Abstract 146P
Background
Colorectal cancer (CRC) is the 3rd most frequent in the world and the 2nd most lethal. Several genome-wide association studies (GWAS) identified three single nucleotide polymorphisms (SNP) in SMAD7 associated with CRC risk. Two meta-analyses concluded that SMAD7’s rs4464148 (T>C) and rs12953717 (C>T) variants increase the risk of CRC and the rs4939827 (T>C) variant has a risk-reducing effect according to one of the meta-analyses, while the T allele has an increased risk according to the other meta-analysis. Nonetheless, there remains the question of whether these intronic SNPs have a prognostic effect on the disease.
Methods
We conducted an observational, retrospective, single-center, longitudinal study of 202 CRC patients, diagnosed from 1999 and 2010. Following DNA isolation from patient blood, the SMAD7 SNPs were genotyped using the Sequenom MAssARRAY iPLEX® Gold platform. In addition to characterizing patient demographics, survival outcomes were assessed using Kaplan-Meier curves, and the effect on the survival outcomes of the different alleles of the three SNPs was evaluated using the Cox proportional hazards model. The maximum follow-up time was 17 years.
Results
Among the 202 patients with CRC, 26 (12,9%) were diagnosed with stage I disease, 52 (25,7%) with stage II, 72 (35,6%) with stage III disease and 52 (25,7%) with stage IV. For the rs4464148 SNP, the genotype was: CC (n= 24), CT (n= 96), and TT (n=82). For the rs4939827, 36 had the CC genotype, 103 the CT, and 63 the TT. For the rs12953717, 55 had the TT genotype, 98 the CT, and 49 the CC. There was no statistically significant difference between each genotype in each of the SNPs using univariate Cox proportional hazards models in overall survival (OS) from the time of diagnosis to the last follow-up.
Conclusions
These three SMAD7 SNPs are not associated with CRC patient outcomes in this study population. Further studies of haplotypes analyses and larger cohorts are needed to clarify SMAD7 SNP’s prognostic value.
Legal entity responsible for the study
The authors.
Funding
Life and Health Sciences Research Institute.
Disclosure
All authors have declared no conflicts of interest.