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

Aims: 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.
Methods: 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.
Results: 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).
Conclusions: 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.
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