Journal
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
Volume 601, Issue 1-2, Pages 1-10Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.mrfmmm.2006.05.023
Keywords
prostate cancer; PhIP; peripheral blood lymphocytes; susceptibility
Funding
- NCI NIH HHS [CA84964, CA90270, CA88304, CA98549] Funding Source: Medline
- NIEHS NIH HHS [ES07784] Funding Source: Medline
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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 (<= 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. (c) 2006 Elsevier B.V. All rights reserved.
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