Genetic variation in base excision repair genes and the prevalence of advanced colorectal adenoma.

Base excision repair (BER) corrects DNA damage caused by oxidative stress and low folate intake, which are putative risk factors for colorectal neoplasia. To examine the relationship between genetic variation in BER genes and colorectal adenoma risk, we conducted a case-control study of 767 cases of advanced colorectal adenoma and 773 controls from the baseline screening exam of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cases included participants diagnosed with advanced left-sided adenoma, and controls were subjects without evidence of a left-sided polyp by sigmoidoscopy, frequency-matched to cases on race and gender. Twenty single nucleotide polymorphisms were genotyped in four BER genes (APEX1, PARP1, POLB, and XRCC1), and conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association with colorectal adenoma. Two variants with possible functional significance were associated with risk. The APEX1 51H variant was associated with a borderline significant decreased risk of colorectal adenoma (OR, 0.66; 95% CI, 0.44-1.00), and the XRCC1 399Q variant was inversely associated with risk among Caucasians (OR, 0.80; 95% CI, 0.64-0.99). Homozygotes at two PARP1 loci (A284A and IVS13+118G>A) were also associated with a decreased risk of colorectal adenoma compared with wild-type carriers (OR, 0.70; 95% CI, 0.49-0.98 for both), which was restricted to advanced adenomas displaying histologically aggressive characteristics (OR, 0.51; 95% CI, 0.33-0.78, P = 0.002 for PARP1 A284A). This study suggests that polymorphisms in APEX1, XRCC1, and PARP1 may be associated with advanced colorectal adenoma.

[1]  U. Vogel,et al.  Polymorphisms of the XRCC1, XRCC3 and XPD genes and risk of colorectal adenoma and carcinoma, in a Norwegian cohort: a case control study , 2006, BMC Cancer.

[2]  Robert N Hoover,et al.  Methods for etiologic and early marker investigations in the PLCO trial. , 2005, Mutation research.

[3]  Yun-Chul Hong,et al.  Polymorphisms of XRCC1 gene, alcohol consumption and colorectal cancer , 2005, International journal of cancer.

[4]  R. Tang,et al.  MS-920: DNA repair gene polymorphisms, diet and colorectal cancer risk in Taiwan. , 2005, Cancer letters.

[5]  R. Brem,et al.  XRCC1 is required for DNA single-strand break repair in human cells , 2005, Nucleic acids research.

[6]  S. Leng,et al.  The Association of XRCC1 Haplotypes and Chromosomal Damage Levels in Peripheral Blood Lymphocyte among Coke-Oven Workers , 2005, Cancer Epidemiology Biomarkers & Prevention.

[7]  Jun Nakamura,et al.  The Arg280His polymorphism in X-ray repair cross-complementing gene 1 impairs DNA repair ability. , 2005, Mutation research.

[8]  M. Stern,et al.  XRCC1 and XRCC3 Polymorphisms and Their Role as Effect Modifiers of Unsaturated Fatty Acids and Antioxidant Intake on Colorectal Adenomas Risk , 2005, Cancer Epidemiology Biomarkers & Prevention.

[9]  R. Tang,et al.  Polymorphisms of the XRCC1, XRCC3, & XPD genes, and colorectal cancer risk: a case-control study in Taiwan , 2005, BMC Cancer.

[10]  M. Y. Kim,et al.  NAD+-Dependent Modulation of Chromatin Structure and Transcription by Nucleosome Binding Properties of PARP-1 , 2004, Cell.

[11]  K. Lohman,et al.  The ADPRT V762A Genetic Variant Contributes to Prostate Cancer Susceptibility and Deficient Enzyme Function , 2004, Cancer Research.

[12]  J. Błasiak,et al.  An association of polymorphism of DNA repair genes XRCC1 and XRCC3 with colorectal cancer. , 2004, Journal of experimental & clinical cancer research : CR.

[13]  Brian Staats,et al.  SNP500Cancer: a public resource for sequence validation and assay development for genetic variation in candidate genes , 2004, Nucleic Acids Res..

[14]  E. Parlanti,et al.  The base excision repair: mechanisms and its relevance for cancer susceptibility. , 2003, Biochimie.

[15]  M. Spitz,et al.  From genotype to phenotype: correlating XRCC1 polymorphisms with mutagen sensitivity. , 2003, DNA repair.

[16]  N. Laird,et al.  Estimation and Tests of Haplotype-Environment Interaction when Linkage Phase Is Ambiguous , 2003, Human Heredity.

[17]  D. Melton,et al.  Lack of involvement of nucleotide excision repair gene polymorphisms in colorectal cancer , 2003, British Journal of Cancer.

[18]  Hiroshi Suzuki,et al.  Parp‐1 deficiency implicated in colon and liver tumorigenesis induced by azoxymethane , 2003, Cancer science.

