title: A subset of genetic susceptibility variants for colorectal cancer also has prognostic value.
abstract: We investigated the possible influence of 86 single-nucleotide polymorphisms (SNPs), known to associate with the risk of colorectal cancer (CRC), on overall survival and time to recurrence (TTR) in 733 Italian CRC patients followed up for up to 84 months after surgery. In the Cox multivariate analysis, adjusted for gender, age, pathological stage and adjuvant chemotherapy (yes/no), the risk of death significantly increased by rare allele count (P<0.05) for rs1801133 (MTHFR), rs4939827 (SMAD7), rs2306283 (SLCO1B1) and rs12898159 (BMP4), whereas for rs736775 (GPX3) the opposite was observed. Two additional SNPs associated with TTR, namely rs16892766 (downstream of EIF3H) and rs10749971 (COLCA2). Our findings show that some genetic variants previously found to associate with CRC risk are also associated with survival after treatment. The identification of alleles defining subgroups of patients with worse clinical outcome may have application in developing pharmacogenetic strategies aimed at personalizing CRC treatment.
authors.affiliation: Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Noci
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Dugo
authors.affiliation: Consortium for Human Molecular Genetics, University of Milano-Bicocca, Monza, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bertola
authors.affiliation: Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Melotti
authors.affiliation: Division of General Surgery B, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Vannelli
authors.affiliation: Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: T A
authors.initials: TA
authors.lastname: Dragani
authors.affiliation: Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Galvan
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012306:Risk; D055815:Young Adult