Practical recommendations for pharmacogenomics-based prescription: 2010 ESF–UB Conference on Pharmacogenetics and Pharmacogenomics

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

• 1  Rosell R, Moran T, Queralt C et al.: Screening for epidermal growth factor receptor mutations in lung cancer. N. Engl. J. Med.361(10),958–967 (2009).
  Medline CASGoogle Scholar
• 2  Maemondo M, Inoue A, Kobayashi K et al.: Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N. Engl. J. Med.362(25),2380–2388 (2010).
  Medline CASGoogle Scholar
• 3  Mok TS, Wu Yl, Thongprasert S et al.: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med.361(10),947–957 (2009).
  Medline CASGoogle Scholar
• 4  Lynch TJ, Bell DW, Sordella R et al.: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med.350(21),2129–2139 (2004).▪▪ First demonstration that gefitinib response depends on EGFR tumoral activating mutations.
  Medline CASGoogle Scholar
• 5  Maheswaran S, Sequist LV, Nagrath S et al.: Detection of mutations in EGFR in circulating lung-cancer cells. N. Engl. J. Med.359(4),366–377 (2008).
  Medline CASGoogle Scholar
• 6  Tsao MS, Sakurada A, Cutz JC et al.: Erlotinib in lung cancer – molecular and clinical predictors of outcome. N. Engl. J. Med.353(2),133–144 (2005).
  Medline CASGoogle Scholar
• 7  Lievre A, Bachet JB, Le Corre D et al.: KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res.66(8),3992–3995 (2006).▪▪ First paper indicating a relationship between KRAS tumoral mutation and resistance to cetuximab.
  Medline CASGoogle Scholar
• 8  Lievre A, Laurent-Puig P: Genetics: predictive value of KRAS mutations in chemoresistant CRC. Nat. Rev. Clin. Oncol.6(6),306–307 (2009).
  Medline CASGoogle Scholar
• 9  Van Cutsem E, Kohne CH, Hitre E et al.: Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N. Engl. J. Med.360(14),1408–1417 (2009).
  Medline CASGoogle Scholar
• 10  Karapetis CS, Khambata-Ford S, Jonker DJ et al.: K-RAS mutations and benefit from cetuximab in advanced colorectal cancer. N. Engl. J. Med.359(17),1757–1765 (2008).▪▪ Clear demonstration that cetuximab response is only present in KRAS wild-type tumors.
  Medline CASGoogle Scholar
• 11  Amado RG, Wolf M, Peeters M et al.: Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J. Clin. Oncol.26(10),1626–1634 (2008).
  Medline CASGoogle Scholar
• 12  Schroth W, Antoniadou L, Fritz P et al.: Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. J. Clin. Oncol.25(33),5187–5193 (2007).
  Medline CASGoogle Scholar
• 13  Schroth W, Goetz MP, Hamann U et al.: Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA302(13),1429–1436 (2009).
  Medline CASGoogle Scholar
• 14  Jin Y, Desta Z, Stearns V et al.: CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J. Natl Cancer Inst.97(1),30–39 (2005).
  Medline CASGoogle Scholar
• 15  Bonanni B, Macis D, Maisonneuve P et al.: Polymorphism in the CYP2D6 tamoxifen-metabolizing gene influences clinical effect but not hot flashes: data from the italian tamoxifen trial. J. Clin. Oncol.24(22),3708–3709; author reply 3709 (2006).
  MedlineGoogle Scholar
• 16  Lim HS, Ju Lee H, Seok Lee K, Sook Lee E, Jang Ij, Ro J: Clinical implications of CYP2D6 genotypes predictive of tamoxifen pharmacokinetics in metastatic breast cancer. J. Clin. Oncol.25(25),3837–3845 (2007).
  Medline CASGoogle Scholar
• 17  Dehal SS, Kupfer D: CYP2D6 catalyzes tamoxifen 4-hydroxylation in human liver. Cancer Res.57(16),3402–3406 (1997).
  Medline CASGoogle Scholar
• 18  Rebsamen MC, Desmeules J, Daali Y et al.: The amplichip CYP450 test: cytochrome P450 2D6 genotype assessment and phenotype prediction. Pharmacogenomics J.9(1),34–41 (2009).
