Inherited variability in a master regulator polymorphism (rs4846126) associates with survival in 5-FU treated colorectal cancer patients

0431922 - ÚEM 2015 RIV NL eng J - Journal Article
Pardini, Barbara - Bermejo, J. L. - Naccarati, Alessio - Di Gaetano, C. - Rosa, F. - Legrand, C. - Novotný, J. - Vodička, Pavel - Kumar, R.
Inherited variability in a master regulator polymorphism (rs4846126) associates with survival in 5-FU treated colorectal cancer patients.
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 766-767, AUG-SEP (2014), s. 7-13. ISSN 0027-5107
R&D Projects: GA ČR GAP304/10/1286; GA ČR(CZ) GAP304/12/1585
Institutional support: RVO:68378041
Keywords : colorectal cancer * genome-wide association studies (GWAS) * EQTL studies
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.680, year: 2014

Treatment with 5-fluorouracil (5-FU) improves survival in many cancers including colorectal cancer. Response to the treatment, overall survival and recurrence show inter-individual variation. In this study we employed a strategy to search eQTL variants influencing the expression of alarge number of genes. We identified four single nucleotide polymorphisms, defined as master regulators of transcription, and genotyped them in a set of 218 colorectal cancer patients undergoing adjuvant 5-FU based therapy. The minor allele variant of the rs4846126 polymorphism was associated with poor overall and progression-free survival. Patients that were homozygous for the variant allele showed two fold increased risk of death (HR 2.20 95%CI 1.05–4.60) and progression (HR 2.88, 95%1.47–5.63). The integration of external information from publicly available gene expression repositories suggested that the rs4846126 polymorphism deserves further investigation. This variant potentially regulates the gene expression of 273 genes with some of them possibly associated to the patient’s responseto 5-FU treatment or colorectal cancer. Present results show that mining of public data repositories in combination with own data can be a fruitful approach to identify markers that affect therapy outcome. In particular, a genetic screen of master regulators may help to search for the polymorphisms involved in treatment responsein cancer patients.
Permanent Link: http://hdl.handle.net/11104/0236445