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Genetic Predictors of Response to Oxaliplatin in Colorectal Cancer

By: Alison Tewksbury
Posted: Monday, March 4, 2019

Despite prior studies demonstrating a differential benefit of oxaliplatin treatment in patients with loss of function single nucleotide polymorphisms in pattern recognition receptors FPR1, TLR3, and TLR4, a recent study published in the Journal of the National Cancer Institute found no evidence to support this association. In a retrospective study of the SCOT and COIN/COIN-B trials, David N. Church, DPhil, of the Wellcome Centre for Human Genetics, and colleagues performed genotyping to assess the association between loss of function variants, disease-free survival, and overall survival in patients receiving oxaliplatin treatment. 

In the SCOT trial, oxaliplatin-based adjuvant chemotherapy was compared with the previous standard of care in high-risk stage II or stage III disease. In the COIN/COIN-B trial, the addition of cetuximab to oxaliplatin-based therapy in metastatic colorectal cancer was assessed.

Genotyping to determine participant status for loss of function variants in FPR1 (rs867228), TLR3 (rs3775291), and TLR4 (rs4986790/rs4986791) was performed through genotyping array or genotype imputation. Of the 2,929 patients from the SCOT trial and the 1,948 patients from the COIN/COIN-B trial cohorts, it was determined that 2,728 and 1,672 patients, respectively, had “functional status of all three [single nucleotide polymorphisms].” Although multiple models were used, no association was found between “any [single nucleotide polymorphism] and [disease-free survival] in the SCOT cohort [hazard ratios ranged from 0.86 to 1.58] or with [overall survival] in either cohort [hazard ratios ranged from 0.81 to 1.82].”

The investigators believe that prior studies may have been limited by smaller size and found no indication of differential benefit from oxaliplatin. “Our results suggest these single nucleotide polymorphisms are unlikely to be clinically useful biomarkers,” they concluded.

Disclosure: The study authors reported no conflicts of interest.



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