Advertisement

Pharmacogenomics and Personalized Medicine for Cancer

  • Dipali Dhawan
  • Harish Padh
Chapter

Abstract

Cancer pharmacogenomics is a growing field with new avenues being explored and applied to the routine practice when validated. There is an enormous amount of data present in literature regarding association studies that have been undertaken around the world with different cancer patient populations. However, some association studies have contradictory results or no association with the studied molecular markers. Many of the genetic tests developed have been translated to the clinic and are being recommended by the US Food and Drug Administration (FDA) as well for a better outcome of the patients when prescribed these medicines. In this chapter we provide an overview of the well-studied molecular markers for efficacy and toxicity of cancer therapeutics and also discuss the evolution of the field of companion diagnostics in cancer.

Keywords

Epidermal Growth Factor Receptor National Comprehensive Cancer Network Epidermal Growth Factor Receptor Mutation National Comprehensive Cancer Network Epidermal Growth Factor Receptor Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Almal SH, Padh H (2012) Implications of gene copy-number variation in health and diseases. J Hum Genet 57(1):6–13PubMedGoogle Scholar
  2. Ando Y, Saka H, Ando M et al (2000) Polymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis. Cancer Res 60:6921–6926PubMedGoogle Scholar
  3. Araujo A, Ribeiro R, Azevedo I et al (2007) Genetic polymorphisms of the epidermal growth factor and related receptor in non-small cell lung cancer – a review of the literature. Oncologist 12:201–210PubMedGoogle Scholar
  4. Asahina H, Yamazaki K, Kinoshita I et al (2006) A phase II trial of gefitinib as first-line therapy for advanced non-small cell lung cancer with epidermal growth factor receptor mutations. Br J Cancer 95:998–1004PubMedCentralPubMedGoogle Scholar
  5. Bäckström G, Taipalensuu J, Melhus H et al (2003) Genetic variation in the ATP-binding cassette transporter gene ABCG2 (BCRP) in a Swedish population. Eur J Pharm Sci 18:359–364PubMedGoogle Scholar
  6. Bean J, Brennan C, Shih JY et al (2007) MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA 104(52):20932–20937PubMedCentralPubMedGoogle Scholar
  7. Beutler E, Gelbart T, Demina A (1998) Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci USA 95:8170–8174PubMedCentralPubMedGoogle Scholar
  8. Bhowmick DA, Zhuang Z, Wait SD, Weil RJ (2004) A functional polymorphism in the EGF gene is found with increased frequency in glioblastoma multiforme patients and is associated with more aggressive disease. Cancer Res 64:1220–1223PubMedGoogle Scholar
  9. Borges S, Desta Z, Li L, Skaar TC, Ward BA, Nguyen A, Jin Y, Storniolo AM, Nikoloff DM, Wu L, Hillman G, Hayes DF, Stearns V, Flockhart DA (2006) Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin Pharmacol Ther 80:61–74PubMedGoogle Scholar
  10. Bosch TM, Kjellberg LM, Bouwers A et al (2005) Detection of single nucleotide polymorphisms in the ABCG2 gene in a Dutch population. Am J Pharmacogenomics 5:123–131PubMedGoogle Scholar
  11. Bosma PJ, Chowdhury JR, Bakker C et al (1995) The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med 333:1171–1175PubMedGoogle Scholar
  12. Buerger H, Gebhardt F, Schmidt H et al (2000) Length and loss of heterozygosity of an intron 1 polymorphic sequence of EGFR is related to cytogenetic alterations and epithelial growth factor receptor expression. Cancer Res 60:854–857PubMedGoogle Scholar
  13. Cascorbi I, Gerloff T, Johne A et al (2001) Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin Pharmacol Ther 69:169–174PubMedGoogle Scholar
  14. Choudhuri S, Klaassen CD (2006) Structure, function, expression, genomic organization, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux transporters. Int J Toxicol 25:231–259PubMedGoogle Scholar
