2010-04-08 14:45:12 UTC

Adenomas, Carcinomas and the Gender Paradox

April 8, 2010

Hemant K. Roy, MD, AGAF

Hemant K. Roy, MD, AGAF

Duckworth Professor of Cancer Research; Director of Research and Vice-Chair, Section of Gastroenterology, NorthShore University HealthSystem, Evanston, IL; Clinical Associate Professor of Medicine, University of Chicago Pritzker School of Medicine, IL  


Laura K. Bianchi, MD

Laura K. Bianchi, MD

Clinical Assistant Professor of Medicine, NorthShore University HealthSystem, Evanston, IL  


In the U.S. this year, it is estimated that 71,380 women and 75,590 men will develop colorectal cancer (CRC), making it the third leading cause of cancer deaths for both genders.1 The lifetime risk is also equivalent (5.5 percent male versus 5.1 percent female),1 further supporting the gender neutrality of CRC. Therefore, CRC screening guidelines do not distinguish between men and women.

Probing more deeply reveals that gender may have a distinct fingerprint in colorectal carcinogenesis. For instance, it is well established that post-menopausal estrogens are effective at preventing CRC, potentially through modulation of the putative tumor suppressor gene, estrogen receptor beta.2 Women more commonly have microsatellite unstable (MSI-high) CRCs and thus have a better prognosis. Moreover, women have a higher propensity for proximal disease. The screening implications of this are clear for flexible sigmoidoscopy, as it only detects one-third of women’s advanced neoplasia (as opposed to two-thirds in men).3

With regards to colonoscopy, a number of recent reports suggest an approximately two-fold increase in incidence of advanced adenomas (AAs) in men versus women.3, 4 The paradox is that women have half the number of AAs, but roughly equivalent lifetime CRC risk. One potential explanation could be that women have more AAs missed on colonoscopy, which is plausible given their predilection for the flatter MSI-high lesions, which are markedly enriched in the CRCs that occur despite colonoscopic surveillance. Alternatively, it is possible that women truly have less AAs, but a larger proportion of adenomas progress to CRC.

Regardless of the mechanism, there are potential implications for this lower AA rate in women because the adenomas (especially AAs) are, in essence, both a risk-stratification marker and a target for intervention. If women have less AAs, but roughly equivalent lifetime risk of CRC, then it would follow that a negative colonoscopy may not portend the same lower long-term risk in women than men. If this line of reasoning is correct, one would anticipate colonoscopy to be somewhat less effective at CRC prevention in women. There is preliminary evidence supporting this hypothesis with observations that colonoscopy appears to be much more effective in protecting against distal rather than proximal CRCs (proximal lesions more common in women).5 In addition, a review of a large Canadian database revealed that women were more likely to develop CRC after undergoing colonoscopy (4.1 percent women versus 2.9 percent men, p < 0.001).6 Finally, a recent report indicated that within three years after a negative colonoscopy, women had a much higher incidence of CRC than men.7

Based on this, in women, our clinical approach is to pay particular attention to the proximal colon with extended withdrawal times and a lower threshold for using adjunctive techniques such as chromo-endoscopy or narrow band imaging (to assess for flat and depressed lesions). We tend to be slightly more aggressive with colonoscopic screening/ surveillance recommendations in women than men, especially in the case of tortuous colons, poor preparation, etc. Finally, if validated, we believe that this adenoma-carcinoma “paradox” in women needs to be factored into all facets of our CRC prevention approach, including screening, surveillance and chemoprevention.


  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225-49.
  2. Kennelly R, Kavanagh DO, Hogan AM, Winter DC. Oestrogen and the colon: potential mechanisms for cancer prevention. Lancet Oncol 2008;9:385-91.
  3. Schoenfeld P, Cash B, Flood A, Dobhan R, Eastone J, Coyle W, Kikendall JW, Kim HM, Weiss DG, Emory T, Schatzkin A, Lieberman D. Colonoscopic screening of average-risk women for colorectal neoplasia. N Engl J Med 2005;352:2061-8.
  4. Nguyen SP, Bent S, Chen YH, Terdiman JP. Gender as a Risk Factor for Advanced Neoplasia and Colorectal Cancer: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2009.
  5. Baxter NN, Goldwasser MA, Paszat LF, Saskin R, Urbach DR, Rabeneck L. Association of colonoscopy and death from colorectal cancer. Ann Intern Med 2009;150:1-8.
  6. Bressler B, Paszat LF, Chen Z, Rothwell DM, Vinden C, Rabeneck L. Rates of new or missed colorectal cancers after colonoscopy and their risk factors: a population-based analysis. Gastroenterology 2007;132:96-102.
  7. Singh H, Nugent Z, Mahmud SM, Demers AA, Bernstein CN. Predictors of Colorectal Cancer After Negative Colonoscopy: A Population-Based Study. Am J Gastroenterol 2009.

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