In extension of a population-based case-control study of prostate cancer among black, white and Asian Americans conducted from 10-1-89 to 8-31-94, we propose to gather cancer pedigree data from all subjects who reported prostate cancer in one or more first-degree relatives, and a random sample of those who did not. Objectives are: i) to compare cases and controls with respect to previously reported personal characteristics (diet, physical activity, body size), while stratifying by number and type of relatives with prostate cancer; ii) to compare observed site-specific cancer incidence In families of cases to that expected from regional incidence rates; iii) to determine if familial prostate cancer patterns suggest a major predisposing gene; iv) to identify families with three or more confirmed prostate cancer cases (including the proband) among first- or second-degree relatives and within these families, to find genetic markers that co-segregate with prostate cancer and thus identify candidate loci for a predisposing gene or genes. Strengths of the project include: 1) detailed family histories, obtained from the same black, white and Asian men who previously provided data on diet, physical activity and body size, permit assessment of the combined effects of genetic susceptibility and lifestyle characteristics on prostate cancer risk; 2) segregation analysis, if supportive of a major predisposing gene, will provide population-based estimates of gene frequency and penetrance and their variation with age and race; 3) some 80 families with three or more cases of prostate cancer (30-40 from the case- control study, 40-50 from Vancouver) permit linkage analysis to identify predisposing genes that could provide important insight into the development of all prostate cancers; 4) banked serum and DNA from the same high-risk individuals will allow future comparison of steroid hormones and their metabolites in carriers and non-carriers of mutated alleles.
