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The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome
PURPOSE: Familial pancreatic cancer describes families with at least two first-degree relatives with pancreatic cancer that do not fulfil the criteria of other inherited tumor syndromes with increased risks of pancreatic cancer. Although much has been learned regarding the aggregation of pancreatic...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Cancer Association
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398394/ https://www.ncbi.nlm.nih.gov/pubmed/27488870 http://dx.doi.org/10.4143/crt.2016.217 |
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author | Lener, Marcin R. Kashyap, Aniruddh Kluźniak, Wojciech Cybulski, Cezary Soluch, Agnieszka Pietrzak, Sandra Huzarski, Tomasz Gronwald, Jacek Lubiński, Jan |
author_facet | Lener, Marcin R. Kashyap, Aniruddh Kluźniak, Wojciech Cybulski, Cezary Soluch, Agnieszka Pietrzak, Sandra Huzarski, Tomasz Gronwald, Jacek Lubiński, Jan |
author_sort | Lener, Marcin R. |
collection | PubMed |
description | PURPOSE: Familial pancreatic cancer describes families with at least two first-degree relatives with pancreatic cancer that do not fulfil the criteria of other inherited tumor syndromes with increased risks of pancreatic cancer. Although much has been learned regarding the aggregation of pancreatic cancer in some families, the genetic basis for this familial aggregation is poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in four genes among individuals from families with diagnosed familial pancreatic cancer syndrome and assessed their possible association with the familial pancreatic cancer (FPC) risk in Poland. MATERIALS AND METHODS: In this study, 400 FPC individuals and 4,000 control subjects were genotyped for founder mutations in BRCA1 (5382insC, 4153delA, C61G), CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), NBS1 (657del5), and PALB2 (509_510delGA, 172_175delTTGT) genes. RESULTS: A statistically significant association was observed between the 172_175delTTGT mutation of the PALB2 gene and an increased risk of FPC syndrome (odds ratio [OR], 10.05; p=0.048). In addition, an increased risk of cancer was observed in the FPC family members with a BRCA1 mutation (OR, 6.72; p=0.006). Novel associations were found between the FPC family members with cancer and CHEK2 mutations (OR, 2.26; p=0.008) with a noticeable contribution of the missense variant, I157T of CHEK2 (OR, 2.17; p=0.026). CONCLUSION: The founder mutations in the genes, BRCA1, PALB2, and CHEK2, cause a small percentage of familial pancreatic cancer syndrome in the Polish population. Following confirmation in larger studies, these mutations can be added to the panel of genes to be tested in families with a diagnosis of FPC syndrome. |
format | Online Article Text |
id | pubmed-5398394 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Korean Cancer Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-53983942017-05-05 The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome Lener, Marcin R. Kashyap, Aniruddh Kluźniak, Wojciech Cybulski, Cezary Soluch, Agnieszka Pietrzak, Sandra Huzarski, Tomasz Gronwald, Jacek Lubiński, Jan Cancer Res Treat Original Article PURPOSE: Familial pancreatic cancer describes families with at least two first-degree relatives with pancreatic cancer that do not fulfil the criteria of other inherited tumor syndromes with increased risks of pancreatic cancer. Although much has been learned regarding the aggregation of pancreatic cancer in some families, the genetic basis for this familial aggregation is poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in four genes among individuals from families with diagnosed familial pancreatic cancer syndrome and assessed their possible association with the familial pancreatic cancer (FPC) risk in Poland. MATERIALS AND METHODS: In this study, 400 FPC individuals and 4,000 control subjects were genotyped for founder mutations in BRCA1 (5382insC, 4153delA, C61G), CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), NBS1 (657del5), and PALB2 (509_510delGA, 172_175delTTGT) genes. RESULTS: A statistically significant association was observed between the 172_175delTTGT mutation of the PALB2 gene and an increased risk of FPC syndrome (odds ratio [OR], 10.05; p=0.048). In addition, an increased risk of cancer was observed in the FPC family members with a BRCA1 mutation (OR, 6.72; p=0.006). Novel associations were found between the FPC family members with cancer and CHEK2 mutations (OR, 2.26; p=0.008) with a noticeable contribution of the missense variant, I157T of CHEK2 (OR, 2.17; p=0.026). CONCLUSION: The founder mutations in the genes, BRCA1, PALB2, and CHEK2, cause a small percentage of familial pancreatic cancer syndrome in the Polish population. Following confirmation in larger studies, these mutations can be added to the panel of genes to be tested in families with a diagnosis of FPC syndrome. Korean Cancer Association 2017-04 2016-07-28 /pmc/articles/PMC5398394/ /pubmed/27488870 http://dx.doi.org/10.4143/crt.2016.217 Text en Copyright © 2017 by the Korean Cancer Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Lener, Marcin R. Kashyap, Aniruddh Kluźniak, Wojciech Cybulski, Cezary Soluch, Agnieszka Pietrzak, Sandra Huzarski, Tomasz Gronwald, Jacek Lubiński, Jan The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome |
title | The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome |
title_full | The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome |
title_fullStr | The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome |
title_full_unstemmed | The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome |
title_short | The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome |
title_sort | prevalence of founder mutations among individuals from families with familial pancreatic cancer syndrome |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398394/ https://www.ncbi.nlm.nih.gov/pubmed/27488870 http://dx.doi.org/10.4143/crt.2016.217 |
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