Biallelic MUTYH gene mutation resulting in fluoropyrimidine-resistant advanced rectal cancer: A case report

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide and the third most common cancer in Thailand. Approximately 2% – 5% of CRC cases are associated with inherited cancer syndromes, whereas the majority is sporadic. Herein, we have reported the case of a 32-year-old male with poorly differentiated middle rectal adenocarcinoma (T4bN1M1, Stage IV) that was refractory to fluoropyrimidine-based chemotherapy. Genetic profiling revealed a homozygous c.934-2A>G mutation in the MUTYH gene, which disrupted the DNA repair. Despite palliative radiation (30 Gy in 10 fractions) and systemic therapies (capecitabine plus oxaliplatin + panitumumab and fluorouracil, leucovorin, and irinotecan + bevacizumab), the disease progressed rapidly. Third-line therapy with Irinotecan plus oxaliplatin demonstrated initial success (partial response). Eventually, disease progression ensued. This report highlights the challenges of managing CRC caused by biallelic MUTYH mutations and emphasizes the importance of comprehensive genomic profiling for guiding therapeutic decisions. A review of similar cases in the literature is also presented.