DPYD (Dihydropyrimidine Dehydrogenase) Variant c.2194G>A (Normal Metabolizer) with Severe Toxicities in Patients Treated with Fluoropyrimidine Based Regimens. A first Case Report from Bihar, India

Abstract The first-line medications used in clinics for colorectal cancer (CRC) are 5-FU based chemotherapy and its prodrug, capecitabine. Nevertheless, there are still relatively few patients responding to 5-FU/capecitabine-based therapy. Up to 30% of patients treated with 5-FU experience early-onset severe toxicity, including diarrhea, nausea, mucositis, stomatitis, myelosuppression, neurotoxicity, and hand-foot syndrome. The catabolism of 5-FU plays a major role in determining its toxicity. DPD enzyme present in the liver and is encoded by DPYD gene, which inactivates most FPs(fluoropyrimidines) molecules, Patients with a deficit in DPD are more likely to have significant treatment-related toxicity while using FP on a regular basis. In the present case report, we have documented the case of a 49-year-old female diagnosed with mCRC stage 4 and evaluated the toxicity produced by the entire dose regimen. The patient had shown grade 4 toxicity from the first dose (5 FU) and continued until shifting to capecitabine and finally adjusting to the S Trio. Despite the high level of toxicity, the patient was found to be negative for the four most common mutant variants of the DPYD gene (c.1905+1G>A [*2A], c.1129‐5923C>G [HapB3], c.1679T>G [*13], and c.2846A>T). However, the c.2194 G/A variant, which is a normal metabolizer, was found to be positive. Therefore, we document to imply that c.2194 G/A should be regarded as a clinically important SNP and advised for protective testing, particularly in the Indian population.