title: Gene-environment interaction of genome-wide association study-identified susceptibility loci and meat-cooking mutagens in the etiology of renal cell carcinoma.
abstract: BACKGROUND
  Meat-cooking mutagens may be associated with renal cell carcinoma (RCC) risk. In the current study, the authors examined associations between meat-cooking mutagens, genetic susceptibility variants, and risk of RCC.
  
  
  METHODS
  The authors used 659 newly diagnosed RCC cases and 699 healthy controls to investigate the association between dietary intake of meat-cooking mutagens and RCC. They examined whether associations varied by risk factors for RCC and genetic susceptibility variants previously identified from genome-wide association studies. Odds ratios and 95% confidence intervals were estimated using tertiles of intake of dietary polycyclic aromatic hydrocarbons/heterocyclic amines.
  
  
  RESULTS
  Dietary intake of the mutagenic compounds 2-amino-3,8-dimethylimidazo-(4,5-f) quinoxaline (MeIQx) and 2-amino-1 methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) were found to be significantly associated with an increased risk of RCC (odds ratios across tertiles: 1.00 [referent], 1.28 [95% confidence interval, 0.94-1.74], and 1.95 [95% confidence interval, 1.43-2.66] [P for trend <.001], respectively; and 1.00 [referent], 1.41 [95% confidence interval, 1.04-1.90], and 1.54 [95% confidence interval, 1.14-2.07] [P for trend =.02], respectively). The authors observed evidence of interactions between PhIP and RCC susceptibility variants in 2 genes: inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) (rs718314; multiplicative P for interaction = .03 and additive P for interaction =.002) and endothelial PAS domain-containing protein 1 (EPAS1) (rs7579899; additive P for interaction =.06).
  
  
  CONCLUSIONS
  The intake of meat may increase the risk of RCC through mechanisms related to the cooking compounds MeIQx and PhIP. These associations may be modified by genetic susceptibility to RCC. Further research is necessary to understand the biological mechanisms underlying these interactions.
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Melkonian
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Daniel
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nizar M
authors.initials: NM
authors.lastname: Tannir
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Karam
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Surena F
authors.initials: SF
authors.lastname: Matin
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D002292:Carcinoma, Renal Cell / Q000139:chemically induced / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D016022:Case-Control Studies; D004198:Disease Susceptibility; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000506:poisoning; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D008297:Male; D008460:Meat; D008875:Middle Aged; D009153:Mutagens / Q000008:administration & dosage* / Q000506:poisoning; D011810:Quinoxalines / Q000008:administration & dosage / Q000506:poisoning; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D007093:Imidazoles; D009153:Mutagens; D011810:Quinoxalines; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
keywords: gene-environment interaction; heterocyclic amines; meat-cooking mutagens; polycyclic aromatic hydrocarbons; renal cell carcinoma