Publication:
DPYD c.1905+1G>A promotes fluoropyrimidine-induced anemia, a prognostic factor in disease-free survival, in colorectal cancer

No Thumbnail Available

Date

2021-04-01

Authors

Deligönül, Adem
Aksoy, Seçil
Tezcan, Gülçin
Tunca, Berrin
Kanat, Özkan
Çubukcu, Erdem
Yılmazlar, Tuncay
Öztürk, Ersin
Egeli, Ünal
Çeçener, Gülşah

Journal Title

Journal ISSN

Volume Title

Publisher

Mary Ann Liebert, Inc

Research Projects

Organizational Units

Journal Issue

Abstract

Background and Aim: In 10-30% of colorectal cancer (CRC) patients, toxic reactions occur after fluoropyrimidine-based chemotherapy. A dihydropyridine dehydrogenase (DPYD) 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 DPYD c.1905 + 1 variants in a Turkish CRC cohort and the potential effects of these variants on fluoropyrimidine-induced hematologic side effects.Materials and Methods: The DPYD 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.Results: The DPYD c.1905 + 1G>A variant was more common in the CRC group than in the healthy control group (p = 0.001). The presence of the c.1905 + 1G>A variant was associated with thrombocytopenia (p = 0.039) and anemia (p = 0.035). CRC patients with fluoropyrimidine-induced anemia had shorter disease-free survival than CRC patients without fluoropyrimidine-induced anemia (p = 0.0009).Conclusions: Before administering fluoropyrimidine-based chemotherapy, genetic screening for the DPYD c.1905 + 1G>A variant should be performed with the aim of preventing anemia and anemia-induced complications in CRC patients.

Description

Keywords

DPYD c.1905+1G > A, Fluoropyrimidine, Anemia, Colorectal cancer, Biochemistry & molecular biology, Genetics & heredity

Citation

Collections

1

Views

0

Downloads

Search on Google Scholar