The NBN founder mutation—Evidence for a country specific difference in age at cancer manifestation
Abstract 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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-02-01
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| Series: | Cancer Reports |
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| Online Access: | https://doi.org/10.1002/cnr2.1700 |
| _version_ | 1797902744989728768 |
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| author | Krystyna H. Chrzanowska Eva Seemanova Raymonda Varon Martin Digweed Dorota Piekutowska‐Abramczuk Karl Sperling Pavel Seeman |
| author_facet | Krystyna H. Chrzanowska Eva Seemanova Raymonda Varon Martin Digweed Dorota Piekutowska‐Abramczuk Karl Sperling Pavel Seeman |
| author_sort | Krystyna H. Chrzanowska |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-10T09:22:38Z |
| format | Article |
| id | doaj.art-d4396e54513c4de8b1e77c21035f9857 |
| institution | Directory Open Access Journal |
| issn | 2573-8348 |
| language | English |
| last_indexed | 2024-04-10T09:22:38Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Reports |
| spelling | doaj.art-d4396e54513c4de8b1e77c21035f98572023-02-20T10:23:21ZengWileyCancer Reports2573-83482023-02-0162n/an/a10.1002/cnr2.1700The NBN founder mutation—Evidence for a country specific difference in age at cancer manifestationKrystyna H. Chrzanowska0Eva Seemanova1Raymonda Varon2Martin Digweed3Dorota Piekutowska‐Abramczuk4Karl Sperling5Pavel Seeman6Department of Medical Genetics The Children's Memorial Health Institute Warsaw PolandDepartment of Clinical Genetics, Institute of Biology and Medical Genetics, 2nd Medical School Charles University Prague Czech RepublicInstitute of Medical and Human Genetics Charité‐Universitätsmedizin Berlin Berlin GermanyInstitute of Medical and Human Genetics Charité‐Universitätsmedizin Berlin Berlin GermanyDepartment of Medical Genetics The Children's Memorial Health Institute Warsaw PolandInstitute of Medical and Human Genetics Charité‐Universitätsmedizin Berlin Berlin GermanyDNA Laboratory, Department of Pediatric Neurology, 2nd Medical School Charles University, University Hospital Motol Prague Czech RepublicAbstract 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.https://doi.org/10.1002/cnr2.1700age of cancer manifestationcancer risk of heterozygotesenvironmental and medical exposure to ionizing radiationNBS |
| spellingShingle | Krystyna H. Chrzanowska Eva Seemanova Raymonda Varon Martin Digweed Dorota Piekutowska‐Abramczuk Karl Sperling Pavel Seeman The NBN founder mutation—Evidence for a country specific difference in age at cancer manifestation Cancer Reports age of cancer manifestation cancer risk of heterozygotes environmental and medical exposure to ionizing radiation NBS |
| title | The NBN founder mutation—Evidence for a country specific difference in age at cancer manifestation |
| title_full | The NBN founder mutation—Evidence for a country specific difference in age at cancer manifestation |
| title_fullStr | The NBN founder mutation—Evidence for a country specific difference in age at cancer manifestation |
| title_full_unstemmed | The NBN founder mutation—Evidence for a country specific difference in age at cancer manifestation |
| title_short | The NBN founder mutation—Evidence for a country specific difference in age at cancer manifestation |
| title_sort | nbn founder mutation evidence for a country specific difference in age at cancer manifestation |
| topic | age of cancer manifestation cancer risk of heterozygotes environmental and medical exposure to ionizing radiation NBS |
| url | https://doi.org/10.1002/cnr2.1700 |
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