Fluorouracil (5-FU), folinic acid, and irinotecan (FOLFIRI) is a standard treatment of metastatic colorectal cancer (mCRC). Our study aimed to investigate genetic variability in candidate genes in relation to patients9 outcomes using two independent cohorts of 417 FOLFIRI-treated mCRC cases recruited in Canada and Italy. We used a haplotype-tagging polymorphism (htSNP) approach to maximize the coverage of genetic variability of the selected genes and genotyping was performed using time-of-flight mass spectrometry iPLEX Sequenom Technology. Associations between polymorphisms and clinical outcomes were tested using Cox proportional hazards model adjusted for covariates. Of the genes tested, RPL28 encodes a ribosomal protein and its silencing was shown to enhance sensitivity to 5-FU and irinotecan in vitro.1 RPL28 rs4806668G>T was associated with a shorter progression-free survival (PFS) in the Canadian (hazard ratio (HR) 3.23, P = 0.013), Italian (HR 3.28, P = 0.021) and combined (HR 3.36, P This work is supported by the Canadian Institutes of Health Research. 1Allen et al. Mol Cancer Ther. 2012 Jan;11(1):119-31 Citation Format: Adrien Labriet, Eric Levesque, Elena De Mattia, Erika Cecchin, Derek Jonker, Felix Couture, David Simonyan, Angela Buonadonna, Mario D9Andrea, Lyne Villeneuve, Giuseppe Toffoli, Chantal Guillemette. RPL28 promoter polymorphism rs4806668 is associated with reduced survival in FOLFIRI-treated metastatic colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3889.