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COX-2 Polymorphism, Use of Nonsteroidal Anti-Inflammatory Drugs, and Risk of Colon Cancer in African Americans (United States)

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Abstract

Introduction

The inducible Cyclooxygenase (COX)-2 enzyme plays an important role in inflammation and carcinogenesis. Recent reports suggest that single nucleotide polymorphisms (SNPs) in the COX-2 gene may alter enzyme function and in turn modify an individual’s risk of colon cancer. We explored the association between the COX-2 Val511Ala SNP and risk of colon cancer among 240 African American cases and 326 African American controls in a population-based, case-control study in North Carolina.

Methods

We used unconditional logistic regression models to determine the odds ratios (ORs) for genotype and risk of colon cancer.

Results

We observed a non-statistically significant inverse association between any Ala COX-2 genotype and risk of colon cancer (OR = 0.62, 95% CI: 0.33, 1.16) among African Americans. The inverse association was present among non-regular NSAID users, use ≤ 3 times/week, (OR = 0.66; 95% CI: 0.32, 1.37) and regular NSAID users, use ≥3 times/week for ≥3 months, (OR = 0.41; 95% CI: 0.11, 1.54).

Conclusions

Our results suggest that the COX-2 Val511Ala SNP does not antagonize the effect of NSAIDs on colon cancer risk and provides support that NSAID use and the COX-2 Val511Ala SNP may contribute to a reduced risk of colon cancer among African Americans.

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Abbreviations

COX:

cyclooxygenase

PTGS:

prostaglandin H synthase

CI:

confidence interval

NCCCS:

North Carolina Colon Cancer Study

NSAID:

nonsteroidal anti-inflammatory drugs

OR:

odds ratio

References

  1. JP Collet C Sharpe E Belzile JF Boivin J Hanley L Abenhaim (1999) ArticleTitleColorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing Br J Cancer 81 62–68 Occurrence Handle10.1038/sj.bjc.6690651 Occurrence Handle1:CAS:528:DyaK1MXmt12htro%3D Occurrence Handle10487613

    Article  CAS  PubMed  Google Scholar 

  2. LA Garcia-Rodriguez C Huerta-Alvarez (2001) ArticleTitleReduced risk of colorectal cancer among long-term users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs Epidemiology 12 88–93 Occurrence Handle1:STN:280:DC%2BD3M7hsFKjtA%3D%3D Occurrence Handle11138826

    CAS  PubMed  Google Scholar 

  3. JE Muscat SD Stellman EL Wynder (1994) ArticleTitleNonsteriodal antiinflammatory drugs and colorectal cancer Cancer 74 1847–1854 Occurrence Handle1:STN:280:ByuA28zmsVM%3D Occurrence Handle8082089

    CAS  PubMed  Google Scholar 

  4. II Peleg MF Lubin GA Cotsonis WS Clark CM Wilcox (1996) ArticleTitleLong-term use of nonsteroidal antiinflammatory drugs and other chemopreventors and risk of subsequent colorectal neoplasia Dig Dis Sci 41 1319–1326 Occurrence Handle10.1007/BF02088554 Occurrence Handle1:CAS:528:DyaK28XltF2isbo%3D Occurrence Handle8689906

    Article  CAS  PubMed  Google Scholar 

  5. O Suh C Mettlin NJ Petrelli (1993) ArticleTitleAspirin use, cancer, and polyps of the large bowel Cancer 72 1171–1177 Occurrence Handle1:STN:280:ByyA3sflvFM%3D Occurrence Handle8339210

    CAS  PubMed  Google Scholar 

  6. T Sturmer RJ Glynn I-M Lee JE Manson JE Buring CH Hennekens (1998) ArticleTitleAspirin use and colorectal cancer: post-trial folow-up data from the physicians’ health study Ann Intern Med 128 713–720 Occurrence Handle1:STN:280:DyaK1c3htlaltw%3D%3D Occurrence Handle9556464