  15. Ciotti M, Basu N, Brangi M et al (1999) Glucuronidation of 7-ethyl-10-hydroxycamptothecin(SN-38) by the human UDP-glucuronosyltransferases encoded at the UGT1 locus. Biochem Biophys Res Commun 260:199–202PubMedGoogle Scholar
  16. Copur S, Aiba K, Drake JC, Allegra CJ, Chu E (1995) Thymidylate synthase gene amplification in human colon cancer cell lines resistant to 5-fluorouracil. Biochem Pharmacol 49:1419–1426PubMedGoogle Scholar
  17. Côté JF, Kirzin S, Kramar A et al (2007) UGT1A1 polymorphism can predict hematologic toxicity in patients treated with irinotecan. Clin Cancer Res 13:3269–3275PubMedGoogle Scholar
  18. Cusatis G, Sparreboom A (2008) Pharmacogenomic importance of ABCG2. Pharmacogenomics 9:1005–1009PubMedGoogle Scholar
  19. Cusatis G, Gregorc V, Li J et al (2006) Pharmacogenetics of ABCG2 and adverse reactions to gefitinib. J Natl Cancer Inst 98:1739–1742PubMedGoogle Scholar
  20. Dassa E, Bouige P (2001) The ABC of ABCs: a phylogenetic and functional classification of ABC systems in living organisms. Res Microbiol 152:211–229PubMedGoogle Scholar
  21. Davison JE, McMullin MF, Catherwood MA (2006) Genotyping of thiopurine methyltransferase in patients with acute leukemia using LightCycler PCR. Leuk Lymphoma 47:1624–1628PubMedGoogle Scholar
  22. de Jong FA, Marsh S, Mathijssen RH et al (2004) ABCG2 pharmacogenetics: ethnic differences in allele frequency and assessment of influence on irinotecan disposition. Clin Cancer Res 10:5889–5894PubMedGoogle Scholar
  23. de Jong FA, Kehrer DF, Mathijssen RH et al (2006) Prophylaxis of irinotecan-induced diarrhea with neomycin and potential role for UGT1A1*28 genotype screening: a double-blind, randomized, placebo-controlled study. Oncologist 11:944–954PubMedGoogle Scholar
  24. Desai AA, Innocenti F, Ratain MJ (2003) Pharmacogenomics: road to anticancer therapeutics nirvana? Oncogene 22:6621–6628PubMedGoogle Scholar
  25. Dhawan D, Padh H (2009) Pharmacogenetics: technologies to detect copy number variations. Curr Opin Mol Ther 11(6):670–680PubMedGoogle Scholar
  26. Dhawan D, Padh H (2011) Omics approaches in cancer biomarker and targeted anticancer drug discovery. In: Barh D, Blum K, Madigan MA (eds) OMICS: biomedical perspectives and applications. CRC Press, Taylor & Francis LLC, Boca RatonGoogle Scholar
  27. Dhawan D, Padh H (2013) Genetic variability and chemotoxicity of 5-Fluorouracil and cisplatin in head and neck cancer patients: a preliminary study. Indian J Med Res 137:125–129PubMedCentralPubMedGoogle Scholar
  28. DNAdirect. Your genes. Your health. Your choices. http://www.dnadirect.com/. Accessed 3 Sept 2012
  29. Engelman JA, Zejnullahu K, Mitsudomi T et al (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316:1039–1043PubMedGoogle Scholar
  30. FDA-Medical devices (Guidance documents) (2011) Draft guidance for industry and food and drug administration staff: in vitro companion diagnostic devices 14 July 2011 (Online)Google Scholar
  31. Feng X, Pearson D, Listiawan M et al (2012) Pharmacogenomic biomarkers for toxicities associated with chemotherapy. US Pharm 37(Oncology suppl):2–7Google Scholar
  32. Ferraldeschi R, Minchell LJ, Roberts SA et al (2009) UGT1A1*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan. Pharmacogenomics 10:733–739PubMedGoogle Scholar
  33. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90:1371–1388PubMedGoogle Scholar
  34. Garcia-Carbonero R, Supko JG (2002) Current perspectives on the clinical experience, pharmacology, and continued development of the camptothecins. Clin Cancer Res 8:641–661PubMedGoogle Scholar
  35. Gardiner SJ, Begg EJ, Barclay ML et al (2000) Genetic polymorphism and outcomes with azathioprine and 6-mercaptopurine. Adverse Drug React Toxicol Rev 19:293–312PubMedGoogle Scholar
