Hereditary prostate cancer and other genetic predispositions to prostate cancer

The incidence of prostate cancer (CaP) and its increase in the last 10 years vary both from country to country and according to the ethnic group, with the highest incidence reported for Afro-Americans and the lowest for Asian men. To date, only three risk factors have been established for CaP: age; familial aggregation of CaP, and ethnic origins. No dietary or environment-related cause has been established. However, some variations in endogenous genetic factors may help explain differences in risk among ethnic groups or geographic areas. Similarly, certain genetic polymorphisms of genes encoding for 5alpha-reductase, androgen receptor or vitamin D, have been associated with different levels of CaP risk, and could explain the variations observed between populations. Different studies support the view that familial CaP may truly be hereditary, and not due to a similar lifestyle. Thus, familial inheritance is a parameter that needs to be considered in recommending screening for high-risk families. Indeed, when 1, 2, and 3 first-degree relatives are affected, the relative risk of first-degree relatives of CaP patients may increase to 2, 5, and 11%, respectively. Some familial forms appear to be associated with transmission of a rare putative dominant gene with a high penetrance (88% at age 85), with the cumulative proportion of CaP attributable to this gene being more marked for younger patients (a 43 versus a 34% risk of CaP appearing before the age of 55 versus 70 years). Using this transmission model and linkage analysis, a predisposing locus on chromosome 1q24-25 (HPC-1) has been described. Moreover, recessive and X-linked transmission has been suggested, showing that a large proportion of familial CaP may not be due to segregation of a few major gene mutations, but rather to familial sharing of alleles at many loci, each contributing to a small increase in cancer risk. Candidate genes may be the same suppressor genes that are involved in other cancers and in sporadic CaP.