Monday, March 7, 2011

Primary prevention of colon cancer, time to act is now!

In this short update we draw attention to the strength of evidence that colon cancer is largely preventable with what we already know. While we have provided more extensive summaries of the overall evidence in the past 1, and have reported in detail on specific lifestyle habits and colon cancer 2,3, our goal here is to provide a quick update to help readers see just how strong the evidence is. For each lifestyle factor we provide a short summary of the evidence.

Data from US based cohorts show that more than 90% of adults have one or more lifestyle factors that they could change to reduce their risk of colon cancer 4 and other chronic diseases like diabetes 5 and heart disease.6 We conclude that if Americans modify the behavioral factors that we summarize here, with changes at an early enough age to reverse risk, then more than 80% of colon cancers could be prevented in the long term 4.  While risk reduction strategies can be evaluated either individually or in combination showing substantial benefits for the population 7, we do not yet have community wide studies showing this benefit in real time – some of the challenge is the time lag from change in a health behavior to subsequent development of genetic changes, growth of tumor, and diagnosis of cancer.8

Table Summary of relative risk, as well as the prevalence, of each of the modifiable and no-modifiable factors related to colon cancer.

Lifestyle factor
Relative risk
Population percentage who can change behavior

Physical activity (>3 hours per week)

Wolin 2
Meat >7 servings per week

Per 5kg/m2

Renehan 10
Alcohol >4 drinks per day vs. never

Fedirko 11
Cigarette smoking

Tsoi 12
Liang 13
Aspirin use
Daily for 5 years
Flossmann 14
Rothwell 15
1200 mg/day

Baron 16
Cho 17
Estrogen use

Grodstein  18
contraceptive use
Martinez 19
Bosetti 20

Non modifiable

Family history
Parent or sibling

Fuchs 21
Per 6 inches
Wei 7


Frazier 22
Approx 50% total population up to date & screened
Atkin 23

The factors are listed based on the strength of the scientific evidence that a particular factor affects colon cancer risk. We also note that the majority of modifiable risk factors also contribute to other health benefits if changes are made to reduce colon cancer risk.

For example, the observational data on physical activity and colon cancer are very consistent 2, the benefits of physical activity for cardiovascular and bone health are well-established 24, and the adverse consequences of physical activity are minimal if it is done sensibly. Furthermore the level of inactivity in the population suggests that the vast majority of Americans could gain health benefits form increasing their level of activity.

Notably, the majority of the population is not engaging in the behaviors known to be most protective against colon cancer: 80% of adults are active less than 3 hours a week 25 and 25% consume more than 7 servings of meat a week.  The observational data on red meat consumption and colon cancer are only a little less consistent 9, there may be cardiovascular benefits to restricting red meat consumption, and the adverse consequences are almost entirely cultural and economic.

The data on obesity and colon cancer are rigorously combined by Renehan and show consistent direct relation between increasing Body Mass Index (BMI) and risk of colon cancer. 10

Calcium supplementation reduces risk of colorectal polyps and colon cancer. A randomized trial shows the does of 1200 mg per day reduces risk of polyps by 20% 16 and that this benefit persists for many years after stopping therapy. 26 In addition, combined data from prospective cohort studies shows this level of calcium intake (1200mg per day) is sufficient for protection against colon cancer and that there is little added benefit from higher intakes. 17 Importantly, the lack of benefit in the randomized trial component of the Women’s Health Initiative that evaluated calcium and vitamin D in relation to colon cancer risk had the mean intake at randomization already at the 1200 mg per day for women in the trial. Thus there was likely little room for benefit in terms of reduction in risk with even high intakes during the trial. 27

Alcohol is a known carcinogen causing cancer of the mouth and throat as well as breast and colon. Data on colon cancer have been combined from 27 cohort studies and 34 case-control studies.11 In the combined analysis risk for colorectal cancer increased with the amount of alcohol consumed. Compared to non-drinkers, those consuming 50 grams per day (4 drinks) had a relative risk of 1.38 (95% confidence interval 1.28 to 1.50). 11 Risk was present in men and women.

