Genetics of Prostate Cancer (PDQ®) - National Cancer Institute

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Genetics of Prostate Cancer (PDQ®) - National Cancer Institute

Introduction

Risk Factors for Prostate Cancer
Multiple Primaries
Risk of Other Cancers in Multiple-Case Families
Family History as a Risk Factor for Prostate Cancer
Inheritance of Prostate Cancer Risk

 [Note: Many of the medical and scientific terms used in this summary are found in the NCI Dictionary of Genetics Terms. When a linked term is clicked, the definition will appear in a separate window.]

 [Note: Many of the genes described in this summary are found in the Online Mendelian Inheritance in Man (OMIM) database. When OMIM appears after a gene name or the name of a condition, click on OMIM for a link to more information.]

The public health burden of prostate cancer is substantial. A total of 241,740 new cases of prostate cancer and 28,170 deaths from the disease are anticipated in the United States in 2012, making it the most frequent nondermatologic cancer among U.S. males.[1] A man’s lifetime risk of prostate cancer is one in six. Prostate cancer is the second leading cause of cancer death in men, exceeded only by lung cancer.

Some men with prostate cancer remain asymptomatic and die from unrelated causes rather than as a result of the cancer itself. This may be due to the advanced age of many men at the time of diagnosis, slow tumor growth, or response to therapy.[2] The estimated number of men with latent prostate carcinoma (i.e., prostate cancer that is present in the prostate gland but never detected or diagnosed during a patient’s life) is greater than the number of men with clinically detected disease. A better understanding is needed of the genetic and biologic mechanisms that determine why some prostate carcinomas remain clinically silent, while others cause serious, even life-threatening illness.[2]

Prostate cancer exhibits tremendous differences in incidence among populations worldwide; the ratio of countries with high and low rates of prostate cancer ranges from 60-fold to 100-fold.[3] Asian men typically have a very low incidence of prostate cancer, with age-adjusted incidence rates ranging from 2 to 10 per 100,000 men. Higher incidence rates are generally observed in northern European countries. African American men, however, have the highest incidence of prostate cancer in the world; within the United States, African American men have a 60% higher incidence rate than white men.[4]

These differences may be due to the interplay of genetic, environmental, and social influences (such as access to health care), which may affect the development and progression of the disease.[5] Differences in screening practices have also had a substantial influence on prostate cancer incidence, by permitting prostate cancer to be diagnosed in some patients before symptoms develop or before abnormalities on physical examination are detectable. An analysis of population-based data from Sweden suggested that a diagnosis of prostate cancer in one brother leads to an early diagnosis in a second brother using prostate-specific antigen (PSA) screening.[6] This may account for an increase in prostate cancer diagnosed in younger men that was evident in nationwide incidence data. A genetic contribution to prostate cancer risk has been documented, but knowledge of the molecular genetics of prostate cancer is still limited. Malignant transformation of prostate epithelial cells and progression of prostate carcinoma are likely to result from a complex series of initiation and promotional events under both genetic and environmental influences.[7]