FaCD Online Syndrome Fact Sheet

Last updated: 01 Sep 2008

Name: Prostate Cancer, Familial Clustering of

Mode of Inheritance: multifact?

Tumor features

prostate cancer

Tumor features (possible)

breast cancer
carcinoid of the small intestine
colorectal cancer
Hodgkin disease (Hodgkin's lymphoma)
leukemia
lung/bronchial cancer
ovarian cancer (i.e. epithelial origin)
pancreatic adenocarcinoma
renal cell cancer
urinary bladder cancer

Comment

Prostate cancer is familial in approximately 15-20 % of cases[1-4] and reported family history is generally reliable[42]. A family history of prostate cancer is a well known risk factor for this tumor[5-10,41,49]. Sons of an affected father have been shown to have relative risks (RR's) of developing this tumor ranging from 1.22 to 3.77, and RR's for men having an affected brother range from 1.9 to 4.7 [2,11-21,40,44]. Additional affected relatives further increase this relative risk, which may be as high as 11 in the presence of 4 affected relatives[11,22-24,44]. A relatively young age at diagnosis is also a risk modifier( e.g. a RR of 16.6 in men having a brother diagnosed with prostate cancer between 45 and 49 years of age has been documented)[3,15,17,20,21,25]. Mono-zygotic twin brothers of prostate cancer patients have been shown to more frequently develop prostate cancer compared with dizygotic brothers, which further indicates the existence of hereditary prostate cancer predisposition[26-28]. In a large Swedish population based cohort study, Grönberg et al.[33] calculated cumulative risks to develop prostate cancer for unaffected men in families with 2 or more cases of prostate cancer: 5%, 15% and 30% by age 60, 70 and 80 years, respectively.

Familial prostate cancer has been suggested to be more aggressive than the sporadic type[34;35]. However, Bova et al.[36] found no difference in biochemical relapses following radical prostatectomy between familial prostate cancer patients (including cases meeting the criteria for hereditary prostate cancer and prostate cancer patients without a family history of prostate cancer. In addition, several authors have demonstrated the absence of significant effects of familiy history of prostate cancer on prostate cancer survival[37,39,51-54]. Interestingly, Hemminki et al.[45] showed that in the Swedish population both good and poor survival in prostate cancer aggregate in families. Norrish et al.[38] observed that compared with sporadic prostate cancer, familial prostate cancers were more likely to be diagnosed in patients at a younger age, after asymptomatic PSA screening and include less frequently extraprostate disease. According to these authors, this might be explained by the observed higher socio-economic and educational status of the familial prostate cancer patients, who might participate more often in screening programs than the sporadic cases. The authors stress that differences in screening behavior reduce the validity of cross-sectional comparison of prognostic variables between sporadic and familial prostate cancer cases.

Some studies have demonstrated that having a first degree relative with breast cancer or ovarian cancer also increases prostate cancer risk [29,30,44,48,50,56] and the same has been suggested for bladder and renal cancer[48]. However, others could not confirm this[31;32]. Hassan et al.[43] observed a 130% increased risk of developing small intestinal neuroendocrine tumors among subjects with family histories of prostate cancer. Familial co-aggregation of prostate cancer with lung cancer, pancreatic and colorectal cancers[55], and association of prostate cancer with Hodgkins disease or leukemia in siblings[56] has also been reported.

A wide range of genetic polymorphisms have been found to be associated with moderate increases or decreases in prostate cancer risk; they are not discussed here. Combinations of these variants may be associated with higher and clinically relevant risks[46,47].

see also hereditary prostate cancer

References

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