Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.

Genome-wide linkage studies have identified the 9q22 chromosomal region as linked with colorectal cancer (CRC) predisposition. A candidate gene in this region is transforming growth factor beta receptor 1 (TGFBR1). Investigation of TGFBR1 has focused on the common genetic variant rs11466445, a short...

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Autores: Ross, Jason P., Lockett, Linda J., Tabor, Bruce, Saunders, Ian W., Young, Graeme P., Macrae, Finlay, Blanco Guillermo, Ignacio, Capellá, G. (Gabriel), Brown, Glenn S, Lockett, Trevor J., Hannan, Garry N.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/59148
Acceso en línea:https://hdl.handle.net/2445/59148
Access Level:acceso abierto
Palabra clave:Càncer colorectal
Malalties hereditàries
Colorectal cancer
Genetic diseases
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spelling Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.Ross, Jason P.Lockett, Linda J.Tabor, BruceSaunders, Ian W.Young, Graeme P.Macrae, FinlayBlanco Guillermo, IgnacioCapellá, G. (Gabriel)Brown, Glenn SLockett, Trevor J.Hannan, Garry N.Càncer colorectalMalalties hereditàriesColorectal cancerGenetic diseasesGenome-wide linkage studies have identified the 9q22 chromosomal region as linked with colorectal cancer (CRC) predisposition. A candidate gene in this region is transforming growth factor beta receptor 1 (TGFBR1). Investigation of TGFBR1 has focused on the common genetic variant rs11466445, a short exonic deletion of nine base pairs which results in truncation of a stretch of nine alanine residues to six alanine residues in the gene product. While the six alanine (*6A) allele has been reported to be associated with increased risk of CRC in some population based study groups this association remains the subject of robust debate. To date, reports have been limited to population-based case-control association studies, or case-control studies of CRC families selecting one affected individual per family. No study has yet taken advantage of all the genetic information provided by multiplex CRC families. Methods: We have tested for an association between rs11466445 and risk of CRC using several family-based statistical tests in a new study group comprising members of non-syndromic high risk CRC families sourced from three familial cancer centres, two in Australia and one in Spain. Results: We report a finding of a nominally significant result using the pedigree-based association test approach (PBAT; p = 0.028), while other family-based tests were non-significant, but with a p-value < 0.10 in each instance. These other tests included the Generalised Disequilibrium Test (GDT; p = 0.085), parent of origin GDT Generalised Disequilibrium Test (GDT-PO; p = 0.081) and empirical Family-Based Association Test (FBAT; p = 0.096, additive model). Related-person case-control testing using the 'More Powerful' Quasi-Likelihood Score Test did not provide any evidence for association (M-QL5; p = 0.41). Conclusions: After conservatively taking into account considerations for multiple hypothesis testing, we find little evidence for an association between the TGFBR1*6A allele and CRC risk in these families. The weak support for an increase in risk in CRC predisposed families is in agreement with recent meta-analyses of case-control studies, which estimate only a modest increase in sporadic CRC risk among 6*A allele carriers.BioMed Central2014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/59148Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: http://dx.doi.org/10.1186/1471-2407-14-475BMC Cancer, 2014, vol. 14, num. 1http://dx.doi.org/10.1186/1471-2407-14-475cc-by (c) Ross JP et al., 2014http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/591482026-05-27T06:46:51Z
dc.title.none.fl_str_mv Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.
title Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.
spellingShingle Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.
Ross, Jason P.
Càncer colorectal
Malalties hereditàries
Colorectal cancer
Genetic diseases
title_short Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.
title_full Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.
title_fullStr Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.
title_full_unstemmed Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.
title_sort Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.
dc.creator.none.fl_str_mv Ross, Jason P.
Lockett, Linda J.
Tabor, Bruce
Saunders, Ian W.
Young, Graeme P.
Macrae, Finlay
Blanco Guillermo, Ignacio
Capellá, G. (Gabriel)
Brown, Glenn S
Lockett, Trevor J.
Hannan, Garry N.
author Ross, Jason P.
author_facet Ross, Jason P.
Lockett, Linda J.
Tabor, Bruce
Saunders, Ian W.
Young, Graeme P.
Macrae, Finlay
Blanco Guillermo, Ignacio
Capellá, G. (Gabriel)
Brown, Glenn S
Lockett, Trevor J.
Hannan, Garry N.
author_role author
author2 Lockett, Linda J.
Tabor, Bruce
Saunders, Ian W.
Young, Graeme P.
Macrae, Finlay
Blanco Guillermo, Ignacio
Capellá, G. (Gabriel)
Brown, Glenn S
Lockett, Trevor J.
Hannan, Garry N.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer colorectal
Malalties hereditàries
Colorectal cancer
Genetic diseases
topic Càncer colorectal
Malalties hereditàries
Colorectal cancer
Genetic diseases
description Genome-wide linkage studies have identified the 9q22 chromosomal region as linked with colorectal cancer (CRC) predisposition. A candidate gene in this region is transforming growth factor beta receptor 1 (TGFBR1). Investigation of TGFBR1 has focused on the common genetic variant rs11466445, a short exonic deletion of nine base pairs which results in truncation of a stretch of nine alanine residues to six alanine residues in the gene product. While the six alanine (*6A) allele has been reported to be associated with increased risk of CRC in some population based study groups this association remains the subject of robust debate. To date, reports have been limited to population-based case-control association studies, or case-control studies of CRC families selecting one affected individual per family. No study has yet taken advantage of all the genetic information provided by multiplex CRC families. Methods: We have tested for an association between rs11466445 and risk of CRC using several family-based statistical tests in a new study group comprising members of non-syndromic high risk CRC families sourced from three familial cancer centres, two in Australia and one in Spain. Results: We report a finding of a nominally significant result using the pedigree-based association test approach (PBAT; p = 0.028), while other family-based tests were non-significant, but with a p-value < 0.10 in each instance. These other tests included the Generalised Disequilibrium Test (GDT; p = 0.085), parent of origin GDT Generalised Disequilibrium Test (GDT-PO; p = 0.081) and empirical Family-Based Association Test (FBAT; p = 0.096, additive model). Related-person case-control testing using the 'More Powerful' Quasi-Likelihood Score Test did not provide any evidence for association (M-QL5; p = 0.41). Conclusions: After conservatively taking into account considerations for multiple hypothesis testing, we find little evidence for an association between the TGFBR1*6A allele and CRC risk in these families. The weak support for an increase in risk in CRC predisposed families is in agreement with recent meta-analyses of case-control studies, which estimate only a modest increase in sporadic CRC risk among 6*A allele carriers.
publishDate 2014
dc.date.none.fl_str_mv 2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/59148
url https://hdl.handle.net/2445/59148
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1186/1471-2407-14-475
BMC Cancer, 2014, vol. 14, num. 1
http://dx.doi.org/10.1186/1471-2407-14-475
dc.rights.none.fl_str_mv cc-by (c) Ross JP et al., 2014
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Ross JP et al., 2014
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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