Occurrence of BRCA1 and BRCA2 mutation in pancreatic cancer patients
Abstract
BRCA1 and BRCA2 may contribute in pancreatic cancer (PC) risk, however the selection criteria for BRCA1 testing are poorly defined. The analysis of Russian founder mutation BRCA1 5382insC in 150 PC patients identified 2 carriers. BRCA2 full-length sequencing of 8 DNA samples revealed 1 mutated allele (BRCA2 5197_5198delTC). All 3 carriers of BRCA1/2 mutations reported personal or familial history of BRCA-related cancers. Thus, BRCA1/2 testing is particularly
About the Authors
A. A. Kashintsev
St.-Petersburg Pediatric Medical University
Russian Federation
Russian Federation
G. A. Yanus
St.-Petersburg Pediatric Medical University, N.N. Petrov Institute of Oncology, St.-Petersburg
Russian Federation
Russian Federation
N. Yu. Kokhanenko
St.-Petersburg Pediatric Medical University
Russian Federation
Russian Federation
V. M. Moiseenko
City Oncological Center, St.-Petersburg, S.M. Beresin Clinical Center, St.-Petersburg
Russian Federation
Russian Federation
M. D. Hanevich
City Oncological Hospital, St.-Petersburg
Russian Federation
Russian Federation
L. D. Roman
Leningrad Regional Oncological Hospital, St.-Petersburg
Russian Federation
Russian Federation
A. G. Ievleva
St.-Petersburg Pediatric Medical University, N.N. Petrov Institute of Oncology, St.-Petersburg
Russian Federation
Russian Federation
A. P. Sokolenko
St.-Petersburg Pediatric Medical University, N.N. Petrov Institute of Oncology, St.-Petersburg
Russian Federation
Russian Federation
E. N. Suspitsin
St.-Petersburg Pediatric Medical University, N.N. Petrov Institute of Oncology, St.-Petersburg
Russian Federation
Russian Federation
A. I. Budovskiy
N.N. Petrov Institute of Oncology, St.-Petersburg
Russian Federation
Russian Federation
A. V. Togo
St.-Petersburg Pediatric Medical University, N.N. Petrov Institute of Oncology, St.-Petersburg
Russian Federation
Russian Federation
N. M. Volkov
N.N. Petrov Institute of Oncology, St.-Petersburg, S.M. Beresin Clinical Center, St.-Petersburg
Russian Federation
Russian Federation
R. V. Fadeev
City Oncological Hospital, St.-Petersburg
Russian Federation
Russian Federation
M. S. Dinikin
City Oncological Hospital, St.-Petersburg
Russian Federation
Russian Federation
A. K. Ivanova
City Oncological Hospital, St.-Petersburg
Russian Federation
Russian Federation
K. G. Shostko
Leningrad Regional Oncological Hospital, St.-Petersburg
Russian Federation
Russian Federation
E. N. Imyanitov
St.-Petersburg Pediatric Medical University, N.N. Petrov Institute of Oncology, St.-Petersburg, I.I. Mechnikov North-West Medical University, St.-Petersburg
Russian Federation
Russian Federation
References
1. Al-Sukhni W., Rothenmund H., Borgida A.E. et al. Germline BRCA1 mutations predispose to pancreatic adenocarcinoma//Hum. Genet. 2008. Vol. 124. P. 271-278
2. Aretini P., D’Andrea E., Pasini B. et al. Different expressivity of BRCA1 and BRCA2: analysis of 179 Italian pedigrees with identified mutation//Breast Cancer Res. Treat. 2003. Vol. 81. P. 71-79
3. van Asperen C.J., Brohet R.M., Meijers-Heijboer E.J. et al. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary//J. Med. Genet. 2005. Vol. 42. P. 711-719
4. Axilbund J.E., Argani P., Kamiyama M. et al. Absence of germline BRCA1 mutations in familial pancreatic cancer patients//Cancer Biol. Ther. 2009. Vol. 8. P. 131-135
5. Barrow E., Robinson L., Alduaij W. et al. Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations//Clin. Genet. 2009. Vol. 75. P. 141-149
6. Brose M.S., Rebbeck T.R., Calzone K.A. et al. Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program//Natl. Cancer Inst. 2002. Vol. 94. P. 1365-1372
7. Chalasani P., Kurtin S., Dragovich T. Response to a third-line mitomycin C (MMC)-based chemotherapy in a patient with metastatic pancreatic adenocarcinoma carrying germline BRCA2 mutation//JOP. 2008. Vol. 9. P. 305-308
8. Couch F.J., Johnson M.R., Rabe K. et al. Germ line Fanconi anemia complementation group C mutations and pancreatic cancer//Cancer Res. 2005. Vol. 65. P. 383-386
9. Couch F.J., Johnson M.R., Rabe K.G. et al. The prevalence of BRCA2 mutations in familial pancreatic cancer//Cancer Epidemiol. Biomarkers Prev. 2007. Vol. 16. P. 342-346
