Colorectal Cancer Coverage from Every Angle
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Is There a Prognostic Role for CDH1 Variants in Colorectal Cancer?

By: Hillary Ojeda
Posted: Monday, January 6, 2020

According to results of a genomic study published in the European Journal of Cancer, an analysis of patients with colorectal cancer showed that six single nucleotide polymorphisms were linked with overall survival. Jeremy P. Cheadle, PhD, of Cardiff University, United Kingdom, and colleagues found that rs9939049 in CDH1 seemed to significantly impact patient survival and warrants additional studies as a prognostic biomarker.

“Furthermore, our meta-analyses did not support a prognostic role for six other risk loci previously associated with survival,” the authors concluded. “Given that our study was well powered to find variants with hazard ratios > 1.18, it is likely that no other low-penetrance colorectal cancer risk loci identified to date have clinically actionable effects on survival.”

Using identified single nucleotide polymorphisms at 83 loci associated with colorectal cancer risk in European countries, 10 lead single nucleotide polymorphisms were genotyped, 72 were imputed, and 1 was neither genotyped nor imputed, for a total of 1,948 patients with advanced disease. The prognostic effects of the single nucleotide polymorphisms were assessed using COIN and COIN-B trial data.

The analysis identified six single nucleotide polymorphisms associated with overall survival (P < .05). The only one that was significant beyond the Bonferroni threshold (a family-wise error threshold) was rs9939049 in CDH1. Through fine mapping, the team discovered that rs12597188, which was associated with poor response to therapy, was the most significant single nucleotide polymorphism at this locus. Compared with single variants alone, no combinations of single nucleotide polymorphisms within pathways had a more significant link with survival.

Disclosure: The study authors reported no conflicts of interest.



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