  36. Gardner ER, Burger H, van Schaik RH et al (2006) Association of enzyme and transporter genotypes with the pharmacokinetics of imatinib. Clin Pharmacol Ther 80:192–201PubMedGoogle Scholar
  37. Gebhart F, Zanker KS, Brandt B et al (1999) Modulation of epidermal growth factor receptor gene transcription by a polymorphic dinucleotide repeat in intron 1. J Biol Chem 274:13176–13180Google Scholar
  38. Glimelius B, Garmo H, Berglund A et al (2011) Prediction of irinotecan and 5-fluorouracil toxicity and response in patients with advanced colorectal cancer. Pharmacogenomics J 11:61–71PubMedCentralPubMedGoogle Scholar
  39. Goekkurt E, Hoehn S, Wolschke C et al (2006) Polymorphisms of glutathione S-transferases (GST) and thymidylate synthase (TS) – novel predictors for response and survival in gastric cancer patients. Br J Cancer 94:281–286PubMedCentralPubMedGoogle Scholar
  40. Goekkurt E, Al-Batran SE, Mogck U et al (2009) Pharmacogenetic analyses of hematotoxicity in advanced gastric cancer patients receiving biweekly fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a translational study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Ann Oncol 20(3):481–485PubMedGoogle Scholar
  41. Goetz MP, Rae JM, Suman VJ, Safgren SL, Ames MM, Visscher DW, Reynolds C, Couch FJ, Lingle WL, Flockhart DA, Desta Z, Perez EA, Ingle JN (2005) Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol 23:9312–9318PubMedGoogle Scholar
  42. Grem JL (2000) 5-Fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development. Invest New Drugs 18:299–313PubMedGoogle Scholar
  43. Han JY, Lim HS, Shin ES et al (2006) Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin. J Clin Oncol 24:2237–2244PubMedGoogle Scholar
  44. Han JY, Lim HS, Yoo YK et al (2007a) Associations of ABCB1, ABCB2, and ABCG2 polymorphisms with irinotecan-pharmacokinetics and clinical outcome in patients with advanced non-small cell lung cancer. Cancer 110:138–147PubMedGoogle Scholar
  45. Han SW, Jeon YK, Lee KH et al (2007b) Intron 1 CA dinucleotide repeat polymorphism and mutations of epidermal growth factor receptor and gefitinib responsiveness in non-small cell lung cancer. Pharmacogenet Genomics 17:313–319PubMedGoogle Scholar
  46. Hasegawa Y, Sarashina T, Ando M et al (2004) Rapid detection of UGT1A1 gene polymorphisms by newly developed invader assay. Clin Chem 50:1479–1480PubMedGoogle Scholar
  47. Hitzl M, Drescher S, van der Kuip H et al (2001) The C3435T mutation in the human MDR1 gene is associated with altered efflux of the P-glycoprotein substrate rhodamine 123 from CD56+ natural killer cells. Pharmacogenetics 11:293–298PubMedGoogle Scholar
  48. Hoffmeyer S, Burk O, von Richter O et al (2000) Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA 97:3473–3478PubMedCentralPubMedGoogle Scholar
  49. Hoggatt J (2011) Personalized medicine-trends in molecular diagnostics. Mol Diagn Ther 15:53–55PubMedGoogle Scholar
  50. Horie N, Aiba H, Oguro K et al (1995) 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 20:191–197PubMedGoogle Scholar
  51. Hoskins JM, Goldberg RM, Qu P et al (2007) UGT1A1*28 genotype and irinotecan-induced neutropenia: dose matters. J Natl Cancer Inst 99:1290–1295PubMedGoogle Scholar
  52. Iacopetta B, Grieu F, Joseph D et al (2001) A polymorphism in the enhancer region of the thymidylate synthase promoter influences the survival of colorectal cancer patients treated with 5-fluorouracil. Br J Cancer 85:827–830PubMedCentralPubMedGoogle Scholar
  53. Ichihara S, Toyooka S, Fujiwara Y et al (2007) The impact of epidermal growth factor receptor gene status on gefitinib-treated Japanese patients with non-small cell lung cancer. Int J Cancer 120:1239–1247PubMedGoogle Scholar
  54. Ichikawa W, Takahashi T, Suto K et al (2006) Orotate phosphoribosyltransferase gene polymorphism predicts toxicity in patients treated with bolus 5-fluorouracil regimen. Clin Cancer Res 12(13):3928–3934PubMedGoogle Scholar
