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Colorectal polyp prevention by daily aspirin use is abrogated among active smokers

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Abstract

Purpose

Based on suggestive findings from a recent study of high-risk Japanese patients, we sought to determine whether the risk of colorectal polyps associated with smoking may be modified by daily use of aspirin in an analysis of a large US screening population.

Methods

This is a cross-sectional study of 2,918 consecutive colonoscopy patients at a university hospital over a 30-month period. Data were abstracted from electronic medical records. Multivariate models of polyp counts were used to examine the competing risks of smoking and aspirin use. Models were further stratified by polyp location (proximal vs. distal) and pathologic subtype (dysplastic vs. serrated).

Results

Incidental rate of polyps was higher among active smokers [incidence rate ratio (IRR) 1.72; 95 % confidence interval (CI) 1.46–2.02] and lower among daily aspirin users (IRR 0.73; 95 % CI 0.61–0.86) compared to those who used neither. Smoking interacts significantly with aspirin use resulting in loss of aspirin protection (IRR 1.69; 95 % CI 1.28–2.24). Stratified analyses demonstrate that aspirin specifically reduces the risk of traditional dysplastic adenomas (IRR 0.72; 95 % CI 0.61–0.86) not serrated/hyperplastic polyps (IRR 0.92; 95 % CI 0.72–1.17) and that the modification of aspirin protection by smoking is primarily observed within the distal colorectum (p < 0.03).

Conclusions

We report for the first time, in a typical risk US clinical population, a lack of protective association of aspirin for polyps among active smokers. Future prospective studies are recommended to confirm this mitigating effect in order to improve the precision of the growing evidence base about the chemopreventive benefit of aspirin in colorectal cancer.

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Abbreviations

CI:

Confidence interval

CMH:

Cochran–Mantel–Haenszel

CRC:

Colorectal cancer

EMR:

Electronic medical record

IRR:

Incidence rate ratio

NSAID:

Nonsteroidal anti-inflammatory drug

OR:

Odds ratio

PDR:

Polyp Detection Rate

References

  1. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767

    Article  PubMed  CAS  Google Scholar 

  2. Drew DA, Devers TJ, O’Brien MJ, Horelik NA, Levine J, Rosenberg DW (2014) HD chromoendoscopy coupled with DNA mass spectrometry profiling identifies somatic mutations in microdissected human proximal aberrant crypt foci. Mol Cancer Res MCR 12:823–829

  3. Kavanagh AM, Giovannucci EL, Fuchs CS, Colditz GA (1998) Screening endoscopy and risk of colorectal cancer in United States men. Cancer Causes Control CCC 9:455–462

    Article  PubMed  CAS  Google Scholar 

  4. Lieberman DA, Williams JL, Holub JL et al (2014) Colonoscopy utilization and outcomes 2000 to 2011. Gastrointest Endosc 80(133–43):e3

    Google Scholar 

  5. Siegel R, Desantis C, Jemal A (2014) Colorectal cancer statistics, 2014. CA Cancer J Clin 64:104–117

    Article  PubMed  Google Scholar 

  6. Potter JD, Slattery ML, Bostick RM, Gapstur SM (1993) Colon cancer: a review of the epidemiology. Epidemiol Rev 15:499–545

    PubMed  CAS  Google Scholar 

  7. Choi SY, Kahyo H (1991) Effect of cigarette smoking and alcohol consumption in the etiology of cancers of the digestive tract. Int J Cancer 49:381–386

    Article  PubMed  CAS  Google Scholar 

  8. Sandler RS, Sandler DP, Comstock GW, Helsing KJ, Shore DL (1988) Cigarette smoking and the risk of colorectal cancer in women. J Natl Cancer Inst 80:1329–1333

    Article  PubMed  CAS  Google Scholar 

  9. Hoff G, Vatn MH, Larsen S (1987) Relationship between tobacco smoking and colorectal polyps. Scand J Gastroenterol 22:13–16

