate genes and gene-environment interactions: basic family designs. , 1999, American journal of epidemiology.

[30]  N M Laird,et al.  A discordant-sibship test for disequilibrium and linkage: no need for parental data. , 1998, American journal of human genetics.

[31]  N Risch,et al.  The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases I. DNA pooling. , 1998, Genome research.

[32]  D J Schaid,et al.  Use of parents, sibs, and unrelated controls for detection of associations between genetic markers and disease. , 1998, American journal of human genetics.

[33]  J. Schwartz,et al.  Immunohistochemical detection of polycyclic aromatic hydrocarbon-DNA damage in human blood vessels of smokers and non-smokers. , 1998, Atherosclerosis.

[34]  P. Vichi,et al.  TFIIH: A Transcription Factor Involved in DNA Repair and Cell-Cycle Regulation , 1998 .

[35]  M. Masson,et al.  XRCC1 Is Specifically Associated with Poly(ADP-Ribose) Polymerase and Negatively Regulates Its Activity following DNA Damage , 1998, Molecular and Cellular Biology.

[36]  R. Wood,et al.  Mechanism of open complex and dual incision formation by human nucleotide excision repair factors , 1997, The EMBO journal.

[37]  P. Hartge,et al.  The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. , 1997, The New England journal of medicine.

[38]  W. Isaacs,et al.  Down-regulation of the KAI1 metastasis suppressor gene during the progression of human prostatic cancer infrequently involves gene mutation or allelic loss. , 1996, Cancer research.

[39]  J. Eyfjörd,et al.  A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes , 1996, Nature Genetics.

[40]  J. D. Thompson,et al.  Germ-line BRCA1 mutations in selected men with prostate cancer. , 1996, American journal of human genetics.

[41]  S. Little,et al.  Amplification‐Refractory Mutation System (ARMS) Analysis of Point Mutations , 1995, Current protocols in human genetics.

[42]  N. Dracopoli,et al.  Current protocols in human genetics , 1994 .

[43]  R. Barkardottir,et al.  Linkage analysis of chromosome 17q markers and breast-ovarian cancer in Icelandic families, and possible relationship to prostatic cancer. , 1993, American journal of human genetics.

[44]  T. Beaty,et al.  Mendelian inheritance of familial prostate cancer. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[45]  P. Hartge,et al.  Excluding controls: misapplications in case-control studies. , 1984, American journal of epidemiology.

[46]  W. Isaacs,et al.  Review of allelic loss and gain in prostate cancer , 2004, World journal of urology.

[47]  O. Ogawa.  Risk Factors for Prostate Cancer , 2004 .

[48]  M. Karagas,et al.  The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene-environment interaction. , 2002, Cancer research.

[49]  E. Bleecker,et al.  Associations between hOGG 1 Sequence Variants and Prostate Cancer Susceptibility 1 , 2002 .

[50]  W. Isaacs,et al.  Protection against 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine cytotoxicity and DNA adduct formation in human prostate by glutathione S-transferase P1. , 2001, Cancer research.

[51]  H Li,et al.  A general test of association for complex diseases with variable age of onset , 2000, Genetic epidemiology.

[52]  G. Abecasis,et al.  A general test of association for quantitative traits in nuclear families. , 2000, American journal of human genetics.

[53]  J K Hewitt,et al.  Combined linkage and association sib-pair analysis for quantitative traits. , 1999, American journal of human genetics.

[54]  J D Tucker,et al.  Characterization of the XRCC1-DNA ligase III complex in vitro and its absence from mutant hamster cells. , 1995, Nucleic acids research.