Risk of Cancer in Relatives of Prostate Cancer Probands

Isaacs, Sarah D.; Kiemeney, Lambertus A.; Baffoe-Bonnie, Agnes; Beaty, Terri H.; Walsh, Patrick C.

doi:10.1093/jnci/87.13.991

Cited by 135 publications

(84 citation statements)

References 7 publications

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“…A study from Washington state reported only one prostate cancer case with a germline BRCA1 mutation (185delAG) with a questionable family history, and an additional five rare allelic polymorphisms in other familial prostate cancer cases (Langston et al, 1996). An additional study failed to identify an increased risk of breast cancer in relatives of patients with prostate cancer (Issacs et al, 1995). One BRCA1 germline mutation carrier with CaP and familial cancer was reported among 24 Japanese CaP patients, no 185delAG or 6174delT mutation carriers were detected among 60 Ashkenazi CaP patients (Lehrer et al, 1998), and one 6174delT BRCA2 mutation carrier was found among 47 Jewish Ashkenazi individuals from 18 families with familial CaP (Wilkens et al, 1999).…”

Section: Discussionmentioning

confidence: 98%

The rate of the founder Jewish mutations in BRCA1 and BRCA2 in prostate cancer patients in Israel

et al. 2000

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Inherited predisposition occurs in 5–10% of all prostate cancer (CaP) patients, but the genes involved in conferring genetic susceptibility remain largely unknown. Several lines of evidence indicate that germline mutations in BRCA1 and BRCA2 might be associated with an increased risk for CaP. Three mutations in these two genes (185delAG and 5382InsC ( BRCA1 ) and 6174delT ( BRCA2 ) occur in about 2.5% of the general Ashkenazi population, and the 185delAG BRCA1 mutation, in up to 1% of non-Ashkenazi Jews. In order to assess the contribution of these germline mutations to prostate cancer in Jewish Israeli patients, we tested 174 unselected prostate cancer patients (95 of Ashkenazi origin) for these mutations by PCR amplification and modified restriction enzyme digests. Patient’s age range was 45–81 years (median 66), and in 24 (14.4%) the disease was diagnosed prior to 55 years of age. Nineteen (11%) and 12 (6.9%) patients had a first or second degree relative with CaP or breast cancer, respectively. Overall, five mutation carriers were detected: 2/152 (1.3%) 185delAG, 2/104 (2%) 5382InsC, and 1/158 (0.6%) 6174delT. In all carriers, the disease was diagnosed after the age of 55, and only one of them had a family history of breast and CaP. In addition, no allelic losses at the BRCA1 locus were demonstrated in 17 patients with a family history of CaP, using seven microsatellite markers. We conclude that the rate of the predominant Jewish BRCA1 and BRCA2 mutations in CaP patients does not significantly differ from that of the general population, and that mutational inactivation of the BRCA1 is rare in familial CaP. Thus, germline BRCA1 and BRCA2 mutations probably contribute little to CaP occurrence, to inherited predisposition, and to early onset disease in Jewish individuals. © 2000 Cancer Research Campaign

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Section: Discussionmentioning

confidence: 98%

The rate of the founder Jewish mutations in BRCA1 and BRCA2 in prostate cancer patients in Israel

et al. 2000

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“…A recent epidemiological analysis by Isaacs et al (1995) failed to identify a significantly increased risk of breast cancer among relatives of prostate cancer patients. Our findings are consistent with the findings of Isaacs et al Furthermore, there is no evidence of genetic linkage between BRCA1 and prostate cancer in high risk families (Eastman, 1996;Stephenson, 1996).…”

Section: Discussionmentioning

confidence: 99%

Absence of 185delAG mutation of the BRCA1 gene and 6174delT mutation of the BRCA2 gene in Ashkenazi Jewish men with prostate cancer

Lehrer

Fodor²,

Stock³

et al. 1998

Br J Cancer

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Summary Epidemiological studies have demonstrated a clustering of breast and prostate cancers in some families. Moreover, there is an increase in the number of cases of prostate cancer in families with inherited mutations of the breast cancer susceptibility gene BRCA 1. We assessed the role of BRCA1 and BRCA2 in prostate cancer. We tested for the BRCAl 185delAG frameshift mutation, found in 0.9% of Ashkenazi Jews, and the BRCA2 6174delT mutation, found in 1% of Ashkenazi Jews, in Ashkenazi Jewish men with prostate cancer. We studied 60 Ashkenazi men with prostate cancer. A family history was obtained by interview or a self-report questionnaire. Histological confirmation of diagnosis was obtained for all subjects. Ethnic background was confirmed for all subjects by self-report or interview. Mutations of BRCA 1 and BRCA2 were detected by amplification of lymphocyte DNA from peripheral blood according to standard polymerase chain reaction (PCR) and dot blot procedures. Patients' ages ranged from 55 to 80 years (mean ± s.d. 70 ± 5.25). There were six men with a family history of prostate cancer; three of these had a father with prostate cancer. Five of the men had a family history of breast cancer, in a mother, a sister or an aunt. None,of the men had a family history of both breast and prostate cancer. None of the 60 men carried the 1 85delAG BRCA 1 or 61 74delT BRCA2 mutations. Of 268 Ashkenazi Jewish women with sporadic breast cancer, tested in an unrelated study, 16 carried either the 1 85delAG mutation of BRCA 1 or the 61 74delT mutation of BRCA2. There was a significant difference in the incidence of the BRCA 1 and BRCA2 mutations in the breast and prostate cancer cases (P = 0.05, two-tailed Fisher's exact test). The contribution of germline BRCA 1 and BRCA2 mutations to prostate cancer incidence is probably small and could be limited to specific subgroups.

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“…203 The association of PC with other cancers is not straightforward, as some studies confirm it 190,208,209 and others do not. 210,211 McCahy et al, 208 found an increase in breast cancer but no increase in ovarian cancer in relatives of PC probands. Introduction of 17q through microcell-mediated chromosome transfer has indicated a TSG for PC in a region of 28 cM (centi-Morgans) at 17q12-22 that includes BRCA1.…”

Section: Brca1 and Brca2 Tsgmentioning

confidence: 99%

Molecular biology of prostate cancer

Karayi

Markham

2004

Prostate Cancer Prostatic Dis

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Development of any cancer reflects a progressive accumulation of alterations in various genes. Oncogenes, tumour suppressor genes, DNA repair genes and metastasis suppressor genes have been investigated in prostate cancer. Here, we review current understanding of the molecular biology of prostate cancer. Detailed understanding of the molecular basis of prostate cancer will provide insights into the aetiology and prognosis of the disease, and suggest avenues for therapeutic intervention in the future.

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Risk of Cancer in Relatives of Prostate Cancer Probands

Cited by 135 publications

References 7 publications

The rate of the founder Jewish mutations in BRCA1 and BRCA2 in prostate cancer patients in Israel

The rate of the founder Jewish mutations in BRCA1 and BRCA2 in prostate cancer patients in Israel

Absence of 185delAG mutation of the BRCA1 gene and 6174delT mutation of the BRCA2 gene in Ashkenazi Jewish men with prostate cancer

Molecular biology of prostate cancer

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