MNAT1 – Colorectal Cancer

A series of multi‐patient studies have examined the association between variants in MNAT1 and treatment outcomes in colorectal cancer. In a prospective cohort of 623 patients, carriers of the MNAT1 variant (rs3783819) showed significantly longer overall survival when treated with oxaliplatin-based chemotherapy (PMID:25778469), while a subsequent study in 1,502 patients replicated these findings and identified an additional variant (rs4151330) with predictive potential (PMID:34862210).

The genetic evidence is underscored by the identification of statistically significant associations in large, independent cohorts. Although family-based segregation data are not available, the robust case series provide valuable insight into the gene-disease relationship. The inheritance in these analyses is assumed to be autosomal, consistent with the germline nature of the predictive markers.

From a genetic standpoint, comprehensive candidate variant analyses in colorectal cancer have demonstrated that MNAT1 variants, notably the one corresponding to rs3783819, are consistently associated with differential overall survival in patients undergoing oxaliplatin therapy. This supports the clinical utility of MNAT1 as a predictive biomarker and suggests that the gene’s contribution is grounded in its role within the DNA repair pathway.

Functional studies of MNAT1 in other tissue contexts highlight its general involvement in DNA repair; however, direct experimental validation in colorectal cancer models remains limited. For instance, functional assessments in contexts such as mammary neoplasms and UV-induced stress responses have not recapitulated the precise biological context of colorectal tumorigenesis, thereby limiting the scope of experimental evidence specific to this disease.

In summary, the integration of genetic evidence from two large-scale studies provides a strong basis for the association between MNAT1 variants and colorectal cancer outcomes, despite a relative paucity of directly relevant functional data. This robust genetic association supports the potential use of MNAT1 variant profiling in tailoring oxaliplatin-based chemotherapy and overall treatment management for colorectal cancer patients.

Key take‑home: MNAT1 represents a promising predictive marker for optimizing therapeutic strategies in colorectal cancer, reinforcing its clinical diagnostic value despite the need for further functional characterization.

References

• The pharmacogenomics journal • 2015 • Genetic variants in DNA repair genes as potential predictive markers for oxaliplatin chemotherapy in colorectal cancer PMID:25778469
• Cancer epidemiology, biomarkers & prevention • 2022 • Validation of Genetic Markers Associated with Survival in Colorectal Cancer Patients Treated with Oxaliplatin-Based Chemotherapy PMID:34862210

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