10. Dagan E. Predominant Ashkenazi BRCA1/2 mutations in families with pancreatic cancer//Genet. Test. 2008. Vol. 12. P. 267-271
11. Ferlay J., Shin H.R., Bray F. et al. GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr, accessed on 29/07/2013
12. Ferrone C.R., Levine D.A., Tang L.H. et al. BRCAgermline mutations in Jewish patients with pancreatic adenocarcinoma//J. Clin. Oncol. 2009. Vol. 27. P. 433-438
13. 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. 2001. Vol. 84. P. 478-481
14. Fogelman D.R., Wolff R.A., Kopetz S. et al. Evidence for the efficacy of Iniparib, a PARP-1 inhibitor, in BRCA2-associated pancreatic cancer//Anticancer Res. 2011 Vol. 31. P. 1417-1420
15. Ghiorzo P., Fornarini G., Sciallero S. et al. CDKN2A is the main susceptibility gene in Italian pancreatic cancer families//J. Med. Genet. 2012. Vol. 49. P. 164-170
16. Ghiorzo P., Pensotti V., Fornarini G. et al. Contribution of germline mutations in the BRCA and PALB2 genes to pancreatic cancer in Italy//Fam. Cancer. 2012. Vol. 11. P. 41-47
17. Goggins M., Sehutte M., Lu J. et al. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas//Cancer Research. 1996. Vol. 56. P. 5360-5364
18. Goldstein A.M., Chan M., Harland M. et al. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL//Cancer Res. 2006. Vol. 66. P. 9818-9828
19. Groen E.J., Roos A., Muntinghe F.L. et al. Extra-intestinal manifestations of familial adenomatous polyposis//Ann. Surg. Oncol. 2008. Vol. 15. P. 2439-2450
20. Hahn S.A., Greenhalf B., Ellis I. et al. BRCA2 germline mutations in familial pancreatic carcinoma//J. Natl. Cancer Inst. 2003. Vol. 95. P. 214-221
21. van der Heijden M.S., Yeo C.J., Hruban R.H., Kern S.E. Fanconi anemia gene mutations in young-onset pancreatic cancer//Cancer Res. 2003. Vol. 63. P. 2585-2588
22. Hollestelle A., Wasielewski M., Martens J.W., Schutte M. Discovering moderate-risk breast cancer susceptibility genes//Curr. Opin. Genet. Dev. 2010. Vol. 20. P. 268-276
23. Imyanitov E.N., Moiseenko M.V. Drug therapy for hereditary cancers//Hered. Cancer Clin. Pract. 2011. Vol. 9. P. 1-16
24. Iqbal J., Ragone A., Lubinski J. et al. The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers//Br. J. Cancer. 2012. Vol. 107. P. 2005-2009
25. Johannsson O., Loman N., Möller T. et al. Incidence of malignant tumours in relatives of BRCA1 and BRCA2 germline mutation carriers//Eur. J. Cancer. 1999. Vol. 35. P. 1248-1257
26. Jones S., Hruban R.H., Kamiyama M. et al. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene//Science. 2009. Vol. 324. P. 217
27. Kastrinos F., Mukherjee B., Tayob N. et al. Risk of pancreatic cancer in families with Lynch syndrome//JAMA. 2009. Vol. 302. P. 1790-1795
28. Klein A.P. Genetic susceptibility to pancreatic cancer//Mol. Carcinog. 2012. Vol. 51. P. 14-24
29. Kim D.H., Crawford B., Ziegler J., Beattie M.S. Prevalence and characteristics of pancreatic cancer in families with BRCA1 and BRCA2 mutations//Fam. Cancer. 2009. Vol. 8. P. 153-158
30. Lal G., Liu G., Schmocker B. et al. Inherited predisposition to pancreatic adenocarcinoma: role of family history and germ-line p16, BRCA1, and BRCA2 mutations//Cancer Res. 2000. Vol. 60. P. 409-416
31. Landi S. Genetic predisposition and environmental risk factors to pancreatic cancer: A review of the literature//Mutat. Res. 2009. Vol. 681. P. 299-307
32. Lawniczak M., Gawin A., Białek A. et al. Is there any relationship between BRCA1 gene mutation and pancreatic cancer development?//Pol. Arch. Med. Wewn. 2008. Vol. 118. P. 645-649
33. van Lier M.G., Wagner A., Mathus-Vliegen E.M. et al. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations//Am. J. Gastroenterol. 2010. Vol. 105. P. 1258-1264
34. Lowery M.A., Kelsen D.P., Stadler Z.K. et al. An emerging entity: pancreatic adenocarcinoma associated with a known BRCAmutation: clinical descriptors, treatment implications, and future directions//Oncologist. 2011. Vol. 16. P. 1397-1402
35. Lubinski J., Phelan C.M., Ghadirian P. et al. Cancer variation associated with the position of the mutation in the BRCA2 gene//Fam. Cancer. 2004. Vol. 3. P. 1-10
36. Lucas A.L., Shakya R., Lipsyc M.D. et al. High Prevalence of BRCA1 and BRCA2 Germline Mutations with Loss of Heterozygosity in a Series of Resected Pancreatic Adenocarcinoma and Other Neoplastic Lesions//Clin. Cancer Res. 2013. Vol. 19. P. 3396-3403
