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Hughes L , Zhu F , Ross E , Gross L , Uzzo RG , Chen DY , Viterbo R , Rebbeck TR , Giri VN
Assessing the clinical role of genetic markers of early-onset prostate cancer among high-risk men enrolled in prostate cancer early detection
Cancer Epidemiol Biomarkers Prev. 2012 Jan;21(1) :53-60
PMID: 22144497    PMCID: PMC3253936    URL: http://www.ncbi.nlm.nih.gov/pubmed/22144497
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Abstract
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.
Notes
Hughes, Lucinda Zhu, Fang Ross, Eric Gross, Laura Uzzo, Robert G Chen, David Y T Viterbo, Rosalia Rebbeck, Timothy R Giri, Veda N 1R03CA150079-01/CA/NCI NIH HHS/United States P30 CA006927/CA/NCI NIH HHS/United States Research Support, N.I.H., Extramural United States Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Cancer Epidemiol Biomarkers Prev. 2012 Jan;21(1):53-60. Epub 2011 Dec 5.