Prostate cancer genetics

Multiple insults are required to form cancer, as cells have back-up mechanisms of protection. As proposed by Alfred Knudson, an individual inherits two copies of genes and both copies must be affected to induce cancer.8 While most prostate cancers appear to be sporadic, 10% are inherited. The first reported prostate cancer susceptibility gene is found on chromosome 1 (HPC1).9 Families that carry the HPC1 gene have multiple affected members and prostate cancer tends to be diagnosed at an earlier age (less than 65). There are other genes that contribute to familial prostate cancer and further characterizations of these abnormalities are active areas of research. Further evidence for a genetic predisposition towards prostate cancer is the difference between racial groups. For example, Black men have a greater incidence of the disease that also tends to present earlier than in White men. However, unlike previously believed, these men do not have more aggressive cancers than their Caucasian counterparts.10 Sporadic, or non-inherited, prostate cancer then represents 90% of the men with this disease. These men tend to harbor genetic abnormalities, and chromosomes 7, 8, 13 and 17 have all been described to have changes in prostate cancer. Some of the mutated genes include Rb, bcl-2, p53, androgen receptor, PTEN, p16, p27 and ras. For example, the mutation of the tumor suppressor gene p53 is very common in advanced disease, but not frequent in localized prostate cancer and thus serves as a good predictor of tumor behavior.11'12

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