Open Access Research article

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

Adela Castillejo1, Trinidad Mata-Balaguer1, Paola Montenegro1, Enrique Ochoa3, Rafael Lázaro4, Ana Martínez-Cantó1, María-Isabel Castillejo1, Carla Guarinos1, Víctor-Manuel Barberá12, Carmen Guillén-Ponce2, Alfredo Carrato1 and José-Luís Soto12*

Author Affiliations

1 Molecular Oncology Group, Elche University Hospital, Camino Almazara 11, 03203 Elche, Spain

2 Genetic Counseling in Cancer Unit, Elche University Hospital, Camino Almazara 11, 03203 Elche, Spain

3 Molecular Biopathology Department. Castellon Provincial Hospital. Avenida Doctor Clara 19, 12002 Castellon de La Plana, Spain

4 Pathology Department, La Plana Hospital, Partida Carinyena Km 0.5, 12540 Vila-real. Spain

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BMC Cancer 2009, 9:193  doi:10.1186/1471-2407-9-193

Published: 18 June 2009



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.


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.


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.


Our results suggest that the TGFBR1*6A allele does not confer an increased risk of colorectal cancer in the Spanish population.