Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A review of gene-drug interactions for nonsteroidal anti-inflammatory drug use in preventing colorectal neoplasia

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective chemopreventive agents for colorectal neoplasia. Polymorphisms in NSAID targets or metabolizing enzymes may affect NSAID efficacy or toxicity. We conducted a literature review to summarize current evidence of gene–drug interactions between NSAID use and polymorphisms in COX1, COX2, ODC, UGT1A6 and CYP2C9 on risk of colorectal neoplasia by searching OVID and PubMed. Of 134 relevant search results, thirteen investigated an interaction. One study reported a significant interaction between NSAID use and the COX1 Pro17Leu polymorphism (P=0.03) whereby the risk reduction associated with NSAID use among homozygous wild-type genotypes was not observed among NSAID users with variant alleles. Recent pharmacodynamic data support the potential for gene–drug interactions for COX1 Pro17Leu. Statistically significant interactions have also been reported for ODC (315G>A), UGT1A6 (Thr181Ala+Arg184Ser or Arg184Ser alone), and CYP2C9 (*2/*3). No statistically significant interactions have been reported for polymorphisms in COX2; however, an interaction with COX2 −765G>C approached significance (P=0.07) in one study. Among seven remaining studies, reported interactions were not statistically significant for COX1, COX2 and ODC gene polymorphisms. Most studies were of limited sample size. Definitions of NSAID use differed substantially between studies. The literature on NSAID–gene interactions to date is limited. Reliable detection of gene–NSAID interactions will require greater sample sizes, consistent definitions of NSAID use and evaluation of clinical trial subjects of chemoprevention studies.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Abbreviations

CI:

confidence interval

COX:

cyclooxygenase

NSAIDs:

nonsteroidal anti-inflammatory drugs

ODC:

ornithine decarboxylase

OR:

odds ratio

PTGS1:

prostaglandin H synthase1

PTGS2:

prostaglandin H synthase 2

hzv:

homozygous variant

References

  1. Estimated New Cancer Cases and Deaths for 2006. National Cancer Institute: Bethesda, MD, 2006.

  2. Cancer Fast Facts Sheet: Cancer of the Colon and Rectum. National Cancer Institute: Bethesda, MD, 2006.

  3. Ekbom A, Helmick C, Zack M, Adami HO . Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med 1990; 323: 1228–1233.

    CAS  Article  PubMed  Google Scholar 

  4. Jess T, Gamborg M, Matzen P, Munkholm P, Sorensen TI . Increased risk of intestinal cancer in Crohn's disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol 2005; 100: 2724–2729.

    Article  PubMed  Google Scholar 

  5. Ulrich CM, Bigler J, Potter JD . Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils, and pharmacogenetics. Nat Rev Cancer 2006; 6: 130–140.

    CAS  Article  PubMed  Google Scholar 

  6. Baron JA, Cole BF, Sandler RS, Haile RW, Ahnen D, Bresalier R et al. A randomized trial of aspirin to prevent colorectal adenomas. New Engl J Med 2003; 348: 891–899.

    CAS  Article  PubMed  Google Scholar 

  7. Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. New Engl J Med 2003; 348: 883–890.

    CAS  Article  PubMed  Google Scholar 

  8. Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon DH, Kim K et al. Celecoxib for the prevention of sporadic colorectal adenomas. New Engl J Med 2006; 355: 873–874.

    CAS  Article  PubMed  Google Scholar 

  9. Arber N, Eagle CJ, Spicak J, Racz I, Dite P, Hajer J et al. Celecoxib for the prevention of colorectal adenomatous polyps. New Engl J Med 2006; 355: 885–895.

    CAS  Article  PubMed  Google Scholar 

  10. Baron JA, Sandler RS, Bresalier RS, Quan H, Riddell R, Lanas A et al. A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterol 2006; 131: 1674–1682.

    CAS  Article  Google Scholar 

  11. Topol EJ . Failing the public health—rofecoxib, merck, and the fda. N Engl J Med 2004; 351: 1707–1709.

    CAS  Article  PubMed  Google Scholar 

  12. Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 2005; 352: 1092–1102.

    CAS  Article  PubMed  Google Scholar 

  13. Solomon DH, Schneeweiss S, Glynn RJ, Kiyota Y, Levin R, Mogun H et al. Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation 2004; 109: 2068–2073.

