title: 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: Department of Environmental Health Sciences, Columbia University, New York, NY, USA.
authors: Deliang
authors: D
authors: Tang
authors: Oleksandr N
authors: ON
authors: Kryvenko
authors: Yun
authors: Y
authors: Wang
authors: Sheri
authors: S
authors: Trudeau
authors: Andrew
authors: A
authors: Rundle
authors: Satoru
authors: S
authors: Takahashi
authors: Tomoyuki
authors: T
authors: Shirai
authors: Benjamin A
authors: BA
authors: Rybicki
mesh_terms: D000368:Aged; D018736:DNA Adducts / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000453:epidemiology*; D012307:Risk Factors
chemical_list: C502239:2-amino-1-methyl-6-phenolimidazo(4,5-b)pyridine-DNA adduct; D018736:DNA Adducts; D007093:Imidazoles
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