    Article  PubMed  CAS  Google Scholar 

  10. Zahm SH, Cocco P, Blair A (1991) Tobacco smoking as a risk factor for colon polyps. Am J Public Health 81:846–849

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Botteri E, Iodice S, Raimondi S, Maisonneuve P, Lowenfels AB (2008) Cigarette smoking and adenomatous polyps: a meta-analysis. Gastroenterology 134:388–395

    Article  PubMed  Google Scholar 

  12. Rex DK, Johnson DA, Anderson JC et al (2009) American College of Gastroenterology guidelines for colorectal cancer screening 2009 [corrected]. Am J Gastroenterol 104:739–750

    Article  PubMed  Google Scholar 

  13. Botteri E, Iodice S, Bagnardi V, Raimondi S, Lowenfels AB, Maisonneuve P (2008) Smoking and colorectal cancer: a meta-analysis. JAMA J Am Med Assoc 300:2765–2778

    Article  CAS  Google Scholar 

  14. Din FV, Theodoratou E, Farrington SM et al (2010) Effect of aspirin and NSAIDs on risk and survival from colorectal cancer. Gut 59:1670–1679

    Article  PubMed  CAS  Google Scholar 

  15. Chan AT, Arber N, Burn J et al (2012) Aspirin in the chemoprevention of colorectal neoplasia: an overview. Cancer Prev Res 5:164–178

    Article  CAS  Google Scholar 

  16. Giardiello FM, Offerhaus GJ, DuBois RN (1995) The role of nonsteroidal anti-inflammatory drugs in colorectal cancer prevention. Eur J Cancer 31A:1071–1076

    Article  PubMed  CAS  Google Scholar 

  17. Thun MJ, Henley SJ, Patrono C (2002) Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst 94:252–266

    Article  PubMed  CAS  Google Scholar 

  18. Chan TA (2002) Nonsteroidal anti-inflammatory drugs, apoptosis, and colon-cancer chemoprevention. Lancet Oncol 3:166–174

    Article  PubMed  CAS  Google Scholar 

  19. Dube C, Rostom A, Lewin G et al (2007) The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 146:365–375

    Article  PubMed  Google Scholar 

  20. Chan AT, Ogino S, Fuchs CS (2007) Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med 356:2131–2142

    Article  PubMed  CAS  Google Scholar 

  21. Greenspan EJ, Madigan JP, Boardman LA et al (2011) Ibuprofen inhibits activation of nuclear {beta}-catenin in human colon adenomas and induces the phosphorylation of GSK-3{beta}. Cancer Prev Res 4:161–171

    Article  CAS  Google Scholar 

  22. Ishikawa H, Mutoh M, Suzuki S, et al (2014) The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomised trial. Gut 63:1755–1759

    Article  PubMed  CAS  Google Scholar 

  23. Bettington M, Walker N, Rosty C et al (2014) Critical appraisal of the diagnosis of the sessile serrated adenoma. Am J Surg Pathol 38:158–166

    Article  PubMed  Google Scholar 

  24. Bosman FT, World Health Organization, International Agency for Research on Cancer (2010) WHO classification of tumours of the digestive system, 4th edn. International Agency for Research on Cancer, Lyon

    Google Scholar 

  25. Gill P, Wang LM, Bailey A, East JE, Leedham S, Chetty R (2013) Reporting trends of right-sided hyperplastic and sessile serrated polyps in a large teaching hospital over a 4-year period (2009–2012). J Clin Pathol 66:655–658

    Article  PubMed  Google Scholar 

  26. Lawless JF (1987) Negative binomial and mixed poisson regression. Can J Stat 15:209–225

    Article  Google Scholar 

  27. Richardson DB, Kaufman JS (2009) Estimation of the relative excess risk due to interaction and associated confidence bounds. Am J Epidemiol 169:756–760