    CAS  Article  PubMed  Google Scholar 

  14. Vane JR . Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature New Biol 1971; 231: 232–235.

    CAS  Article  PubMed  Google Scholar 

  15. Taketo MM . Cyclooxygenase-2 inhibitors in tumorigenesis (part i). J Natl Cancer Inst 1998; 90: 1529–1536.

    CAS  Article  PubMed  Google Scholar 

  16. Smith WL, DeWitt DL, Garavito RM . Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 2000; 69: 145–182.

    CAS  Article  PubMed  Google Scholar 

  17. Gupta RA, Dubois RN . Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer 2001; 1: 11–21.

    CAS  Article  PubMed  Google Scholar 

  18. Ostrowski J, Wocial T, Skurzak H, Bartnik W . Do altering in ornithine decarboxylase activity and gene expression contribute to antiproliferative properties of cox inhibitors? Br J Cancer 2003; 88: 1143–1151.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Gerner EW, Meyskens Jr FL . Polyamines and cancer: old molecules, new understanding. Nat Rev Cancer 2004; 4: 781–792.

    CAS  Article  PubMed  Google Scholar 

  20. Babbar N, Ignatenko NA, Casero RA, Gerner EW . Cyclooxygenase-independent induction of apoptosis by sulindac sulfone is mediated by polyamines in colon cancer. J Biol Chem 2003; 278: 47762–47775.

    CAS  Article  PubMed  Google Scholar 

  21. Janne J, Poso H, Raina A . Polyamines in rapid growth and cancer. Biochim Biophys Acta 1978; 473: 241–293.

    CAS  PubMed  Google Scholar 

  22. Kingsnorth AN, Lumsden AB, Wallace HM . Polyamines in colorectal cancer. Br J Surg 1984; 71: 791–794.

    CAS  Article  PubMed  Google Scholar 

  23. Scorcioni F, Corti A, Davalli P, Astancolle S, Bettuzzi S . Manipulation of the expression of regulatory genes of polyamine metabolism results in specific alterations of the cell-cycle progression. Biochem J 2001; 354: 217–223.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Porter CW, Herrera-Ornelas L, Pera P, Petrelli NF, Mittelman A . Polyamine biosynthetic activity in normal and neoplastic human colorectal tissue. Cancer 1987; 60: 1275–1281.

    CAS  Article  PubMed  Google Scholar 

  25. LaMuraglia GM, Lacaine F, Malt RA . High ornithine decarboxylase activity and polyamine levels in human colorectal neoplasia. Ann Surg 1986; 204: 89–93.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. Koo HB, Sigurdson ER, Daly JM, Berenson M, Groshen S, Decosse JJ . Ornithine decarboxylase levels in the rectal mucosa of patients with colonic neoplasia. J Surg Oncol 1988; 38: 240–243.

    CAS  Article  PubMed  Google Scholar 

  27. Wolter F, Ulrich S, Stein J . Molecular mechanisms of the chemopreventive effects of resveratrol and its analogs in colorectal cancer: key role of polyamines? J Nutr 2004; 134: 3219–3222.

    CAS  Article  PubMed  Google Scholar 

  28. Turchanowa L, Dauletbaev N, Milovic V, Stein J . Nonsteroidal anti-inflammatory drugs stimulate spermidine/spermine acetyltransferase and deplete polyamine content in colon cancer cells. Eur J Clin Invest 2001; 31: 887–893.

    CAS  Article  PubMed  Google Scholar 

  29. Carbone PP, Douglas JA, Larson PO, Verma AK, Blair IA, Pomplun M et al. Phase i chemoprevention study of piroxicam and alpha-difluoromethylornithine. Cancer Epidemiol Biomarkers Prev 1998; 7: 907–912.

    CAS  PubMed  Google Scholar 

  30. Martinez ME, O'Brien TG, Fultz KE, Babbar N, Yerushalmi H, Qu N et al. Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene. Proc Natl Acad Sci USA 2003; 100: 7859–7864.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. Miners JO, Birkett DJ . Cytochrome p4502c9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol 1998; 45: 525–538.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. Kuehl GE, Lampe JW, Potter JD, Bigler J . Glucuronidation of nonsteroidal anti-inflammatory drugs (nsaids): identifying the enzymes responsible in human liver microsomes. Drug Metabol Dispos 2005; 33: 1027–1035.

    CAS  Article  Google Scholar 

  33. Takahashi H, Kashima T, Nomoto S, Iwade K, Tainaka H, Shimizu T et al. Comparisons between in-vitro and in-vivo metabolism of (s)-warfarin: catalytic activities of cdna-expressed cyp2c9, its leu359 variant and their mixture versus unbound clearance in patients with the corresponding cyp2c9 genotypes. Pharmacogene 1998; 8: 365–373.

