Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer among High-Risk Men Enrolled in Prostate Cancer Early Detection

作者：Hughes Lucinda; Zhu Fang; Ross Eric; Gross Laura; Uzzo Robert G; Chen David Y T; Viterbo Rosalia; Rebbeck Timothy R; Giri Veda N^*

来源：Cancer Epidemiology Biomarkers & Prevention, 2012, 21(1): 53-60.

DOI：10.1158/1055-9965.EPI-11-0727

Background: Men with familial prostate cancer and African American men are at risk for developing prostate cancer at younger ages. Genetic markers predicting early-onset prostate cancer may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset prostate cancer in a longitudinal cohort of high-risk men enrolled in prostate cancer early detection with significant African American participation.
Methods: Eligibility criteria include ages 35 to 69 with a family history of prostate cancer or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset prostate cancer [rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)] were genotyped. Cox models were used to evaluate time to prostate cancer diagnosis and prostate-specific antigen (PSA) prediction for prostate cancer by genotype. Harrell's concordance index was used to evaluate predictive accuracy for prostate cancer by PSA and genetic markers.
Results: Four hundred and sixty participants with complete data and >= 1 follow-up visit were included. Fifty-six percent were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to prostate cancer diagnosis (P = 0.005) and influenced prediction for prostate cancer by the PSA (P < 0.001). When combined with PSA, rs6983561 improved predictive accuracy for prostate cancer compared with PSA alone among African American men (PSA 0.57 vs. PSA + rs6983561 = 0.75, P = 0.03).
Conclusions: Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing prostate cancer risk assessment. Further study is warranted to validate these findings.
Impact: Genetic markers of early-onset prostate cancer have potential to refine and personalize prostate cancer early detection for high-risk men. Cancer Epidemiol Biomarkers Prev; 21(1); 53-60.

• 出版日期2012-1