37. Maisonneuve P., Marshall B.C., Lowenfels A.B. Risk of pancreatic cancer in patients with cystic fibrosis//Gut. 2007. Vol. 56. P. 1327-1328
38. Mocci E., Milne R.L., Méndez-Villamil E.Y. et al. Risk of pancreatic cancer in breast cancer families from the breast cancer family registry//Cancer Epidemiol. Biomarkers Prev. 2013. Vol. 22. P. 803-811
39. Moiseyenko V.M., Volkov N.M., Suspistin E.N. et al. Evidence for predictive role of BRCA1 and bTUBIII in gastric cancer//Med. Oncol. 2013. Vol. 30. P. 54-57
40. Moran A., O’Hara C., Khan S. et al. Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations//Fam. Cancer. 2012. Vol. 11. P. 235-242
41. Murphy K.M., Brune K.A., Griffin C. et al. Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%//Cancer Res. 2002. Vol. 62. P. 3789-3793
42. Ozçelik H., Schmocker B., Di Nicola N. et al. Germline BRCA2 6174delT mutations in Ashkenazi Jewish pancreatic cancer patients//Nat. Genet. 1997. Vol. 16. P. 17-18
43. Raimondi S., Maisonneuve P., Lowenfels A.B. Epidemiology of pancreatic cancer: an overview//Nat. Rev. Gastroenterol. Hepatol. 2009. Vol. 6. P. 699-708
44. Real F.X., Malats N., Lesca G. et al. Family history of cancer and germline BRCA2 mutations in sporadic exocrine pancreatic cancer//Gut. 2002. Vol. 50 P. 653-657
45. Rebours V., Lévy P., Ruszniewski P. An overview of hereditary pancreatitis//Dig. Liver Dis. 2012. Vol. 44. P. 8-15
46. Risch H.A., McLaughlin J.R., Cole D.E. et al. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada//J. Natl. Cancer Inst. 2006. Vol. 98. P. 1694-1706
47. Roberts N.J., Jiao Y., Yu J. et al. ATM mutations in patients with hereditary pancreatic cancer//Cancer Discov. 2012. Vol. 2. P. 41-46
48. Saufferlein T., Bachet J.B., van Cutsen E. et al. Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up//Ann. Oncol. 2012. Vol. 23. P. 33-40
49. Slater E.P., Langer P., Fendrich V. et al. Prevalence of BRCA2 and CDKN2a mutations in German familial pancreatic cancer families//Fam. Cancer. 2010. Vol. 9. P. 335-343
50. Sokolenko A.P., Iyevleva A.G., Mitiushkina N.V. et al. Hereditary breast-ovarian cancer syndrome in Russia//Acta Naturae. 2010. Vol. 2. P. 31-35
51. Sokolenko A.P., Rozanov M.E., Mitiushkina N.V. et al. Founder mutations in early-onset, familial and bilateral breast cancer patients from Russia//Fam. Cancer. 2007. Vol. 6. P. 281-286
52. Solomon S., Das S., Brand R., Whitcomb D.C. Inherited pancreatic cancer syndromes//Cancer J. 2012. Vol. 18. P. 485-491
53. Stadler Z.K., Salo-Mullen E., Patil S.M. et al. Prevalence of BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and pancreatic cancer//Cancer. 2012. Vol. 118. P. 493-499
54. The Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers//J. Natl. Cancer Inst. 1999. Vol. 91. P. 1310-1316
55. Thompson D., Easton D.F. Breast Cancer Linkage Consortium. Cancer Incidence in BRCA1 mutation carriers//J. Natl. Cancer Inst. 2002. Vol. 94. P. 1358-1365
56. Tonin P., Weber B., Offit K. et al. Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families//Nat. Med. 1996. Vol. 2. P. 1179-1183
57. Tulinius H., Olafsdottir G.H., Sigvaldason H. et al. The effect of a single BRCA2 mutation on cancer in Iceland//J. Med. Genet. 2002. Vol. 39. P. 457-462
58. Walsh T., King M.C. Ten genes for inherited breast cancer//Cancer Cell. 2007. Vol. 11. P. 103-105
59. Wang X., Szabo C., Qian C. et al. Mutational analysis of thirty-two double-strand DNA break repair genes in breast and pancreatic cancers//Cancer Res. 2008. Vol. 68. P. 971-975
60. Wolpin B.M., Chan A.T., Hartge P. et al. ABO blood group and the risk of pancreatic cancer//J. Natl. Cancer Inst. 2009. Vol. 101. P. 424-431
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For citations:
Kashintsev A.A., Yanus G.A., Kokhanenko N.Yu., Moiseenko V.M., Hanevich M.D., Roman L.D., Ievleva A.G., Sokolenko A.P., Suspitsin E.N., Budovskiy A.I., Togo A.V., Volkov N.M., Fadeev R.V., Dinikin M.S., Ivanova A.K., Shostko K.G., Imyanitov E.N. Occurrence of BRCA1 and BRCA2 mutation in pancreatic cancer patients. Siberian journal of oncology. 2013;(5):39-44. (In Russ.)
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