A DPYD variant (Y186C) in individuals of african ancestry is associated with reduced DPD enzyme activity

Clinical Pharmacology and Therapeutics

Volumn 94, Issue 1, 2013, Pages 158-166

  Offer, S M ^a   Lee, A M ^a   Mattison, L K ^a,b   Fossum, C ^a   Wegner, N J ^a   Diasio, R B ^a  

^a MAYO CLINIC CANCER CENTER   (United States)

^b United States Patent and Trademark Office   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIHYDROPYRIMIDINE DEHYDROGENASE; FLUOROURACIL;

ADULT; AFRICAN AMERICAN; ALLELE; ARTICLE; CONTROLLED STUDY; DPYD GENE; ENZYME ACTIVITY; EUROPEAN AMERICAN; FEMALE; GENE; GENE LINKAGE DISEQUILIBRIUM; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE; HETEROZYGOTE; HOMOZYGOTE; HUMAN; HUMAN EXPERIMENT; MALE; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; RACE DIFFERENCE; TREATMENT RESPONSE;

ADULT; AFRICAN AMERICANS; ANTIMETABOLITES, ANTINEOPLASTIC; COHORT STUDIES; DIHYDROURACIL DEHYDROGENASE (NADP); EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; FLUOROURACIL; HUMANS; MALE; NEOPLASMS; YOUNG ADULT;

EID: 84879413456     PISSN: 00099236     EISSN: 15326535     Source Type: Journal    
DOI: 10.1038/clpt.2013.69     Document Type: Article

References (42)