    Article  PubMed  PubMed Central  Google Scholar 

  28. Knol MJ, VanderWeele TJ (2012) Recommendations for presenting analyses of effect modification and interaction. Int J Epidemiol 41:514–520

    Article  PubMed  PubMed Central  Google Scholar 

  29. Boroff ES, Gurudu SR, Hentz JG, Leighton JA, Ramirez FC (2013) Polyp and adenoma detection rates in the proximal and distal colon. Am J Gastroenterol 108:993–999

    Article  PubMed  Google Scholar 

  30. Cole BF, Logan RF, Halabi S et al (2009) Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J Natl Cancer Inst 101:256–266

    Article  PubMed  CAS  Google Scholar 

  31. Pommergaard HC, Burcharth J, Rosenberg J, Raskov H (2015) Aspirin, calcitriol, and calcium do not prevent adenoma recurrence in a randomized controlled trial. Gastroenterology. doi:10.1053/j.gastro.2015.09.010

    PubMed  Google Scholar 

  32. Jamal A, Agaku IT, O’Connor E, King BA, Kenemer JB, Neff L (2014) Current cigarette smoking among adults—United States, 2005–2013. MMWR Morb Mortal Wkly Rep 63:1108–1112

    PubMed  Google Scholar 

  33. Nishihara R, Lochhead P, Kuchiba A et al (2013) Aspirin use and risk of colorectal cancer according to BRAF mutation status. JAMA J Am Med Assoc 309:2563–2571

    Article  CAS  Google Scholar 

  34. Chen D, Huang JF, Liu K et al (2014) BRAFV600E mutation and its association with clinicopathological features of colorectal cancer: a systematic review and meta-analysis. PLoS One 9:e90607

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  35. Fu X, Zhang X (2014) BRAF mutation as a potential marker to identify the proximal colon serrated polyps with malignant potential. Int J Clin Exp Pathol 7:7319–7322

    PubMed  PubMed Central  Google Scholar 

  36. Nishihara R, Morikawa T, Kuchiba A et al (2013) A prospective study of duration of smoking cessation and colorectal cancer risk by epigenetics-related tumor classification. Am J Epidemiol 178:84–100

    Article  PubMed  PubMed Central  Google Scholar 

  37. Samowitz WS, Albertsen H, Sweeney C et al (2006) Association of smoking, CpG island methylator phenotype, and V600E BRAF mutations in colon cancer. J Natl Cancer Inst 98:1731–1738

    Article  PubMed  CAS  Google Scholar 

  38. Wallace K, Grau MV, Ahnen D et al (2009) The association of lifestyle and dietary factors with the risk for serrated polyps of the colorectum. Cancer Epidemiol Biomark Prev 18:2310–2317

    Article  Google Scholar 

  39. Rosty C, Hewett DG, Brown IS, Leggett BA, Whitehall VL (2013) Serrated polyps of the large intestine: current understanding of diagnosis, pathogenesis, and clinical management. J Gastroenterol 48:287–302

    Article  PubMed  PubMed Central  Google Scholar 

  40. Samadder NJ, Curtin K, Tuohy TM et al (2014) Characteristics of missed or interval colorectal cancer and patient survival: a population-based study. Gastroenterology 146:950–960

    Article  PubMed  Google Scholar 

  41. Dodou D, de Winter JC (2012) The relationship between distal and proximal colonic neoplasia: a meta-analysis. J Gen Intern Med 27:361–370

    Article  PubMed  PubMed Central  Google Scholar 

  42. Nosho K, Kure S, Irahara N et al (2009) A prospective cohort study shows unique epigenetic, genetic, and prognostic features of synchronous colorectal cancers. Gastroenterology 137(1609–20):e1–e3

    PubMed  Google Scholar 

  43. Lochhead P, Chan AT, Nishihara R et al (2015) Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression. Mod Pathol 28:14–29

    Article  PubMed  PubMed Central  Google Scholar 

  44. Raju GS, Vadyala V, Slack R et al (2013) Adenoma detection in patients undergoing a comprehensive colonoscopy screening. Cancer Med 2:391–402

