Racial difference in prostate cancer cell telomere lengths in men with higher grade prostate cancer: A clue to the racial disparity in prostate cancer outcomes

Abstract

Background: Black men have worse prostate cancer outcomes following treatment than White men even when accounting for prognostic factors. However, biological explanations for this racial disparity have not been fully identified. We previously showed that more variable telomere lengths among cancer cells and shorter telomere lengths in cancer-associated stromal (CAS) cells individually and together (“telomere biomarker”) are associated with prostate cancer-related death in surgically treated men independent of currently used prognostic indicators. Here, we hypothesize that Black-White differences in the telomere biomarker and/or in its components may help explain the racial disparity in prostate cancer outcomes. Methods: Black [higher grade (Gleason ≥4þ3) ¼ 34 and lower grade ¼ 93] and White (higher grade ¼ 34 and lower grade ¼ 89) surgically treated men were frequency matched on age, pathologic stage, and grade. We measured telomere lengths in cancer and CAS cells using a robust telomere-specific FISH assay. Tissue microarray and grade-specific distributional cutoff points without regard to race were evaluated. Results: Among men with higher grade disease, the proportion of Black men (47.1%) with more variable cancer cell telomere lengths was 2.3-times higher (P ¼ 0.02) than that in White men (20.6%). In contrast, among men with lower grade disease, cancer cell telomere length variability did not differ by race. The proportion of men with shorter CAS cell telomeres did not differ by race for either higher or lower grade disease. Conclusions: A greater proportion of Black men with higher grade disease have an adverse prostate cancer cell telomere phenotype than White men with higher grade disease. Impact: Our findings suggest a possible explanation for the racial disparity in prostate cancer outcomes.