A Single Nucleotide Polymorphism in the MGMT Gene is a Novel Prognostic Biomarker in Patients with Metastatic Colorectal Cancer.

ABSTRACT

Background: Discovery of novel biomarkers of prognosis and drug response remains an elusive, yet critical goal. Thus, accurate and rapid screening of an array of pertinent mutations/SNPs is an essential step in cancer management. Methods: Using a high-throughput multiplex PCR microarray technique, we simultaneously screened the mutational status/SNP of 32 hotspots in multiple genes for metastatic colorectal cancer (mCRC) from 126 formalin fixed paraffin embedded samples from 78 patients. The efficacy of the technology was validated by cross-comparison with conventional Sanger sequencing and pyrosequencing. The clinical outcome was corroborated to the mutational status to determine prognostic and predictive significance of the 32 loci. Results: In a statistically robust multivariate model, patients with the TT genotype of the MGMT gene (rs1625649) enjoyed a significantly longer survival (61.8 months) when compared to those with GG or heterozygous GT genotype (29.3 months) [HR 0.30; 95% CI 0.10-0.89, P= 0.03], with a 70% reduced risk of death from mCRC. Conclusion: The rs1625649 SNP within MGMT is a novel and potentially valuable prognostic biomarker for mCRC patients.