title: Effects of phenotypes in heterocyclic aromatic amine (HCA) metabolism-related genes on the association of HCA intake with the risk of colorectal adenomas.
abstract: BACKGROUND
  Heterocyclic aromatic amines (HCA), formed by high-temperature cooking of meat, are well-known risk factors for colorectal cancer (CRC). Enzymes metabolizing HCAs may influence the risk of CRC depending on the enzyme activity level. We aimed to assess effect modification by polymorphisms in the HCA-metabolizing genes on the association of HCA intake with colorectal adenoma (CRA) risk, which are precursors of CRC.
  
  
  METHODS
  A case-control study nested in the EPIC-Heidelberg cohort was conducted. Between 1994 and 2005, 413 adenoma cases were identified and 796 controls were matched to cases. Genotypes were determined and used to predict phenotypes (i.e., enzyme activities). Odds ratios (OR) and corresponding 95 % confidence intervals (CI) were calculated by logistic regression analysis.
  
  
  RESULTS
  CRA risk was positively associated with PhIP, MeIQx, and DiMeIQx (p trend = 0.006, 0.022, and 0.045, respectively) intake. SULT1A1 phenotypes modified the effect of MeIQx on CRA risk (p                            (Interaction) > 0.01) such that the association of MeIQx intake with CRA was stronger for slow than for normal phenotypes. Other modifying effects by phenotypes did not reach statistical significance.
  
  
  CONCLUSIONS
  HCA intake is positively associated with CRA risk, regardless of phenotypes involved in the metabolizing process. Due to the number of comparisons made in the analysis, the modifying effect of SULT1A1 on the association of HCA intake with CRA risk may be due to chance.
authors: Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, University of Zurich, Hirschengraben 84, 8001 Zürich, Switzerland.
authors: Aline
authors: A
authors: Barbir
authors: Jakob
authors: J
authors: Linseisen
authors: Silke
authors: S
authors: Hermann
authors: Rudolf
authors: R
authors: Kaaks
authors: Birgit
authors: B
authors: Teucher
authors: Monika
authors: M
authors: Eichholzer
authors: Sabine
authors: S
authors: Rohrmann
mesh_terms: D000236:Adenoma / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000588:Amines / Q000008:administration & dosage / Q000009:adverse effects*; D015239:Arylsulfotransferase / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D003296:Cooking; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008460:Meat / Q000009:adverse effects*; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors; D013696:Temperature
chemical_list: D000588:Amines; D006571:Heterocyclic Compounds; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human