Familial Cancer

, Volume 8, Issue 2, pp 153–158 | Cite as

Prevalence and characteristics of pancreatic cancer in families with BRCA1 and BRCA2 mutations

  • Daniel H. Kim
  • Beth Crawford
  • John Ziegler
  • Mary S. Beattie


A growing body of research describes cancers other than breast and ovarian in families with BRCA1/2 mutations, but the prevalence and characteristics of pancreatic cancer in these families has not been well described. This study was designed to: (1) estimate the prevalence of pancreatic cancer in BRCA1/2 positive families; (2) ascertain age of onset and gender distribution of pancreatic cancer in this cohort; and (3) compare age and gender characteristics of pancreatic cancer in BRCA1/2 positive families with those of the general population. Within the UCSF Cancer Risk Program cohort, 24/219 (11.0%) BRCA1 and 17/156 (10.9%) BRCA2 families had at least 1 individual with pancreatic cancer. In the 24 BRCA1 families, median age of diagnosis was 59 (range 45–80) in males, and 68 (range 38–87) in females (male:female ratio = 2.00). In the 17 BRCA2 families, median age of diagnosis was 67 (range 39–78) in males and 59 (range 46–81) in females (male:female ratio = 1.11). The SEER database, which describes cancer characteristics in a representative sample of the US population, reports a median age of 70 in males and 74 in females (male:female ratio = 0.96) over the same time period. Additionally, mean ages of diagnosis of pancreatic cancer in BRCA1/2 families differ significantly from the SEER mean (P = 0.0014 for BRCA1 and P = 0.011 for BRCA2 by unpaired t-test). Our findings suggest that families with early onset pancreatic cancer and features of hereditary breast and ovarian cancer should be considered for BRCA1/2 testing.


BRCA1 BRCA2 Genetic testing Hereditary cancer Pancreatic cancer 



Surveillance Epidemiology and End Results



This publication was supported by NIH/NCRR/OD UCSF-CTSI Grant Number KL2 RR024130. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.