    CAS  Article  Google Scholar 

  34. Rettie AE, Wienkers LC, Gonzalez FJ, Trager WF, Korzekwa KR . Impaired (s)-warfarin metabolism catalysed by the r144c allelic variant of cyp2c9. Pharmacogenet 1994; 4: 39–42.

    CAS  Article  Google Scholar 

  35. Ciotti M, Marrone A, Potter C, Owens IS . Genetic polymorphism in the human ugt1a6 (planar phenol) udp-glucuronosyltransferase: pharmacological implications. Pharmacogenet 1997; 7: 485–495.

    CAS  Article  Google Scholar 

  36. Lampe JW, Bigler J, Horner NK, Potter JD . Udp-glucuronosyltransferase (ugt1a1*28 and ugt1a6*2) polymorphisms in caucasians and asians: relationships to serum bilirubin concentrations. Pharmacogenet 1999; 9: 341–349.

    CAS  Article  Google Scholar 

  37. Ulrich CM, Bigler J, Sparks R, Whitton J, Sibert JG, Goode EL et al. Polymorphisms in ptgs1 (=cox-1) and risk of colorectal polyps. Cancer Epidemiol Biomarkers Prev 2004; 13: 889–893.

    CAS  PubMed  Google Scholar 

  38. Ulrich CM, Whitton J, Yu JH, Sibert J, Sparks R, Potter JD et al. Ptgs2 (cox-2) −765 g>c promoter variant reduces risk of colorectal adenoma among nonusers of nonsteroidal anti-inflammatory drugs. Cancer Epidemiol Biomarkers Prev 2005; 14: 616–619.

    CAS  Article  PubMed  Google Scholar 

  39. Goodman JE, Bowman ED, Chanock SJ, Alberg AJ, Harris CC . Arachidonate lipoxygenase (alox) and cyclooxygenase (cox) polymorphisms and colon cancer risk. Carcinogenesis 2004; 25: 2467–2472.

    CAS  Article  PubMed  Google Scholar 

  40. Koh WP, Yuan JM, Van Den Berg D, Lee HP, Yu MC . Interaction between cyclooxygenase-2 gene polymorphism and dietary n-6 polyunsaturated fatty acids on colon cancer risk: The Singapore Chinese Health Study. Br J Cancer 2004; 90: 1760–1764.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. Lin HJ, Lakkides KM, Keku TO, Reddy ST, Louie AD, Kau IH et al. Prostaglandin h synthase 2 variant (val511ala) in African Americans may reduce the risk for colorectal neoplasia. Cancer Epidemio Biomarkers Prev 2002; 11: 1305–1315.

    CAS  Google Scholar 

  42. Cox DG, Pontes C, Guino E, Navarro M, Osorio A, Canzian F et al. Polymorphisms in prostaglandin synthase 2/cyclooxygenase 2 (ptgs2/cox2) and risk of colorectal cancer. Br J Cancer 2004; 91: 339–343.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. Barry EL, Baron JA, Bhat S, Grau MV, Burke CA, Sandler RS et al. Ornithine decarboxylase polymorphism modification of response to aspirin treatment for colorectal adenoma prevention. J Natl Cancer Inst 2006; 98: 1494–1500.

    CAS  Article  PubMed  Google Scholar 

  44. Orbe J, Beloqui O, Rodriguez JA, Belzunce MS, Roncal C, Paramo JA . Protective effect of the g-765c cox-2 polymorphism on subclinical atherosclerosis and inflammatory markers in asymptomatic subjects with cardiovascular risk factors. Clin Chim Acta 2006; 368: 138–143.

    CAS  Article  PubMed  Google Scholar 

  45. Solomon SD, Pfeffer MA, McMurray JJ, Fowler R, Finn P, Levin B et al. Effect of celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas. Circulation 2006; 114: 1028–1035.

    CAS  Article  PubMed  Google Scholar 

  46. Fritsche E, Baek SJ, King LM, Zeldin DC, Eling TE, Bell DA . Functional characterization of cyclooxygenase-2 polymorphisms. J Pharmacol Exp Ther 2001; 299: 468–476.

    CAS  PubMed  Google Scholar 

  47. Guo Y, Harris RB, Rosson D, Boorman D, O'Brien TG . Functional analysis of human ornithine decarboxylase alleles. Cancer Res 2000; 60: 6314–6317.

    CAS  PubMed  Google Scholar 

  48. Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E et al. Suppression of intestinal polyposis in apc delta716 knockout mice by inhibition of cyclooxygenase 2 (cox-2). Cell 1996; 87: 803–809.

