The Prevalence of DPYD*9A(c.85TC) Genotype and the Genotype-Phenotype Correlation in Patients with Gastrointestinal Malignancies Treated With Fluoropyrimidines: Updated Analysis

Autor: Peter J. Hosein, Girijesh Kumar Patel, Ajay P. Singh, William R. Taylor, Bin Wang, Gwendolyn A. McMillin, Sachin Pai, Arthur E. Frankel, Moh’d Khushman, Anu Singh Maharjan, Cindy Nelson, Saad Awan
Rok vydání: 2019
Předmět:
Adult
Male
medicine.medical_specialty
Antimetabolites
Antineoplastic
Heterozygote
Dihydropyrimidine Dehydrogenase Deficiency
Drug-Related Side Effects and Adverse Reactions
Genotyping Techniques
Colorectal cancer
Gastroenterology
Polymorphism
Single Nucleotide
Severity of Illness Index
03 medical and health sciences
symbols.namesake
Young Adult
0302 clinical medicine
Internal medicine
Genotype
Antineoplastic Combined Chemotherapy Protocols
medicine
Dihydropyrimidine dehydrogenase
Humans
Genotyping
Fisher's exact test
Capecitabine
Dihydrouracil Dehydrogenase (NADP)
Genetic Association Studies
Aged
Gastrointestinal Neoplasms
Retrospective Studies
Aged
80 and over
business.industry
Homozygote
Cancer
Middle Aged
medicine.disease
Oncology
030220 oncology & carcinogenesis
Cohort
symbols
030211 gastroenterology & hepatology
DPYD
Female
Fluorouracil
business
Zdroj: Clinical colorectal cancer. 18(3)
ISSN: 1938-0674
Popis: Introduction The dihydropyrimidine dehydrogenase gene (DPYD)*9A (c.85T>C) genotype is relatively common. The correlation between DPYD*9A genotype and dihydropyrimidine dehydrogenase (DPD) deficiency phenotype is controversial. In a cohort of 28 patients, DPYD*9A was the most commonly diagnosed variant (13 patients [46%]) and there was a noticeable genotype-phenotype correlation. In this study we genotyped a larger cohort of a mixed racial background to explore the prevalence of DPYD*9A variant and to confirm the genotype-phenotype correlation. Patients and Methods Between 2011 and 2018, in addition to genotyping for high-risk DPYD variants (DPYD*2A, DPYD*13 and DPYD*9B), genotyping for DPYD*9A variant was performed on 113 patients with gastrointestinal malignancies treated with fluoropyrimidines. Fluoropyrimidines-associated toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). Fisher exact test was used for statistical analysis. Results Heterozygous and homozygous DPYD*9A genotypes were identified in 46 (41%) and 11 (10%) patients, respectively. Among patients with DPYD*9A genotypes (n = 57), men and women represented 30 (53%) and 27 (47%) patients, respectively. Caucasian, African American, and other ethnicities represented 29 (50.9%), 26 (45.6%), and 2 (3.5%) patients, respectively. Grade 3/4 toxicities were experienced in 26 patients with DPYD*9A genotype (3 patients had homozygous status) and in 20 patients with wild type DPYD*9A (P = .4405). In patients who received full-dose fluoropyrimidines (n = 85), Grade 3/4 toxicities were experienced in 22 patients with DPYD*9A genotype (2 patients had homozygous status), and in 17 patients with wild type DPYD (P = .8275). Conclusion In our updated analysis, the prevalence of heterozygous and homozygous DPYD*9A genotypes were 41% and 10%, respectively. The correlation between DPYD*9A genotype and DPD clinical phenotype was not reproduced. The noticeable correlation that we previously reported is likely because of small sample size and selection bias.
Databáze: OpenAIRE
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