Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Genetic polymorphisms and tumoral mutational profile over survival in advanced colorectal cancer patients: an exploratory study

Juan Pablo Cayún
ORCID logo ,
Leslie Carol Cerpa
,
Alicia Colombo
ORCID logo ,
Dante Daniel Cáceres
,
José Luis Leal
,
Felipe Reyes
,
Carolina Gutierrez
,
Susan Calfunao
,
Nelson Miguel Varela
* ,
Luis Abel Quiñones
*
Version 1 : Received: 13 July 2023 / Approved: 14 July 2023 / Online: 14 July 2023 (08:19:14 CEST)

How to cite: Cayún, J.P.; Cerpa, L.C.; Colombo, A.; Cáceres, D.D.; Leal, J.L.; Reyes, F.; Gutierrez, C.; Calfunao, S.; Varela, N.M.; Quiñones, L.A. Genetic polymorphisms and tumoral mutational profile over survival in advanced colorectal cancer patients: an exploratory study. Preprints 2023, 2023070972. https://doi.org/10.20944/preprints202307.0972.v1 Cayún, J.P.; Cerpa, L.C.; Colombo, A.; Cáceres, D.D.; Leal, J.L.; Reyes, F.; Gutierrez, C.; Calfunao, S.; Varela, N.M.; Quiñones, L.A. Genetic polymorphisms and tumoral mutational profile over survival in advanced colorectal cancer patients: an exploratory study. Preprints 2023, 2023070972. https://doi.org/10.20944/preprints202307.0972.v1

Abstract

Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug. Genetic polymorphisms have emerged as potential predictive biomarkers of response to chemotherapy, but conclusive evidence is lacking. Additionally, the interplay between hereditary variations and acquired mutations in the EGFR pathway remains unknown. This study aimed to investigate the role of genetic variants associated with 5FU-based chemotherapy on therapeutic effectiveness, considering their interaction with the EGFR pathway mutations. In a retrospective cohort of 63 patients diagnosed with metastatic colorectal cancer, a multivariate analysis revealed that liver metastases, DPYD, ABCB1 and MTHFR polymorphisms are independent indicators of a poor prognostic, irrespective of EGFR pathway mutations. BRAF V600E wild-type status and high-risk drug-metabolism polymorphisms correlated with a poor prognosis in this Chilean cohort. Additionally, findings from the genomics of drug sensitivity (GDSC) project demonstrated that cell lines with wild-type BRAF have higher IC50 values for 5-FU compared to BRAF-mutated cell lines. In conclusion, the genetic polymorphisms DPYD rs1801265, ABCB1 rs1045642 and MTHFR rs180113 may serve as useful biomarkers for predicting a poor prognosis in patients undergoing 5-fluorouracil chemotherapy, regardless of EGFR pathway mutations.

Keywords

colorectal cancer; pharmacogenomics; biomarkers

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.