title: Genetic polymorphisms in DNA repair and oxidative stress pathways may modify the association between body size and postmenopausal breast cancer.
abstract: OBJECTIVE
  Obesity is associated with increased bioavailability of estrogen, hyperinsulinemia, and chronic inflammation, all of which may promote tumor growth. Given DNA repair and oxidative stress pathways may work together with these mechanisms to influence carcinogenesis, we hypothesized that genetic variation in these pathways may modify the obesity-postmenopausal breast cancer (BC) association.
  
  
  METHODS
  Resources from a population-based case-control study (990 cases and 970 controls) were used to construct logistic regression models. Body mass index (BMI, weight [kilogram]/height [square meter]) was assessed 1 year before reference date. We characterized interactions between BMI and 29 genetic polymorphisms in oxidative stress and DNA repair pathways.
  
  
  RESULTS
  Age-adjusted odds ratios (95% confidence intervals) for postmenopausal BC were 1.24 (1.00-1.52) and 1.35 (1.09-1.71) for 25 ≥ BMI < 30 and BMI ≥ 30 kg/m(2), respectively. We observed multiplicative interactions (P ≤ .05) for eight gene polymorphisms in DNA repair and oxidative stress pathways. For example, among MPO variant allele carriers, obesity was associated with a twofold increased risk of postmenopausal BC (2.13 [1.35-3.36]); however, in wild-type homozygotes, the relationship was less pronounced (1.33 [0.93-1.89]). Our findings were no longer significant after Bonferroni correction.
  
  
  CONCLUSIONS
  Obesity may be particularly deleterious for postmenopausal BC development in the presence of biologically plausible DNA repair or oxidative stress genotypes.
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill. Electronic address: lauren.mccullough@unc.edu.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: McCullough
authors.affiliation: Department of Epidemiology, Columbia University, New York, NY.
authors.forename: Sybil M
authors.initials: SM
authors.lastname: Eng
authors.affiliation: Department of Nutrition, University of North Carolina, Chapel Hill.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Bradshaw
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Cleveland
authors.affiliation: Department of Epidemiology and Biostatistics, University of South Carolina, Columbia.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Steck
authors.affiliation: Department of Epidemiology, Columbia University, New York, NY.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Terry
authors.affiliation: Department of Environmental Health Sciences, Columbia University, New York, NY.
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Epidemiology, Columbia University, New York, NY; Department of Medicine, Columbia University, New York, NY.
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Crew
authors.affiliation: Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine ASCR, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Rossner
authors.affiliation: Department of Population Health, New York University School of Medicine, New York.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.affiliation: Department of Preventive Medicine, Ichan School of Medicine at Mt. Sinai, New York, NY.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Teitelbaum
authors.affiliation: Department of Epidemiology, Columbia University, New York, NY; Department of Medicine, Columbia University, New York, NY.
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Neugut
authors.affiliation: Department of Environmental Health Sciences, Columbia University, New York, NY.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill.
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D049628:Body Size / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017698:Postmenopause; D012307:Risk Factors; D055815:Young Adult
keywords: Body mass index; Breast cancer; DNA repair; Epidemiology; Oxidative stress