    Article  PubMed  PubMed Central  Google Scholar 

  45. Butterly L, Robinson CM, Anderson JC et al (2014) Serrated and adenomatous polyp detection increases with longer withdrawal time: results from the New Hampshire Colonoscopy Registry. Am J Gastroenterol 109:417–426 46

    Article  PubMed  PubMed Central  Google Scholar 

  46. Anderson JC, Swede H, Rustagi T et al (2012) Aberrant crypt foci as predictors of colorectal neoplasia on repeat colonoscopy. Cancer Causes Control 23:355–361

    Article  PubMed  Google Scholar 

  47. Burnett-Hartman AN, Passarelli MN, Adams SV et al (2013) Differences in epidemiologic risk factors for colorectal adenomas and serrated polyps by lesion severity and anatomical site. Am J Epidemiol 177:625–637

    Article  PubMed  PubMed Central  Google Scholar 

  48. Siddiqui AA, Nazario H, Mahgoub A, Patel M, Cipher D, Spechler SJ (2009) For patients with colorectal cancer, the long-term use of statins is associated with better clinical outcomes. Dig Dis Sci 54:1307–1311

    Article  PubMed  Google Scholar 

  49. Siddiqui A, Nazario HE, Patel M, Mahgoub A, Spechler SJ (2009) Reduction in low-density lipoprotein cholesterol levels during statin therapy is associated with a reduced incidence of advanced colon polyps. Am J Med Sci 338:378–381

    Article  PubMed  Google Scholar 

  50. Liu Y, Tang W, Wang J et al (2014) Association between statin use and colorectal cancer risk: a meta-analysis of 42 studies. Cancer Causes Control CCC 25:237–249

    Article  PubMed  CAS  Google Scholar 

  51. Ng K, Ogino S, Meyerhardt JA et al (2011) Relationship between statin use and colon cancer recurrence and survival: results from CALGB 89803. J Natl Cancer Inst 103:1540–1551

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  52. Lee JE, Baba Y, Ng K et al (2011) Statin use and colorectal cancer risk according to molecular subtypes in two large prospective cohort studies. Cancer Prev Res 4:1808–1815

    Article  CAS  Google Scholar 

  53. Limburg PJ, Mahoney MR, Ziegler KL et al (2011) Randomized phase II trial of sulindac, atorvastatin, and prebiotic dietary fiber for colorectal cancer chemoprevention. Cancer Prev Res 4:259–269

    Article  CAS  Google Scholar 

  54. Coogan PF, Smith J, Rosenberg L (2007) Statin use and risk of colorectal cancer. J Natl Cancer Inst 99:32–40

    Article  PubMed  Google Scholar 

  55. Bertagnolli MM, Hsu M, Hawk ET, Eagle CJ, Zauber AG, Adenoma Prevention with Celecoxib Study I (2010) Statin use and colorectal adenoma risk: results from the adenoma prevention with celecoxib trial. Cancer Prev Res 3:588–596

    Article  CAS  Google Scholar 

  56. Leufkens AM, Van Duijnhoven FJ, Siersema PD et al (2011) Cigarette smoking and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study. Clin Gastroenterol Hepatol 9:137–144

    Article  PubMed  Google Scholar 

  57. Verla-Tebit E, Lilla C, Hoffmeister M, Brenner H, Chang-Claude J (2006) Cigarette smoking and colorectal cancer risk in Germany: a population-based case–control study. Int J Cancer 119:630–635

    Article  PubMed  CAS  Google Scholar 

  58. Slattery ML, Potter JD, Friedman GD, Ma KN, Edwards S (1997) Tobacco use and colon cancer. Int J Cancer 70:259–264

    Article  PubMed  CAS  Google Scholar 

  59. Weijenberg MP, Aardening PW, de Kok TM, de Goeij AF, van den Brandt PA (2008) Cigarette smoking and KRAS oncogene mutations in sporadic colorectal cancer: results from the Netherlands Cohort Study. Mutat Res 652:54–64

