The NBN founder mutation-Evidence for a country specific difference in age at cancer manifestation.
NBS
age of cancer manifestation
cancer risk of heterozygotes
environmental and medical exposure to ionizing radiation
Journal
Cancer reports (Hoboken, N.J.)
ISSN: 2573-8348
Titre abrégé: Cancer Rep (Hoboken)
Pays: United States
ID NLM: 101747728
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
revised:
22
06
2022
received:
29
09
2021
accepted:
28
07
2022
entrez:
22
2
2023
pubmed:
23
2
2023
medline:
25
2
2023
Statut:
ppublish
Résumé
Nijmegen breakage syndrome (NBS) is an autosomal-recessive chromosome instability disorder characterized by, among others, hypersensitivity to X-irradiation and an exceptionally high risk for lymphoid malignancy. The vast majority of NBS patients is homozygous for a common Slavic founder mutation, c.657del5, of the NBN gene, which is involved in the repair of DNA double-strand breaks (DSBs). The founder mutation also predisposes heterozygous carriers to cancer, apparently however, with a higher risk in the Czech Republic/Slovakia (CS) than in Poland. To examine whether the age of cancer manifestation and cancer death of NBN homozygotes is different between probands from CS and Poland. The study is restricted to probands born until 1989, before replacement of the communist regime by a democratic system in CS and Poland, and a substantial transition of the health care systems. Moreover, all patients were recruited without knowledge of their genetic status since the NBN gene was not identified until 1998. Here, we show that cancer manifestation of NBN homozygotes is at a significantly earlier age in probands from CS than from Poland. This is explained by the difference in natural and medical radiation exposure, though within the permissible dosage. It is reasonable to assume that this finding also sheds light on the higher cancer risk of NBN heterozygotes in CS than in Poland. This has implications for genetic counseling and individualized medicine also of probands with other DNA repair defects.
Sections du résumé
BACKGROUND
Nijmegen breakage syndrome (NBS) is an autosomal-recessive chromosome instability disorder characterized by, among others, hypersensitivity to X-irradiation and an exceptionally high risk for lymphoid malignancy. The vast majority of NBS patients is homozygous for a common Slavic founder mutation, c.657del5, of the NBN gene, which is involved in the repair of DNA double-strand breaks (DSBs). The founder mutation also predisposes heterozygous carriers to cancer, apparently however, with a higher risk in the Czech Republic/Slovakia (CS) than in Poland.
AIM
To examine whether the age of cancer manifestation and cancer death of NBN homozygotes is different between probands from CS and Poland.
METHODS
The study is restricted to probands born until 1989, before replacement of the communist regime by a democratic system in CS and Poland, and a substantial transition of the health care systems. Moreover, all patients were recruited without knowledge of their genetic status since the NBN gene was not identified until 1998.
RESULTS
Here, we show that cancer manifestation of NBN homozygotes is at a significantly earlier age in probands from CS than from Poland. This is explained by the difference in natural and medical radiation exposure, though within the permissible dosage.
CONCLUSION
It is reasonable to assume that this finding also sheds light on the higher cancer risk of NBN heterozygotes in CS than in Poland. This has implications for genetic counseling and individualized medicine also of probands with other DNA repair defects.
Identifiants
pubmed: 36806726
doi: 10.1002/cnr2.1700
pmc: PMC9939984
doi:
Substances chimiques
Nuclear Proteins
0
Cell Cycle Proteins
0
NBN protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1700Informations de copyright
© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.
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