    CAS  PubMed  Google Scholar 

  7. W Smalley WA Ray J Daugherty MR Griffen (1999) ArticleTitleUse of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: a population-based study Arch Intern Med. 159 161–166 Occurrence Handle10.1001/archinte.159.2.161 Occurrence Handle1:CAS:528:DyaK1MXhsF2rsLg%3D Occurrence Handle9927099

    Article  CAS  PubMed  Google Scholar 

  8. C La Vecchia E Negri S Franceschi et al. (1997) ArticleTitleAspirin and colorectal cancer Br J Cancer 76 675–677 Occurrence Handle1:STN:280:ByiH2cjmtlQ%3D Occurrence Handle9303370

    CAS  PubMed  Google Scholar 

  9. RF Logan J Little PG Hawtin JD Hardcastle (1993) ArticleTitleEffect of aspirin and non-steroidal anti-inflammatory drugs on colorectal adenomas: case-control study of subjects participating in the Nottingham faecal occult blood screening programme BMJ 307 285–289 Occurrence Handle1:STN:280:ByyA1crptVM%3D Occurrence Handle8374373

    CAS  PubMed  Google Scholar 

  10. E Giovannucci EB Rimm MJ Stampfer GA Colditz A Ascherio WC Willett (1994) ArticleTitleAspirin use and the risk for colorectal cancer and adenoma in male health professionals Ann Intern Med 121 241–246 Occurrence Handle1:STN:280:ByuA3M7ltlQ%3D Occurrence Handle8037405

    CAS  PubMed  Google Scholar 

  11. E Giovannucci KM Egan DJ Hunter et al. (1995) ArticleTitleAspirin and the risk of colorectal cancer in women N Engl J Med 333 609–614 Occurrence Handle10.1056/NEJM199509073331001 Occurrence Handle1:CAS:528:DyaK2MXoslSgtb4%3D Occurrence Handle7637720

    Article  CAS  PubMed  Google Scholar 

  12. L Rosenberg FR Palmer AG Zauber ME Warshauer PD Stolley S Sharpiro (1991) ArticleTitleA hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer J Natl Cancer Inst 83 355–358 Occurrence Handle1:STN:280:By6C2c%2FmsFU%3D Occurrence Handle1759994

    CAS  PubMed  Google Scholar 

  13. L Rosenberg C Louik S Shapiro (1998) ArticleTitleNonsteroidal anti-inflammatory drug use and reduced risk of large bowel carcinoma Cancer 82 2326–2333 Occurrence Handle10.1002/(SICI)1097-0142(19980615)82:12<2326::AID-CNCR5>3.0.CO;2-Q Occurrence Handle1:STN:280:DyaK1c3pslCntQ%3D%3D Occurrence Handle9635524

    Article  CAS  PubMed  Google Scholar 

  14. NJ Shaheen WL Straus RS Sandler (2002) ArticleTitleChemoprevention of gastrointestinal malignancies with nonsteroidal antiinflammatory drugs Cancer 94 950–963 Occurrence Handle10.1002/cncr.10333 Occurrence Handle1:CAS:528:DC%2BD38XitVKhs7o%3D Occurrence Handle11920463

    Article  CAS  PubMed  Google Scholar 

  15. MJ Thun SJ Henley C Patrono (2002) ArticleTitleNonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues J Natl Cancer Inst 94 252–266 Occurrence Handle1:CAS:528:DC%2BD38Xit1ygtb8%3D Occurrence Handle11854387

    CAS  PubMed  Google Scholar 

  16. MJ Thun MM Namboodiri EE Calle D Flanders CW Heath SuffixJr. (1993) ArticleTitleAspirin use and risk of fatal cancer Cancer Res 53 1322–1327 Occurrence Handle1:CAS:528:DyaK3sXktl2qtLY%3D Occurrence Handle8443812

    CAS  PubMed  Google Scholar 

  17. K Krishnan MT Ruffin Suffix4th DE Brenner (2000) ArticleTitleChemoprevention for colorectal cancer Crit Rev Oncol Hematol 33 199–219 Occurrence Handle1:STN:280:DC%2BD3c3kvVemtw%3D%3D Occurrence Handle10789493