    Article  PubMed  CAS  Google Scholar 

  60. Newcomb PA, Storer BE, Marcus PM (1995) Cigarette smoking in relation to risk of large bowel cancer in women. Cancer Res 55:4906–4909

    PubMed  CAS  Google Scholar 

  61. Corley DA, Jensen CD, Marks AR et al (2014) Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med 370:1298–1306

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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Acknowledgment

This study was supported by National Institutes of Health Grant Number 1R01 CA159976 awarded to Daniel W. Rosenberg, and the State of Connecticut Department of Public Health, Biomedical Research Application Number 2012-0913 awarded to Daniel W. Rosenberg.

Author contributions

David A. Drew, James J. Grady, Helen Swede, Daniel W. Rosenberg, Richard G. Stevens, and Thomas J. Devers were involved in the study concept and design; David A. Drew, Allen Mo, Faripour Forouhar, Gretchen Egan, and Thomas J. Devers were involved in the acquisition of data; David A. Drew, Gyuhyeong Goh, Allen Mo, James J. Grady, Faripour Forouhar, Daniel W. Rosenberg, Richard G. Stevens, and Thomas J. Devers analysed and interpreted the data; David A. Drew, Faripour Forouhar, Daniel W. Rosenberg, and Richard G. Stevens drafted the manuscript; David A. Drew, Gyuhyeong Goh, James J. Grady, Helen Swede, Daniel W. Rosenberg, Richard G. Stevens, and Thomas J. Devers critically revised the manuscript for important intellectual content; David A. Drew, Gyuhyeong Goh, James J. Grady, Helen Swede, and Richard G. Stevens were involved in the statistical analysis; James J. Grady, Daniel W. Rosenberg, Richard G. Stevens, and Thomas J. Devers supervised the study; and Daniel W. Rosenberg funded the study.

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Authors and Affiliations

  1. Center for Molecular Medicine, UConn Health, 263 Farmington Ave., Farmington, CT, 06030-3101, USA

    David A. Drew, Allen Mo, Gretchen Egan & Daniel W. Rosenberg

  2. Colon Cancer Prevention Program, Neag Comprehensive Cancer Center, UConn Health, Farmington, CT, USA

    David A. Drew, Allen Mo, Gretchen Egan, Daniel W. Rosenberg & Thomas J. Devers

  3. Connecticut Institute for Clinical and Translational Science, UConn Health, Farmington, CT, USA

    Gyuhyeong Goh & James J. Grady

  4. Department of Pathology, UConn Health, Farmington, CT, USA

    Faripour Forouhar

  5. Division of Epidemiology and Biostatistics, UConn Health, Farmington, CT, USA

    Helen Swede & Richard G. Stevens

  6. Department of Community Medicine and Health Care, UConn Health, Farmington, CT, USA

    Helen Swede & Richard G. Stevens

  7. Division of Gastroenterology, School of Medicine, UConn Health, Farmington, CT, USA

    Thomas J. Devers

  8. Department of Statistics, University of Connecticut, Storrs, CT, USA

    Gyuhyeong Goh

  9. Department of Statistics, Kansas State University, Kansas, KS, USA

    Gyuhyeong Goh

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  1. David A. Drew
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  2. Gyuhyeong Goh
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  3. Allen Mo
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  7. Helen Swede
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  8. Daniel W. Rosenberg
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  10. Thomas J. Devers
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Corresponding author

Correspondence to Daniel W. Rosenberg.

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Drew, D.A., Goh, G., Mo, A. et al. Colorectal polyp prevention by daily aspirin use is abrogated among active smokers. Cancer Causes Control 27, 93–103 (2016). https://doi.org/10.1007/s10552-015-0686-1

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  • DOI: https://doi.org/10.1007/s10552-015-0686-1

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