  55. Illmer T, Schuler US, Thiede C et al (2002) MDR1 gene polymorphisms affect therapy outcome in acute myeloid leukemia patients. Cancer Res 62:4955–4962PubMedGoogle Scholar
  56. Imai Y, Nakane M, Kage K et al (2002) C421A polymorphism in the human breast cancer resistance protein gene is associated with low expression of Q141K protein and low-level drug resistance. Mol Cancer Ther 1:611–616PubMedGoogle Scholar
  57. Ingelman-Sundberg M, Sim SC, Gomez A, Rodriguez-Antona C (2007) Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic, and clinical aspects. Pharmacol Ther 116:496–526PubMedGoogle Scholar
  58. Innocenti F, Undevia SD, Iyer L et al (2004) Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 22:1382–1388PubMedGoogle Scholar
  59. Inoue A, Suzuki T, Fukuhara T et al (2006) Prospective phase II study for chemotherapy naive patients with advanced non-small cell lung cancer with epidermal growth factor receptor gene mutations. J Clin Oncol 24(21):3340–3346PubMedGoogle Scholar
  60. Isla D, Sarries C, Rosell R et al (2004) Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer. Ann Oncol 15:1194–1203PubMedGoogle Scholar
  61. Iyer L, Hall D, Das S et al (1999) Phenotype-genotype correlation of in vitro SN-38 (active metabolite of irinotecan) and bilirubin glucuronidation in human liver tissue with UGT1A1 promoter polymorphism. Clin Pharmacol Ther 65:576–582PubMedGoogle Scholar
  62. Iyer L, Das S, Janisch L et al (2002) UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogenomics J 2:43–47PubMedGoogle Scholar
  63. Jada SR, Lim R, Wong CI et al (2007) Role of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C_A polymorphisms in irinotecan-induced neutropenia in Asian cancer patients. Cancer Sci 98:1461–1467PubMedGoogle Scholar
  64. Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA (2005) CYP2D6 genotype. Antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 97:30–39PubMedGoogle Scholar
  65. Kaneda S, Takeishi K, Ayusawa D et al (1987) Role in translation of a triple tandemly repeated sequence in the 5′-untranslated region of human thymidylate synthase mRNA. Nucleic Acids Res 15:1259–1270PubMedCentralPubMedGoogle Scholar
  66. Kawakami K, Watanabe G (2003) Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene. Cancer Res 63:6004–6007PubMedGoogle Scholar
  67. Kawakami K, Omura K, Kanehira E et al (1999) Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers. Anticancer Res 19:3249–3252PubMedGoogle Scholar
  68. Khosrow-Shahi F, Doyle K, Naigamwalla D (2009) Detecting the future: a perspective on the rising value of diagnostics in oncology therapeutics. Oncol Bus Rev March:8–17Google Scholar
  69. Kim RB, Leake BF, Choo EF et al (2001) Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin Pharmacol Ther 70:189–199PubMedGoogle Scholar
  70. Kirchheiner J, Fuhr U, Brockmoller J (2005) Pharmacogenetics-based therapeutic recommendations – ready for clinical practice? Nat Rev Drug Discov 4:639–647PubMedGoogle Scholar
  71. Kobayashi D, Ieiri I, Hirota T et al (2005) Functional assessment of ABCG2 (BCRP) gene polymorphisms to protein expression in human placenta. Drug Metab Dispos 33:94–101PubMedGoogle Scholar
  72. Kroetz DL, Pauli-Magnus C, Hodges LM et al (2003) Sequence diversity and haplotype structure in the human ABCB1 (MDR1, multidrug resistance transporter) gene. Pharmacogenetics 13:481–494PubMedGoogle Scholar
  73. Krynetski EY, Evans WE (1999) Pharmacogenetics as a molecular basis for individualized drug therapy: the thiopurine S-methyltransferase paradigm. Pharm Res 16:342–349PubMedGoogle Scholar
  74. Krynetski EY, Tai HL, Yates CR et al (1996) Genetic polymorphism of thiopurine S-methyltransferase: clinical importance and molecular mechanisms. Pharmacogenetics 6:279–290PubMedGoogle Scholar
  75. Kweekel DM, Gelderblom H, Van der Straaten T et al (2008) UGT1A1*28 genotype and irinotecan dosage in patients with metastatic colorectal cancer: a Dutch Colorectal Cancer Group study. Br J Cancer 99:275–282PubMedCentralPubMedGoogle Scholar
