HOW TO PREVENT CANCERS

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Of Aspirin, Ibuprofen, and Blood Tests: A Big Week in Liver Cancer Prevention

Friday, November 30, 2012 0 comments

It's been a big week for liver cancer prevention - not something we often get a chance to write here at CNiC.

As we reported on Tuesday, the US Preventive Services Task Force released new draft screening recommendations for the hepatitis C virus (HCV) - an infection that can greatly increase the risk of liver damage and later cancer. Testing can find those who are infected and lead to therapies that can reduce risk.

Now, come new results from a large government study linking aspirin use to a significantly lower risk of liver cancer. The study, the National Institutes of Health-AARP Diet and Health Study followed over 300,000 men and women age 50 - 71 for multiple years and found that the use of aspirin and other non-steriodal anti-inflammatories (NSAIDS) - like ibuprofen and indomethacin - lowered the risk of liver cancer by close to 40 percent and the risk of death from liver disease by just over 50 percent (study). Aspirin use alone (without any other NSAIDS) was linked to a nearly 50 percent lower risk of liver cancer. Just taking NSAIDS other than aspirin did not appear to lower risk of liver cancer but did lower the risk of death from liver disease by about 25 percent.

The study didn't have information on the dosage of aspirin used by those in the study; so it's unclear whether low-dose aspirin (approximately 81mg) had similar benefits to full dose aspirin (typically 325mg). Same for the non-aspirin NSAIDS.

Previous studies looking at the link between aspirin/NSAIDS and liver disease were much smaller than this recent study and had inconclusive results. Yet, the manner in which aspirin works in the body fits nicely with a hypothesis of cancer prevention. Inflammation is thought to play a potential role in the pathway from normal cells to cancer, so interrupting this pathway by keeping down inflammation - as aspirin and other NSAIDS do - is believed to be one possible way to cut the risk of certain cancers.

Regular long-term aspirin use is also linked to a lower risk of colon cancer (CNiC post). And men age 45-79 and women age 55-79 are generally encouraged to take a daily aspirin to prevent cardiovascular disease (UPSTF guideline). If these promising early results for liver cancer are replicated in other studies, it'll add even more weight to the evidence of health benefits with regular aspirin use.

As with all drugs, though, aspirin and other NSAIDS are not without certain risks. Intestinal bleeding is a particular concern with aspirin and can be a very serious condition. Those prone to bleeding - and other potentially serious side effects of NSAIDS - are usually discouraged from taking them. Talking with a doctor is the best way to determine if the benefits of a regular aspirin outweigh the risks.

It's estimated that Americans alone take an astounding 30 billion aspirins each year. Increasingly, it seems this may be money well spent.

Timing is everything: Renewing the debate on aspirin

Monday, January 16, 2012 0 comments

This week on the NY Times Well Blog is a discussion of whether the health benefits of aspirin have been oversold (or the health risks underreported). The spark to this renewed discussion is a Cochrane review of the aspirin data. What gets lost in the debate, is how important timing is when considering the health benefits of aspirin use. As we've previously noted here on CNiC, the benefits of aspirin use for colorectal cancer risk reduction and reduction in colorectal cancer mortality really become apparent after a decade or more of use. With a mean follow-up of 6 years, the latest review by Seshasai et al, wouldn't capture the full benefit of regular aspirin use.

Nuts for Nuts

Wednesday, August 10, 2011 0 comments

Limiting red meat intake is one of the key messages in our cancer prevention education programs and we've talked about it before on CNiC. Red meat significantly increases risk of colon cancer and may also increase risk of lung, esophageal, stomach and pancreatic cancers.

But as with many of the things you can do to lower your cancer risk, eating less red meat isn't just about cancer. Eating red meat also increases your risk of heart disease and diabetes. The good news is that making a simple switch can change that risk. Our colleagues at Harvard report today on the NY Times Well Blog that replacing just one serving a day of red meat with nuts, low fat dairy or whole grains can lower diabetes risk.

What does this add to our knowledge? We've known that red and processed meats increase risk and the Harvard data adds to that, but few studies have been able to examine the effect of behavior change. The Harvard study modeled the change to see what happened to risk. This means, regardless of what you've been doing to now, you can change what you're doing and change your risk. So go nuts for nuts (or whole grains).

Physical activity prevents colon cancer

Wednesday, March 16, 2011 0 comments

In a detailed review of evidence from 20 studies one of us, Kathleen Wolin, reports that higher levels of physical activity protect against colon cancer (see study) and now the precursor lesions, colon polyps (see study) . The evidence is consistent across study design, approaches to assessment of physical activity, and the populations studied. Key features of this extensive review include the thorough search of the literature and use of state of the art statistical approaches to combine the evidence on activity and colon cancer risk.

By evaluating both colon polyps, the precursor lesion from which the majority if colon cancers develop, as well as colon cancer, Wolin is able to show that sustaining activity over the lifetime will lead to the greatest reduction in colon cancer. The parallel evidence from our previous work estimating the overall benefit of activity against colon cancer, sustained activity at the level of one hour of walking per day from age 30 to age 70 will reduce colon cancer by half compared to those who do not exercise at all (see table of results). This significant 50 percent reduction in new cases of colon cancer is a benefit that most of us can achieve. In addition, exercise reduces risk of heart disease and diabetes as well as other major chronic conditions.

Colon cancer is largely preventable. In addition to a healthy diet, maintaining a healthy weight and being physically active, screening significantly reduces the risk of both the diagnosis of colon cancer and death from colon cancer. See our related post,

New Results Further Confirm that Screening Prevents Death from Colon Cancer

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

Monday, March 7, 2011 0 comments

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*	*Reference*	*Population percentage who can change behavior*
Modifiable			Women	Men
Physical activity (>3 hours per week)	0.75	Wolin ²	80%	80%
Meat >7 servings per week	1.5	WCRF ⁹	25%	25%
Obesity Per 5kg/m2	1.24	Renehan ¹⁰	40%	35%
Alcohol >4 drinks per day vs. never	1.5	Fedirko ¹¹	5%	10%
Cigarette smoking	1.4	Tsoi ¹² Liang ¹³	20%	20%
Aspirin use Daily for 5 years	0.5	Flossmann ¹⁴ Rothwell ¹⁵	80%	70%
Calcium 1200 mg/day	0.80	Baron ¹⁶ Cho ¹⁷	20%	25%
Estrogen use	0.80	Grodstein ¹⁸	~	n/a
Oral contraceptive use	0.80	Martinez ¹⁹ Bosetti ²⁰	~	n/a
Non modifiable
Family history Parent or sibling	1.8	Fuchs ²¹	5%	5%
Height Per 6 inches	1.2	Wei ⁷	~	~
Screening
Colonoscopy	0.5	Frazier ²²	Approx 50% total population up to date & screened
Sigmoidoscopy	0.5	Atkin ²³	Approx 50% total population up to date & screened

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.

Screening

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.

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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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