Prevalence and Predictors of <i>BRCA1</i> and <i>BRCA2</i> Mutations in a Population-Based Study of Breast Cancer in White and Black American Women Ages 35 to 64 Years

Malone, Kathleen E.; Daling, Janet R.; Doody, David R.; Hsu, Li; Bernstein, Leslie; Coates, Ralph J.; Marchbanks, Polly A.; Simon, Michael S.; McDonald, Jill A.; Norman, Sandra A.; Strom, Brian L.; Burkman, Ronald T.; Ursin, Giske; Deapen, Dennis; Weiss, Linda K.; Folger, Suzanne G.; Madeoy, Jennifer; Friedrichsen, Danielle M.; Suter, Nicola M.; Humphrey, Mariela C.; Spirtas, Robert; Ostrander, Elaine A.

doi:10.1158/0008-5472.can-06-0503

Cited by 328 publications

(269 citation statements)

References 50 publications

(60 reference statements)

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“…As the proteintruncating BRCA2 mutations were detected in Caucasians only, the prevalence of such mutations in whites is 0.78% (95%CI 0.09 -2.81%). Recently, Malone et al (2006) reported a weighted prevalence of protein-truncating BRCA2 mutations of 0.1% (95%CI 0.0 -0.3%) among US population-based Caucasian control women aged 35 -64 years. Assuming that the prevalence of disease-associated BRCA2 mutations among Caucasian men in the general population is similar to the prevalence of such mutations reported for US Caucasian women, the estimated RR of prostate cancer in white men o55 years of age associated with carrying a protein-truncating BRCA2 mutation is 7.78 (95%CI 1.80 -9.37).…”

Section: Resultsmentioning

confidence: 99%

“…As both disease-associated BRCA2 mutation carriers were Caucasian, the prevalence of such mutations in whites is 0.78% (95%CI 0.09 -2.81%); the estimated RR of prostate cancer is 7.8 (95%CI 1.8 -9.4) in Caucasian BRCA2 mutation carriers. Although this represents a substantially elevated RR of earlier-onset prostate cancer associated with carrying a germline protein-truncating BRCA2 mutation, such mutations are very rare (B0.1%) in the general US population (Malone et al, 2006). The estimated cumulative risk (i.e.…”

Section: Discussionmentioning

confidence: 97%

“…In addition, owing to the high cost of genetic sequencing and the rarity of germline BRCA2 protein-truncating mutations in the general population, it was not feasible to screen the large number of control men that would be required for direct case -control comparisons. Therefore, we used the previously reported prevalence of BRCA2 mutations in Caucasian control women from the general US population (Malone et al, 2006) to estimate the RR. There is no reason to believe that the prevalence of BRCA2 mutations in the general population would be substantially different between men and women, as the gene is located on chromosome 13.…”

Section: Discussionmentioning

confidence: 99%

“…All coding and non-coding regions of the BRCA2 gene were screened for mutations using 47 primer pairs described previously (Malone et al, 2000(Malone et al, , 2006Agalliu et al, 2007). Exons 5 and 6 were amplified in a single fragment and longer exons were amplified using multiple PCR reactions.…”

Section: Brca2 Gene Sequencingmentioning

confidence: 99%

“…The prevalence of germline protein-truncating BRCA2 mutations in the general population was taken from a recently published study of US women aged 35 -64 years (Malone et al, 2006), and was used to estimate the RR of prostate cancer in men aged o55 years associated with carrying a BRCA2 mutation.…”

