Correlation between DPYD gene variation and KRAS wild type status in colorectal cancer.

Failure and side effects of combined cytotoxic therapy are challenges in the treatment of metastatic colorectal cancer (CRC). DPYD gene variations can potentially predict toxicity to 5-fluorouracil (FU)-based therapy and KRAS-, NRAS-, BRAF-, PIK3CA-wild type status is a known prerequisite for epidermal growth factor receptor (EGFR) inhibitor therapy. This study was performed to search for a possible link between these therapeutic markers.,The DPYD gene variations c.496A>G, c.1679T>G, c.2846A>T and KRAS/NRAS/BRAF/PIK3CA mutational status were determined in non-neoplastic, primary CRC and metastatic CRC tissue from 115 patients.,The polymorphism c.496A>G was the DPYD gene variant with the highest detection rate (12.9%), occurred predominantly in females (86.7%, p=0.0044) and was exclusively seen in KRAS wild type primary CRC (15/65 (23.1%) vs 0/51 (0%) in KRAS-mutated primary CRC, respectively, p=0.0001).,This genetic profile could define a patient group requiring alternative combined therapeutic approaches. Global testing of large patient cohorts is necessary to prove this concept.