Autosomal dominant inheritance of prostate cancer: A confirmatory study

Objectives. To confirm, in a study of a large, independent cohort of famili es with prostate cancer, the findings of three segregation analyses that ha ve suggested the existence of an inherited form of prostate cancer with an autosomal dominant inheritance mode. Methods. Between January 1991 and December 1993, 1199 pedigrees were ascert ained through single, unrelated, prostate cancer probands who presented for radical prostatectomy at the Division of Urologic Surgery, Washington Univ ersity Medical Center in St. Louis, Missouri. Maximum likelihood segregatio n analysis was used to test specifically for mendelian inheritance of prost ate cancer. Results. Segregation analyses revealed that the familial aggregation of pro state cancer can be best explained by the autosomal dominant inheritance of a rare (q = 0.0037) high-risk allele. According to the best-fitting autoso mal dominant model, 97% of all carriers will be affected by 85 years of age compared with 10% of noncarriers. furthermore, the autosomal dominant mode l predicts that the high-risk allele accounts for a large proportion (65%) of all patients diagnosed with prostate cancer before 56 years of age. Howe ver, of all prostate cancer cases, a relatively small proportion is inherit ed (8% by 85 years old). Conclusions. These results are in agreement with earlier reports of segrega tion analyses of prostate cancer and strengthen the evidence that prostate cancer is inherited in a mendelian fashion within a subset of families. URO LOGY 57: 97-101, 2001. (C) 2001, Elsevier Science Inc.