Researchers from Vanderbilt-Ingram Cancer Center have discovered new genes that put individuals at a higher risk for developing colon and rectal cancers, also known as colorectal cancer.
The findings were recently published in the Journal of the National Cancer Institute (JNCI).
The researchers utilized a large Transcriptomic-Wide Association Study (TWAS) and an alternative approach known as splicing-TWAS.
They identified oncogenic roles for two previously unreported genes, TRPS1 and METRNL, and confirmed susceptibility with another recently reported gene, C14orfl66.
In total, 57 genes associated with colorectal cancer risk were identified; 16 of these had not been reported in previous Genome-Wide Association Studies (GWAS).
The research team performed RNA sequencing in normal colon tissues and incorporated genotyping data from 423 European descendants. This helped them build genetic prediction models of gene expression and alternative splicing.
This study is believed to be the first to use a TWAS approach systematically to explore the associations of genetically predicted alternative splicing with colorectal cancer risk.
“More than 200 common genetic variants have been associated with colorectal cancer through GWAS, but the underlying biological mechanisms for most of these risk loci remain unclear,” said Dr. Xingyi Guo, the study’s senior author.
According to Dr. Guo, ongoing efforts are necessary to identify novel susceptibility genes.
“By combining population-based analyses with functional investigations, we can gain insights into the biological mechanisms responsible for colorectal cancer, which could help in the prevention and treatment of this prevalent disease,” he added.
The study was limited to individuals of European ancestry, and the researchers emphasized the need for further studies to assess the relevance of these genes in non-European populations.
Future TWAS analyses are likely to reveal additional significant genes for cancer risk.
The discovery of new genes linked to colorectal cancer susceptibility opens up avenues for targeted prevention and treatment strategies.
This study brings science one step closer to understanding the genetic factors that contribute to colorectal cancer, with the hope of improving outcomes for patients in the future.
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The research findings can be found in JNCI: Journal of the National Cancer Institute.
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