    CAS  PubMed  Google Scholar 

  18. VE Steele ET Hawk JL Viner RA Lubet (200) ArticleTitleMechanisms and applications of non-steroidal anti-inflammatory drugs in the chemoprevention of cancer Mutat Res 3 137–144

    Google Scholar 

  19. JR Vane RM Botting (1998) ArticleTitleAnti-inflammatory drugs and their mechanism of action Inflamm Res 4 S78–S87

    Google Scholar 

  20. JR Vane YS Bakhle RM Botting (1998) ArticleTitleCyclooxygenases 1 and 2 Annu Rev Pharmacol Toxicol 38 97–120 Occurrence Handle10.1146/annurev.pharmtox.38.1.97 Occurrence Handle1:CAS:528:DyaK1cXivF2itro%3D Occurrence Handle9597150

    Article  CAS  PubMed  Google Scholar 

  21. CS Williams W Smalley RN DuBois (1997) ArticleTitleAspirin use and potential mechanisms for colorectal cancer prevention The J Clin Invest 100 1325–1329 Occurrence Handle1:CAS:528:DyaK2sXmt1Cqs7o%3D

    CAS  Google Scholar 

  22. JR Vane RM Botting (1998) ArticleTitleMechanism of action of nonsteroidal anti-inflammatory drugs Am J Med 104 2S–8S Occurrence Handle10.1016/S0002-9343(97)00203-9 Occurrence Handle1:CAS:528:DyaK1cXivFajur4%3D Occurrence Handle9572314

    Article  CAS  PubMed  Google Scholar 

  23. JH Paik JH Ju JY Lee MD Boudreau DH Hwang (2000) ArticleTitleTwo opposing effects of non-steroidal anti-inflammatory drugs on the expression of the inducible cyclooxygenase J Bio Chem 275 28173–28179 Occurrence Handle1:CAS:528:DC%2BD3cXmsVKkt74%3D

    CAS  Google Scholar 

  24. SJ Shiff B Rigas (1997) ArticleTitleNonsteroidal anti-inflammatory drugs and colorectal cancer: evolving concepts of their chemoprevention actions Gastroenterology 113 1992–1998 Occurrence Handle1:CAS:528:DyaK2sXotFWjs7o%3D Occurrence Handle9394740

    CAS  PubMed  Google Scholar 

  25. H Sano Y Kawahito RL Wilder et al. (1995) ArticleTitleExpression of cyclooxygenase-1 and -2 in human colorectal cancer Cancer Res 55 3785–3789 Occurrence Handle1:CAS:528:DyaK2MXnvVelsbg%3D Occurrence Handle7641194

    CAS  PubMed  Google Scholar 

  26. J Shao H Sheng H Inoue JD Morrow RN DuBois (2000) ArticleTitleRegulation of constitutive cyclooxygenase-2 expression in colon carcinoma cells J Bio Chem 275 33951–33956 Occurrence Handle1:CAS:528:DC%2BD3cXnvVyjtLk%3D

    CAS  Google Scholar 

  27. RA Soslow AJ Dannenberg D Rush et al. (2000) ArticleTitleCOX-2 is expressed in human pulmonary, colon, and mammary tumors Cancer 89 2637–2645 Occurrence Handle10.1002/1097-0142(20001215)89:12<2637::AID-CNCR17>3.0.CO;2-B Occurrence Handle1:CAS:528:DC%2BD3MXitFWisw%3D%3D Occurrence Handle11135226

    Article  CAS  PubMed  Google Scholar 

  28. A Ristimaki N Honkanen H Jankala P Sipponen M Harkonen (1997) ArticleTitleExpression of cyclooxygnease-2 in human gastric carcinoma Cancer Res 57 1276–1280 Occurrence Handle1:CAS:528:DyaK2sXit1Oju7c%3D Occurrence Handle9102213

    CAS  PubMed  Google Scholar 

  29. BS Reedy Y Hirose R Lubet et al. (2000) ArticleTitleChemoprevention of colon cancer by specific cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of carcinogenesis Cancer Res 60 293–297

