A genome screen of families with multiple cases of prostate cancer: Evidence of genetic heterogeneity

We conducted a genomewide screen for prostate cancer-susceptibility genes o n the basis of data from 98 families from the United States and Canada that had three or more verified diagnoses of prostate cancer among first- and s econd-degree relatives. We found a statistically significant excess of mark ers for which affected relatives exhibited modest amounts of excess allele- sharing; however, no single chromosomal region contained markers with exces s allele-sharing of sufficient magnitude to indicate unequivocal evidence o f linkage. Positive linkage signals of nominal statistical significance wer e found in two regions (5p-q and 12p) that have been identified as weakly p ositive in other data sets and in region 19p, which has not been identified previously. All these signals were considerably stronger for analyses rest ricted to families with mean age at onset below the median than for analyse s of families with mean age at onset above the median. The data provided li ttle support for any of the putative prostate cancer-susceptibility genes i dentified in other linkage studies.