  76. Largillier R, Etienne-Grimaldi MC, Formento JL et al (2006) Pharmacogenetics of capecitabine in advanced breast cancer patients. Clin Cancer Res 12:5496–5502PubMedGoogle Scholar
  77. Lecomte T, Ferraz J, Zinzindohoué F et al (2004) Thymidylate synthase gene polymorphism predicts toxicity in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy. Clin Cancer Res 10:5880–5888PubMedGoogle Scholar
  78. Leichman CG, Lenz HJ, Leichman L et al (1997) Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluorouracil and weekly leucovorin. J Clin Oncol 15:3223–3229PubMedGoogle Scholar
  79. Lennard L (1992) The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol 43:329–339PubMedGoogle Scholar
  80. Li J, Cusatis G, Brahmer J et al (2007) Association of variant ABCG2 and the pharmacokinetics of epidermal growth factor receptor tyrosine kinase inhibitors in cancer patients. Cancer Biol Ther 6:432–438PubMedGoogle Scholar
  81. Litos IK, Emmanouilidou E, Glynou KM et al (2007) Rapid genotyping of CYP2D6, CYP2C19 and TPMT polymorphisms by primer extension reaction in a dipstick format. Anal Bioanal Chem 389:1849–1857PubMedGoogle Scholar
  82. Liu W, Innocenti F, Chen P et al (2003) Interethnic difference in the allelic distribution of human epidermal growth factor receptor intron 1 polymorphism. Clin Cancer Res 9:1009–1012PubMedGoogle Scholar
  83. Liu W, Innocenti F, Wu MH et al (2005) A functional common polymorphism in a Sp1 recognition site of the epidermal growth factor receptor. Cancer Res 65:46–53PubMedGoogle Scholar
  84. Luo HR, Lü XM, Yao YG et al (2002) Length polymorphism of thymidylate synthase regulatory region in Chinese populations and evolution of the novel alleles. Biochem Genet 40:41–51PubMedGoogle Scholar
  85. Lynch TJ, Bell DW, Sordella R et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small cell lung cancer to gefitinib. N Engl J Med 350:2129–2139PubMedGoogle Scholar
  86. Maitland M, Vasisht K, Ratain M (2006) TPMT, UGT1A1 and DPYD: genotyping to ensure safer cancer therapy? Trends Pharmacol Sci 27(8):432–437PubMedGoogle Scholar
  87. Mandola MV, Stoehlmacher J, Muller-Weeks S et al (2003) 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 63:2898–2904PubMedGoogle Scholar
  88. Mandola MV, Stoehlmacher J, Zhang W et al (2004) A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels. Pharmacogenetics 14:319–327PubMedGoogle Scholar
  89. Marcuello E, Altés A, del Rio E et al (2004a) Single nucleotide polymorphism in the 5′ tandem repeat sequences of thymidylate synthase gene predicts for response to fluorouracil-based chemotherapy in advanced colorectal cancer patients. Int J Cancer 112:733–737PubMedGoogle Scholar
  90. Marcuello E, Altés A, Menoyo A et al (2004b) UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer. Br J Cancer 91:678–682PubMedCentralPubMedGoogle Scholar
  91. Marsh S, Ameyaw MM, Githang’a J et al (2000) Novel thymidylate synthase enhancer region alleles in African populations. Hum Mutat 16:528PubMedGoogle Scholar
  92. Martinez-Balibrea E, Abad A, Aranda E et al (2008) Pharmacogenetic approach for capecitabine or 5-fluorouracil selection to be combined with oxaliplatin as first-line chemotherapy in advanced colorectal cancer. Eur J Cancer 44:1229–1237PubMedGoogle Scholar
  93. McLeod HL, Lin JS, Scott EP et al (1994) Thiopurine methyltransferase activity in American white subjects and black subjects. Clin Pharmacol Ther 55:15–20PubMedGoogle Scholar
  94. McLeod HL, Krynetski EY, Relling MV et al (2000) Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia. Leukemia 14:567–572PubMedGoogle Scholar
  95. McLeod HL, Sargent DJ, Marsh S et al (2010) Pharmacogenetic predictors of adverse events and response to chemotherapy in metastatic colorectal cancer: results from North American Gastrointestinal Intergroup Trial N9741. J Clin Oncol 28:3227–3233PubMedCentralPubMedGoogle Scholar