    CAS  Article  PubMed  Google Scholar 

  49. Samowitz WS, Wolff RK, Curtin K, Sweeney C, Ma KN, Andersen K et al. Interactions between cyp2c9 and ugt1a6 polymorphisms and nonsteroidal anti-inflammatory drugs in colorectal cancer prevention. Clin Gastroenterol Hepatol 2006; 4: 894–901.

    CAS  Article  PubMed  Google Scholar 

  50. Maree AO, Curtin RJ, Chubb A, Dolan C, Cox D, O'Brien J et al. Cyclooxygenase-1 haplotype modulates platelet response to aspirin. J Thromb Haemost 2005; 3: 2340–2345.

    CAS  Article  PubMed  Google Scholar 

  51. Sansbury LB, Millikan RC, Schroeder JC, North KE, Moorman PG, Keku TO et al. Cox-2 polymorphism, use of nonsteroidal anti-inflammatory drugs, and risk of colon cancer in African Americans (United States). Cancer Causes Control 2006; 17: 257–266.

    Article  PubMed  Google Scholar 

  52. Chulada PC, Thompson MB, Mahler JF, Doyle CM, Gaul BW, Lee C et al. Genetic disruption of ptgs-1, as well as ptgs-2, reduces intestinal tumorigenesis in min mice. Cancer Res 2000; 60: 4705–4708.

    CAS  PubMed  Google Scholar 

  53. Hansen-Petrik MB, McEntee MF, Jull B, Shi H, Zemel MB, Whelan J . Prostaglandin e(2) protects intestinal tumors from nonsteroidal anti-inflammatory drug-induced regression in apc(min/+) mice. Cancer Res 2002; 62: 403–408.

    CAS  PubMed  Google Scholar 

  54. Fries S, Grosser T, Price TS, Lawson JA, Kapoor S, DeMarco S et al. Marked inter-individual variability in the response to selective inhibitors of cyclooxygenase-2. Gastroenterol 2006; 130: 55–64.

    CAS  Article  Google Scholar 

  55. Ulrich CM, Bigler J, Sibert J, Greene EA, Sparks R, Carlson CS et al. Cyclooxygenase 1 (cox1) polymorphisms in African-American and Caucasian populations. Hum Mutat 2002; 20: 409–410.

    Article  PubMed  Google Scholar 

  56. Halushka MK, Walker LP, Halushka PV . Genetic variation in cyclooxygenase 1: effects on response to aspirin. Clin Pharmacol Ther 2003; 73: 122–130.

    CAS  Article  PubMed  Google Scholar 

  57. Scott BT, Hasstedt SJ, Bovill EG, Callas PW, Valliere JE, Wang L et al. Characterization of the human prostaglandin h synthase 1 gene (ptgs1): exclusion by genetic linkage analysis as a second modifier gene in familial thrombosis. Blood Coagul Fibrinolysis 2002; 13: 519–531.

    CAS  Article  PubMed  Google Scholar 

  58. Kulmacz RJ, Wang LH . Comparison of hydroperoxide initiator requirements for the cyclooxygenase activities of prostaglandin h synthase-1 and -2. J Biol Chem 1995; 270: 24019–24023.

    CAS  Article  PubMed  Google Scholar 

  59. Siezen CL, Tijhuis MJ, Kram NR, van Soest EM, de Jong DJ, Fodde R et al. Protective effect of nonsteroidal anti-inflammatory drugs on colorectal adenomas is modified by a polymorphism in peroxisome proliferator-activated receptor delta. Pharmacogenet Genomics 2006; 16: 43–50.

    CAS  Article  PubMed  Google Scholar 

  60. Papafili A, Hill MR, Brull DJ, McAnulty RJ, Marshall RP, Humphries SE et al. Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response (comment). Arterioscler, Thromb Vasc Biol 2002; 22: 1631–1636.

    CAS  Article  Google Scholar 

  61. Bigler J, Whitton J, Lampe JW, Fosdick L, Bostick RM, Potter JD . Cyp2c9 and ugt1a6 genotypes modulate the protective effect of aspirin on colon adenoma risk. Cancer Res 2001; 61: 3566–3569.

    CAS  PubMed  Google Scholar 

  62. Chan AT, Tranah GJ, Giovannucci EL, Hunter DJ, Fuchs CS . Genetic variants in the ugt1a6 enzyme, aspirin use, and the risk of colorectal adenoma. J Natl Cancer Inst 2005; 97: 457–460.

