Abstract
<div>Abstract<p><b>Background:</b> Increased risk of pancreatic cancer has been reported in breast cancer families carrying <i>BRCA1</i>and <i>BRCA2</i> 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.</p><p><b>Methods:</b> 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 <i>BRCA1</i> and/or <i>BRCA2</i> 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).</p><p><b>Results:</b><i>BRCA1</i> mutation carriers were at increased risk of pancreatic cancer [SIR = 4.11; 95% confidence interval (CI), 2.94–5.76] as were <i>BRCA2</i> 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).</p><p><b>Conclusions:</b> Germline mutations in <i>BRCA1 and BRCA2</i> 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.</p><p><b>Impact:</b> 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. <i>Cancer Epidemiol Biomarkers Prev; 22(5); 803–11. ©2013 AACR</i>.</p></div>
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