Increased risk of severe fluoropyrimidine-associated toxicity in patients carrying a G to C substitution in the first 28-bp tandem repeat of the thymidylate synthase 2R allele

International Journal of Cancer

Volumn 138, Issue 1, 2016, Pages 245-253

  Meulendijks, Didier ^a   Jacobs, Bart A W ^a   Aliev, Abidin ^a   Pluim, Dick ^a   Van Werkhoven, Erik ^a   Deenen, Maarten J ^b   Beijnen, Jos H ^a,c   Cats, Annemieke ^a   Schellens, Jan H M ^a,c  

^a NETHERLANDS CANCER INSTITUTE   (Netherlands)

^b CATHARINA HOSPITAL   (Netherlands)

^c UTRECHT UNIVERSITY   (Netherlands)

Author keywords

5 fluorouracil; capecitabine; fluoropyrimidines; thymidylate synthase; toxicity

Indexed keywords

CAPECITABINE; CYSTEINE; DOCETAXEL; GLYCINE; THYMIDYLATE SYNTHASE; 5' UNTRANSLATED REGION; ANTINEOPLASTIC ANTIMETABOLITE; FLUOROURACIL; PYRIMIDINE; PYRIMIDINE DERIVATIVE;

ADULT; AGED; ALLELE; AMINO ACID SUBSTITUTION; ARTICLE; BLOOD TOXICITY; CONTROLLED STUDY; DIARRHEA; DRUG DOSE REDUCTION; DRUG WITHDRAWAL; FEBRILE NEUTROPENIA; FEMALE; FEVER; GASTROINTESTINAL TOXICITY; GENE EXPRESSION; GENETIC ASSOCIATION; GENETIC RISK; GENOTYPE; HAND FOOT SYNDROME; HOSPITALIZATION; HUMAN; INTRADUCTAL CARCINOMA; LEUKOPENIA; MAJOR CLINICAL STUDY; MALE; MULTIPLE CYCLE TREATMENT; NEUTROPENIA; PHARMACOGENETICS; PRIORITY JOURNAL; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM; STOMACH CANCER; TANDEM REPEAT; THYMIDYLATE SYNTHASE GENE; 5' UNTRANSLATED REGION; ANTAGONISTS AND INHIBITORS; CASE CONTROL STUDY; DRUG RESISTANCE; GENETICS; METABOLISM; MIDDLE AGED; MONONUCLEAR CELL; VERY ELDERLY; YOUNG ADULT;

5' UNTRANSLATED REGIONS; ADULT; AGED; AGED, 80 AND OVER; ALLELES; ANTIMETABOLITES, ANTINEOPLASTIC; CASE-CONTROL STUDIES; DRUG RESISTANCE; DRUG RESISTANCE, NEOPLASM; FEMALE; FLUOROURACIL; GENE EXPRESSION; GENOTYPE; HUMANS; LEUKOCYTES, MONONUCLEAR; MALE; MIDDLE AGED; PHARMACOGENETICS; POLYMORPHISM, SINGLE NUCLEOTIDE; PYRIMIDINES; TANDEM REPEAT SEQUENCES; THYMIDYLATE SYNTHASE; YOUNG ADULT;

EID: 84944264183     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.29694     Document Type: Article

References (29)

