Clinical significance of TLR1 I602S polymorphism for patients with metastatic colorectal cancer treated with FOLFIRI plus bevacizumab
Menée sur une cohorte initiale de 228 patients atteints d'un cancer colorectal métastatique, puis validée sur une cohorte complémentaire de 297 patients, cette étude suggère qu'un polymorphisme à simple nucléotide du gène TLR1 pourrait servir de biomarqueur pour prédire la réponse à un traitement combinant une chimiothérapie FOLFIRI et le bévacizumab
The purpose of this study was to evaluate the clinical significance of single nucleotide polymorphisms in <i>TLR1, TLR2, TLR6,</i> and <i>TAK1</i> in patients with metastatic colorectal cancer (mCRC). We genotyped 9 SNPs of TLR1, TLR2, TLR6, and TAK1 in mCRC patients treated with 1st-line FOLFIRI (combination therapy of irinotecan, 5-fluorouracil and folinic acid) plus bevacizumab, using a discovery cohort (TRIBE trial, n=228) and a validation cohort (FIRE-3 trial, n=297), and analyzed for the association with response rate (RR), progression-free survival (PFS), and overall survival (OS). There was a significant association of <i>TLR1</i> rs5743618 (T1805G) with the clinical outcome. In the TRIBE cohort, a homozygous wild-type genotype (T/T), associated with a significantly lower RR compared to variant T/G and G/G genotypes (43% vs. 62%, P=0.025), and this observation was validated in the FIRE-3 cohort (46% vs. 65%, P=0.021). In addition, those patients with the T/T genotype had significantly worse PFS (median: 8.2 vs. 10.5 months, HR: 1.57, 95%CI: 1.09-2.28, P=0.014) and OS (median: 19.9 vs. 27.9 months, HR: 1.63, 95%CI: 1.14-2.35, P=0.007), compared to those with other genotypes in the TRIBE cohort. These differences remained statistically significant in multivariate analysis. Our data suggest that <i>TLR1</i> rs5743618 could serve as a predictor of clinical response to FOLFIRI plus bevacizumab in mCRC patients.
Molecular Cancer Therapeutics , résumé, 2016