In 10-30% of colorectal cancer (CRC) patients, toxic reactions occur after fluoropyrimidine-based chemotherapy. A dihydropyridine dehydrogenase ( gene variant, c.1905 + 1G>A, leads to intolerance to fluoropyrimidines. Due to the low frequency of this variant in many populations, the prevalence of fluoropyrimidine-induced hematologic side effects in CRC patients with the c.1905 + 1G>A variant is unclear. In this study, we investigated the prevalence of the c.1905 + 1 variants in a Turkish CRC cohort and the potential effects of these variants on fluoropyrimidine-induced hematologic side effects. The c.1905 + 1 variant was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis and confirmed by Sanger sequencing in peripheral blood samples of 100 CRC patients who received fluoropyrimidine-based chemotherapy and 60 healthy volunteers. The association of c.1905 + 1 variants with susceptibility to hematologic side effects was evaluated. The c.1905 + 1G>A variant was more common in the CRC group than in the healthy control group ( = 0.001). The presence of the c.1905 + 1G>A variant was associated with thrombocytopenia ( = 0.039) and anemia ( = 0.035). CRC patients with fluoropyrimidine-induced anemia had shorter disease-free survival than CRC patients without fluoropyrimidine-induced anemia ( = 0.0009). Before administering fluoropyrimidine-based chemotherapy, genetic screening for the c.1905 + 1G>A variant should be performed with the aim of preventing anemia and anemia-induced complications in CRC patients.
About The Expert
Adem Deligonul
Secil Aksoy
Gulcin Tezcan
Berrin Tunca
Ozkan Kanat
Erdem Cubukcu
Tuncay Yilmazlar
Ersin Ozturk
Unal Egeli
Gulsah Cecener
Adem Alemdar
Turkkan Evrensel
References
PubMed