Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H.
Common genetic variation at human 8q23.3 is significantly associated with colorectal cancer (CRC) risk. To elucidate the basis of this association we compared the frequency of common variants at 8q23.3 in 1,964 CRC cases and 2,081 healthy controls. Reporter gene studies showed that the single nucleo...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-09-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC2940760?pdf=render |
| _version_ | 1811278976797114368 |
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| author | Alan M Pittman Silvia Naranjo Sanni E Jalava Philip Twiss Yussanne Ma Bianca Olver Amy Lloyd Jayaram Vijayakrishnan Mobshra Qureshi Peter Broderick Tom van Wezel Hans Morreau Sari Tuupanen Lauri A Aaltonen M Eva Alonso Miguel Manzanares Angela Gavilán Tapio Visakorpi José Luis Gómez-Skarmeta Richard S Houlston |
| author_facet | Alan M Pittman Silvia Naranjo Sanni E Jalava Philip Twiss Yussanne Ma Bianca Olver Amy Lloyd Jayaram Vijayakrishnan Mobshra Qureshi Peter Broderick Tom van Wezel Hans Morreau Sari Tuupanen Lauri A Aaltonen M Eva Alonso Miguel Manzanares Angela Gavilán Tapio Visakorpi José Luis Gómez-Skarmeta Richard S Houlston |
| author_sort | Alan M Pittman |
| collection | DOAJ |
| description | Common genetic variation at human 8q23.3 is significantly associated with colorectal cancer (CRC) risk. To elucidate the basis of this association we compared the frequency of common variants at 8q23.3 in 1,964 CRC cases and 2,081 healthy controls. Reporter gene studies showed that the single nucleotide polymorphism rs16888589 acts as an allele-specific transcriptional repressor. Chromosome conformation capture (3C) analysis demonstrated that the genomic region harboring rs16888589 interacts with the promoter of gene for eukaryotic translation initiation factor 3, subunit H (EIF3H). We show that increased expression of EIF3H gene increases CRC growth and invasiveness thereby providing a biological mechanism for the 8q23.3 association. These data provide evidence for a functional basis for the non-coding risk variant rs16888589 at 8q23.3 and provides novel insight into the etiological basis of CRC. |
| first_indexed | 2024-04-13T00:46:42Z |
| format | Article |
| id | doaj.art-76ea75af14214caa92660695b7398130 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-13T00:46:42Z |
| publishDate | 2010-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-76ea75af14214caa92660695b73981302022-12-22T03:10:00ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042010-09-0169e100112610.1371/journal.pgen.1001126Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H.Alan M PittmanSilvia NaranjoSanni E JalavaPhilip TwissYussanne MaBianca OlverAmy LloydJayaram VijayakrishnanMobshra QureshiPeter BroderickTom van WezelHans MorreauSari TuupanenLauri A AaltonenM Eva AlonsoMiguel ManzanaresAngela GavilánTapio VisakorpiJosé Luis Gómez-SkarmetaRichard S HoulstonCommon genetic variation at human 8q23.3 is significantly associated with colorectal cancer (CRC) risk. To elucidate the basis of this association we compared the frequency of common variants at 8q23.3 in 1,964 CRC cases and 2,081 healthy controls. Reporter gene studies showed that the single nucleotide polymorphism rs16888589 acts as an allele-specific transcriptional repressor. Chromosome conformation capture (3C) analysis demonstrated that the genomic region harboring rs16888589 interacts with the promoter of gene for eukaryotic translation initiation factor 3, subunit H (EIF3H). We show that increased expression of EIF3H gene increases CRC growth and invasiveness thereby providing a biological mechanism for the 8q23.3 association. These data provide evidence for a functional basis for the non-coding risk variant rs16888589 at 8q23.3 and provides novel insight into the etiological basis of CRC.http://europepmc.org/articles/PMC2940760?pdf=render |
| spellingShingle | Alan M Pittman Silvia Naranjo Sanni E Jalava Philip Twiss Yussanne Ma Bianca Olver Amy Lloyd Jayaram Vijayakrishnan Mobshra Qureshi Peter Broderick Tom van Wezel Hans Morreau Sari Tuupanen Lauri A Aaltonen M Eva Alonso Miguel Manzanares Angela Gavilán Tapio Visakorpi José Luis Gómez-Skarmeta Richard S Houlston Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H. PLoS Genetics |
| title | Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H. |
| title_full | Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H. |
| title_fullStr | Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H. |
| title_full_unstemmed | Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H. |
| title_short | Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H. |
| title_sort | allelic variation at the 8q23 3 colorectal cancer risk locus functions as a cis acting regulator of eif3h |
| url | http://europepmc.org/articles/PMC2940760?pdf=render |
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