α-Methylacyl-CoA racemase expression and lethal prostate cancer in the Physicians’ Health Study and Health Professionals Follow-up Study
Dhillon, Preet K.
Mucci, Lorelei A.
Rubin, Mark A.
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CitationBarry, Marc, Preet K. Dhillon, Meir J. Stampfer, Sven Perner, Jing Ma, Edward Giovannucci, Tobias Kurth, Lorelei A. Mucci, and Mark A. Rubin. 2011. “α-Methylacyl-CoA Racemase Expression and Lethal Prostate Cancer in the Physicians’ Health Study and Health Professionals Follow-up Study.” The Prostate 72 (3): 301–6. https://doi.org/10.1002/pros.21432.
AbstractBACKGROUND a-Methylacyl-CoA racemase (AMACR) is an enzyme that serves as a diagnostic biomarker of prostate cancer in clinical practice. Recent studies suggest that low AMACR expression is associated with biochemical recurrence and the development of fatal disease.METHODS. We conducted a prospective cohort study among 920 men aged 47-84 years, who were diagnosed with prostate cancer in the Physicians' Health Study and the Health Professionals Follow-up Study cohorts, and whose resected tissue specimens were available for immunohistochemical analysis. We used Cox proportional hazards regression to evaluate the association of AMACR expression with lethal prostate cancer over a 20-year follow-up period. RESULTS . In total, 68 men died from prostate cancer, and an additional 18 developed bony metastases during follow-up. We found that lower AMACR intensity was associated with higher prostate-specific antigen levels (P = 0.003) and more advanced clinical stage (P = 0.06) at diagnosis, and a nonsignificant trend for higher risk of lethal outcomes. The hazard ratio (HR) comparing the lowest to the highest quartile of AMACR expression intensity was 1.53 ((95% CI: 0.86-2.73), P-for-trend across quartiles = 0.07); this trend was further attenuated after adjustment for age, Gleason score, stage, and cohort with a HR of 1.24 (95% CI: 0.69-2.22), P-for-trend = 0.23.
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