Germline variants could modify survival of metastatic colorectal cancer patients (mCRC). 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 and in public datasets. In the combined cohort, rs9921399T>C was associated with prolonged OS (hazard ratio [HR] = 0.40) whereas rs17501011G>A (HR = 2.08) and 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 rs17501011A variant reduced reporter-gene activity (p < 0.05) whereas tumor expression was associated with shorter survival (p ≤ 0.013). We identified a combination of genetic determinants that could predict mCRC survival.
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