2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts in benign prostate and subsequent risk for prostate cancer.

Abstract

Despite convincing evidence that 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)--a heterocyclic amine generated by cooking meats at high temperatures--is carcinogenic in animal models, it remains unclear whether PhIP exposure leads to increased cancer risk in humans. PhIP-DNA adduct levels were measured in specimens from 534 prostate cancer case-control pairs nested within a historical cohort of men with histopathologically benign prostate specimens. We estimated the overall and race-stratified risk of subsequent prostate cancer associated with higher adduct levels. PhIP-DNA adduct levels in benign prostate were significantly higher in Whites than African Americans (0.274 optical density units (OD) ±0.059 vs. 0.256 OD ±0.054; p<0.0001). Prostate cancer risk for men in the highest quartile of PhIP-DNA adduct levels was modestly increased [odds ratio (OR) = 1.25; 95% confidence interval (CI) = 0.76-2.07]. In subset analyses, the highest risk estimates were observed in White patients diagnosed more than 4 years after cohort entry (OR = 2.74; 95% CI = 1.01-7.42) or under age 65 (OR = 2.80; 95% CI = 0.87-8.97). In Whites, cancer risk associated with high-grade prostatic intraepithelial neoplasia combined with elevated PhIP-DNA adduct levels (OR = 3.89; 95% CI = 1.56-9.73) was greater than risk associated with either factor alone. Overall, elevated levels of PhIP-DNA adducts do not significantly increase prostate cancer risk. However, our data show that White men have higher PhIP-DNA adduct levels in benign prostate tissue than African American men, and suggest that in certain subgroups of White men high PhIP-DNA adduct levels may predispose to an increased risk for prostate cancer.

• Authors: Deliang Tang, Oleksandr N Kryvenko, Yun Wang, Sheri Trudeau, Andrew Rundle, Satoru Takahashi, Tomoyuki Shirai, Benjamin A Rybicki
• Journal: International journal of cancer (Int J Cancer) Vol. 133 Issue 4 Pg. 961-71 (Aug 15 2013) ISSN: 1097-0215 [Electronic] United States
• PMID: 23400709 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2013 UICC.

Chemical References

• 2-amino-1-methyl-6-phenolimidazo(4,5-b)pyridine-DNA adduct
• DNA Adducts
• Imidazoles

Topics

• Aged
• DNA Adducts (metabolism)
• Humans
• Imidazoles (metabolism)
• Immunohistochemistry
• Male
• Prostatic Hyperplasia (metabolism)
• Prostatic Neoplasms (epidemiology)
• Risk Factors