1. Laurie, J.A. et al. Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fuorouracil. The North Central Cancer Treatment Group and the Mayo Clinic. J. Clin. Oncol. 7, 1447-1456 (1989).
2. Moertel, C.G. et al. Levamisole and fuorouracil for adjuvant therapy of resected colon carcinoma. N. Engl. J. Med. 322, 352-358 (1990).
3. de Gramont, A. et al. Leucovorin and fuorouracil with or without oxaliplatin as frst-line treatment in advanced colorectal cancer. J. Clin. Oncol. 18, 2938-2947 (2000).
4. Goldberg, R.M. et al. A randomized controlled trial of fuorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J. Clin. Oncol. 22, 23-30 (2004).
5. André, T. et al.; Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fuorouracil, and leucovorin as adjuvant treatment for colon cancer. N. Engl. J. Med. 350, 2343-2351 (2004).
6. Okamoto, I. & Fukuoka, M. S-1: a new oral fuoropyrimidine in the treatment of patients with advanced non-small-cell lung cancer. Clin. Lung Cancer 10, 290-294 (2009).
7. Longley, D.B., Harkin, D.P. & Johnston, P.G. 5-fuorouracil: mechanisms of action and clinical strategies. Nat. Rev. Cancer 3, 330-338 (2003).
8. Boisdron-Celle, M. et al. 5-Fluorouracil-related severe toxicity: a comparison of diferent methods for the pretherapeutic detection of dihydropyrimidine dehydrogenase defciency. Cancer Lett. 249, 271-282 (2007).
9. Heggie, G.D., Sommadossi, J.P., Cross, D.S., Huster, W.J. & Diasio, R.B. Clinical pharmacokinetics of 5-fuorouracil and its metabolites in plasma, urine, and bile. Cancer Res. 47, 2203-2206 (1987).
10. Diasio, R.B., Beavers, T.L. & Carpenter, J.T. Familial defciency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fuorouracil-induced toxicity. J. Clin. Invest. 81, 47-51 (1988).
11. Harris, B.E., Carpenter, J.T. & Diasio, R.B. Severe 5-fuorouracil toxicity secondary to dihydropyrimidine dehydrogenase defciency. A potentially more common pharmacogenetic syndrome. Cancer 68, 499-501 (1991).
12. Jessup, J.M., Stewart, A., Greene, F.L. & Minsky, B.D. Adjuvant chemotherapy for stage III colon cancer: implications of race/ethnicity, age, and diferentiation. JAMA 294, 2703-2711 (2005).
13. Sanof, H.K., Sargent, D.J., Green, E.M., McLeod, H.L. & Goldberg, R.M. Racial diferences in advanced colorectal cancer outcomes and pharmacogenetics: a subgroup analysis of a large randomized clinical trial. J. Clin. Oncol. 27, 4109-4115 (2009).
14. McCollum, A.D. et al. Outcomes and toxicity in African-American and Caucasian patients in a randomized adjuvant chemotherapy trial for colon cancer. J. Natl. Cancer Inst. 94, 1160-1167 (2002).
15. Sugihara, K. et al. Safety analysis of FOLFOX4 treatment in colorectal cancer patients: a comparison between two Asian studies and four Western studies. Clin. Colorectal Cancer 11, 127-137 (2012).
16. Han, H.S. et al. Racial diferences in acute toxicities of neoadjuvant or adjuvant chemotherapy in patients with early-stage breast cancer. Eur. J. Cancer 47, 2537-2545 (2011).
17. Mattison, L.K., Fourie, J., Desmond, R.A., Modak, A., Saif, M.W. & Diasio, R.B. Increased prevalence of dihydropyrimidine dehydrogenase defciency in African-Americans compared with Caucasians. Clin. Cancer Res. 12, 5491-5495 (2006).
18. Abecasis, G.R. et al. A map of human genome variation from population-scale sequencing. Nature 467, 1061-1073 (2010).
19. Abecasis, G.R. et al. An integrated map of genetic variation from 1, 092 human genomes. Nature 491, 56-65 (2012). 1000 Genomes Project Browser. http://browser.1000genomes.org/. Accessed December 2012.
20. Exome Variant Server. http://evs.gs.washington.edu/EVS/. Accessed January 2013.
21. Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559-575 (2007).
22. Ezzeldin, H.H., Lee, A.M., Mattison, L.K. & Diasio, R.B. Methylation of the DPYD promoter: an alternative mechanism for dihydropyrimidine dehydrogenase defciency in cancer patients. Clin. Cancer Res. 11, 8699-8705 (2005).
23. Altshuler, D.M. et al. Integrating common and rare genetic variation in diverse human populations. Nature 467, 52-58 (2010).
24. Schwab, M. et al.; German 5-FU Toxicity Study Group. Role of genetic and nongenetic factors for fuorouracil treatment-related severe toxicity: a prospective clinical trial by the German 5-FU Toxicity Study Group. J. Clin. Oncol. 26, 2131-2138 (2008).
25. Gross, E. et al. Strong association of a common dihydropyrimidine dehydrogenase gene polymorphism with fuoropyrimidine-related toxicity in cancer patients. PLoS ONE 3, e4003 (2008).
26. Amstutz, U., Farese, S., Aebi, S. & Largiadèr, C.R. Dihydropyrimidine dehydrogenase gene variation and severe 5-fuorouracil toxicity: a haplotype assessment. Pharmacogenomics 10, 931-944 (2009).
27. Vreken, P., Van Kuilenburg, A.B., Meinsma, R. & van Gennip, A.H. Identifcation of novel point mutations in the dihydropyrimidine dehydrogenase gene. J. Inherit. Metab. Dis. 20, 335-338 (1997).
28. Vreken, P., Van Kuilenburg, A.B., Meinsma, R. & van Gennip, A.H. Dihydropyrimidine dehydrogenase (DPD) defciency: identifcation and expression of missense mutations C29R, R886H and R235W. Hum. Genet. 101, 333-338 (1997).
29. Seck, K. et al. Analysis of the DPYD gene implicated in 5-fuorouracil catabolism in a cohort of Caucasian individuals. Clin. Cancer Res. 11, 5886-5892 (2005).
30. Kleibl, Z. et al. Infuence of dihydropyrimidine dehydrogenase gene (DPYD) coding sequence variants on the development of fuoropyrimidine-related toxicity in patients with high-grade toxicity and patients with excellent tolerance of fuoropyrimidine-based chemotherapy. Neoplasma 56, 303-316 (2009).
31. Ofer, S.M., Wegner, N.J., Fossum, C., Wang, K. & Diasio, R.B. Phenotypic profling of DPYD variations relevant to 5-fuorouracil sensitivity using realtime cellular analysis and in vitro measurement of enzyme activity. Cancer Res. 73, 1958-1968 (2013).
32. Dobritzsch, D., Schneider, G., Schnackerz, K.D. & Lindqvist, Y. Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fuorouracil. EMBO J. 20, 650-660 (2001).
33. Zhou, W. & Freed, C.R. Tyrosine-to-cysteine modifcation of human alpha-synuclein enhances protein aggregation and cellular toxicity. J. Biol. Chem. 279, 10128-10135 (2004).
34. Maekawa, K. et al. Genetic variations and haplotype structures of the DPYD gene encoding dihydropyrimidine dehydrogenase in Japanese and their ethnic diferences. J. Hum. Genet. 52, 804-819 (2007).
35. Lu, Z., Zhang, R. & Diasio, R.B. Population characteristics of hepatic dihydropyrimidine dehydrogenase activity, a key metabolic enzyme in 5-fuorouracil chemotherapy. Clin. Pharmacol. Ther. 58, 512-522 (1995).
36. Lu, Z., Zhang, R., Carpenter, J.T. & Diasio, R.B. Decreased dihydropyrimidine dehydrogenase activity in a population of patients with breast cancer: implication for 5-fuorouracil-based chemotherapy. Clin. Cancer Res. 4, 325-329 (1998).
37. Morsman, J.M. et al. Evaluation of dihydropyrimidine dehydrogenase activity in South-west Asian, Kenyan and Ghanaian populations. Br. J. Clin. Pharmacol. 50, 269-272 (2000).
38. Swen, J.J. et al. Pharmacogenetics: from bench to byte-an update of guidelines. Clin. Pharmacol. Ther. 89, 662-673 (2011).
39. Harris, B.E., Song, R., Soong, S.J. & Diasio, R.B. Relationship between dihydropyrimidine dehydrogenase activity and plasma 5-fuorouracil levels with evidence for circadian variation of enzyme activity and plasma drug levels in cancer patients receiving 5-fuorouracil by protracted continuous infusion. Cancer Res. 50, 197-201 (1990).
40. Johnson, M.R., Hageboutros, A., Wang, K., High, L., Smith, J.B. & Diasio, R.B. Life-threatening toxicity in a dihydropyrimidine dehydrogenase-defcient patient after treatment with topical 5-fuorouracil. Clin. Cancer Res. 5, 2006-2011 (1999).
41. Ezzeldin, H., Okamoto, Y., Johnson, M.R. & Diasio, R.B. A high-throughput denaturing high-performance liquid chromatography method for the identifcation of variant alleles associated with dihydropyrimidine dehydrogenase defciency. Anal. Biochem. 306, 63-73 (2002).
42. Wigginton, J.E., Cutler, D.J. & Abecasis, G.R. A note on exact tests of Hardy-Weinberg equilibrium. Am. J. Hum. Genet. 76, 887-893 (2005).