TGFBR1 SNP’s are a genetic marker potentially useful for colorectal cancer screening.

Abstract

e14591 Background: Colonoscopy (CS) used for colorectal cancer (CRC) screening is relatively expensive and intrusive. We have shown that CRC in Caucasian patients have a high frequency of certain TGFBR1 SNP’s relative to normal controls. Here we extend the results to these SNP frequencies in normal tissue of the patients and the concordance of three different SNP’s in the TGFBR1 gene across patients and subjects. Methods: Tumor samples were obtained from 188 CRC patients and from 98 healthy control. After gDNA extraction, selected amplicons were amplified by PCR, followed by melting curve analysis. The statistical evaluation of the genotype frequency for the different SNPs comparing CRC patients with controls was carried out using logistic regression. Results: Results previously reported were confirmed:- a highly significant association between TGFBR1 SNP genotype and colorectal cancer (P<0.000001). For example, with the TGFBR1 SNP rs334348, the frequency of the GG genotype was 43% for patients but 11% for controls, while the AA frequency was only 18% for patients and 43% for controls. All CRC patients and controls were typed for three SNP's in the TGFBR1 gene and the concordance was found to be perfect. That is, only 3 of the 27 possible genotypes were observed:- (i) rs334348, AA; rs334349, AA; rs1591, CC; (ii) rs334348, AG; rs334349, AC; rs1591, CT; and (iii) rs334348, GG; rs334349, CC; rs1591, TT. Blood and tumor samples from patients had the same identical SNP pattern. Conclusions: The perfect concordance of the three SNP types in tumors and leukocytes shows that it reflects the underlying genotype of the patient rather than a somatic mutation in the tumour. Thus SNP type is a characteristic of subjects and a potential genetic marker for CRC susceptibility. We suggest that subjects aged 50 years or older be offered a test for a TGFBR1 variant. In case of a positive result, subjects should be informed that they are at risk of CRC, and strongly encouraged to have a colonoscopy. For this suggestion to become a definitive recommendation a cost-effectiveness analysis of the use of TGFBR1 SNP typing would be useful ( although such typing is inexpensive) and a prospective study of colonoscopy with TGFBR1 typing is mandatory.