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The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study
BACKGROUND: TGF-β receptor type I is a mediator of growth inhibitory signals. TGFBR1*6A (rs11466445) is a common polymorphic variant of the TGF-β receptor I gene and has been associated with tumour susceptibility. Nevertheless, the role of this polymorphism as a risk factor for colorectal cancer is...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2708189/ https://www.ncbi.nlm.nih.gov/pubmed/19538729 http://dx.doi.org/10.1186/1471-2407-9-193 |
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author | Castillejo, Adela Mata-Balaguer, Trinidad Montenegro, Paola Ochoa, Enrique Lázaro, Rafael Martínez-Cantó, Ana Castillejo, María-Isabel Guarinos, Carla Barberá, Víctor-Manuel Guillén-Ponce, Carmen Carrato, Alfredo Soto, José-Luís |
author_facet | Castillejo, Adela Mata-Balaguer, Trinidad Montenegro, Paola Ochoa, Enrique Lázaro, Rafael Martínez-Cantó, Ana Castillejo, María-Isabel Guarinos, Carla Barberá, Víctor-Manuel Guillén-Ponce, Carmen Carrato, Alfredo Soto, José-Luís |
author_sort | Castillejo, Adela |
collection | PubMed |
description | BACKGROUND: TGF-β receptor type I is a mediator of growth inhibitory signals. TGFBR1*6A (rs11466445) is a common polymorphic variant of the TGF-β receptor I gene and has been associated with tumour susceptibility. Nevertheless, the role of this polymorphism as a risk factor for colorectal cancer is controversial. The aim of this study was to assess the association between TGFBR1*6A and colorectal cancer, age, sex, tumour location and tumour stage in a Spanish population. METHODS: The case-control study involved 800 Spanish subjects: 400 sporadic colorectal cancer patients and 400 age-, sex-, and ethnic-matched controls. The odds ratio (OR) and 95% confidence interval (95% CI) for the TGFBR1*6A polymorphism were calculated using unconditional logistic regression adjusted for age and sex. Analysis of somatic mutations at the GCG repeat of TGFBR1 exon 1 and germline allele-specific expression were also conducted to obtain further information on the contribution of the TGFBR1*6A allele to CRC susceptibility. RESULTS: There was no statistically significant association between the TGFBR1*6A allele and CRC (p > 0.05). The OR was 1.147 (95% CI: 0.799–1.647) for carriers of the TGFBR1*6A allele and 0.878 (95% CI: 0.306–2.520) for homozygous TGFBR1*6A individuals compared with the reference. The frequency of the polymorphism was not affected by age, sex or tumour stage. The TGFBR1*6A allele was more prevalent among colon tumour patients than among rectal tumour patients. Tumour somatic mutations were found in only two of 69 cases (2.9%). Both cases involved a GCG deletion that changed genotype 9A/9A in normal DNA to genotype 9A/8A. Interestingly, these two tumours were positive for microsatellite instability, suggesting that these mutations originated because of a deficient DNA mismatch repair system. Allele-specific expression of the 9A allele was detected in seven of the 14 heterozygous 9A/6A tumour cases. This could have been caused by linkage disequilibrium of the TGFBR1*6A allele with mutations that cause allele-specific expression, as was recently suggested. CONCLUSION: Our results suggest that the TGFBR1*6A allele does not confer an increased risk of colorectal cancer in the Spanish population. |
format | Text |
id | pubmed-2708189 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-27081892009-07-09 The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study Castillejo, Adela Mata-Balaguer, Trinidad Montenegro, Paola Ochoa, Enrique Lázaro, Rafael Martínez-Cantó, Ana Castillejo, María-Isabel Guarinos, Carla Barberá, Víctor-Manuel Guillén-Ponce, Carmen Carrato, Alfredo Soto, José-Luís BMC Cancer Research Article BACKGROUND: TGF-β receptor type I is a mediator of growth inhibitory signals. TGFBR1*6A (rs11466445) is a common polymorphic variant of the TGF-β receptor I gene and has been associated with tumour susceptibility. Nevertheless, the role of this polymorphism as a risk factor for colorectal cancer is controversial. The aim of this study was to assess the association between TGFBR1*6A and colorectal cancer, age, sex, tumour location and tumour stage in a Spanish population. METHODS: The case-control study involved 800 Spanish subjects: 400 sporadic colorectal cancer patients and 400 age-, sex-, and ethnic-matched controls. The odds ratio (OR) and 95% confidence interval (95% CI) for the TGFBR1*6A polymorphism were calculated using unconditional logistic regression adjusted for age and sex. Analysis of somatic mutations at the GCG repeat of TGFBR1 exon 1 and germline allele-specific expression were also conducted to obtain further information on the contribution of the TGFBR1*6A allele to CRC susceptibility. RESULTS: There was no statistically significant association between the TGFBR1*6A allele and CRC (p > 0.05). The OR was 1.147 (95% CI: 0.799–1.647) for carriers of the TGFBR1*6A allele and 0.878 (95% CI: 0.306–2.520) for homozygous TGFBR1*6A individuals compared with the reference. The frequency of the polymorphism was not affected by age, sex or tumour stage. The TGFBR1*6A allele was more prevalent among colon tumour patients than among rectal tumour patients. Tumour somatic mutations were found in only two of 69 cases (2.9%). Both cases involved a GCG deletion that changed genotype 9A/9A in normal DNA to genotype 9A/8A. Interestingly, these two tumours were positive for microsatellite instability, suggesting that these mutations originated because of a deficient DNA mismatch repair system. Allele-specific expression of the 9A allele was detected in seven of the 14 heterozygous 9A/6A tumour cases. This could have been caused by linkage disequilibrium of the TGFBR1*6A allele with mutations that cause allele-specific expression, as was recently suggested. CONCLUSION: Our results suggest that the TGFBR1*6A allele does not confer an increased risk of colorectal cancer in the Spanish population. BioMed Central 2009-06-18 /pmc/articles/PMC2708189/ /pubmed/19538729 http://dx.doi.org/10.1186/1471-2407-9-193 Text en Copyright ©2009 Castillejo et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Castillejo, Adela Mata-Balaguer, Trinidad Montenegro, Paola Ochoa, Enrique Lázaro, Rafael Martínez-Cantó, Ana Castillejo, María-Isabel Guarinos, Carla Barberá, Víctor-Manuel Guillén-Ponce, Carmen Carrato, Alfredo Soto, José-Luís The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study |
title | The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study |
title_full | The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study |
title_fullStr | The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study |
title_full_unstemmed | The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study |
title_short | The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study |
title_sort | tgfbr1*6a allele is not associated with susceptibility to colorectal cancer in a spanish population: a case-control study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2708189/ https://www.ncbi.nlm.nih.gov/pubmed/19538729 http://dx.doi.org/10.1186/1471-2407-9-193 |
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