    Google Scholar 

  30. H Murata S Kawano S Tsuji et al. (1999) ArticleTitleCyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma J Bio Chem 94 451–455 Occurrence Handle1:CAS:528:DyaK1MXhtlSjsLs%3D

    CAS  Google Scholar 

  31. CE Eberhart RJ Coffey A Radhika FM Giardiello S Ferrenbach RN Dubois (1994) ArticleTitleUp-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas Gastroenterology 107 1183–1188 Occurrence Handle1:STN:280:ByqD3M7isFY%3D Occurrence Handle7926468

    CAS  PubMed  Google Scholar 

  32. II Singer DW Kawa S Schloemann T Tessner T Riehl WF Stenson (1998) ArticleTitleCyclooxygenase 2 is induced in colonic epithelial cells in inflammatory bowel disease Gastroenterology 115 297–306 Occurrence Handle10.1016/S0016-5085(98)70196-9 Occurrence Handle1:CAS:528:DyaK1cXltl2nsr0%3D Occurrence Handle9679035

    Article  CAS  PubMed  Google Scholar 

  33. JM Rhodes BJ Campbell (2002) ArticleTitleInflammation and colorectal cancer: IBD-associated and sporadic cancer compared Trends Mol Med 8 10–15 Occurrence Handle10.1016/S1471-4914(01)02194-3 Occurrence Handle1:CAS:528:DC%2BD38Xls1CjsQ%3D%3D Occurrence Handle11796261

    Article  CAS  PubMed  Google Scholar 

  34. WL Smith DL DeWitt (1996) ArticleTitleProstaglandin endoperoxide H syntase-1 and 2: the mechanism by which extracellular stimuli activate phospholipases are unresolved Adv Immunol 62 167–215 Occurrence Handle1:CAS:528:DyaK28XlsFyht7k%3D Occurrence Handle8781269

    CAS  PubMed  Google Scholar 

  35. DG Cox C Pontes E Guino et al. (2004) ArticleTitlePolymorphisms in prostaglandin synthase 2/cyclooxygenase 2 (PTGS2/COX2) and risk of colorectal cancer Br J Cancer 19 339–343

    Google Scholar 

  36. HJ Lin KM Lakkides T Keku et al. (2002) ArticleTitleProstaglandin H Syntase 2 Variant (Val511Ala) in African Americans may reduce the risk for colorectal neoplasia Cancer Epidemiol Biomarkers Prev 11 1305–1315 Occurrence Handle1:CAS:528:DC%2BD38XpsVyksr8%3D Occurrence Handle12433707

    CAS  PubMed  Google Scholar 

  37. E Frische SJ Baek LM King DC Zeldin TE Eling DA Bell (2001) ArticleTitleFunctional characterization of cyclooxygenase-2 polymorphisms JPET 299 468–476

    Google Scholar 

  38. CJ Hawkey (1999) ArticleTitleCOX-2 inhibitors Lancet 353 307–314 Occurrence Handle1:CAS:528:DyaK1MXhsF2lsrw%3D Occurrence Handle9929039

    CAS  PubMed  Google Scholar 

  39. T Keku R Millikan K Worley et al. (2002) ArticleTitle5,10-Methylenetetrahydrofolate reductase codon 677 and 1298 polymorphism and colon cancer in african americans and whites Cancer Epidemiol Biomararkers Prev 11 1611–1621 Occurrence Handle1:CAS:528:DC%2BD3sXmsF2lsw%3D%3D

    CAS  Google Scholar 

  40. TE Aldrich D Vann PG Moorman B Newman (1995) ArticleTitleRapid reporting of cancer incidence in a population-based study of breast cancer: one constructive use of a central cancer registry Breast Cancer Res Treat 35 61–64 Occurrence Handle10.1007/BF00694746 Occurrence Handle1:STN:280:ByqA3sjjvFI%3D Occurrence Handle7612905

