O-0027 Single Nucleotide Polymorphisms (SNPS) in the p53, SMAD7 and TGFBR1 Genes Associated with Advanced Colorectal Cancer in Caucasian Patients Compared to Healthy Controls.

Abstract

ABSTRACT Introduction In order to evaluate various SNP's in different genes and chromosomal locations in Caucasian patients as markers of the predisposition to the colorectal cancer (CRC) disease, we analyzed the frequency of different tumour-associated single-nucleotide polymorphisms in several genes including p53 and SMAD7 of Caucasian CRC patients as compared to a healthy Caucasian control population. Methods Tumour samples were obtained from 188 CRC patients at the adenocarcinoma stage and from 98 healthy control individuals. After gDNA extraction, selected amplicons were amplified by PCR, followed by melting curve analysis. The statistical evaluation of the difference in genotype frequency at the different SNPs comparing CRC patients with healthy controls was carried out using the Chi-squared test. Results When analyzing 188 tumour samples and comparing with 98 healthy controls, a significant difference in the genotype distribution of the G429C SNP in the p53 gene was observed (P = 0.046). Similarly, a significant difference was found for rs4939827 C > T in the SMAD7 gene (P = 0.037), although no significant differences were found for rs4464148 T > C (P = 0.585) or rs12953717 C > T (P = 0.197) also in SMAD7. Differences in genotype distribution for CHR9 C > A rs719725 and CHR8 G > A rs7014346 were almost significant (P = 0.050 and P = 0.054 respectively). Significant results previously reported for two other genes were confirmed:- PAI, 5G vs. 4G, rs1799899 (P = 0.047) and TGFBR1 A > G rs334348, G > A rs334349 and A > C rs1591 (P Conclusion The results for p53, SMAD7, PAI, CHR8 and CHR9 are suggestive rather than conclusive and invite confirmation through further study. Concerning the association between the TGFBR1 SNP's and colorectal cancer, on the other hand, the results are already clear. For example, with the TGFBR1 SNP rs334348, the frequency of the GG genotype was as much as 43% for the CRC patients but 11% for the controls, while the frequency of the AA genotype was only 18% for the patients and 43% for the controls. Adding further markers like SNPs for SMAD7, PAI, CHR8 and CHR9 is not significant, p53 though statistically borderline (P = 0.046) does not add clinical relevance.