  Medline CASGoogle Scholar
• 19  Van Kuilenburg AB, Meijer J, Mul AN et al.: Analysis of severely affected patients with dihydropyrimidine dehydrogenase deficiency reveals large intragenic rearrangements of DPYD and a de novo interstitial deletion del(1)(p13.3p21.3). Hum. Genet.125(5–6),581–590 (2009).
  Medline CASGoogle Scholar
• 20  Amstutz U, Farese S, Aebi S, Largiader CR: Dihydropyrimidine dehydrogenase gene variation and severe 5-fluorouracil toxicity: a haplotype assessment. Pharmacogenomics10(6),931–944 (2009).
  CASGoogle Scholar
• 21  Capitain O, Boisdron-Celle M, Poirier AL, Abadie-Lacourtoisie S, Morel A, Gamelin E: The influence of fluorouracil outcome parameters on tolerance and efficacy in patients with advanced colorectal cancer. Pharmacogenomics J.8(4),256–267 (2008).
  Medline CASGoogle Scholar
• 22  Morel A, Boisdron-Celle M, Fey L et al.: Clinical relevance of different dihydropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Mol. Cancer Ther.5(11),2895–2904 (2006).
  Medline CASGoogle Scholar
• 23  Schwab M, Zanger UM, Marx C et al.: Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: a prospective clinical trial by the german 5-FU toxicity study group. J. Clin. Oncol.26(13),2131–2138 (2008).▪▪ Very good paper with one of the largest patients cohort investigating different genetic risk factors of 5-fluorouracil related adverse drug reactions.
  Medline CASGoogle Scholar
• 24  Magne N, Etienne-Grimaldi MC, Cals L et al.: Dihydropyrimidine dehydrogenase activity and the IVS14+1G>A mutation in patients developing 5FU-related toxicity. Br. J. Clin. Pharmacol.64(2),237–240 (2007).
  Medline CASGoogle Scholar
• 25  Mcleod HL, Sargent DJ, Marsh S et al.: Pharmacogenetic predictors of adverse events and response to chemotherapy in metastatic colorectal cancer: results from North American Gastrointestinal Intergroup Trial n9741. J. Clin. Oncol.28(20),3227–3233 (2010).
  Medline CASGoogle Scholar
• 26  Boisdron-Celle M, Remaud G, Traore S et al.: 5-fluorouracil-related severe toxicity: a comparison of different methods for the pretherapeutic detection of dihydropyrimidine dehydrogenase deficiency. Cancer Lett.249(2),271–282 (2007).
  Medline CASGoogle Scholar
• 27  Teml A, Schaeffeler E, Schwab M: Pretreatment determination of TPMT – state of the art in clinical practice. Eur. J. Clin. Pharmacol.65(3),219–221 (2009).
  Medline CASGoogle Scholar
• 28  Schwab M, Schaffeler E, Marx C et al.: Azathioprine therapy and adverse drug reactions in patients with inflammatory bowel disease: impact of thiopurine S-methyltransferase polymorphism. Pharmacogenetics12(6),429–436 (2002).
  Medline CASGoogle Scholar
• 29  Kaskas BA, Louis E, Hindorf U et al.: Safe treatment of thiopurine S-methyltransferase deficient Crohn’s disease patients with azathioprine. Gut52(1),140–142 (2003).
  Medline CASGoogle Scholar
• 30  Wadelius M, Chen L, Lindh J et al.: The largest prospective warfarin-treated cohort supports genetic forecasting. Blood113,784–792 (2009).
  Medline CASGoogle Scholar
• 31  International Warfarin Pharmacogenetics Consortium, Klein TE, Altman RB et al.: Estimation of the warfarin dose with clinical and pharmacogenetic data. N. Engl. J. Med.360(8),753–764 (2009).
  Medline CASGoogle Scholar
• 32  Rieder MJ, Reiner AP, Gage BF et al.: Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N. Engl. J. Med.352(22),2285–2293 (2005).▪▪ Clear association of VKORC1 variants and warfarin dose requirements and the functionality of the variants.
  Medline CASGoogle Scholar
• 33  Schwartz U, Ritchie M, Bradford Y et al.: Genetic determinants of response to warfarin during initial anticoagulation. N. Engl. J. Med.358,999–1008 (2008).
  MedlineGoogle Scholar
• 34  Aithal GP, Day CP, Kesteven PJ, Daly AK: Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet353(9154),717–719 (1999).▪ First demonstration that CYP2C9 polymorphisms are risk factors of bleeding in patients treated with warfarin.
