Population BRCA1 and BRCA2 Mutation Frequencies and Cancer Penetrances: A Kin–Cohort Study in Ontario, Canada

Abstract

BRCA1 and BRCA2 mutations may be more frequent in general populations than previously thought and may be associated with various types of cancers.

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

“…This prevalence is similar to the estimates of 0.12 and 0.07% for BRCA2 protein-truncating mutations in the general UK population (Peto et al, 1999;Antoniou et al, 2002). By contrast, a recent population-based study of ovarian cancer in Ontario, Canada, estimated a higher carrier frequency of protein-truncating BRCA2 mutations of 0.69% (95%CI 0.43% -1.10%) in the general population (Risch et al, 2006). However, the Canadian estimate was based on data from ovarian cancer patients.…”

“…However, the Canadian estimate was based on data from ovarian cancer patients. In addition, the ovarian cancer patient population was enriched with subjects, such as Ashkenazi Jews, known to have a higher prevalence of BRCA2 disease-associated founder mutations (Risch et al, 2006).…”

“…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).…”

BRCA1 and BRCA2 mutations correlate with TP53 abnormalities and presence of immune cell infiltrates in ovarian high-grade serous carcinoma

“…[18][19][20][21][22][23][24] Germline mutations in BRCA1 and BRCA2 are present in B18% of ovarian cancer patients with high-grade serous carcinoma. [25][26][27] When combined with BRCA deficiencies that result from somatic mutations or epigenetic silencing, it appears that up to half of all high-grade serous ovarian cancers (hereditary and sporadic) have BRCA dysfunction. 15,[26][27][28][29][30] BRCA1 and BRCA2 genes encode functionally related proteins that play a critical role in repair of DNA double-strand breaks.…”

Incidence and predictors of positive and negative effects of BRCA1/2 genetic testing on familial relationships: a 3-year follow-up study

“…2,3 To a lesser degree, BRCA1/2 mutations also predispose males to certain types of cancer. 4,5 The psychological adjustment of individuals undergoing genetic testing for cancer susceptibility has been studied extensively. [6][7][8] In general, no major long-term adverse psychological consequences seem to result from the genetic testing process with the exception of a consistently present subgroup of individuals who report distress.…”