1. Caudle KE, Thorn CF, Klein TE, et al., Clinical pharmacogenetics implementation consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther 2013; 94: 640-5.
2. Deenen MJ, Cats A, Sechterberger MK, et al., Safety, pharmacokinetics (PK), and cost-effectiveness of upfront genotyping of DPYD in fluoropyrimidine therapy. J Clin Oncol 2011; 29 (Suppl); abstr 3606.
3. Horie N, Aiba H, Oguro K, et al., Functional analysis and DNA polymorphism of the tandemly repeated sequences in the 5′-terminal regulatory region of the human gene for thymidylate synthase. Cell Struct Funct 1995; 20: 191-7.
4. Kawakami K, Omura K, Kanehira E, et al., Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers. Anticancer Res 1999; 19: 3249-52.
5. Kawakami K, Salonga D, Park JM, et al., Different lengths of a polymorphic repeat sequence in the thymidylate synthase gene affect translational efficiency but not its gene expression. Clin Cancer Res 2001; 7: 4096-101.
6. Pullarkat ST, Stoehlmacher J, Ghaderi V, et al., Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics J 2001; 1: 65-70.
7. Rosmarin D, Palles C, Church D, et al., Genetic markers of toxicity from capecitabine and other fluorouracil-based regimens: Investigation in the QUASAR2 Study, systematic review, and meta-analysis. J Clin Oncol 2014; 32: 1031-9.
8. Mandola MV, Stoehlmacher J, Muller-Weeks S, et al., A novel single nucleotide polymorphism within the 5′ tandem repeat polymorphism of the thymidylate synthase gene abolishes USF-1 binding and alters transcriptional activity. Cancer Res 2003; 63: 2898-904.
9. Lincz LF, Scorgie FE, Garg MB, et al., Identification of a novel single nucleotide polymorphism in the first tandem repeat sequence of the thymidylate synthase 2R allele. Int J Cancer 2007; 120: 1930-4.
10. Gusella M, Bolzonella C, Crepaldi G, et al., A novel G/C single-nucleotide polymorphism in the double 28-bp repeat thymidylate synthase allele. Pharmacogenomics J 2006; 6: 421-4.
11. De Bock CE, Garg MB, Scott N, et al., Association of thymidylate synthase enhancer region polymorphisms with thymidylate synthase activity in vivo. Pharmacogenomics J 2011; 11: 307-14.
12. Marcuello E, Altés A, del Rio E, et al., Single nucleotide polymorphism in the 5′ tandem repeat sequences ofthymidylate synthase gene predicts for response to fluorouracil-based chemotherapy in advanced colorectal cancer patients. Int J Cancer 2004; 112: 733-7.
13. Morganti M, Ciantelli M, Giglioni B, et al., Relationships between promoter polymorphisms in the thymidylate synthase gene and mRNA levels in colorectal cancers. Eur J Cancer 2005; 41: 2176-83.
14. Pluim D, Schilders KAA, Jacobs BAW, et al., Pharmacodynamic assay of thymidylate synthase activity in peripheral blood mononuclear cells. Anal Bioanal Chem 2013; 405: 2495-503.
15. Pluim D, Jacobs BAW, Deenen MJ, et al., Improved pharmacodynamic assay for dihydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells. Bioanalysis 2015; 7: 519-29.
16. Wigginton JE, Cutler DJ, Abecasis GR., A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet 2005; 76: 887-93.
17. Rutgers E, Piccart-Gebhart MJ, Bogaerts J, et al., The EORTC 10041/BIG 03-04 MINDACT trial is feasible: Results of the pilot phase. Eur J Cancer 2011; 47: 2742-9.
18. Marsh S, Ameyaw MM, Githang'a J, et al., Novel thymidylate synthase enhancer region alleles in African populations. Hum Mutat 2000; 16: 528.
19. The Protein Atlas. Available from: Http://www.proteinatlas.org/accessed on December 21, 2014.
20. Corre S, Galibert M-D., Upstream stimulating factors: Highly versatile stress-responsive transcription factors. Pigment Cell Res 2005; 18: 337-48.
21. Sirito M, Lin Q, Maity T, Sawadogo M., Ubiquitous expression of the 43- and 44-kDa forms of transcription factor USF in mammalian cells. Nucleic Acids Res 1994; 22: 427-33.
22. Zhang ZC, Nechushtan H, Jacob-Hirsch J, et al., Growth-dependent and PKC-mediated translational regulation of the upstream stimulating factor-2 (USF2) mRNA in hematopoietic cells. Oncogene 1998; 16: 763-9.
23. Mauritz R, Giovannetti E, Beumer IJ, et al., Polymorphisms in the enhancer region of the thymidylate synthase gene are associated with thymidylate synthase levels in normal tissues but not in malignant tissues of patients with colorectal cancer. Clin Colorectal Cancer 2009; 8: 146-54.
24. Dolnick BJ., The rTS signaling pathway as a target for drug development. Clin Colorectal Cancer 2005; 5: 57-60.
25. Chu E, Koeller DM, Casey JL, et al., Autoregulation of human thymidylate synthase messenger RNA translation by thymidylate synthase. Proc Natl Acad Sci USA 1991; 88: 8977-81.
26. Rosmarin D, Palles C, Pagnamenta A, et al., A candidate gene study of capecitabine-related toxicity in colorectal cancer identifies new toxicity variants at DPYD and a putative role for ENOSF1 rather than TYMS. Gut 2015; 64: 1-10.
27. Pluim D, Jacobs BAW, Krähenbühl MD, et al., Correction of peripheral blood mononuclear cell cytosolic protein for hemoglobin contamination. Anal Bioanal Chem 2013; 405: 2391-5.
28. Deenen MJ, Tol J, Burylo AM, et al., Relationship between single nucleotide polymorphisms and haplotypes in DPYD and toxicity and efficacy of capecitabine in advanced colorectal cancer. Clin Cancer Res 2011; 17: 3455-68.
29. Werk AN, Cascorbi I., Functional gene variants of CYP3A4. Clin Pharmacol Ther 2014; 96: 340-8.