Premium
Increased cancer risk of heterozygotes with NBS1 germline mutations in poland
Author(s) -
Steffen Jan,
Varon Raymonda,
Mosor Maria,
Maneva Galina,
Maurer Martin,
Stumm Markus,
Nowakowska Dorota,
Rubach Maryna,
Kosakowska Ewa,
Ruka Włodzimierz,
Nowecki Zbigniew,
Rutkowski Piotr,
Demkow Tomasz,
Sadowska Małgorzata,
Bidziński Mariusz,
Gawrychowski Krzysztof,
Sperling Karl
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20239
Subject(s) - germline mutation , cancer , medicine , heterozygote advantage , mutation , loss of heterozygosity , colorectal cancer , nijmegen breakage syndrome , melanoma , oncology , proband , population , cancer research , genotype , genetics , biology , allele , gene , dna damage , dna , environmental health , ataxia telangiectasia
It has been suggested based on familial data that Nijmegen breakage syndrome (NBS) heterozygotes have an increased risk of malignant tumors. We found 15 carriers of the 657del5 mutation and 8 carriers of the R215W molecular variant of the NBS1 gene among 1,289 consecutive patients from Central Poland with various cancers and only 10 and 4 such carriers, respectively, in 1,620 controls from this region. Most of the 657del5 mutation carriers were found among patients with melanoma (4/105), non‐Hodgkin lymphoma (2/42) and breast cancer (4/224) and of the 234 patients with colorectal carcinoma 3 carried the 657del5 mutation and 3 others the R215W molecular variant. The frequencies of 657del5 mutation carriers among patients with melanoma and non‐Hodgkin lymphoma and of R215W carriers in patients with colorectal cancer were significantly higher than in controls ( p < 0.01, < 0.05 and < 0.05 respectively). The pooled frequencies of 657del5 and R215W mutations in all cancer patients were also significantly higher than in controls ( p < 0.05). Two carriers of the 657del5 mutation had second primary tumors. Malignant tumors among parents and siblings of 657del5 mutation carriers (14/77) were twice more frequent than in population controls. Three carriers of this mutation (2 probands with melanoma) reported melanoma in relatives. These results suggest strongly that NBS1 heterozygosity may be associated with elevated risk of some cancers. Larger studies are needed to evaluate the impact of the high frequency of germline NBS1 mutations on the cancer burden in the Slav populations. © 2004 Wiley‐Liss, Inc.