Does a family history of prostate cancer result in more aggressive disease?

Abstract

Current epidemiologic and genetic data suggest the hypothetical paradigm that prostate cancer occurs in three forms: sporadic, familial, and hereditary ( Figure 1). Sporadic cases are not associated with familial inheritance patterns, while familial cancer is de®ned as simple clustering of two or more cases within a family. The existence of hereditary prostate cancer, a subset of the familial form, is suggested by three epidemiologic observations enumerated by Carter et al 1 : (1) relatives of patients younger than 55 y are at higher risk of getting prostate cancer than those with older affected relatives; (2) there is stronger familial clustering in families with early onset of prostate cancer; and (3) the number of affected family members and their age at onset are the most important determinants of risk among relatives. 1 It has been estimated that the hereditary form of this disease accounts for 43% of early onset cancers (age 55 y or younger) but only 9% of all prostate cancer occurring by age 85 y. 2 Eeles et al 3 have summarized the published literature concerning familial clustering of prostate cancer. In casecontrol studies the relative risk of prostate cancer in ®rst-degree relatives of affected men ranges from 1.76 ± 11. In studies comparing the percentage of cases vs controls with a positive family history of prostate cancer, the relative risk ranges from 0.64 ± 7.5. Cohort studies in the United States 4 and Sweden 5 estimate relative risks of prostate cancer of 2.2 and 1.70, respectively, in men with affected relatives. Using segregation analysis in nuclear families Carter et al 1 estimated hazard ratios ranging from 1.4 ± 7

Family history of prostate and breast cancer and the risk of prostate cancer in the PSA era

“…As in previous studies (12,13), we found that the risk of PCa was higher in men whose relatives were diagnosed with PCa when they were <60 years old (Table 3). We also observed that, a family history of PCa was equally related to aggressive and non-aggressive PCa (Table 3), which conflicted with previous findings (13,37,38). Similarly, men with a family history of PCa had a significantly higher risk of PCa than men without a family history of the disease, regardless of tumor grade.…”

Human prostate cancer risk factors

“…Family history has been associated consistently with prostate cancer risk in epidemiologic studies 94–111. Prostate cancer appears to have a stronger familial aggregation than colon or breast cancer, two malignancies with well recognized familial components 112.…”

Plasminogen activator inhibitor type‐1 (PAI‐1) polymorphism 4G/5G is associated with prostate cancer among men with a positive family history

“…Several studies found that this risk increased further with additional affected first degree relatives, and the increase in risk due to family history is consistent across countries and ethnic groups studied [20]. In addition, a positive family history may also be associated with a poor prognosis of disease, including both a greater risk of biochemical relapse and metastasis [21]. Given the importance of family history on prostate cancer risk and progression, the identification of genetic factors underlying prostate cancer in family history positive samples can provide valuable markers for diagnosing and treating this disease.…”