The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: A case-control study

Adela Castillejo, Trinidad Mata-Balaguer, Paola Montenegro, Enrique Ochoa, Rafael Lázaro, Ana Martínez-Cantó, María Isabel Castillejo, Carla Guarinos, Víctor Manuel Barberá, Carmen Guillén-Ponce, Alfredo Carrato, José Luís Soto

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Abstract

Background: TGF-β receptor type I is a mediator of growth inhibitory signals. TGFBR1z.ast;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. © 2009 Castillejo et al; licensee BioMed Central Ltd.
Original languageAmerican English
JournalBMC Cancer
DOIs
StatePublished - 18 Jun 2009
Externally publishedYes

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    Castillejo, A., Mata-Balaguer, T., Montenegro, P., Ochoa, E., Lázaro, R., Martínez-Cantó, A., Castillejo, M. I., Guarinos, C., Barberá, V. M., Guillén-Ponce, C., Carrato, A., & Soto, J. L. (2009). The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: A case-control study. BMC Cancer. https://doi.org/10.1186/1471-2407-9-193