[19]  W. Bilker,et al.  Detection of proximal adenomatous polyps with screening sigmoidoscopy: a systematic review and meta-analysis of screening colonoscopy. , 2003, Archives of internal medicine.

[20]  E. Giovannucci.  Epidemiologic studies of folate and colorectal neoplasia: a review. , 2002, The Journal of nutrition.

[21]  T. Lindahl,et al.  Down-regulation of DNA repair synthesis at DNA single-strand interruptions in poly(ADP-ribose) polymerase-1 deficient murine cell extracts. , 2002, DNA repair.

[22]  R. Pastorelli,et al.  Effect of dna repair gene polymorphisms on BPDE‐DNA adducts in human lymphocytes , 2002, International journal of cancer.

[23]  H. Norppa,et al.  Genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes: role in mutagen sensitivity. , 2002, Carcinogenesis.

[24]  K. Caldecott,et al.  Central Role for the XRCC1 BRCT I Domain in Mammalian DNA Single-Strand Break Repair , 2002, Molecular and Cellular Biology.

[25]  D. Schaid,et al.  Score tests for association between traits and haplotypes when linkage phase is ambiguous. , 2002, American journal of human genetics.

[26]  Alison L. Livingston,et al.  Inherited variants of MYH associated with somatic G:C→T:A mutations in colorectal tumors , 2002, Nature Genetics.

[27]  G. Matullo,et al.  DNA adduct levels and DNA repair polymorphisms in traffic‐exposed workers and a general population sample , 2001, International journal of cancer.

[28]  H. Mohrenweiser,et al.  Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. , 2001, Carcinogenesis.

[29]  J. Hoeijmakers.  Genome maintenance mechanisms for preventing cancer , 2001, Nature.

[30]  M. Weinfeld,et al.  XRCC1 Stimulates Human Polynucleotide Kinase Activity at Damaged DNA Termini and Accelerates DNA Single-Strand Break Repair , 2001, Cell.

[31]  P C Prorok,et al.  Design of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. , 2000, Controlled clinical trials.

[32]  A. Medline,et al.  Possible mechanisms relating diet and risk of colon cancer. , 2000, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[33]  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.

[34]  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.

[35]  K. Fidelis,et al.  Functional characterization of Ape1 variants identified in the human population. , 2000, Nucleic acids research.

[36]  H. Blanché,et al.  New polymorphisms in the human poly(ADP-ribose) polymerase-1 coding sequence: lack of association with longevity or with increased cellular poly(ADP-ribosyl)ation capacity , 2000, Journal of Molecular Medicine.

[37]  S. Oei,et al.  ATP for the DNA Ligation Step in Base Excision Repair Is Generated from Poly(ADP-ribose)* , 2000, The Journal of Biological Chemistry.

[38]  M. Prakash Hande,et al.  Functions of poly(ADP-ribose) polymerase in controlling telomere length and chromosomal stability , 1999, Nature Genetics.

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

[40]  R J Carroll,et al.  Comparison of the 60- and 100-item NCI-block questionnaires with validation data. , 1999, Nutrition and cancer.

[41]  B. Ames,et al.  Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[42]  R. Roeder,et al.  Poly(ADP-ribose) polymerase enhances activator-dependent transcription in vitro. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[43]  T. Curran,et al.  Identification of redox/repair protein Ref-1 as a potent activator of p53. , 1997, Genes & development.

[44]  E. Giovannucci,et al.  Tobacco, colorectal cancer, and adenomas: a review of the evidence. , 1996, Journal of the National Cancer Institute.

[45]  C. Robson,et al.  Identification of residues in the human DNA repair enzyme HAP1 (Ref-1) that are essential for redox regulation of Jun DNA binding , 1993, Molecular and cellular biology.

[46]  T. Curran,et al.  Redox activation of Fos‐Jun DNA binding activity is mediated by a DNA repair enzyme. , 1992, The EMBO journal.

[47]  S. Winawer,et al.  Effects of cumene hydroperoxide on adenosine diphosphate ribosyl transferase in mononuclear leukocytes of patients with adenomatous polyps in the colon. , 1988, Carcinogenesis.

[48]  W. Willett,et al.  Reproducibility and validity of a semiquantitative food frequency questionnaire. , 1985, American journal of epidemiology.

[49]  S. Winawer,et al.  Unscheduled DNA synthesis in mononuclear leukocytes from patients with colorectal polyps. , 1985, Cancer research.

[50]  W. Enker,et al.  Reduced capacity for DNA repair synthesis in patients with or genetically predisposed to colorectal cancer. , 1983, Journal of the National Cancer Institute.

[51]  F. Farzaneh,et al.  DNA strand breaks and ADP-ribosyl transferase activation during cell differentiation , 1982, Nature.

[52]  February 1 , 1966 .