IMPORTANCE—Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE—To identify mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND PARTICIPANTS—Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19 581 carriers of BRCA1 mutations and 11 900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. EXPOSURES—Mutations of BRCA1 or BRCA2. MAIN OUTCOMES AND MEASURES—Breast and ovarian cancer risks.

Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer

PASINI, Barbara;
2015

Abstract

IMPORTANCE—Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE—To identify mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND PARTICIPANTS—Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19 581 carriers of BRCA1 mutations and 11 900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. EXPOSURES—Mutations of BRCA1 or BRCA2. MAIN OUTCOMES AND MEASURES—Breast and ovarian cancer risks.
JAMA
313
13
1347
1361
http://www.ncbi.nlm.nih.gov/pubmed/25849179
BRCA1 and BRCA2 genes, mutation type and position, cancer risk
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