Researchers have identified two new genetic variants linked to poorer survival in patients with colorectal cancer (CRC).
Previous studies using additive genetic models failed to identify robust evidence of associations between CRC risk variants and survival outcomes. However, additive models can be prone to false negative detection if the underlying inheritance mode is recessive.
This study tested all currently known CRC-risk variants (n=129) in a discovery analysis of 5675 patients from a Scottish cohort. Significant associations were validated in 2474 CRC cases from UK Biobank.
The researchers found that the TT genotype of the intron variant rs7495132 in the CRTC3 gene was associated with clinically relevant poorer CRC-specific survival in both the discovery (HR 1.97; 95% CI 1.41-2.74, P=6.1x10-5) and validation analysis (HR 1.69; 95% CI 1.03-2.79; P=0.038).
In addition, the GG genotype of rs10161980 (intronic variant of AL139383.1 lncRNA) was associated with worse overall survival in the discovery cohort (HR 1.24; 95% CI 1.10-1.39; P=3.4x10-4) and CRC-specific survival in the validation cohort (HR 1.26; 95% CI 1.01-1.56; P=0.040).
The genetic associations discovered in this study provide prospects for future investigations to incorporate rs10161980 and rs7495132 genotypes into individual prediction models for survival outcomes.
The findings also suggest that recessive genetic effects should be considered in future genetic association studies on survival of CRC.