  96. Monaghan G, Ryan M, Seddon R et al (1996) Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert’s syndrome. Lancet 347:578–581PubMedGoogle Scholar
  97. Morel A, Boisdron-Celle M, Fey L et al (2006) Clinical relevance of different dihydropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Mol Cancer Ther 5:2895–2904PubMedGoogle Scholar
  98. Morganti M, Ciantelli M, Giglioni B et al (2005) Relationships between promoter polymorphisms in the thymidylate synthase gene and mRNA levels in colorectal cancers. Eur J Cancer 41:2176–2183PubMedGoogle Scholar
  99. Moriai T, Kobrin MS, Hope C, Speck L, Korc M (1994) A variant epidermal growth factor receptor exhibits altered type-α transforming growth factor binding and transmembrane signaling. Proc Natl Acad Sci USA 91:10217–10221PubMedCentralPubMedGoogle Scholar
  100. Nagar S, Remmel RP (2006) Uridine diphosphoglucuronosyltransferase pharmacogenetics and cancer. Oncogene 25:1659–1672PubMedGoogle Scholar
  101. Nakamura T, Sakaeda T, Horinouchi M et al (2002) Effect of the mutation (C3435T) at exon 26 of the MDR1 gene on expression level of MDR1 messenger ribonucleic acid in duodenal enterocytes of healthy Japanese subjects. Clin Pharmacol Ther 71:297–303PubMedGoogle Scholar
  102. Nasedkina TV, Fedorova OE, Glotov AS et al (2006) Rapid genotyping of common deficient thiopurine S-methyltransferase alleles using the DNA microchip technique. Eur J Hum Genet 14:991–998PubMedGoogle Scholar
  103. Naylor S, Cole T (2010) Companion diagnostics in the pharmaceutical industry part II: business models. Drug Discov World 11(3):61–68Google Scholar
  104. Nie Q, Wang Z, Zhang GC et al (2007) The epidermal growth factor receptor intron 1 (CA)n microsatellite polymorphism is a potential predictor of treatment outcome in patients with advanced lung cancer treated with gefitinib. Eur J Pharmacol 570:175–181PubMedGoogle Scholar
  105. Nishimura R, Nagao K, Miyayama H et al (1999) Thymidylate synthase levels as a therapeutic and prognostic predictor in breast cancer. Anticancer Res 19:5621–5626PubMedGoogle Scholar
  106. Nomura M, Shigematsu H, Lin L et al (2007) Polymorphisms, mutations, and amplification of the EGFR gene in non-small cell lung cancers. PLoS Med 4(4):E125PubMedCentralPubMedGoogle Scholar
  107. Otterness D, Szumlanski C, Lennard L et al (1997) Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms. Clin Pharmacol Ther 62:60–73PubMedGoogle Scholar
  108. Paez JG, Janne PA, Lee JC et al (2005) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500Google Scholar
  109. Park DJ, Stoehlmacher J, Zhang W et al (2002) Thymidylate synthase gene polymorphism predicts response to capecitabine in advanced colorectal cancer. Int J Colorectal Dis 17:46–49PubMedGoogle Scholar
  110. Petain A, Kattygnarath D, Azard J et al (2008) Population pharmacokinetics and pharmacogenetics of imatinib in children and adults. Clin Cancer Res 14:7102–7109PubMedGoogle Scholar
  111. Pillot GA, Read WL, Hennenfent KL et al (2006) A phase II study of irinotecan and carboplatin in advanced non-small cell lung cancer with pharmacogenomic analysis: final report. J Thorac Oncol 1:972–978PubMedGoogle Scholar
  112. Pullarkat S, Stoehlmacher J, Ghaderi V et al (2001) Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics J 1:65–70PubMedGoogle Scholar
  113. Raijmakers MT, Jansen PL, Steegers EA et al (2000) Association of human liver bilirubin UDP-glucuronyltransferase activity with a polymorphism in the promoter region of the UGT1A1 gene. J Hepatol 33:348–351PubMedGoogle Scholar
  114. Ratain MJ (2006) From bedside to bench to bedside to clinical practice: an odyssey with irinotecan. Clin Cancer Res 12:1658–1660PubMedGoogle Scholar
