Characteristics of Prostate Cancer in Families Potentially Linked to the Hereditary Prostate Cancer 1 (HPC1) Locus

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Abstract
Context. —Approximately 9% of prostate cancer cases have been estimated to result from inheritance of mutated prostate cancer susceptibility genes. Few data exist as to whether there are clinical differences between prostate cancers that are inherited and those that occur in the general population. Objective. —To investigate phenotypic characteristics of families potentially linked to the hereditary prostate cancer 1 (HPC1) locus on chromosome 1q24-25. Design. —Retrospective case study in which clinical data were extracted from medical and pathological records. Families. —A total of 74 North American families with hereditary prostate cancer. Prostate cancer cases from the National Cancer Data Base were used as a reference population for comparison. Main Outcome Measures. —The families were divided into 2 groups: either potentially linked (33 families with 133 men with prostate cancer), and thus likely to be carrying an alteredHPC1gene, or potentially unlinked (41 families with 172 men with prostate cancer), on the basis of haplotype analysis in the region ofHPC1. The age at diagnosis of prostate cancer, serum prostate-specific antigen levels, digital rectal examination status, stage, grade, primary treatment of prostate cancers, and occurrence of other cancers were compared between the groups. Rresults. —The mean age at diagnosis of prostate cancer for men in potentially linked families was significantly lower than for men in potentially unlinked families (63.7 vs 65.9 years, respectively,P=.01; mean age at diagnosis in the reference population was 71.6 years). Higher-grade cancers (grade 3) were more common in potentially linked families, and advanced-stage disease was found in 41% of the case patients in potentially linked families compared with 31% in both the potentially unlinked families and the reference groups (P=.03 for the latter comparison). In the other clinical parameters, we found no significant differences between the groups. A modest excess of breast cancer and colon cancer was found in potentially linked families in comparison with potentially unlinked families, but this difference was not statistically significant. Conclusions. —Families that provide evidence for segregation of an alteredHPC1gene are characterized by multiple cases of prostate cancer that, in most respects, are indistinguishable from nonhereditary cases. However, 3 characteristics were observed: younger age at diagnosis, higher-grade tumors, and more advanced-stage disease. Our study shows that a significant fraction of hereditary prostate cancers are diagnosed in advanced stages, emphasizing the clinical importance of early detection in men potentially carrying prostate cancer susceptibility genes. These findings support the current recommendations to screen men with a positive family history of prostate cancer beginning at age 40 years.