Cancer Epidemiol Biomarkers Prev. 2013 May;22(5):803-11. doi: 10.1158/1055-9965.EPI-12-0195. Epub 2013 Mar 1.
Risk of pancreatic cancer in breast cancer families from the breast cancer family registry.
Mocci E, Milne RL, Méndez-Villamil EY, Hopper JL, John EM, Andrulis IL, Chung WK, Daly M, Buys SS, Malats N, Goldgar DE.
SourceCorresponding Author: David E. Goldgar, Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT 84132. firstname.lastname@example.org.
BACKGROUND:Increased risk of pancreatic cancer has been reported in breast cancer families carrying BRCA1and BRCA2 mutations; however, pancreatic cancer risk in mutation-negative (BRCAX) families has not been explored to date. The aim of this study was to estimate pancreatic cancer risk in high-risk breast cancer families according to the BRCA mutation status.
METHODS:A retrospective cohort analysis was applied to estimate standardized incidence ratios (SIR) for pancreatic cancer. A total of 5,799 families with ≥1 breast cancer case tested for mutations in BRCA1 and/or BRCA2 were eligible. Families were divided into four classes: BRCA1, BRCA2, BRCAX with ≥2 breast cancer diagnosed before age 50 (class 3), and the remaining BRCAX families (class 4).
RESULTS:BRCA1 mutation carriers were at increased risk of pancreatic cancer [SIR = 4.11; 95% confidence interval (CI), 2.94-5.76] as were BRCA2 mutation carriers (SIR = 5.79; 95% CI, 4.28-7.84). BRCAX family members were also at increased pancreatic cancer risk, which did not appear to vary by number of members with early-onset breast cancer (SIR = 1.31; 95% CI, 1.06-1.63 for class 3 and SIR = 1.30; 95% CI, 1.13-1.49 for class 4).
CONCLUSIONS:Germline mutations in BRCA1 and BRCA2 are associated with an increased risk of pancreatic cancer. Members of BRCAX families are also at increased risk of pancreatic cancer, pointing to the existence of other genetic factors that increase the risk of both pancreatic cancer and breast cancer. Impact: This study clarifies the relationship between familial breast cancer and pancreatic cancer. Given its high mortality, pancreatic cancer should be included in risk assessment in familial breast cancer counseling. Cancer Epidemiol Biomarkers Prev; 22(5); 803-11. ©2013 AACR.
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