    Article  CAS  PubMed  Google Scholar 

  41. M Ouellet MD Percival (2001) ArticleTitleMechanism of acetaminophen inhibition of cyclooxygenase isoforms Arch Biochem Biophys 387 273–280 Occurrence Handle10.1006/abbi.2000.2232 Occurrence Handle1:CAS:528:DC%2BD3MXhsFOhs7k%3D Occurrence Handle11370851

    Article  CAS  PubMed  Google Scholar 

  42. GA Kune S Kune LF Watson (1988) ArticleTitleColorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study Cancer Res 48 4399–4404 Occurrence Handle1:STN:280:BieB2s%2FjvFw%3D Occurrence Handle3390835

    CAS  PubMed  Google Scholar 

  43. HT Sorensen S Friis B Norgard et al. (2003) ArticleTitleRisk of cancer in a large cohort of nonaspirin NSAID users: a population-based study Br J Cancer 88 1687–1692 Occurrence Handle1:CAS:528:DC%2BD3sXktVentLo%3D Occurrence Handle12771981

    CAS  PubMed  Google Scholar 

  44. CC Hsieh P Maisonneuve P Boyle GJ Macfarlane C Roberston (1991) ArticleTitleAnalysis of quantitative data by quantiles in epidemiologic studies: classification according to cases, noncases, or all subjects? Epidemiology 2 137–140 Occurrence Handle1:STN:280:By2D3s7psF0%3D Occurrence Handle1932311

    CAS  PubMed  Google Scholar 

  45. W Willett MJ Stampfer (1986) ArticleTitleTotal energy intake: implications for epidemiologic analysis Am J Epidemiol 124 17–27 Occurrence Handle1:STN:280:BimB3sbhvV0%3D Occurrence Handle3521261

    CAS  PubMed  Google Scholar 

  46. W Willett (1990) Nutritional Epidemiology Oxford University Press Oxford, United Kingdom

    Google Scholar 

  47. National Heart L, Blood Institute (2004) The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. In: http://www.nhlbi.nih.gov/guidelines/obesity/practgde.htm, ed. Bethesda MD: National Institutes of Health. Washington, DC

  48. Ainsworth BE, Haskell WL, Whitt MC, et al. (2000) Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 32

  49. MT Richardson BE Ainsworth DR Jacobs AS Leon (2001) ArticleTitleValidation of the stanford 7-day recall to assess habitual physical activity Ann Epidemiol 11 145–153 Occurrence Handle10.1016/S1047-2797(00)00190-3 Occurrence Handle1:STN:280:DC%2BD3M7ptlGkuw%3D%3D Occurrence Handle11164131

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Funding supported by the Population Sciences Research Award from the UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, the Lineberger Comprehensive Cancer Center Core Grant (P30-CA16086), the Center for Environmental Health and Susceptibility (NIEHS P30-ES10126), and the National Institutes of Health (R01-CA66635). These analyses were conducted while Dr. Sansbury was a National Institutes of Health predoctoral trainee (T32-CA09330) at the University of North Carolina at Chapel Hill.

Conflict of interest: Dr. Sandler has received grant support and serves as a consultant to Merck.

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Authors and Affiliations

  1. Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, NIH, DHHS, 6116 Executive Boulevard, MSC 8325, Suite 702, Room 7207, Bethesda, MD, 20892-8325, USA

    Leah B. Sansbury

  2. Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA

    Robert C. Millikan, Jane C. Schroeder, Kari E. North & Robert S. Sandler

  3. Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill, NC, USA

    Robert C. Millikan, Jane C. Schroeder, Allan Rene’ de Cotret & Jon Player

  4. Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA

    Patricia G. Moorman

  5. Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA

    Temitope O. Keku & Robert S. Sandler

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  1. Leah B. Sansbury
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  2. Robert C. Millikan
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Correspondence to Leah B. Sansbury.

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Sansbury, L.B., Millikan, R.C., Schroeder, J.C. et al. COX-2 Polymorphism, Use of Nonsteroidal Anti-Inflammatory Drugs, and Risk of Colon Cancer in African Americans (United States). Cancer Causes Control 17, 257–266 (2006). https://doi.org/10.1007/s10552-005-0417-0

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