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Dihydropyrimidine dehydrogenase gene (DPYD) polymorphism among Caucasian and non-Caucasian patients with 5-FU- and capecitabine-related toxicity using full sequencing of DPYD.
Cancer Genomics Proteomics 2013 Mar-Apr; 10(2):89-92CG

Abstract

BACKGROUND

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of the degradation of pyrimidine base, and plays a pivotal role in the pharmacogenetic syndrome of 5-fluorouracil (5-FU). Deficiency of DPD activity leads to severe toxicities, even death, following administration of 5-FU. Several studies have demonstrated that molecular defects of the dihydropyrimidine dehydrogenase gene (DPYD) lead to the deficiency of DPD activity and cause this pharmacogenetic syndrome. We present the analysis of DPYD genotyping in untreated Caucasian patients (control group) and Caucasian patients with 5-FU/CAP-related grade 3/4 toxicities (toxicity group) who underwent a capecitabine TheraGuide 5-FU testing.

PATIENTS AND METHODS

Full sequencing of DPYD was performed in the Myriad Genetic Laboratories, Inc. as part of TheraGuide 5-FU test.

RESULTS

Among 227 patients from the toxicity group, 27 (12%) had deleterious mutations in DPYD: twelve (5%) had IVS14 +1 G>A, eleven (5%) had D949V and four (2%) had other mutations. Only 7/192 (4%) patients from the control group had DPYD genotype abnormalities: two (1%) had IVS14 +1 G>A, four (2%) had D949V and one (1%) had other mutation. Genotype abnormalities were observed more frequently in the toxicity group (p=0.001). Among 65 patients with toxicities due to capecitabine, nine (14%) had mutated DPYD, which was more frequent than in the control group (p=0.006).

CONCLUSION

Mutated DPYD is frequently observed in Caucasian patients who experience toxicities while receiving 5-FU/capecitabine. Screening of patients for DPYD mutations prior to administration of 5-FU/capecitabine using new pharmacogenetic testing methods, may help for identify those patients who are at greatest risk for adverse effects, allowing a more individualized approach to their chemotherapy management.

Authors+Show Affiliations

Tufts Medical Center, Tufts University School of Medicine, Division of Hematology/Oncology, Department of Medicine, Director, GI Oncology Program, 800 Washington Street, Box 245, Boston, MA 02111, USA. wsaif@tuftsmedicalcenter.org

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23603345

Citation

Saif, Muhammad Wasif. "Dihydropyrimidine Dehydrogenase Gene (DPYD) Polymorphism Among Caucasian and non-Caucasian Patients With 5-FU- and Capecitabine-related Toxicity Using Full Sequencing of DPYD." Cancer Genomics & Proteomics, vol. 10, no. 2, 2013, pp. 89-92.
Saif MW. Dihydropyrimidine dehydrogenase gene (DPYD) polymorphism among Caucasian and non-Caucasian patients with 5-FU- and capecitabine-related toxicity using full sequencing of DPYD. Cancer Genomics Proteomics. 2013;10(2):89-92.
Saif, M. W. (2013). Dihydropyrimidine dehydrogenase gene (DPYD) polymorphism among Caucasian and non-Caucasian patients with 5-FU- and capecitabine-related toxicity using full sequencing of DPYD. Cancer Genomics & Proteomics, 10(2), pp. 89-92.
Saif MW. Dihydropyrimidine Dehydrogenase Gene (DPYD) Polymorphism Among Caucasian and non-Caucasian Patients With 5-FU- and Capecitabine-related Toxicity Using Full Sequencing of DPYD. Cancer Genomics Proteomics. 2013;10(2):89-92. PubMed PMID: 23603345.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dihydropyrimidine dehydrogenase gene (DPYD) polymorphism among Caucasian and non-Caucasian patients with 5-FU- and capecitabine-related toxicity using full sequencing of DPYD. A1 - Saif,Muhammad Wasif, PY - 2013/4/23/entrez PY - 2013/4/23/pubmed PY - 2013/11/19/medline SP - 89 EP - 92 JF - Cancer genomics & proteomics JO - Cancer Genomics Proteomics VL - 10 IS - 2 N2 - BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of the degradation of pyrimidine base, and plays a pivotal role in the pharmacogenetic syndrome of 5-fluorouracil (5-FU). Deficiency of DPD activity leads to severe toxicities, even death, following administration of 5-FU. Several studies have demonstrated that molecular defects of the dihydropyrimidine dehydrogenase gene (DPYD) lead to the deficiency of DPD activity and cause this pharmacogenetic syndrome. We present the analysis of DPYD genotyping in untreated Caucasian patients (control group) and Caucasian patients with 5-FU/CAP-related grade 3/4 toxicities (toxicity group) who underwent a capecitabine TheraGuide 5-FU testing. PATIENTS AND METHODS: Full sequencing of DPYD was performed in the Myriad Genetic Laboratories, Inc. as part of TheraGuide 5-FU test. RESULTS: Among 227 patients from the toxicity group, 27 (12%) had deleterious mutations in DPYD: twelve (5%) had IVS14 +1 G>A, eleven (5%) had D949V and four (2%) had other mutations. Only 7/192 (4%) patients from the control group had DPYD genotype abnormalities: two (1%) had IVS14 +1 G>A, four (2%) had D949V and one (1%) had other mutation. Genotype abnormalities were observed more frequently in the toxicity group (p=0.001). Among 65 patients with toxicities due to capecitabine, nine (14%) had mutated DPYD, which was more frequent than in the control group (p=0.006). CONCLUSION: Mutated DPYD is frequently observed in Caucasian patients who experience toxicities while receiving 5-FU/capecitabine. Screening of patients for DPYD mutations prior to administration of 5-FU/capecitabine using new pharmacogenetic testing methods, may help for identify those patients who are at greatest risk for adverse effects, allowing a more individualized approach to their chemotherapy management. SN - 1790-6245 UR - https://www.unboundmedicine.com/medline/citation/23603345/Dihydropyrimidine_dehydrogenase_gene__DPYD__polymorphism_among_Caucasian_and_non_Caucasian_patients_with_5_FU__and_capecitabine_related_toxicity_using_full_sequencing_of_DPYD_ L2 - http://cgp.iiarjournals.org/cgi/pmidlookup?view=long&pmid=23603345 DB - PRIME DP - Unbound Medicine ER -