For aspirin, it is now clear that eicosanoids and the COX pathway play a role in neoplasia. However, there is no certain knowledge about dose and regimen, and the side effects of gastrointestinal and cerebral bleeding are well known. Evidence from several randomized trials suggests that a daily does of 75 mg is sufficient to obtain the benefit of reduce colon cancer with no added benefit form higher doses. 15 Importantly, data show that the benefit accrues some years after starting daily aspirin. 15 Furthermore, when dose and duration are taken into account the data from randomized trials and the prospective cohort studies show equivalent benefits from use of aspirin. 14 In sum, the data from randomized trials for prevention of cardiovascular disease agree with observational data when dose and duration are considered together 14,15,28. Five years of use gives approximately 50 percent reduction in risk of death from colon cancer through 20 years of follow-up.

Cigarette smoking is a cause of many cancers. Colon cancer has been added to the list of sites where smoking now is directly related to increased risk of cancer. Combining data from 28 prospective cohort studies Tsoi and colleagues reported that current smokers had an increased risk of colorectal cancer (RR 1.20) and that the risk was stronger among men (RR=1.38). Longer duration of smoking and number of cigarettes smoked per day also increased risk of colorectal cancer. 12

Among women use of oral contraceptives is related to reduced risk of colorectal cancer. 19,20 In addition, among postmenopausal women, those who currently use hormone therapy have reduced risk of colon cancer. 18

Family History
Strong evidence shows that this common malignancy has an inherited component. Those with family history gain added benefit from changing lifestyle factors and from screening. Recommendations for screening now indicate that hose with a family history should begin screening at a younger age. Obviously you need to let your health care providers know about your family history if they are to order screening tests at the appropriate age.

Given that most Americans are not engaging in behaviors known to prevent development of malignancy, early detection of polyps and colon cancer must become routine and commonplace.

For most diseases, screening is considered ‘secondary prevention’ because it detects early forms of cancer, but does not prevent the actual development of disease.

However, colon cancer screening can be considered either primary prevention or secondary prevention because the tests have the ability to detect, and often remove, both precancerous polyps and carcinomas. Approaches to colon cancer screening are cost-effective22 and are now widely integrated into primary care.  Primary prevention via screening involves the removal of precancerous polyps that may have progressed to carcinoma if left undetected. Evidence suggests that removal of polyps in a population does lead to a significant reduction in the incidence of colon cancer. 23 A randomized trial of flexible sigmoidoscopy included 113,195 people assigned to the control group and 57,237 assigned to flexible sigmoidoscopy. 23 During follow-up of 11 years colon cancer incidence was significantly reduced in the screened group (23 percent reduction compared to that in the unscreened group). Mortality from colon cancer was reduced by 31 percent. Both reductions were statistically significant providing further support for recommendations that screening reduced incidence and mortality form this cancer.

