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Genetics of Prostate Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Introduction

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Family history of prostate cancer

As with breast and colon cancer, familial clustering of prostate cancer has been reported frequently.[11,12,13,14,15] From 5% to 10% of prostate cancer cases are believed to be primarily caused by high-risk inherited genetic factors or prostate cancer susceptibility genes. Results from several large case-control studies and cohort studies representing various populations suggest that family history is a major risk factor in prostate cancer.[12,16,17] A family history of a brother or father with prostate cancer increases the risk of prostate cancer, and the risk is inversely related to the age of the affected relative.[13,14,15,16,17] However, at least some familial aggregation is due to increased prostate cancer screening in families thought to be at high risk.[18]

Although many of the prostate cancer studies examining risks associated with family history have used hospital-based series, several studies described population-based series. The latter are thought to provide information that is more generalizable. The Massachusetts Male Aging Study of 1,149 Boston-area men found a relative risk (RR) of 3.3 (95% confidence interval [CI], 1.8–5.9) for prostate cancer among men with a family history of the disease.[19] This effect was independent of environmental factors, such as smoking, alcohol use, and physical activity. Further associations between family history and risk of prostate cancer were characterized in an 8-year to 20-year follow-up of 1,557 men aged 40 to 86 years who had been randomly selected as controls for a population-based case-control study conducted in Iowa from 1987 to 1989. At baseline, 4.6% of the cohort reported a family history of prostate cancer in a brother or father, and this was positively associated with prostate cancer risk after adjustment for age (RR, 3.2; 95% CI, 1.8–5.7) or after adjustment for age, alcohol, and dietary factors (RR, 3.7; 95% CI, 1.9–7.2).[20]

A meta-analysis of 33 epidemiologic case-control and cohort-based studies has provided more detailed information regarding risk ratios related to family history of prostate cancer. Risk appeared to be greater for men with affected brothers than for men with affected fathers in this meta-analysis. Although the reason for this difference in risk is unknown, possible hypotheses have included X-linked or recessive inheritance. In addition, risk increased with increasing numbers of affected close relatives. Risk also increased when a first-degree relative (FDR) was diagnosed with prostate cancer before age 65 years. (See Table 1 for a summary of the RRs related to a family history of prostate cancer.)[21]

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