Research study reveals genetic variants linked to chemotherapy toxicity

A pioneering research conducted at the Sultan Qaboos Comprehensive Cancer Care & Research Centre (SQCCCRC) has shed light on a groundbreaking discovery regarding the relationship between genetic variants and severe toxicity reactions among Omani patients with gastrointestinal tumours.

The study, led by Dr. Ahmed Al Ghoche, senior specialist oncologist in the gastrointestinal cancer programme at SQCCCRC, revealed that specific genetic variations within the DPYD (dihydropyrimidine dehydrogenase) gene could predict adverse reactions such as neutropenia and diarrhoea in Omani patients undergoing chemotherapy. “Among the 53 Omani cancer patients receiving FP chemotherapy for gastrointestinal cancers, 28 encountered associated toxicities, while 25 did not,” said Dr. Al Ghoche, who served as the principal investigator of the research study titled “DPYD Gene Variants and Chemotherapy-Induced Toxicity in Omani Patients with Gastrointestinal Tumours.”

Mitigate toxicity risks

Highlighting the significance of personalised medicine, the study stressed the potential of genetic testing in tailoring chemotherapy dosages to mitigate toxicity risks and improve patient care.

Fluoropyrimidine (FP)-based drugs, integral in treating various cancers, are known for their significant toxicity profiles, with the most severe reactions attributed to deficiencies in the dihydropyrimidine dehydrogenase (DPYD) enzyme.

The DPYD gene, responsible for encoding the DPD enzyme crucial for metabolising FP drugs, exhibits genetic polymorphisms that can result in enzyme deficiency, leading to heightened mortality and morbidity.

“While DPYD gene polymorphisms have been documented across different populations, our study marks the first investigation of such variants in the Omani population,” said Dr. Shoaib Al Zadjali, Head of Research Lab at SQCCCRC.

Despite the relatively low prevalence of DPYD gene variants observed in the study, the findings underscore the necessity for further research involving larger cohorts to validate these results and ascertain their clinical implications.

Reducing risk

“Identifying these genetic variants before commencing treatment can facilitate dose adjustments, reducing the risk of toxicity and ultimately enhancing treatment outcomes,” the research study concluded. The groundbreaking insights provided by this research hold promise in revolutionising cancer treatment strategies, paving the way for more tailored and effective therapeutic approaches in the Omani population and beyond.