Related CNiC posts

Colon Cancer Screening - Just a (great) first step 

Literature cited

1.            Tomeo C, Colditz G, Willett W, et al. Harvard report on cancer prevention Volume 3: Prevention of colon cancer in the United States. Cancer Causes and Control. 1999;10:167-180.
2.            Wolin KY, Yan Y, Colditz GA, Lee IM. Physical activity and colon cancer prevention: a meta-analysis. Br J Cancer. Feb 24 2009;100(4):611-616.
3.            Colditz G, Cannuscio C, Frazier A. Physical activity and colon cancer. Cancer Causes Control. 1997;8.
4.            Platz E, Willett W, Colditz G, Rimm E, Spiegelman D, Giovannucci E. Proportion of colon cancer risk that might be preventable in a cohort of middle-aged US men. Cancer Causes Control. 2000;11:579-588.
5.            Hu FB, Manson JE, Stampfer MJ, et al. Diet, lifetsyle, and risk of type 2 diabetes mellitus in women. N Eng J  Med. 2001;345:790-797.
6.            Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC. Primary Prevention of Coronary Heart Disease in Women through Diet and Lifestyle. N Engl J Med. July 6, 2000 2000;343(1):16-22.
7.            Wei EK, Colditz GA, Giovannucci EL, Fuchs CS, Rosner BA. Cumulative Risk of Colon Cancer up to Age 70 Years by Risk Factor Status Using Data From the Nurses' Health Study. Am J Epidemiol. Sep 1 2009.
8.            Wei EK, Wolin KY, Colditz GA. Time course of risk factors in cancer etiology and progression. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Sep 10 2010;28(26):4052-4057.
9.            World Cancer Research Fund. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. Washington, DC: AICR; 2007.
10.            Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. Feb 16 2008;371(9612):569-578.
11.            Fedirko V, Tramacere I, Bagnardi V, et al. Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. Feb 9 2011.
12.            Tsoi KK, Pau CY, Wu WK, Chan FK, Griffiths S, Sung JJ. Cigarette smoking and the risk of colorectal cancer: a meta-analysis of prospective cohort studies. Clin Gastroenterol Hepatol. Jun 2009;7(6):682-688 e681-685.
13.            Liang PS, Chen TY, Giovannucci E. Cigarette smoking and colorectal cancer incidence and mortality: systematic review and meta-analysis. Int J Cancer. May 15 2009;124(10):2406-2415.
14.            Flossmann E, Rothwell PM. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet. May 12 2007;369(9573):1603-1613.
15.            Rothwell PM, Wilson M, Elwin CE, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet. Nov 20 2010;376(9754):1741-1750.
16.            Baron J, Beach M, Mandel J, et al. Calcium supplements for the prevention of colorectal adenomas.
Calcium Polyp Prevention Study Group. N Engl J Med. 1999;340:101-107.
17.            Cho E, Smith-Warner SA, Spiegelman D, et al. Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies. J Natl Cancer Inst. Jul 7 2004;96(13):1015-1022.
18.            Grodstein F, Newcomb PA, Stampfer MJ. Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis. Am J Med. May 1999;106(5):574-582.
19.            Martinez M, Grodstein F, Giovannucci E, et al. A prospective study of reproductive factors, oral contraceptive use, and risk of colorectal cancer. Cancer Epidemiol Biomarker Prev. 1997;6:1-5.
20.            Bosetti C, Bravi F, Negri E, La Vecchia C. Oral contraceptives and colorectal cancer risk: a systematic review and meta-analysis. Hum Reprod Update. Sep-Oct 2009;15(5):489-498.
21.            Fuchs CS, Giovannucci EL, Colditz GA, Hunter DJ, Speizer FE, Willett WC. A prospective study of family history and the risk of colorectal cancer. N Engl J Med. 1994;331:1669-1674.
22.            Frazier AL, Colditz GA, Fuchs CS, Kuntz KM. Cost-effectiveness of screening for colorectal cancer in the general population. JAMA. Oct 18 2000;284(15):1954-1961.
23.            Atkin WS, Edwards R, Kralj-Hans I, et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet. May 8 2010;375(9726):1624-1633.
24.            U.S. Department of Health and Human Services. Physical activity and health:  A  Report of the Surgeon General. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion.; 1996 1996.
25.            U. S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, The President's Council on Physical Fitness and Sports. Physical Activity and Health: A  Report of the Surgeon General. Washington, DC: Office of the Surgeon General;1996.
26.            Grau MV, Baron JA, Sandler RS, et al. Prolonged effect of calcium supplementation on risk of colorectal adenomas in a randomized trial. J Natl Cancer Inst. Jan 17 2007;99(2):129-136.
27.            Martinez ME, Marshall JR, Giovannucci E. Diet and cancer prevention: the roles of observation and experimentation. Nat Rev Cancer. Aug 7 2008.
28.            Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. Jan 1 2011;377(9759):31-41.

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