title: Genetic polymorphisms of phase I metabolizing enzyme genes, their interaction with lifetime grilled and smoked meat intake, and breast cancer incidence.
abstract: To examine associations between 22 CYP single nucleotide polymorphisms (SNPs) and breast cancer incidence and their interactions with grilled-smoked meat intake, a source of polycyclic aromatic hydrocarbons.
  
  
  
  White women with first primary in situ or invasive breast cancer (n = 988) and frequency-matched controls (n = 1021) from a population-based study were interviewed to assess lifetime grilled-smoked meat intake. SNPs with minor allele frequencies of greater than 0.05 were selected because of their links to carcinogenesis. We used multivariable unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
  
  
  
  Breast cancer was inversely associated with CYP1A1 rs104C8943 AG + GG genotype (OR = 0.71, 95% CI = 0.50-0.99; vs. AA genotype) and positively associated with CYP1B1 rs10175338 TT genotype (OR = 1.59, 95% CI = 1.12-2.26; vs. GG genotype) and the CYP3A4 rs2242480 CT + TT genotype (OR = 1.25, 95% CI = 1.00-1.56; vs. CC genotype). The sum of the number of "at-risk" alleles for the CYP SNPs was positively associated with breast cancer incidence (4-6 "at-risk" alleles OR = 2.33, 95% CI = 1.37-3.99 vs. 0-1 alleles; PTrend< .01). We observed multiplicative and additive interactions (P < .05) between grilled-smoked meat intake (low vs. high) with CYP1A1 rs1048943 and CYP1B1 rs10175338 SNPs.
  
  
  
  Phase I metabolizing enzyme gene SNPs may play a role in breast cancer development and may modify the grilled-smoked meat intake-breast cancer association.
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill. Electronic address: hparada@live.unc.edu.
authors.forename: Humberto
authors.initials: H
authors.lastname: Parada
authors.affiliation: Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Steck
authors.affiliation: Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Cleveland
authors.affiliation: Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Teitelbaum
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY.
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Neugut
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill.
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008460:Meat / Q000009:adverse effects*; D008875:Middle Aged; D009518:New York / Q000453:epidemiology; D016017:Odds Ratio; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000706:statistics & numerical data
chemical_list: D011084:Polycyclic Aromatic Hydrocarbons; D019363:Cytochrome P-450 CYP1A1
keywords: Breast cancer; Cytochrome p450 enzymes; Gene–environment interactions; Grilled and smoked meat; Polymorphism