Prevalence and Characteristics of Pancreatic Cancer in Families with BRCA1 and BRCA2 Mutations

Overview

Journal Fam Cancer

Publisher Springer

Specialty Oncology

Date 2008 Oct 16

PMID 18855126

Citations 15

Authors

Daniel H Kim

Beth Crawford

John Ziegler

Mary S Beattie

Affiliations

Soon will be listed here.

Abstract

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.

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References

Lichtenstein P, Holm N, Verkasalo P, Iliadou A, Kaprio J, Koskenvuo M . Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000; 343(2):78-85. DOI: 10.1056/NEJM200007133430201. View

Bermejo-Perez M, Marquez-Calderon S, Llanos-Mendez A . Effectiveness of preventive interventions in BRCA1/2 gene mutation carriers: a systematic review. Int J Cancer. 2007; 121(2):225-31. DOI: 10.1002/ijc.22817. View

Thompson D, Easton D . Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002; 94(18):1358-65. DOI: 10.1093/jnci/94.18.1358. View

Offit K, Levran O, Mullaney B, Mah K, Nafa K, Batish S . Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia. J Natl Cancer Inst. 2003; 95(20):1548-51. DOI: 10.1093/jnci/djg072. View

King M, Marks J, Mandell J . Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003; 302(5645):643-6. DOI: 10.1126/science.1088759. View

Evans D, Howell A . Are BRCA1- and BRCA2-related breast cancers associated with increased mortality?. Breast Cancer Res. 2003; 6(1):E7. PMC: 314459. DOI: 10.1186/bcr748. View

Robson M, Chappuis P, Satagopan J, Wong N, Boyd J, Goffin J . 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. 2003; 6(1):R8-R17. PMC: 314444. DOI: 10.1186/bcr658. View

Liede A, Karlan B, Narod S . Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J Clin Oncol. 2004; 22(4):735-42. DOI: 10.1200/JCO.2004.05.055. View

Tonin P, Weber B, Offit K, Couch F, Rebbeck T, Neuhausen S . Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families. Nat Med. 1996; 2(11):1179-83. DOI: 10.1038/nm1196-1179. View

10.

Goggins M, Schutte M, Lu J, Moskaluk C, Weinstein C, Petersen G . Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res. 1996; 56(23):5360-4. View

11.

Ozcelik H, Schmocker B, di Nicola N, Shi X, Langer B, Moore M . Germline BRCA2 6174delT mutations in Ashkenazi Jewish pancreatic cancer patients. Nat Genet. 1997; 16(1):17-8. DOI: 10.1038/ng0597-17. View

12.

. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst. 1999; 91(15):1310-6. DOI: 10.1093/jnci/91.15.1310. View

13.

Robles-Diaz L, Goldfrank D, Kauff N, Robson M, Offit K . Hereditary ovarian cancer in Ashkenazi Jews. Fam Cancer. 2004; 3(3-4):259-64. DOI: 10.1007/s10689-004-9552-0. View

14.

Whittemore A, Gong G, John E, McGuire V, Li F, Ostrow K . Prevalence of BRCA1 mutation carriers among U.S. non-Hispanic Whites. Cancer Epidemiol Biomarkers Prev. 2004; 13(12):2078-83. View

15.

Lynch H, Deters C, Snyder C, Lynch J, Villeneuve P, Silberstein J . BRCA1 and pancreatic cancer: pedigree findings and their causal relationships. Cancer Genet Cytogenet. 2005; 158(2):119-25. DOI: 10.1016/j.cancergencyto.2004.01.032. View

16.

Antoniou A, Pharoah P, Narod S, Risch H, Eyfjord J, Hopper J . 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. 2005; 42(7):602-3. PMC: 1736090. DOI: 10.1136/jmg.2004.024133. View

17.

van Asperen C, Brohet R, Meijers-Heijboer E, Hoogerbrugge N, Verhoef S, Vasen H . Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet. 2005; 42(9):711-9. PMC: 1736136. DOI: 10.1136/jmg.2004.028829. View

18.

Lee R, Beattie M, Crawford B, Mak J, Stewart N, Komaromy M . Recruitment, genetic counseling, and BRCA testing for underserved women at a public hospital. Genet Test. 2005; 9(4):306-12. DOI: 10.1089/gte.2005.9.306. View

19.

Chenevix-Trench G, Healey S, Lakhani S, Waring P, Cummings M, Brinkworth R . Genetic and histopathologic evaluation of BRCA1 and BRCA2 DNA sequence variants of unknown clinical significance. Cancer Res. 2006; 66(4):2019-27. DOI: 10.1158/0008-5472.CAN-05-3546. View

20.

Petersen G, de Andrade M, Goggins M, Hruban R, Bondy M, Korczak J . Pancreatic cancer genetic epidemiology consortium. Cancer Epidemiol Biomarkers Prev. 2006; 15(4):704-10. DOI: 10.1158/1055-9965.EPI-05-0734. View