The evolving role of familial history for prostate cancer

Abstract

Background. Family history of prostate cancer is a risk factor for prostate cancer occurrence. Differently from other neoplasms no major predisposing gene has been identified. Material and methods. This review article presents the controversial results of studies about the prognostic and predictive role of family history in prostate cancer, reports the discovered predisposing genes, and biologic and pathologic findings. Results. Mortality from PC remains a significant health care problem, but no trial investigated if it changed in presence of positive family history. The largest family study yet published concluded that men with family history are diagnosed and die at earlier ages than men without it. However, it failed to stress the prognostic value of family history. Genome-wide association studies of prostate cancer have identified a number of genetic variants at different loci in different populations. Prostate neoplasms of patients with positive family history exhibit a different pattern of expression of genes related with estrogen and androgen metabolism within the tumor. High-penetrance and low-penetrance genes in diagnosis and prognosis of prostate cancer, difficulties to define a classification and to quantify relative risks of single genes, documented gene-environment interactions are discussed. Conclusion. Family history stands for both shared genetic and environmental factors and their interaction. The availability of prostate-specific antigen test could explain partly the high familial risk, among brothers or shortly after the diagnosis of prostate cancer. Polymorphisms in genes associated with prostate cancer probably represent the most part of familial prostate cancer burden. An increasing knowledge of disregulated cellular pathways of lethal prostate cancer could define which of all genetic alterations have a role in defining new preventive and therapeutic strategies.