Section: Statistical Analysesmentioning

confidence: 99%

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Rare germline mutations in the BRCA2 gene are associated with early-onset prostate cancer

et al. 2007

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Studies of families who segregate BRCA2 mutations have found that men who carry disease-associated mutations have an increased risk of prostate cancer, particularly early-onset disease. A study of sporadic prostate cancer in the UK reported a prevalence of 2.3% for protein-truncating BRCA2 mutations among patients diagnosed at ages p55 years, highlighting the potential importance of this gene in prostate cancer susceptibility. To examine the role of protein-truncating BRCA2 mutations in relation to early-onset prostate cancer in a US population, 290 population-based patients from King County, Washington, diagnosed at ages o55 years were screened for germline BRCA2 mutations. The coding regions, intron -exon boundaries, and potential regulatory elements of the BRCA2 gene were sequenced. Two distinct protein-truncating BRCA2 mutations were identified in exon 11 in two patients. Both cases were Caucasian, yielding a mutation prevalence of 0.78% (95% confidence interval (95%CI) 0.09 -2.81%) and a relative risk (RR) of 7.8 (95%CI 1.8 -9.4) for early-onset prostate cancer in white men carrying a protein-truncating BRCA2 mutation. Results suggest that protein-truncating BRCA2 mutations confer an elevated RR of early-onset prostate cancer. However, we estimate that o1% of early-onset prostate cancers in the general US Caucasian population can be attributed to these rare disease-associated BRCA2 mutations. British Journal of Cancer (2007) (BCLC, 1999;Johannsson et al, 1999;Eerola et al, 2001;Tulinius et al, 2002;Bermejo and Hemminki, 2004;van Asperen et al, 2005), kin-cohort studies of cancer incidence among relatives of population-based breast or ovarian cancer cases (Loman et al, 2003;Risch et al, 2006), as well as studies of populations who harbour founder BRCA2 mutations (Sigurdsson et al, 1997;Struewing et al, 1997, Kirchhoff et al, 2004 suggest that men who carry a diseaseassociated BRCA2 allele have an increased relative risk (RR) of prostate cancer (two-to five-fold elevation). Two of the family studies in which data were stratified on age at diagnosis of prostate cancer reported that the RR was even higher (seven-to eight-fold increase) in men diagnosed before age 65 years (BCLC, 1999;van Asperen et al, 2005). These findings suggest that proteintruncating BRCA2 mutations may play a role in prostate cancer susceptibility. However, the majority of studies that have investigated the role of BRCA2 mutations in hereditary prostate cancer (HPC) families, which usually include men diagnosed with prostate cancer at younger ages, have reported no diseaseassociated mutations (Wilkens et al, 1999;Gayther et al, 2000;Sinclair et al, 2000;Agalliu et al, 2007).To date, only one study has assessed the contribution of BRCA2 mutations in early-onset sporadic prostate cancer (Edwards et al, 2003). In a case series of 263 men in the UK diagnosed with prostate cancer at younger ages (p55 years), and who were not selected on the basis of either breast or prostate cancer family history, the prevalence of protein-truncating BRCA2 mu...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Brca2 Gene Sequencingmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

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Rare germline mutations in the BRCA2 gene are associated with early-onset prostate cancer

et al. 2007

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Prevalence of Pathogenic BRCA1 Mutation Carriers in 5 US Racial/Ethnic Groups

John¹,

Miron²,

Gong³

et al. 2007

JAMA

292

243

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Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean

et al. 2021

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IMPORTANCE Rates of breast and ovarian cancer are high in the Caribbean; however, to date, few published data quantify the prevalence of inherited cancer in the Caribbean population. OBJECTIVE To determine whether deleterious variants in genes that characterize the hereditary breast and ovarian cancer syndrome are associated with the development of breast and ovarian cancer in the English-and Creole-speaking Caribbean populations.

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Prevalence and Predictors of BRCA1 and BRCA2 Mutations in a Population-Based Study of Breast Cancer in White and Black American Women Ages 35 to 64 Years

Cited by 328 publications

References 50 publications

Rare germline mutations in the BRCA2 gene are associated with early-onset prostate cancer

Rare germline mutations in the BRCA2 gene are associated with early-onset prostate cancer

Prevalence of Pathogenic BRCA1 Mutation Carriers in 5 US Racial/Ethnic Groups

Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean

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