  Medline CASGoogle Scholar
• 35  Van Schie RM, Wadelius MI, Kamali F et al.: Genotype-guided dosing of coumarin derivatives: The European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) trial design. Pharmacogenomics10(10),1687–1695 (2009).
  CASGoogle Scholar
• 36  Simon T, Verstuyft C, Mary-Krause M et al.: Genetic determinants of response to clopidogrel and cardiovascular events. N. Engl. J. Med.360(4),363–375 (2009).
  Medline CASGoogle Scholar
• 37  Mega J, Close S, Wiviott S et al.: Cytochrome P-450 polymorphisms and response to clopidogrel. N. Engl. J. Med.360(4),354–362 (2009).
  Medline CASGoogle Scholar
• 38  Sibbing D, Stegherr J, Latz W et al.: CYP450 2C19 loss-of-function polymorphism and stent thrombosis following percutaneous coronary intervention. Eur. Heart J.30(8),916–922 (2009).
  Medline CASGoogle Scholar
• 39  Mallal S, Phillips E, Carosi G et al.: HlA-B*5701 screening for hypersensitivity to abacavir. N. Engl. J. Med.358,568–579 (2008).▪ Largest pharmacogenetic randomized clinical trial ever performed demontrating the usefulness of HLA-B*5701 screening.
  MedlineGoogle Scholar
• 40  Daly A, Donaldson P, Bhatnagar P et al.: HlA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat. Genet.41,816–819 (2009).▪ Genome-wide association study that identified HLA-B*5701 as a risk factor of fluclixacillin mediated drug-induced liver injury.
  Medline CASGoogle Scholar
• 41  Niemi M: Transporter pharmacogenetics and statin toxicity. Clin. Pharmacol. Ther.87(1),130–133 (2010).▪ Excellent review on the topic.
  Medline CASGoogle Scholar
• 42  Search Collaborative Group, Link E, Parish S et al.: SLCO1B1 variants and statin-induced myopathy – a genomewide study. N. Engl. J. Med.359(8),789–799 (2008).▪▪ Genome-wide association study that clearly demonstrated that SLC01B1 is related to statin myopathy.
  Medline CASGoogle Scholar
• 43  Niemi M, Pasanen MK, Neuvonen PJ: SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatin. Clin. Pharmacol. Ther.80(4),356–366 (2006).
  Medline CASGoogle Scholar
• 44  Pasanen MK, Neuvonen M, Neuvonen PJ, Niemi M: SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. Pharmacogenet. Genomics16(12),873–879 (2006).
  Medline CASGoogle Scholar
• 45  Pasanen MK, Fredrikson H, Neuvonen PJ, Niemi M: Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. Clin. Pharmacol. Ther.82(6),726–733 (2007).
  Medline CASGoogle Scholar
• 46  Thervet E, Loriot MA, Barbier S et al.: Optimization of initial tacrolimus dose using pharmacogenetic testing. Clin. Pharmacol. Ther.87(6),721–726 (2010).▪ Only randomized clinical trial demontrating the usefulness of CYP3A5 screening before tacrolimus dosing in renal transplantation.
  Medline CASGoogle Scholar
• 47  Zhao W, Elie V, Roussey G et al.: Population pharmacokinetics and pharmacogenetics of tacrolimus in de novo pediatric kidney transplant recipients. Clin. Pharmacol. Ther.86(6),609–618 (2009).
  Medline CASGoogle Scholar
• 101  European Science Foundation–University of Barcelona Conference in Biomedicine on Pharmacogenetics and Pharmacogenomics in Sant Feliu de Guixols, Spain, 6–10 June 2010: Practical Applications in Routine Medical Practice www.esf.org/index.php?id=6450
  Google Scholar
• 102  Home Page of the Human CYP450 Allele Nomenclature Committee www.cypalleles.ki.se/
  Google Scholar
• 103  Warfarin dosing www.warfarindosing.org
  Google Scholar
• 104  Coumadin (warfarin) US FDA label www.accessdata.fda.gov/drugsatfda_docs/label/2010/009218s108lbl.pdf
  Google Scholar
• 105  Table of valid genomic biomarkers in the context of approved drug labels www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm
  Google Scholar
• 106  Plavix (clopidogrel) FDA label www.accessdata.fda.gov/drugsatfda_docs/label/2010/020839s042lbl.pdf
  Google Scholar