Racial differences in clinical and pathological associations with PhIP-DNA adducts in prostate

Abstract

African-American men have a higher dietary intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which is the most abundant heterocyclic amine in cooked meats and is carcinogenic in rat prostate through the formation of DNA adducts. To determine the clinical and demographic factors associated with PhIP-DNA adduct levels, the biologically effective dose of PhIP in human prostate, we immunohistochemically measured PhIP-DNA adducts in a study of 162 Caucasian and 102 African-American men who underwent radical prostatectomy for prostate cancer. A strong correlation between PhIP-DNA adduct levels in prostate tumor and adjacent non-tumor cells was observed (rho = 0.62; p < 0.0001); however, non-tumor cells had significantly higher adduct levels compared with tumor (0.167 optical density (OD) units +/- 0.043 vs. 0.104 OD +/- 0.027; p < 0.0001). Race was not associated with PhIP-DNA adduct levels in either tumor or non-tumor cells, but race-specific associations were observed. In prostate tumor and non-tumor cells, tumor volume had the strongest association with PhIP-DNA adducts in Caucasians, whereas in African-Americans prostate volume was most strongly associated with adduct levels in tumor cells and advanced Gleason grade had the strongest association in non-tumor cells. In race interaction models, while the only statistically significant interaction was between African-American race and advanced Gleason grade in non-tumor cells (beta = 0.029; p = 0.02), in tumor cells we observed opposite effects by race (positive for African-Americans, negative for Caucasians) for older age and high PSA levels at diagnosis. In conclusion, while PhIP-DNA adduct levels in prostate cells do not vary significantly by race, our results suggest that PhIP exposure may have stronger effects on prostate tumor differentiation in African-American men.

FIGURE 1

PhIP-DNA adduct staining intensity frequency distribution in 264 prostate cancer patients based on optical density scores in tumor and adjacent non-tumor prostate cells.

FIGURE 2

Correlation between PhIP-DNA adduct optical density scores in tumor and adjacent non-tumor prostate cells in 264 prostate cancer patients.

FIGURE 3

PhIP-DNA adduct staining in prostate epithelial non-tumor (Panel A) and tumor cells of Gleason primary Grade 3 (Panel B) and 4 (Panel C). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]