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Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer
Hereditary factors are presumed to play a role in one third of colorectal cancer (CRC) cases. However, in the majority of familial CRC cases the genetic basis of predisposition remains unexplained. This is particularly true for families with few affected individuals. To identify susceptibility genes...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798264/ https://www.ncbi.nlm.nih.gov/pubmed/24146633 http://dx.doi.org/10.1371/journal.pgen.1003876 |
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author | Gylfe, Alexandra E. Katainen, Riku Kondelin, Johanna Tanskanen, Tomas Cajuso, Tatiana Hänninen, Ulrika Taipale, Jussi Taipale, Minna Renkonen-Sinisalo, Laura Järvinen, Heikki Mecklin, Jukka-Pekka Kilpivaara, Outi Pitkänen, Esa Vahteristo, Pia Tuupanen, Sari Karhu, Auli Aaltonen, Lauri A. |
author_facet | Gylfe, Alexandra E. Katainen, Riku Kondelin, Johanna Tanskanen, Tomas Cajuso, Tatiana Hänninen, Ulrika Taipale, Jussi Taipale, Minna Renkonen-Sinisalo, Laura Järvinen, Heikki Mecklin, Jukka-Pekka Kilpivaara, Outi Pitkänen, Esa Vahteristo, Pia Tuupanen, Sari Karhu, Auli Aaltonen, Lauri A. |
author_sort | Gylfe, Alexandra E. |
collection | PubMed |
description | Hereditary factors are presumed to play a role in one third of colorectal cancer (CRC) cases. However, in the majority of familial CRC cases the genetic basis of predisposition remains unexplained. This is particularly true for families with few affected individuals. To identify susceptibility genes for this common phenotype, we examined familial cases derived from a consecutive series of 1514 Finnish CRC patients. Ninety-six familial CRC patients with no previous diagnosis of a hereditary CRC syndrome were included in the analysis. Eighty-six patients had one affected first-degree relative, and ten patients had two or more. Exome sequencing was utilized to search for genes harboring putative loss-of-function variants, because such alterations are likely candidates for disease-causing mutations. Eleven genes with rare truncating variants in two or three familial CRC cases were identified: UACA, SFXN4, TWSG1, PSPH, NUDT7, ZNF490, PRSS37, CCDC18, PRADC1, MRPL3, and AKR1C4. Loss of heterozygosity was examined in all respective cancer samples, and was detected in seven occasions involving four of the candidate genes. In all seven occasions the wild-type allele was lost (P = 0.0078) providing additional evidence that these eleven genes are likely to include true culprits. The study provides a set of candidate predisposition genes which may explain a subset of common familial CRC. Additional genetic validation in other populations is required to provide firm evidence for causality, as well as to characterize the natural history of the respective phenotypes. |
format | Online Article Text |
id | pubmed-3798264 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37982642013-10-21 Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer Gylfe, Alexandra E. Katainen, Riku Kondelin, Johanna Tanskanen, Tomas Cajuso, Tatiana Hänninen, Ulrika Taipale, Jussi Taipale, Minna Renkonen-Sinisalo, Laura Järvinen, Heikki Mecklin, Jukka-Pekka Kilpivaara, Outi Pitkänen, Esa Vahteristo, Pia Tuupanen, Sari Karhu, Auli Aaltonen, Lauri A. PLoS Genet Research Article Hereditary factors are presumed to play a role in one third of colorectal cancer (CRC) cases. However, in the majority of familial CRC cases the genetic basis of predisposition remains unexplained. This is particularly true for families with few affected individuals. To identify susceptibility genes for this common phenotype, we examined familial cases derived from a consecutive series of 1514 Finnish CRC patients. Ninety-six familial CRC patients with no previous diagnosis of a hereditary CRC syndrome were included in the analysis. Eighty-six patients had one affected first-degree relative, and ten patients had two or more. Exome sequencing was utilized to search for genes harboring putative loss-of-function variants, because such alterations are likely candidates for disease-causing mutations. Eleven genes with rare truncating variants in two or three familial CRC cases were identified: UACA, SFXN4, TWSG1, PSPH, NUDT7, ZNF490, PRSS37, CCDC18, PRADC1, MRPL3, and AKR1C4. Loss of heterozygosity was examined in all respective cancer samples, and was detected in seven occasions involving four of the candidate genes. In all seven occasions the wild-type allele was lost (P = 0.0078) providing additional evidence that these eleven genes are likely to include true culprits. The study provides a set of candidate predisposition genes which may explain a subset of common familial CRC. Additional genetic validation in other populations is required to provide firm evidence for causality, as well as to characterize the natural history of the respective phenotypes. Public Library of Science 2013-10-17 /pmc/articles/PMC3798264/ /pubmed/24146633 http://dx.doi.org/10.1371/journal.pgen.1003876 Text en © 2013 Gylfe et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Gylfe, Alexandra E. Katainen, Riku Kondelin, Johanna Tanskanen, Tomas Cajuso, Tatiana Hänninen, Ulrika Taipale, Jussi Taipale, Minna Renkonen-Sinisalo, Laura Järvinen, Heikki Mecklin, Jukka-Pekka Kilpivaara, Outi Pitkänen, Esa Vahteristo, Pia Tuupanen, Sari Karhu, Auli Aaltonen, Lauri A. Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer |
title | Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer |
title_full | Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer |
title_fullStr | Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer |
title_full_unstemmed | Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer |
title_short | Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer |
title_sort | eleven candidate susceptibility genes for common familial colorectal cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798264/ https://www.ncbi.nlm.nih.gov/pubmed/24146633 http://dx.doi.org/10.1371/journal.pgen.1003876 |
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