The risk of prostate cancer may also increase in men who have a family history of breast cancer. Approximately 9.6% of the Iowa cohort had a family history of breast and/or ovarian cancer in a mother or sister at baseline, and this was positively associated with prostate cancer risk (age-adjusted RR = 1.7; 95% CI, 1.0-3.0; multivariate RR = 1.7; 95% CI, 0.9-3.2). Men with a family history of both prostate and breast/ovarian cancer were also at increased risk of prostate cancer (RR = 5.8; 95% CI, 2.4-14.0). Other studies, however, did not find an association between family history of female breast cancer and risk of prostate cancer.[37,43] A family history of prostate cancer also increases the risk of breast cancer among female relatives. The association between prostate cancer and breast cancer in the same family may be explained, in part, by the increased risk of prostate cancer among men with BRCA1/BRCA2mutations in the setting of hereditary breast/ovarian cancer or early-onset prostate cancer.[45,46,47,48] (Refer to the BRCA1 and BRCA2 subsection of the Prostate Cancer Susceptibility Loci section of this summary for more information.)
Family history has been shown to be a risk factor for men of different races and ethnicities. In a population-based case-control study of prostate cancer among African Americans, whites, and Asian Americans in the United States (Los Angeles, San Francisco, and Hawaii) and Canada (Vancouver and Toronto), 5% of controls and 13% of all cases reported a father, brother, or son with prostate cancer. These prevalence estimates were somewhat lower among Asian Americans compared with African Americans or whites. A positive family history was associated with a twofold to threefold increase in relative risk in each of the three ethnic groups. The overall odds ratio associated with a family history of prostate cancer was 2.5 (95% CI, 1.9-3.3) with adjustment for age and ethnicity.
Evidence for inherited forms of prostate cancer can be found in several U.S. and international studies.[30,34,50,51,52,53] It was first noted in 1956 that men with prostate cancer reported a higher frequency of the disease among relatives than did controls. Shortly thereafter, it was reported that deaths from prostate cancer were increased among fathers and brothers of men who died of prostate cancer versus controls who died of other causes.
Refer to the PDQ summary on Prevention of Prostate Cancer for more information about risk factors for prostate cancer in the general population.
Inheritance of Prostate Cancer Risk
Many types of epidemiologic studies (case-control, cohort, twin, family) strongly suggest that prostate cancer susceptibility genes exist in the population. An analysis of monozygotic and dizygotic twin pairs in Scandinavia concluded that 42% (CI, 29-50) of prostate cancer risk may be accounted for by heritable factors. This is in agreement with a previous U.S. study that showed a concordance of 7.1% between dizygotic twin pairs compared with a 27% concordance between monozygotic twin pairs. The first segregation analysis was performed in 1992 using families from 740 consecutive probands who had radical prostatectomies between 1982 and 1989. The study results suggested that familial clustering of disease among men with early-onset prostate cancer was best explained by the presence of a rare (frequency of 0.003) autosomal dominant, highly penetrantallele(s). Hereditary prostate cancer susceptibility genes were predicted to account for almost half of early-onset disease (age 55 years or younger). In addition, early-onset disease has been further supported to have a strong genetic component from the study of common variants associated with disease onset before age 55 years.