title: Human sensitivity to PhIP: a novel marker for prostate cancer risk.
abstract: 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been implicated in the development of colon, prostate and mammary gland tumors in rats. In this study, we developed a modified in vitro mutagen sensitivity assay, with activated PhIP (N-OH-PhIP) as the challenge mutagen and chromosome aberrations as the endpoint, and applied it in a pilot prostate cancer case-control study of 81 cases and 84 age and ethnicity-matched controls. Our results showed significantly higher baseline breaks among the cases, mean+/-S.E.=1.86+/-0.23 versus 0.96+/-0.14 in controls; P=0.006. Individuals with high baseline breaks (dichotomized at the control median) had a 36% increased risk for PC (OR=1.36; 95% CI=1.08-1.72). In stratified analysis, high baseline breaks was associated in younger participants (< or = 60 years) with an OR of 1.71 (1.14-2.57) and in those with a positive family history of PC, an OR of 1.43 (0.97-2.11). PhIP treatment induced significantly higher breaks in cases, mean+/-S.E.=5.07+/-0.39 versus 3.83+/-0.24 in controls; P=0.05. Higher PhIP-induced breaks was associated with an overall 17% increased risk for PC (OR=1.17; 95% CI=1.03-1.33), a significantly increased risks (OR=1.19; 95% CI=1.00-1.41) among younger participants, non-smokers (OR=1.39, 1.03-1.88) and 1.20 (1.00-1.45) among those with no family history of PC. Results from this pilot study demonstrate differential sensitivity to PhIP among subgroups and therefore, this assay have potential as a susceptibility marker for prostate cancer risk.
authors.affiliation: Department of Epidemiology, Unit 1340, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA. relzein@mdanderson.org
authors.forename: Randa
authors.initials: R
authors.lastname: El-Zein
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Etzel
authors.forename: Mirtha S
authors.initials: MS
authors.lastname: Lopez
authors.forename: Yun
authors.initials: Y
authors.lastname: Gu
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.forename: Sara S
authors.initials: SS
authors.lastname: Strom
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects*; D019457:Chromosome Breakage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics
chemical_list: D007093:Imidazoles; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine