Abstract
Inherited predisposition occurs in 5–10% of all gastrointestinal (GI) cancer patients, but with the exception of colorectal cancer (CRC), the genes involved in conferring genetic susceptibility remain largely unknown. Indirect evidence indicates that germline mutations in BRCA2 might be associated with an increased risk for various GI malignancies. A single mutation (6174delT) occurs in the BRCA2 gene in high-risk breast ovarian cancer families of Jewish Ashkenazi origin, in about 1% of the general Ashkenazi population, and rarely in non-Ashkenazi Jews. In order to assess the contribution of this germline mutation to non-CRC GI cancer in Jewish Israeli patients, we tested 70 unselected, consecutive Jewish Ashkenazi patients with gastrointestinal malignancies for this mutation by PCR amplification and modified restriction enzyme digests. Patients’ age range was 38–90 years (mean 65.8±11.8 years). The most common malignancies were gastric cancer (n = 35) and exocrine pancreatic cancer (n = 23). Overall, 6 mutation carriers were detected: 3/23 (13%) of the patients with pancreatic cancer, 2/35 (5.7%) of patients with gastric cancer and 1/4 (25%) of patients with bile duct cancer. The 8.6% mutation carrier rate among patients is a rate significantly higher than that of the general Ashkenazi population (1.16%P = 0.0002). We conclude that the rate of the predominant Jewish BRCA2 mutation in patients with gastric and pancreatic cancer significantly differ from that of the general population of the same ethnic origin. Thus, BRCA2 mutations probably contribute to gastrointestinal tumorigenesis other then colon cancer, and the surveillance scheme for mutation carriers should incorporate this information. © 2001 Cancer Research Campaign
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References
Abeliovich D, Kaduri L, Lerer I, Weinberg N, Amir G, Sagi M, Zlotogora J, Heching N and Peretz T (1997) The founder mutation 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer among Ashkenazi women. Am J Hum Genet 60: 505–514
Bar-Sade RB, Kruglikova A, Modan B, Gak E, Hirsh-Yechezkel G, Theodor L, Novikov I, Gershoni-Baruch R, Risel S, Papa MZ, Ben-Baruch G and Friedman E (1998) The 185delAG BRCA1 mutation originated before the dispersion of Jews in the diaspora and is not limited to Ashkenazim. Hum Mol Genet 7: 801–805
Breast Cancer Linkage Consortium (1999) Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 91: 1310–1316
Easton DF, Matthews FE, Ford D, Swerdlow AJ and Peto J (1996) Cancer mortality in relatives of women with ovarian cancer: the OPCS Study. Office of Population Censuses and Surveys. Int J Cancer 65: 284–294
Falk RT, Pickle LW, Fontham ET, Correa P and Fraumeni JF Jr (1988) Life-style risk factors for pancrcetic cancer in Louisiana: a case-control study. Am J Epidemiol 128: 324–336
Fernandez E, La Vecchia C, D’Avanzo B, Negri E and Franceschi S (1994) Family history and the risk of liver, gallbladder, and pancrcatic cancer. Cancer Epidemiol Biomarkers Prev 3: 209–212
Ghadirian P, Boyle P, Simard A, Baillargeon J, Maisonneuve P and Perret C (1991) Reported family aggregation of pancrcatic cancer within a population-based case-control study in the Francophone community in Montreal, Canada. Int J Pancreatol 10: 183–196
Goggins M, Schutte M, Lu J, Moskaluk CA, Weinstein CL, Petersen GM, Yeo CJ, Jackson CE, Lynch HT, Hruban RH and Kern SE (1996) Germlinc BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res 56: 5360–5364
Hartge P, Struewing JP, Wacholder S, Brody LC and Tucker MA (1999) The prevalence of common BRCA1 and BRCA2 mutations among Ashkenazi Jews. Am J Hum Genet 64: 963–970
Hu N, Roth MJ, Emmert-Buck MR, Tang ZZ, Polymeropolous M, Wang QH, Goldstein AM, Han XY, Dawsey SM, Ding T, Giffen C and Taylor PR (1999). Allelic loss in esophageal squamous cell carcinoma patients with and without family history of upper gastrointestinal tract cancer. Clin Cancer Res 5: 3476–3482
Israel Cancer Registry (1998). Cancer in Israel: facts and figures, 1992–1995, Jerusalem
Katagiri T, Nakamura Y and Miki Y (1996) Mutations in the BRCA2 gene in hepatocellular carcinomas. Cancer Res 56: 4575–4577
Lal G, Liu G, Schmocker B, Kaurah P, Ozcelik H, Narod SA, Redston M and Gallinger S (2000) Inherited predisposition to pancrcetic adenocarcinoma: role of family history and germ-line p16, BRCA1, and BRCA2 mutations. Cancer Res 60: 409–416
Lissowska J, Groves FD, Sobin LH, Fraumeni JF, Jr; Nasierowska-Guttmejer A, Radziszewski J, Regula J, Hsing AW, Zatonski W, Blot WJ and Chow WH (1999) Family history and risk of stomach cancer in Warsaw, Poland. Eur J Cancer Prev 8: 223–227
Lynch HT, Fasuro L and Lynch JF (1992) Familial pancreatic cancer. A family study. Pancreas 7: 511–515
Odduoux C, Streuwing JP, Clayton CM, Neuhausen S, Brody LC, Kaback M, Haas B, Norton L, Borgen P, Jhanwar S, Goldgar D, Ostrer H and Offit K (1996) The carrier frequency of the BRCA2 6174delT mutation among Ashkenazi Jewish individuals is approximately 1%. Nat Genet 14: 188–190
Ozcelik H, Schmocker B, Di Nicola N, Shi XH, Langer B, Moore M, Taylor BR, Narod SA, Darlington G, Andrulis IL, Gallinger S and Redston M (1997) Germline BRCA2 6174delT mutations in Ashkenazi Jewish pancreatic cancer patients. Nat Genet 16: 17–18
Palli D, Galli M, Caporaso NE, Cipriani F, Decarli A, Saieva C, Fraumeni JF Jr and Buiatti E (1994) Family history and risk of stomach cancer in Italy. Cancer Epidemiol Biomarkers Prev 3: 15–18
Phelan CM, Lancaster JM, Tonin P, Gumbs C, Cochran C, Carter R, Ghadirian P, Perret C, Moslchi R, Dion F, Faucher MC, Dole K, Karimi S, Foulkes W, Lounis H, Warner E, Goss P, Anderson D, Larsson C, Narod SA and Futreal PA (1996) Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families. Nat Genet 13: 120–122
Roa BB, Boyd AA, Volick K and Richards CS (1996) Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat Genet 14: 185–187
Rohlfs EM, Learning WG, Friedman KJ, Couch FJ, Weber BL and Silverman LM (1997) Direct detection of mutations in the breast and ovarian cancer susceptibility gene BRCA1 by PCR-mediated site-directed mutagenesis. Clin Chem 43: 24–29
Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, Timmerman MM, Brody LC and Tucker MA (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336: 1401–1408
Struewing JP, Coriaty ZM, Ron E, Livoff A, Konichezky M, Cohen P, Resnick MB, Lifzchiz-Mcrecrl B, Lew S and Iscovich J (1999) Founder BRCA1/2 mutations among male patients with breast cancer in Israel. Am J Hum Genet 65: 1800–1802
Thorlacius S, Sigurdsson S, Bjarnadottir H, Olafsdottir G, Jonasson JG, Tryggvadottir L, Tulinius H and Eyfjord JE (1997) Study of a single BRCA2 mutation with high carrier frequency in a small population. Am J Hum Genet 60: 1079–1084
Tulinius H, Egilsson V, Olafsdottir GH and Sigvaldason H (1992) Risk of prostate, ovarian and endometrial cancer among relatives of women with breast cancer. Br Med J 305: 855–857
Zanghieri G, Di Gregorio C, Sacchetti C, Fante R, Sassatelli R, Cannizzo G, Carriero A, Ponz DE and Leon M (1990) Familial occurrence of gastric cancer in the 2-year experience of a population-based registry. Cancer 66: 2047–2051
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Figer, A., Irmin, L., Geva, R. et al. The rate of the 6174delT founder Jewish mutation in BRCA2 in patients with non-colonic gastrointestinal tract tumours in Israel. Br J Cancer 84, 478–481 (2001). https://doi.org/10.1054/bjoc.2000.1605
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DOI: https://doi.org/10.1054/bjoc.2000.1605
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