Fluoropyrimidine-Induced Severe Toxicities Associated with Rare DPYD Polymorphisms: Case Series from Saudi Arabia and a Review of the Literature

被引：5

作者：

Bukhari, Nedal ^{[1
,2
]}

Alshangiti, Abdulraheem ^{[1
]}

Tashkandi, Emad ^{[3
,4
]}

Algarni, Mohammed ^{[5
,6
]}

Al-Shamsi, Humaid O. ^{[7
,8
,9
]}

Al-Khallaf, Hamoud ^{[10
]}

机构：

[1] King Fahad Specialist Hosp, Dept Med Oncol, Dammam 31444, Saudi Arabia

[2] Imam Abdulrahman Bin Faisal Univ, Dept Internal Med, Dammam 34212, Saudi Arabia

[3] King Abdullah Med City, Oncol Ctr, Mecca 24246, Saudi Arabia

[4] Umm Al Qura Univ, Coll Med, Mecca 24211, Saudi Arabia

[5] King Abdul Aziz Med City, Oncol Dept, Riyadh 11426, Saudi Arabia

[6] King Saud bin Abdulaziz Univ Hlth Sci, Riyadh 11481, Saudi Arabia

[7] Burjeel Med City, Burjeel Canc Inst, Dept Oncol, Abu Dhabi 999041, U Arab Emirates

[8] Emirates Oncol Soc, Dubai 22107, U Arab Emirates

[9] Univ Sharjah, Coll Med, Sharjah 999041, U Arab Emirates

[10] King Fahad Specialist Hosp, Dept Pathol & Lab Med, Dammam 31444, Saudi Arabia

来源：

CLINICS AND PRACTICE | 2021年 / 11卷 / 03期

关键词：

dihydropyrimidine dehydrogenase; 5-Fluorouuracil; chemotherapy; DPYD; polymorphism; CAPECITABINE; VARIANTS; SAFETY;

D O I：

10.3390/clinpract11030062

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Dihydropyrimidine dehydrogenase (DPD) is the major enzyme in the catabolism of 5-Fluorouracil (5-FU) and its prodrug capecitabine. We report cases from our institute with colorectal cancer who experienced severe toxicities to standard dose 5-FU based chemotherapy. DPYD gene sequencing revealed rare different polymorphisms that prompted dose adjustments of administered 5-FU and capecitabine. To our knowledge, this is the first case series looking at DPYD polymorphisms in the Saudi Arabian population.

引用

页码：467 / 471

页数：5

共 20 条

[11] Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue [J].

Miwa, M ;

Ura, M ;

Nishida, M ;

Sawada, N ;

Ishikawa, T ;

Mori, K ;

Shimma, N ;

Umeda, I ;

Ishitsuka, H .

EUROPEAN JOURNAL OF CANCER, 1998, 34 (08) :1274-1281

[12] Three different polymorphisms of the DPYD gene associated with severe toxicity following administration of 5-FU: a case report [J].

Mukherji, Deborah ;

Massih, Sarah Abdel ;

Tfayli, Arafat ;

Kanso, Mariam ;

Faraj, Walid .

JOURNAL OF MEDICAL CASE REPORTS, 2019, 13 (01)

[13] An Evaluation of the Diagnostic Accuracy of a Panel of Variants in DPYD and a Single Variant in ENOSF1 for Predicting Common Capecitabine Related Toxicities [J].

Palles, Claire ;

Fotheringham, Susan ;

Chegwidden, Laura ;

Lucas, Marie ;

Kerr, Rachel ;

Mozolowski, Guy ;

Rosmarin, Dan ;

Taylor, Jenny C. ;

Tomlinson, Ian ;

Kerr, David .

CANCERS, 2021, 13 (07)

[14]

Pullarkat S. T., 2001, Pharmacogenomics Journal, V1, P65

[15] Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology [J].

Richards, Sue ;

Aziz, Nazneen ;

Bale, Sherri ;

Bick, David ;

Das, Soma ;

Gastier-Foster, Julie ;

Grody, Wayne W. ;

Hegde, Madhuri ;

Lyon, Elaine ;

Spector, Elaine ;

Voelkerding, Karl ;

Rehm, Heidi L. .

GENETICS IN MEDICINE, 2015, 17 (05) :405-424

[16]

Saif MW, 2013, CANCER GENOM PROTEOM, V10, P89

[17]

SNEADER W, 2005, DRUG DISCOVERY, P255

[18]

Van Kuilenburg A.B.P., 2002, PURINE PYRIMIDINE ME, P247

[19]

van Kuilenburg Andre B P, 2019, JIMD Rep, V45, P65, DOI 10.1007/8904_2018_138

[20] Severe fluoropyrimidine toxicity due to novel and rare DPYD missense mutations, deletion and genomic amplification affecting DPD activity and mRNA splicing [J].

van Kuilenburg, Andre B. P. ;

Meijer, Judith ;

Maurer, Dirk ;

Dobritzsch, Doreen ;

Meinsma, Rutger ;

Los, Maartje ;

Knegt, Lia C. ;

Zoetekouw, Lida ;

Jansen, Rob L. H. ;

Dezentje, Vincent ;

van Huis-Tanja, Lieke H. ;

van Kampen, Roel J. W. ;

Hertz, Jens Michael ;

Hennekam, Raoul C. M. .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2017, 1863 (03) :721-730

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