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. 2019 Nov;20(17):1179-1187.
doi: 10.2217/pgs-2019-0091. Epub 2019 Nov 8.

Combination of Germline Variations Associated With Survival of Folinic Acid, Fluorouracil and Irinotecan-Treated Metastatic Colorectal Cancer Patients

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Combination of Germline Variations Associated With Survival of Folinic Acid, Fluorouracil and Irinotecan-Treated Metastatic Colorectal Cancer Patients

Adrien Labriet et al. Pharmacogenomics. .
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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.

Keywords: biomarkers; irinotecan; metastatic colorectal cancer; pharmacogenomics; polymorphisms.

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