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Detection of Subclinical Cancers by Prostate-specific Antigen Screening in Asymptomatic Men from High-Risk Prostate Cancer Families¹

Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital [M. P. M., J. S., O-P. K.], and Departments of Clinical Chemistry [P. M.] and Surgery Division of Urology [T. L. J. T.], Tampere University Hospital, FIN-33101 Tampere, Finland; and Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892-4470 [O-P. K.]

Positive family history is a significant risk factor for prostate cancer. Improved knowledge of the epidemiology and molecular basis of hereditary prostate cancer has led to a need for counseling and clinical follow-up for men with a positive family history of prostate cancer. However, very little information is available on the efficacy of early screening procedures, such as serum prostate-specific antigen (PSA) measurements, in the management of genetically predisposed, high-risk individuals. In a nationwide study, we obtained family histories from 2099 Finnish prostate cancer patients and identified 302 families with two or more affected cases. Here, 209 asymptomatic 45–75-year-old males from these families were included in a study to determine the frequency of serum PSA positivity and the prevalence of subclinical prostate cancers. Serum PSA was elevated in 21 (10.0%) of these high-risk individuals. Seven prostate cancers (3.3%) and two high-grade prostatic intraepithelial neoplasia lesions were diagnosed, with three cancers occurring in men ages 59 years. Men from prostate cancer families with an average age of onset of <60 years had a significantly higher frequency of PSA positivity (28.6%, P = 0.01) as well as cancers (14.3%, P = 0.02) than those with a later age of onset. The results suggest that prostate cancer development in genetically predisposed individuals is preceded by a subclinical period when PSA detection is possible. Serum PSA screening may be particularly useful in men with a family history of early-onset prostate cancer.

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