  115. Rouits E, Boisdron-Celle M, Dumont A et al (2004) Relevance of different UGT1A1 polymorphisms in irinotecan-induced toxicity: a molecular and clinical study of 75 patients. Clin Cancer Res 10:5151–5159PubMedGoogle Scholar
  116. Rustum YM, Harstrick A, Cao S et al (1997) Thymidylate synthase inhibitors in cancer therapy: direct and indirect inhibitors. J Clin Oncol 15:389–400PubMedGoogle Scholar
  117. Ruzzo A, Graziano F, Kawakami K et al (2006) Pharmacogenetic profiling and clinical outcome of patients with advanced gastric cancer treated with palliative chemotherapy. J Clin Oncol 24:1883–1891PubMedGoogle Scholar
  118. Sahasranaman S, Howard D, Roy S (2008) Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol 64:753–767PubMedGoogle Scholar
  119. Sai K, Kaniwa N, Itoda M et al (2003) Haplotype analysis of ABCB1/MDR1 blocks in a Japanese population reveals genotype-dependent renal clearance of irinotecan. Pharmacogenetics 13:741–757PubMedGoogle Scholar
  120. Sai K, Saeki M, Saito Y et al (2004) UGT1A1 haplotypes associated with reduced glucuronidation and increased serum bilirubin in irinotecan-administered Japanese patients with cancer. Clin Pharmacol Ther 75:501–515PubMedGoogle Scholar
  121. Schaeffeler E, Zanger UM, Eichelbaum M et al (2008) Highly multiplexed genotyping of thiopurine S-methyltransferase variants using MALD-TOF mass spectrometry: reliable genotyping in different ethnic groups. Clin Chem 54:1637–1647PubMedGoogle Scholar
  122. Schinkel AH, Jonker JW (2003) Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev 55:3–29PubMedGoogle Scholar
  123. Schwab M, Eichelbaum M, Fromm MF (2003) Genetic polymorphisms of the human MDR1 drug transporter. Annu Rev Pharmacol Toxicol 43:285–307PubMedGoogle Scholar
  124. Sequist LV, Bell DW, Lynch TJ, Haber DA (2007) Molecular predictors of response to epidermal growth factor receptor antagonists in non-small cell lung cancer. J Clin Oncol 25(5):587–595PubMedGoogle Scholar
  125. Sequist LV, Martins RG, Spigel D et al (2008) First-line gefitinib in patients with advanced non-small cell lung cancer harboring somatic EGFR mutations. J Clin Oncol 26(15):2442–2449PubMedGoogle Scholar
  126. Sharma R, Hoskins JM, Rivory LP, Zucknick M, London R, Liddle C, Clarke SJ (2008) Thymidylate synthase and methyltetrahydrofolate reductase gene polymorphisms and toxicity to capecitabine in advanced colorectal cancer patients. Clin Cancer Res 14:817–825PubMedGoogle Scholar
  127. Siegsmund M, Brinkmann U, Schaffeler E et al (2002) Association of the P-glycoprotein transporter MDR1 (C3435T) polymorphism with the susceptibility to renal epithelial tumors. J Am Soc Nephrol 13:1847–1854PubMedGoogle Scholar
  128. Spire-Vayron de la Moureyre C, Debuysère H, Sabbagh N et al (1998) Detection of known and new mutations in the thiopurine S-methyltransferase gene by single-strand conformation polymorphism analysis. Hum Mutat 12:177–185PubMedGoogle Scholar
  129. Stewart CF, Panetta JC, O’Shaughnessy MA et al (2007) UGT1A1 promoter genotype correlates with SN-38 pharmacokinetics, but not severe toxicity in patients receiving low-dose irinotecan. J Clin Oncol 25:2594–2600PubMedGoogle Scholar
  130. Stoehlmacher J, Park DJ, Zhang W et al (2004) A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer 91:344–354PubMedCentralPubMedGoogle Scholar
  131. Swann PF, Waters TR, Moulton DC et al (1996) Role of postreplicative DNA mismatch repair in the cytotoxic action of thioguanine. Science 273:1109–1111PubMedGoogle Scholar
  132. Tai HL, Krynetski EY, Yates CR et al (1996) Thiopurine S-methyltransferase deficiency: two nucleotide transitions define the most prevalent mutant allele associated with loss of catalytic activity in Caucasians. Am J Hum Genet 58:694–702PubMedCentralPubMedGoogle Scholar
  133. Tai HL, Krynetski EY, Schuetz EG et al (1997) Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) encoded by mutant alleles in humans (TPMT*3A, TPMT*2): mechanisms for the genetic polymorphism of TPMT activity. Proc Natl Acad Sci USA 94:6444–6449PubMedCentralPubMedGoogle Scholar
