BRCA1 and BRCA2 mutations in a population-based study of male breast cancer

Basham, Victoria M.; Lipscombe, Julian; Ward, John; Gayther, Simon A.; Ponder, Bruce A.J.; Easton, Douglas F.; Pharoah, Paul D.P.

doi:10.1186/bcr419

Cited by 167 publications

(136 citation statements)

References 18 publications

(21 reference statements)

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“…Our results are in agreement with the studies of Bergthorsson et al (2001), de la Hoya et al (2002 and Ford et al (1998); however, others failed to demonstrate such a predictive value (Couch et al, 1997;Steinmann et al, 2001). Male breast cancer in combination with a family history of breast/ovarian cancer was indicative of finding a BRCA2 mutation (P ¼ 0.002), which is consistent with a recent population-based British study (Basham et al, 2002). In none of the four Belgian sporadic male breast cancer patients a mutation was identified.…”

Section: Discussionsupporting

confidence: 93%

BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian breast/ovarian cancer families

et al. 2004

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Worldwide variation in the distribution of BRCA1 and BRCA2 mutations is well recognised, and for the Belgian population no comprehensive studies about BRCA1/2 mutation spectra or frequencies have been published. We screened the complete coding region of both genes in 451 individuals from 349 Belgian families referred to a family cancer clinic and identified 49 families with a BRCA1 and 26 families with a BRCA2 mutation. Six major recurrent mutations (BRCA1 IVS5 þ 3A4G, 2478 -2479insG, E1221X and BRCA2 IVS6 þ 1G4A, 6503-6504delTT, 9132delC) accounted for nearly 60% of all mutations identified. Besides 75 true pathogenic mutations, we identified several variants of unknown clinical significance. In combination with a family history, an early average age of female breast cancer diagnosis (Po0.001), and the presence of a relative with ovarian cancer (Po0.0001) or multiple primary breast cancers (P ¼ 0.002), increased the chance for finding a mutation. Male breast cancer was indicative of a BRCA2 mutation segregating in the family (P ¼ 0.002). Mutations in the 5 0 -end of BRCA1 and BRCA2 were associated with a significantly increased risk for ovarian cancer relative to the central portion of the gene. Our study suggests a role for additional breast cancer susceptibility genes in the Belgian population, since mutation detection ratios were low in high-risk breast cancer-only families as compared to breast -ovarian cancer families. Given the large proportion of recurring mutations, molecular testing can now be organised in a more cost-effective way. Our data allow optimisation of genetic counselling and disease prevention in Belgian breast/ovarian cancer families. Since the mapping and the cloning of two genes that confer susceptibility to both breast and ovarian cancer, BRCA1 and BRCA2 (Miki et al, 1994;Wooster et al, 1995;Tavtigian et al, 1996), it became possible to offer genetic testing to families with a predisposition for breast and/or ovarian cancer. Consequently, individuals at risk can now be identified as candidates for surveillance programmes. A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but population-specific variation in the distribution of BRCA1/2 mutations is well recognised. In some populations or ethnic groups, founder mutations form a sufficient proportion of the total to justify the adoption of specific molecular screening strategies.To date, no comprehensive studies in the Belgian population have been published. Only data from small series are available (Claes et al, 1999a, b) or from studies in which the analysis was restricted to a few BRCA1/2 exons or to BRCA1 only Sibille-Hoang et al, 1998;Goelen et al, 1999). We performed mutation screening of the complete coding region of BRCA1 and BRCA2 in 349 unrelated Belgian families referred to our family cancer clinic and report here the nature and distribution of the mutations identified. We found phenotypic differences between families in whom a disease-causing mutation was identified vs BRCA1/2 muta...

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Section: Discussionsupporting

confidence: 93%

BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian breast/ovarian cancer families

et al. 2004

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“…(18) Similar to other studies (19)(20)(21)(22) we found no BRCA1 mutation carriers among our 16 non-Jewish patients.…”

Section: Discussionsupporting

confidence: 81%

Similar prevalence of founder BRCA1 and BRCA2 mutations among Ashkenazi and non-Ashkenazi men with breast cancer: Evidence from 261 cases in Israel, 1976–1999

Chodick

Struewing

Ron

et al. 2008

European Journal of Medical Genetics

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To evaluate the potential contribution of mutations in the BRCA1 and BRCA2 genes to male breast cancer (MBC), we expanded a previous study to screen a total of 261 Israeli men diagnosed with breast carcinoma. A total of 21 BRCA2 6174delT and eight BRCA1 185delAG mutations were found. Similar frequencies of BRCA1 and BRCA2 mutation carriers were found among Ashkenazi (12.8%) and non-Ashkenazi Jews (9.1%). The combined prevalence of BRCA1/BRCA2 founder mutations among Ashkenazi Jewish men is slightly higher than for women, due to a higher frequency of BRCA2 mutations.

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“…The risk of breast cancer in female first-degree relatives of male breast cancer patients has been estimated to be 2.4 times greater than the risk in the general population (Basham et al, 2002), consistent with a common genetic susceptibility to male and female breast cancer. However, BRCA1 and BRCA2 alone cannot explain all the observed FRRs (Basham et al, 2002).…”

Section: Risks Of Cancers At Other Sites and Risks Of Second Cancersmentioning

confidence: 90%

“…However, BRCA1 and BRCA2 alone cannot explain all the observed FRRs (Basham et al, 2002). To allow for this residual effect, we assumed that the polygenic component in the model also applied to male patients.…”

Section: Risks Of Cancers At Other Sites and Risks Of Second Cancersmentioning

confidence: 99%

The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions

et al. 2008

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Multiple genetic loci confer susceptibility to breast and ovarian cancers. We have previously developed a model (BOADICEA) under which susceptibility to breast cancer is explained by mutations in BRCA1 and BRCA2, as well as by the joint multiplicative effects of many genes (polygenic component). We have now updated BOADICEA using additional family data from two UK population-based studies of breast cancer and family data from BRCA1 and BRCA2 carriers identified by 22 population-based studies of breast or ovarian cancer. The combined data set includes 2785 families (301 BRCA1 positive and 236 BRCA2 positive). Incidences were smoothed using locally weighted regression techniques to avoid large variations between adjacent intervals. A birth cohort effect on the cancer risks was implemented, whereby each individual was assumed to develop cancer according to calendar period-specific incidences. The fitted model predicts that the average breast cancer risks in carriers increase in more recent birth cohorts. For example, the average cumulative breast cancer risk to age 70 years among BRCA1 carriers is 50% for women born in 1920 -1929 and 58% among women born after 1950. The model was further extended to take into account the risks of male breast, prostate and pancreatic cancer, and to allow for the risk of multiple cancers. BOADICEA can be used to predict carrier probabilities and cancer risks to individuals with any family history, and has been implemented in a user-friendly Web-based program

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BRCA1 and BRCA2 mutations in a population-based study of male breast cancer

Cited by 167 publications

References 18 publications

BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian breast/ovarian cancer families

BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian breast/ovarian cancer families

Similar prevalence of founder BRCA1 and BRCA2 mutations among Ashkenazi and non-Ashkenazi men with breast cancer: Evidence from 261 cases in Israel, 1976–1999

The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions

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