title: Nucleotide excision repair gene polymorphisms, meat intake and colon cancer risk.
abstract: OBJECTIVE
  Much of the DNA damage from colon cancer-related carcinogens, including heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH) from red meat cooked at high temperature, are repaired by the nucleotide excision repair (NER) pathway. Thus, we examined whether NER non-synonymous single nucleotide polymorphisms (nsSNPs) modified the association between red meat intake and colon cancer risk.
  
  
  METHODS
  The study consists of 244 African-American and 311 white colon cancer cases and population-based controls (331 African Americans and 544 whites) recruited from 33 counties in North Carolina from 1996 to 2000. Information collected by food frequency questionnaire on meat intake and preparation methods were used to estimate HCA and benzo(a)pyrene (BaP, a PAH) intake. We tested 7 nsSNPs in 5 NER genes: XPC A499V and K939Q, XPD D312N and K751Q, XPF R415Q, XPG D1104H, and RAD23B A249V. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression.
  
  
  RESULTS
  Among African Americans, we observed a statistically significant positive association between colon cancer risk and XPC 499 AV+VV genotype (OR=1.7, 95% CI: 1.1, 2.7, AA as referent), and an inverse association with XPC 939 QQ (OR=0.3, 95%CI: 0.2, 0.8, KK as referent). These associations were not observed among whites. For both races combined, there was interaction between the XPC 939 genotype, well-done red meat intake and colon cancer risk (OR=1.5, 95% CI=1.0, 2.2 for high well-done red meat and KK genotype as compared to low well-done red meat and KK genotype, pinteraction=0.05).
  
  
  CONCLUSIONS
  Our data suggest that NER nsSNPs are associated with colon cancer risk and may modify the association between well-done red meat intake and colon cancer risk.
authors.affiliation: Department of Epidemiology and Biostatistics, Cancer Prevention and Control Program, Arnold School of Public Health, University of South Carolina, 915 Greene Street, RM 236, Columbia, SC 29208, USA. Electronic address: ssteck@sc.edu.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Steck
authors.affiliation: Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, Suite 4C-466, 5150 Centre Avenue, Pittsburgh, PA 15232, USA. Electronic address: BUTLERL3@upmc.edu.
authors.forename: Lesley M
authors.initials: LM
authors.lastname: Butler
authors.affiliation: Division of Gastroenterology and Hepatology, School of Medicine, University of North Carolina, 103 Mason Farm Road, 7340-C Medical Biomolecular Research Building, CB#7032, Chapel Hill, NC 27599-7032, USA. Electronic address: tokeku@med.unc.edu.
authors.forename: Temitope
authors.initials: T
authors.lastname: Keku
authors.affiliation: Department of Epidemiology and Biostatistics, Cancer Prevention and Control Program, Arnold School of Public Health, University of South Carolina, 915 Greene Street, RM 236, Columbia, SC 29208, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Antwi
authors.affiliation: Cancer Epidemiology Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina at Chapel Hill, CB#7555, 4157 Bioinformatics Building, Chapel Hill, NC 27599-7555, USA. Electronic address: galanko@med.unc.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Galanko
authors.affiliation: Cancer Epidemiology Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina at Chapel Hill, CB#7555, 4157 Bioinformatics Building, Chapel Hill, NC 27599-7555, USA. Electronic address: rsandler@med.unc.edu.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
authors.affiliation: Sylvester Comprehensive Cancer Center and Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. Electronic address: JHu@med.miami.edu.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Hu
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000208:ethnology / Q000235:genetics*; D000328:Adult; D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001580:Benzopyrenes / Q000008:administration & dosage; D002273:Carcinogens / Q000008:administration & dosage; D002417:Cattle; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000208:ethnology / Q000235:genetics*; D003296:Cooking; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006571:Heterocyclic Compounds / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008460:Meat / Q000009:adverse effects*; D008875:Middle Aged; D009657:North Carolina; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D011795:Surveys and Questionnaires; D044465:White People
chemical_list: D001580:Benzopyrenes; D002273:Carcinogens; D004268:DNA-Binding Proteins; D006571:Heterocyclic Compounds; C086984:XPC protein, human
keywords: Case-control study; Colon cancer; DNA repair; Diet; Meat; Polymorphism