    CAS  Article  PubMed  Google Scholar 

  63. Hubner RA, Muir KR, Liu JF, Logan RF, Grainge M, Armitage N et al. Genetic variants of ugt1a6 influence risk of colorectal adenoma recurrence. Clin Cancer Res 2006; 12: 6585–6589.

    CAS  Article  PubMed  Google Scholar 

  64. Poole E, Bigler J, Whitton J, Potter J, Sibert J, Ulrich C . Prostacyclin synthase and arachidonate 5-lipoxygenase polymorphisms and risk of colorectal polyps. Cancer Epidemiol Biomarkers Prev 2006; 15: 502–508.

    CAS  Article  PubMed  Google Scholar 

  65. Singh G . Gastrointestinal complications of prescription and over-the-counter nonsteroidal anti-inflammatory drugs: a view from the aramis database. Arthritis, rheumatism, and aging medical information system. Am J Ther 2000; 7: 115–121.

    CAS  Article  PubMed  Google Scholar 

  66. Hansson L, Zanchetti A, Carruthers S, Dahlof B, Elmfeldt D, Julius S et al. Effects of intensive blood pressure lowering and low dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (hot) randomised trial. Lancet 1998; 351: 1755–1762.

    CAS  Article  PubMed  Google Scholar 

  67. Steering Committee of the Physicians' Health Study Research Group. Final report on the aspirin component of the ongoing physicians' health study. N Engl J Med 1989; 321: 129–135.

    Article  Google Scholar 

  68. McAdam BF, Catella-Lawson F, Mardini IA, Kapoor S, Lawson JA, FitzGerald GA . Systemic biosynthesis of prostacyclin by cyclooxygenase (cox)-2: the human pharmacology of a selective inhibitor of cox-2. Proc Natl Acad Sci USA 1999; 96: 272–277.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  69. Catella-Lawson F, McAdam B, Morrison BW, Kapoor S, Kujubu D, Antes L et al. Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids. J Pharmacol Exp Ther 1999; 289: 735–741.

    CAS  PubMed  Google Scholar 

  70. Cheng Y, Austin SC, Rocca B, Koller BH, Coffman TM, Grosser T et al. Role of prostacyclin in the cardiovascular response to thromboxane a2. Science 2002; 296: 539–541.

    CAS  Article  PubMed  Google Scholar 

  71. Psaty BM, Potter JD . Risks and benefits of celecoxib to prevent recurrent adenomas. N Engl J Med 2006; 355: 950–952.

    CAS  Article  PubMed  Google Scholar 

  72. Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the class study: a randomized controlled trial. Celecoxib long-term arthritis safety study. JAMA 2000; 284: 1247–1255.

    CAS  Article  PubMed  Google Scholar 

  73. Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005; 352: 1071–1080.

    CAS  Article  PubMed  Google Scholar 

  74. Motsko SP, Rascati KL, Busti AJ, Wilson JP, Barner JC, Lawson KA et al. Temporal relationship between use of nsaids, including selective cox-2 inhibitors, and cardiovascular risk. Drug Safety 2006; 29: 621–632.

    CAS  Article  PubMed  Google Scholar 

  75. Peterson SK, Watts BG, McGivern B, Burke S, Latchford A, Phillips R et al. FAP-Affected Adults' Responses to Reported Cardiovascular Risks Associated with Celecoxib, Paper presented at Collaborative Group of the Americas on Inherited Colon Cancer, 2005; Salt Lake City, UT.

    Google Scholar 

  76. Ovid, medline®. Ovid Technologies Inc., Copyright 2000–2007.

  77. Ali IU, Luke BT, Dean M, Greenwald P . Allelic variants in regulatory regions of cyclooxygenase-2: association with advanced colorectal adenoma. Br J Cancer 2005; 93: 953–959.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Work was supported by grants from the National Institutes of Health R01 CA114467; R03 CA123577; R25 CA094880 and R25 CA092408-06. We thank Rachel Galbraith for her technical assistance with the article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C M Ulrich.

Additional information

Duality of Interest

None declared.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Cross, J., Poole, E. & Ulrich, C. A review of gene-drug interactions for nonsteroidal anti-inflammatory drug use in preventing colorectal neoplasia. Pharmacogenomics J 8, 237–247 (2008). https://doi.org/10.1038/sj.tpj.6500487

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.tpj.6500487

Keywords

  • nonsteroidal anti-inflammatory drugs
  • cyclooxygenase
  • prostaglandin H synthase
  • colorectal cancer
  • colorectal adenoma
  • pharmacogenetics

Further reading

Search

Quick links