A common variant of the MACC1 gene is significantly associated with overall survival in colorectal cancer patients

The study included 318 subjects with histopathologically proven colorectal cancer at the Academic Teaching Hospital Feldkirch, Austria. Survival data were provided by the federal agency for statistics in Austria. Genomic DNA was isolated from formalin-fixed paraffin-embedded specimens; six tagging SNPs (rs1990172, rs3114446, rs10275612, rs3095007, rs3095009, and rs7780032), capturing most of the common variants of the MACC1 locus, were genotyped by SNaPshot assays.Over a mean follow up period of 5.3 (± 1.0) years, 94 deaths were recorded. Carriers of the G-allele of SNP rs1990172 showed a significantly decreased overall survival (additive HR = 1.38 [1.05-1.82]; p = 0.023). Multivariate analysis adjusted for age and UICC tumor stage confirmed this result (HR = 1.49 [1.12-1.98]; p = 0.007). Other investigated genetic variants of the MACC1 gene were not significantly associated with overall survival (p-values > 0.05).For the first time, our study investigated the influence of MACC1 tagging polymorphisms on overall survival suggesting SNP rs1990172 as a predictor for reduced overall survival in colorectal cancer patients. Further studies will be required to validate our findings.Colorectal cancer (CRC) is one of the most frequent malignancies in the Western world and one of the leading causes of cancer related deaths [1,2]. Metastatic dissemination of primary tumors is directly linked to patient's survival and accounts for about 90% of all CRC deaths [3]. Local invasion and the formation of metastases are clinically the most relevant processes involved in carcinogenesis, but their molecular mechanisms are not fully understood. There is growing evidence that the genetic heterogeneity of CRC has a major influence on its prognosis and the search for adequate molecular prognostic markers has come into focus of translational cancer research.A significant success in this effort has been the identification of the metastasis-associated in colon cancer-1 (MACC1) gene as a crucia