  134. Tamura K, Okamoto I, Negoro S et al (2008) Multicentre prospective phase II trial of gefitinib for advanced non-small cell lung cancer with epidermal growth factor receptor mutations: results of the West Japan Thoracic Oncology Group trial (WJTOG0403). Br J Cancer 98:907–914PubMedCentralPubMedGoogle Scholar
  135. Toffoli G, Cecchin E, Corona G et al (2006) The role of UGT1A1*28 polymorphism in the pharmacodynamics and pharmacokinetics of irinotecan in patients with metastatic colorectal cancer. J Clin Oncol 24:3061–3068PubMedGoogle Scholar
  136. Uchida K, Hayashi K, Kawakami K et al (2004) Loss of heterozygosity at the thymidylate synthase (TS) locus on chromosome 18 affects tumor response and survival in individuals heterozygous for a 28-bp polymorphism in the TS gene. Clin Cancer Res 10:433–439PubMedGoogle Scholar
  137. Ulrich CM, Bigler J, Velicer CM et al (2000) Searching expressed sequence tag databases: discovery and confirmation of a common polymorphism in the thymidylate synthase gene. Cancer Epidemiol Biomarkers Prev 9:1381–1385PubMedGoogle Scholar
  138. Van Kuilenburg AB, Meinsma R, Zoetekouw L, Van Gennip AH (2002) Increased risk of grade IV neutropenia after administration of 5-fluorouracil due to a dihydropyrimidine dehydrogenase deficiency: high prevalence of the IVS14+1g>a mutation. Int J Cancer 101:253–258PubMedGoogle Scholar
  139. Villafranca E, Okruzhnov Y, Dominguez MA et al (2001) Polymorphisms of the repeated sequences in the enhancer region of the thymidylate synthase gene promoter may predict downstaging after preoperative chemoradiation in rectal cancer. J Clin Oncol 19:1779–1786PubMedGoogle Scholar
  140. Wang D, Johnson AD, Papp AC et al (2005) Multidrug resistance polypeptide 1 (MDR1, ABCB1) variant 3435C>t affects mRNA stability. Pharmacogenet Genomics 15:693–704PubMedGoogle Scholar
  141. Wei X, Elizondo G, Sapone A et al (1998) Characterization of the human dihydropyrimidine dehydrogenase gene. Genomics 51:391–400PubMedGoogle Scholar
  142. Welsh SJ, Titley J, Brunton L et al (2000) Comparison of thymidylate synthase (TS) protein up-regulation after exposure to TS inhibitors in normal and tumor cell lines and tissues. Clin Cancer Res 6:2538–2546PubMedGoogle Scholar
  143. Yates CR, Krynetski EY, Loennechen T et al (1997) Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann Intern Med 126:608–614PubMedGoogle Scholar
  144. Yen J, McLeod H (2007) Should DPD analysis be required prior to prescribing fluoropyrimidines? Eur J Cancer 43:1011–1016PubMedGoogle Scholar
  145. Yoshida K, Yatabe Y, Park JY et al (2007) Prospective validation for prediction of gefitinib sensitivity by epidermal growth factor receptor mutation in patients with non-small cell lung cancer. J Thorac Oncol 2(1):22–28PubMedGoogle Scholar
  146. Young D (2006) Genetics examined in tamoxifen’s effectiveness: recurrence warning urged for labeling. Am J Health Syst Pharm 63:2286–2296PubMedGoogle Scholar
  147. Zamber CP, Lamba JK, Yasuda K et al (2003) Natural allelic variants of breast cancer resistance protein (BCRP) and their relationship to BCRP expression in human intestine. Pharmacogenetics 13:19–28PubMedGoogle Scholar
  148. Zhang W, Weissfeld JL, Romkes M, Land SR, Grandis JR, Siegfried JM (2007) Association of the EGFR intron 1 CA repeat length with lung cancer risk. Mol Carcinog 46(5):372–380PubMedGoogle Scholar

Copyright information

© Springer India 2013

Authors and Affiliations

  1. 1.Department of Cellular and Molecular BiologyB.V. Patel Pharmaceutical Education and Research Development CentreAhmedabadIndia
  2. 2.Institute of Life SciencesAhmedabad UniversityAhmedabadIndia
  3. 3.Department of Cellular and Molecular BiologyB.V. Patel Pharmaceutical Education and Research Development (PERD) CentreAhmedabadIndia

Personalised recommendations