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

Lehrer, Steven F.; Fodor, F; Stock, Richard G.; Stone, Nelson N.; Eng, Charis; Song, Honglin; McGovern, Margaret M.

doi:10.1038/bjc.1998.576

Cited by 51 publications

(35 citation statements)

References 19 publications

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“…Of note, had we excluded patients with personal or familial history of BC from the patient cohort as well as from the control group analysed, the lack of association between these mutations and CRC would be even more striking. Taken together with the recent publications showing these specific mutations do not increase the risk for prostate cancer in this ethnic group (Lehrer et al, 1998;Hubert et al, 1999;Vazina et al, 2000), we can conclude that the predominant Ashkenazi Jewish BRCA1 and BRCA2 mutations do not contribute to the pathogenesis of CRC. Thus, it seems that the two major indications for performing BRCA1/2 genetic testing in men are the personal risk for developing BC (Struewing et al, 1999) and the risk of transmitting the mutated alleles to their daughters.…”

Section: Discussionsupporting

confidence: 78%

The frequency of the predominant Jewish mutations in BRCA1 and BRCA2 in unselected Ashkenazi colorectal cancer patients

et al. 2001

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It is presently unclear whether carriers of BRCA1 mutations have an increased risk for colorectal cancer (CRC). To gain insight into this issue, 225 unselected Ashkenazi Jewish CRC patients were tested for the presence of the three common Jewish BRCA1/2 germline mutations: 185delAG and 5382insC ( BRCA1 ) and 6174delT ( BRCA2 ). A total of four carriers was found (4/225, 1.78%). This frequency is similar to the estimated normal Ashkenazi population frequency, thus suggesting that these specific mutations do not contribute to CRC predisposition.© 2001 Cancer Research Campaign http://www.bjcancer.com

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Section: Discussionsupporting

confidence: 78%

The frequency of the predominant Jewish mutations in BRCA1 and BRCA2 in unselected Ashkenazi colorectal cancer patients

et al. 2001

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“…It demonstrated that BRCA2 mutation carriers have a relative risk (RR) of PRCA of 4.65 rising to 7.33 below the age of 65 years and BRCA1 mutation carriers have an RR of PRCA of 1.82 under the age of 65 years (BCLC, 1999; Thompson et al, 2002). Similar data have been recorded in the AJ population (Struewing et al, 1997;Warner et al, 1999;Giusti et al, 2003), although smaller clinical studies have generally not demonstrated an increased frequency of founder BRCA1/2 mutations among Jewish men with PRCA (Lehrer et al, 1998;Hubert et al, 1999;Nastiuk et al, 1999;Vazina et al, 2000). In the current data set, six men were identified from a previous study conducted at The Institute of Cancer Research, as described in the Materials and Methods section.…”

Section: Discussionmentioning

confidence: 71%

Prostate cancer in male BRCA1 and BRCA2 mutation carriers has a more aggressive phenotype

et al. 2008

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There is a high and rising prevalence of prostate cancer (PRCA) within the male population of the United Kingdom. Although the relative risk of PRCA is higher in male BRCA2 and BRCA1 mutation carriers, the histological characteristics of this malignancy in these groups have not been clearly defined. We present the histopathological findings in the first UK series of BRCA1 and BRCA2 mutation carriers with PRCA. The archived histopathological tissue sections of 20 BRCA1/2 mutation carriers with PRCA were collected from histopathology laboratories in England, Ireland and Scotland. The cases were matched to a control group by age, stage and serum PSA level of PRCA cases diagnosed in the general population. Following histopathological evaluation and re-grading according to current conventional criteria, Gleason scores of PRCA developed by BRCA1/2 mutation carriers were identified to be significantly higher (Gleason scores 8, 9 or 10, P ¼ 0.012) than those in the control group. Since BRCA1/2 mutation carrier status is associated with more aggressive disease, it is a prognostic factor for PRCA outcome. Targeting screening to this population may detect disease at an earlier clinical stage which may therefore be beneficial. British Journal of Cancer (2008) Prostate cancer (PRCA) is the most commonly diagnosed malignancy in men in the United Kingdom. It is thought to be composed of aggressive and indolent varieties. Indolent PRCA may exist for many years without causing symptoms or shortening life expectancy. Aggressive PRCA may cause symptoms difficult to palliate with conventional treatments and is likely to shorten life expectancy. Distinguishing which men are at risk of which types of disease could have far-reaching consequences not only in the treatment and follow-up of patients but also in the surveillance of groups at risk of aggressive PRCA.The morphology of breast cancer found in female BRCA1 and BRCA2 germline mutation carriers has been studied extensively. The histopathological features of breast tumours from patients with BRCA1 and BRCA2 mutations differ from each other and from sporadic breast cancers . BRCA1 and BRCA2 breast cancers are of higher grade (Lakhani, 2001). BRCA1-associated tumours are more likely to be oestrogen, progesterone receptor and Her2 receptor negative, express TP53 protein, and demonstrate medullary/atypical medullary morphology. Lakhani (2001) predicts that a woman diagnosed with high-grade, oestrogen receptor-negative breast cancer before the age of 30 years has a 40-45% chance of harbouring a BRCA1 mutation, compared with a 4-5% chance if these parameters are not met (Lakhani, 2001). Many of the features identified in breast cancer in women who are BRCA1 mutation carriers are associated with a poor prognosis. If similar data were available for men with PRCA who are carriers of these mutations, weighing up the options for radical treatment or active surveillance could be simplified with this added information.Despite studies on the incidence of PRCA in male BRCA1 and BRCA2 mutation...

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“…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). Recently, three mutation carriers (two with the 185delAG and one harbouring 6174delT) were identified among 87 unselected prostate cancer patients from Israel (Hubert et al, 1999).…”

Section: Discussionmentioning

confidence: 98%

“…Indeed, the lifetime risk for developing CaP in Ashkenazi BRCA1 or BRCA2 mutation carriers was estimated at 16% (Struewing et al, 1997). However, direct mutational analysis of 60 unselected Jewish Ashkenazi CaP patients did not reveal any BRCA1 or BRCA2 mutation carrier (Lehrer et al, 1998).…”

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confidence: 99%

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

Cited by 51 publications

References 19 publications

The frequency of the predominant Jewish mutations in BRCA1 and BRCA2 in unselected Ashkenazi colorectal cancer patients

The frequency of the predominant Jewish mutations in BRCA1 and BRCA2 in unselected Ashkenazi colorectal cancer patients

Prostate cancer in male BRCA1 and BRCA2 mutation carriers has a more aggressive phenotype

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

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