About 7-15% of men in the US have a first degree relative with prostate cancer.15,35-36\u00a0\u00a0Family history of prostate cancer in first-degree relatives (brother, father, children) is a significant risk factor for prostate cancer with relative risk of 2 for diagnosis of prostate cancer; The risk is significantly higher if the first degree relative was diagnosed before the age of 65, RR=2.25 vs RR=1.67 for age >65.37\u00a0\u00a0\u00a0Relative risk increases to 2.5-3 if more than one first degree relative has been diagnosed with prostate cancer.\u00a0\u00a0 With three or more first degree relative with prostate cancer, the risk increase is estimated to be as high 5-11 fold higher.38-39\u00a0\u00a0\u00a0\u00a0The risk is only slightly increased for second degree relative (grandfather, uncle, cousin) with prostate cancer.<\/p>\n
It is important to note that family history of BRCA1\/2 associated breast or ovarian cancer in first-degree female relatives (mother, sister, daughter), and presumptively male relatives, is a risk factor for developing prostate cancer with RR=1.22.37\u00a0The increased risk is attributable to families carrying BRCA1\/2 mutations.\u00a0 BRCA genes are autosomal dominant with 50% chance of inheritance.\u00a0 In addition, men with BRCA genes have an 8% lifetime risk of breast cancer.<\/p>\n
Given that men in the relevant age group of 50-75 with PSA 2-10 have 17-25% chance of being diagnosed with prostate cancer, addition of family history in the first degree relative of prostate or breast cancer doubles the risk to 34-50%.\u00a0\u00a0For example, for men with a family history of prostate cancer, 30.4% in placebo arm and 23% in the dutasteride arm of the REDUCE trial were diagnosed with prostate cancer, equivalent to 32% higher risk.15<\/b><\/p>\n
Especially for men with multiple first-degree relatives diagnosed at young age or with advanced disease, the high risk of harboring prostate cancer makes it reasonable for many of them to be offered a prostate biopsy independently of PSA level.<\/p>\n