Segregation Analysis Evidence Of Major Susceptibility Genes

The evidence from twin studies and family studies supports the importance of genetic factors in the development of prostate cancer. However, these studies cannot infer the genetic model of inheritance. To identify a specific inheritance model of hereditary prostate cancer, complex segregation analysis can be used. So far, there are four complex segregation analyses of prostate cancer that support an autosomal dominant inheritance model for prostate cancer susceptibility, especially for early-onset disease.1,3,5,29 A prostate cancer susceptibility gene was estimated to be rare in the general population, with a frequency of about 0.0031 to 0.006.5 The pen-etrance of such a rare susceptibility gene was estimated to be ~88% by age 85 for carriers and 3%-5% for noncarriers. However, other inheritance models have been suggested for prostate cancer. The segregation analyses by Schaid et al.5 confirmed that dominant inheritance was the best-fitting model for families with early-onset prostate cancer cases. However, this model did not adequately explain family data when the index cases were diagnosed at an older age (>70 years). Cui et al.29 also suggested that two-locus models, combining autosomal dominant with either autosomal recessive or X-linked inheritance, fit their family data better than any single-locus model. The results from segregation analyses begin to illustrate the heterogeneous nature of prostate cancer.

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