Seemanová E, Hoch J, Seeman P. Heterozygous carriers of Slavic mutation 657del5 of NBN gene in patients with colorectal cancer
Authors:
Eva Seemanová 1; Jiří Hoch 2; prof. MUDr. Pavel Seeman, Ph.D. 3
Authors‘ workplace:
Univerzita Karlova v Praze, 2. lékařská fakulta a FN Motol, Ústav biologie a lékařské genetiky
1; Univerzita Karlova v Praze, 2. lékařská fakulta a FN Motol, Chirurgická klinika
2; Univerzita Karlova v Praze, 2. lékařská fakulta a FN Motol, DNA laboratoř Kliniky dětské neurologie
3
Published in:
Čas. Lék. čes. 2011; 150: 97-99
Category:
Original Article
Overview
Background.
Nijmegen breakage syndrome (NBS) is one of the chromosomal instability syndromes due to DNA repair disorder. The syndrome is autosomal recessive determined, in homozygotes is characterized by many disorders including high predisposition to lymphoreticular malignancy in childhood and adolescence.
Methods.
Laboratory findings represent low level of immunoglobulins, B and T lymphocytes, increased sensitivity to the mutagens, especially hyperradiosensitivity and increased chromosomal instability. Heterozygotes show also elevated radiosensitivity and have an increased cancer risk in adult age. There is no predilection of the malignancy. Colorectal cancer was found often among the relatives of patients with NBS. Majority of the NBS patients are of the Central and Eastern European origin and carry the common founder mutation 657del5 in the NBN gene. The formation of second malignancy both in homozygotes and heterozygotes can be prevented by excluding any radiation.
The aim of study is estimation of frequency of 657del5 heterozygotes among patients with colorectal cancer.
Results and conclusions.
Within a group of 161 patients with colorectal cancer 5 heterozygotes with 657del5 mutation were registered, e.g. 5‑times higher incidence than expected. The elemental prevention in patients with proved positivity of Slavic mutation in NBN gene is to exclude any radiation.
Key words:
NBN gene, 657del5 mutation, heterozygous mutation carriers, cancer risk, colorectal cancer.
Se.
Sources
1. The International NBS Study: Nijmegen breakage syndrome. Arch Dis Child 2000; 82: 400–406.
2. Taalman RD, Hustinx TW, Weemaes CM, Seemanová E, Schmidt A, Passarge E, Scheres JM. Futher delineation of Nijmegen breakage syndrome. Am J Med Genet 1989; 32(3): 425–431.
3. Neubauer S, Arutyunyan R, Stumm M, Dork T, et al. Radiosensitivity of ataxia telangiectasia and Nijmegen breakage syndrome homozygotes and heterozygotes as determined by three-color FISH chromosome painting. Radiat Res 2002; 157(3): 312–321.
4. Burger S, Schindler D, Fehn M, Muhl B, Mahrhofer H, Flentje M, Hohn H. Radiation-induced DNA damane and repair in peripheral blood mononuclear cell from Nijmegen breakage syndrome patients and carriers assessed by the Comet assay. Environ Mol Mutagen 2006; 47(4): 260–270.
5. Varon R, Vissinga C, Platzer M, Digweed M. Sperling, K. et al. Nibrin, a novel DNA double strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 1998; 93: 467–476.
6. Varon R, Seemanová E, Chrzanowska K, et al. Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation 657del5 in three Slav populations. Eur J Hum Genet 2000; 8: 900–902.
7. Seemanová E. An increased risk for malignant neoplasms in heterozygotes for a syndrome of microcephaly, normal inteligence, growth retardation, remarkable facies, immunodeficiency and chromosomal instability. Mutat Res 1990; 238: 321–324.
8. Seemanová E, Jarolín P, Seeman P, Varon R, Digweed M, Swift M, Sperling K. Cancer risk of heterozygotes with NBS founder mutation. J Natl Cancer Inst 2007; 99(24): 1875–1880.
9. Steffen J, Varon R, Mosor M, et al. Increased cancer risk of heterozygotes with NBS1 germine mutation in Poland. Int.J.Cancer 2004; 111: 67–71.
10. Seemanová E, Hoch J, Herzogová J, Kawaciuk I, Janda J, Kohoutová M, Seeman P, Varon R, Sperling K. Mutace v tumor supresor genu NBS1 u dospělých pacientů s malignitami. Čas Lék čes 2006; 145(3): 201–203.
11. Herold A, Lehur P-A, Matzel K, OęConnell R. Coloproctology (European Manual of Medicine). Berlin: Springer-Verlag 2008: 215–217.
12. Guidelines for the Management of Colorectal Cancer. Association of Coloproctology of Great Britain and Ireland. London: UK 2007.
13. Weitz J, Koch M, Debus J, Hohler T, Galle PR, Buchler MW. Colorectal Cancer. Seminar. Lancet 2005; 365: 1413–1418.
14. Hohenberger W, Lahmer G, Fietkau R, Croner RS, Merkel S, Göhl J, Sauer R. Neoadjuvante Radiochemotherapie des Rektumskarzinoms. Chirurg 2009; 80: 294–302.
15. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resetcable rectal cancer. N Engl J Med 2001; 345(9): 638–646.
16. Swedish rectal cancer trial. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 1997; 336(14): 980–987.
17. Nigro ND, Vaitevicius VK, Considine B. jr. Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum 1993; 36(7): 709–711.
18. Tanzanella C, Antoccia A, Spadoni E, di Masi A, et al. Chromosome instability and nibrin protein variants in NBS heterozygotes. Eur J Hum Genet 2003; 9: 297–303.
19. Seeman P, Gebertová K, Paděrová K, Sperling K, Seemanová E. Nijmegen breakage syndrome in 13% age-matched Czech children with primary microcephaly. Pediatr Neurolog 2004; 30(3): 195–200.
20. Swift M, Kupper LL, Chase CL. Effective testing of gene-disease associations. Am J Hum Genet 1990; 47: 266–274.
Labels
Addictology Allergology and clinical immunology Angiology Audiology Clinical biochemistry Dermatology & STDs Paediatric gastroenterology Paediatric surgery Paediatric cardiology Paediatric neurology Paediatric ENT Paediatric psychiatry Paediatric rheumatology Diabetology Pharmacy Vascular surgery Pain managementArticle was published in
Journal of Czech Physicians
Most read in this issue
- Seemanová E, Hoch J, Seeman P. Heterozygous carriers of Slavic mutation 657del5 of NBN gene in patients with colorectal cancer
- Nagy I, Vinklerová V. The role of breastfeeding in the infant nourishment
- Ručka D, Lubanda JC, Karetová D, Skalická L, Vařejka P, Mrázek V, Linhart A. Carotid plaque exulcerated
- Marková I. Possibilities of health status examination in young men in the Czech Republic