| Summary: | <p>Abstract</p> <p>Background</p> <p>TGF-β receptor type I is a mediator of growth inhibitory signals. <it>TGFBR1*6A </it>(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 <it>TGFBR1*6A </it>and colorectal cancer, age, sex, tumour location and tumour stage in a Spanish population.</p> <p>Methods</p> <p>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 <it>TGFBR1 </it>exon 1 and germline allele-specific expression were also conducted to obtain further information on the contribution of the <it>TGFBR1*6A </it>allele to CRC susceptibility.</p> <p>Results</p> <p>There was no statistically significant association between the <it>TGFBR1*6A </it>allele and CRC (p > 0.05). The OR was 1.147 (95% CI: 0.799–1.647) for carriers of the <it>TGFBR1*6A </it>allele and 0.878 (95% CI: 0.306–2.520) for homozygous <it>TGFBR1*6A </it>individuals compared with the reference. The frequency of the polymorphism was not affected by age, sex or tumour stage. The <it>TGFBR1*6A </it>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.</p> <p>Allele-specific expression of the <it>9A </it>allele was detected in seven of the 14 heterozygous 9A/6A tumour cases. This could have been caused by linkage disequilibrium of the <it>TGFBR1*6A </it>allele with mutations that cause allele-specific expression, as was recently suggested.</p> <p>Conclusion</p> <p>Our results suggest that the <it>TGFBR1*6A </it>allele does not confer an increased risk of colorectal cancer in the Spanish population.</p>
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