Genetic predisposition to prostate cancer: possible explanations for ethnic differences in risk.

Abstract

It seems unlikely that the large ethnic differences in prostate cancer risk can be explained completely by ethnic differences in diet or other lifestyle characteristics. Instead, the differences may be due to ethnic variation in endogenous factors, such as androgen metabolism or inherited susceptibility. We have reviewed the literature for evidence and support of ethnic variation in genetic susceptibility to prostate cancer as a reason for the ethnic differences in rates. We distinguish two types of ethnic variation: 1) variation in the prevalence of certain alleles of specific genes that confer modestly increased risk. Such variation might be reflected in ethnic differences in serum levels of androgens, their metabolites, or indicators of metabolism in the prostate; 2) variation in the prevalence of rare germline mutations conferring substantially increased risk. Such variation would be reflected in ethnic differences in familial aggregation of prostate cancer. We discuss the evidence in support of each of these two possibilities. Ethnic variation in polymorphic alleles of genes associated with modest fluctuations in risk could explain a large proportion of the ethnic difference in cancer risk. In contrast, rare mutations associated with substantially increased risk are likely to account for a smaller fraction of these differences.