Combination of germline variations associated with survival of folinic acid, fluorouracil and irinotecan-treated metastatic colorectal cancer patients

Adrien Labriet, Éric Lévesque, Elena De Mattia, Erika Cecchin, Derek Jonker, Félix Couture, David Simonyan, Angela Buonadonna, Mario D'andrea, Lyne Villeneuve, Giuseppe Toffoli, Chantal Guillemette

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: Germline variants could modify survival of metastatic colorectal cancer patients (mCRC). Patients & methods: The association of 285 haplotype-tagging SNPs in 11 candidate genes and overall survival (OS) was tested in two cohorts totalizing 417 FOLFIRI-treated mCRC. Gene expression was investigated in vitro and in public datasets. Results: In the combined cohort, CES1 rs9921399T>C was associated with prolonged OS (hazard ratio [HR] = 0.40) whereas ABCC1 rs17501011G>A (HR = 2.08) and UGT1 rs1113193G>A (HR = 2.12) were associated with shorter OS (p ≤ 0.005). A combined effect of these polymorphisms was observed with HR of 1.98-2.97 (p < 0.05). The ABCC1 rs17501011A variant reduced reporter-gene activity (p < 0.05) whereas ABCC1 tumor expression was associated with shorter survival (p ≤ 0.013). Conclusion: We identified a combination of genetic determinants that could predict mCRC survival.

Original languageEnglish
Pages (from-to)1179-1187
Number of pages9
JournalPharmacogenomics
Volume20
Issue number17
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • biomarkers
  • irinotecan
  • metastatic colorectal cancer
  • pharmacogenomics
  • polymorphisms

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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