  1. 1.
    Lichtenstein P, Holm NV, Verkasalo PK et al (2000) Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343(2):78–85. doi: 10.1056/NEJM200007133430201 PubMedCrossRefGoogle Scholar
  2. 2.
    King MC, Marks JH, Mandell JB, New York Breast Cancer Study Group (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302(5645):643–646. doi: 10.1126/science.1088759 PubMedCrossRefGoogle Scholar
  3. 3.
    Antoniou AC, Pharoah PD, Narod S et al (2005) Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies. J Med Genet 42(7):602–603. doi: 10.1136/jmg.2004.024133 PubMedCrossRefGoogle Scholar
  4. 4.
    Thompson D, Easton DF, Breast Cancer Linkage Consortium (2002) Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst 94(18):1358–1365PubMedGoogle Scholar
  5. 5.
    The Breast Cancer Linkage Consortium (1999) Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 91(15):1310–1316. doi: 10.1093/jnci/91.15.1310 CrossRefGoogle Scholar
  6. 6.
    van Asperen CJ, Brohet RM, Meijers-Heijboer EJ, Netherlands Collaborative Group on Hereditary Breast Cancer (HEBON) et al (2005) Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet 42(9):711–719. doi: 10.1136/jmg.2004.028829 PubMedCrossRefGoogle Scholar
  7. 7.
    Goggins M, Schutte M, Lu J et al (1996) Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res 56(23):5360–5364PubMedGoogle Scholar
  8. 8.
    Lynch HT, Deters CA, Snyder CL et al (2005) BRCA1 and pancreatic cancer: pedigree findings and their causal relationships. Cancer Genet Cytogenet 158(2):119–125. doi: 10.1016/j.cancergencyto.2004.01.032 PubMedCrossRefGoogle Scholar
  9. 9.
    Liede A, Karlan BY, Narod SA (2004) Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J Clin Oncol 22(4):735–742. doi: 10.1200/JCO.2004.05.055 PubMedCrossRefGoogle Scholar
  10. 10.
    Offit K, Levran O, Mullaney B et al (2003) Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia. J Natl Cancer Inst 95(20):1548–1551PubMedGoogle Scholar
  11. 11.
    Lee R, Beattie M, Crawford B et al (2005) Recruitment, genetic counseling, and BRCA testing for underserved women at a public hospital. Genet Test 9(4):306–312PubMedCrossRefGoogle Scholar
  12. 12.
    Berry DA, Iversen ES Jr, Gudbjartsson DF et al (2002) BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes. J Clin Oncol 20(11):2701–2712. doi: 10.1200/JCO.2002.05.121 PubMedCrossRefGoogle Scholar
  13. 13.
    Ries LAG, Melbert D, Krapcho M et al (2007) SEER cancer statistics review, 1975–2004. National Cancer Institute, Bethesda,, based on November 2006 SEER data submission, posted to the SEER web site
  14. 14.
    Petersen GM, de Andrade M, Goggins M et al (2006) Pancreatic cancer genetic epidemiology consortium. Cancer Epidemiol Biomarkers Prev 15(4):704–710. doi: 10.1158/1055-9965.EPI-05-0734 PubMedCrossRefGoogle Scholar
  15. 15.
    Greer JB, Whitcomb DC (2007) Role of BRCA1 and BRCA2 mutations in pancreatic cancer. Gut 56(5):601–605. doi: 10.1136/gut.2006.101220 PubMedCrossRefGoogle Scholar
  16. 16.
    Tonin P, Weber B, Offit K et al (1996) Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families. Nat Med 2(11):1179–1183. doi: 10.1038/nm1196-1179 PubMedCrossRefGoogle Scholar
  17. 17.
    Evans DG, Howell A (2004) Are BRCA1- and BRCA2-related breast cancers associated with increased mortality? Breast Cancer Res 6(1):E7. doi: 10.1186/bcr748 PubMedCrossRefGoogle Scholar
  18. 18.
    Robson ME, Chappuis PO, Satagopan J et al (2004) A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment. Breast Cancer Res 6(1):R8–R17. doi: 10.1186/bcr658 PubMedCrossRefGoogle Scholar
  19. 19.
    Robles-Díaz L, Goldfrank DJ, Kauff ND et al (2004) Hereditary ovarian cancer in Ashkenazi Jews. Fam Cancer 3(3–4):259–264. doi: 10.1007/s10689-004-9552-0 PubMedCrossRefGoogle Scholar
  20. 20.
    Whittemore AS, Gong G, John EM (2004) Prevalence of BRCA1 mutation carriers among U.S. non-Hispanic Whites. Cancer Epidemiol Biomarkers Prev 13(12):2078–2083PubMedGoogle Scholar
  21. 21.
    Bermejo-Pérez MJ, Márquez-Calderón S, Llanos-Méndez A (2007) Effectiveness of preventive interventions in BRCA1/2 gene mutation carriers: a systematic review. Int J Cancer 121(2):225–231. doi: 10.1002/ijc.22817 PubMedCrossRefGoogle Scholar
  22. 22.
    Canto MI, Goggins M, Hruban RH et al (2006) Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol 4(6):766–781. doi: 10.1016/j.cgh.2006.02.005 PubMedCrossRefGoogle Scholar
  23. 23.
    Chenevix-Trench G, Healey S, Lakhani S et al (2006) Genetic and histopathologic evaluation of BRCA1 and BRCA2 DNA sequence variants of unknown clinical significance. Cancer Res 66(4):2019–2027. doi: 10.1158/0008-5472.CAN-05-3546 PubMedCrossRefGoogle Scholar
  24. 24.
    Ozcelik H, Schmocker B, Di Nicola N et al (1997) Germline BRCA2 6174delT mutations in Ashkenazi Jewish pancreatic cancer patients. Nat Genet 16(1):17–18. doi: 10.1038/ng0597-17 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Daniel H. Kim
    • 1
  • Beth Crawford
    • 2
  • John Ziegler
    • 2
    • 3
  • Mary S. Beattie
    • 2
    • 3
    • 4
  1. 1.School of MedicineUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Cancer Risk Program, Helen Diller Family Comprehensive Cancer CenterUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.Department of MedicineUniversity of California, San FranciscoSan FranciscoUSA
  4. 4.Department of EpidemiologyUniversity of CaliforniaSan FranciscoUSA

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