Advancing biology of "normal DNA" and understanding of tumors all point to prevention

At UICC, World Cancer Congress (August 28, 2012), Dr. Blackburn (http://biochemistry.ucsf.edu/labs/blackburn/) emphasizes that telomere length reflects accumulated stresses and that shortening telomeres are related to increased risk of cancer and other chronic diseases typically associated with aging. Importantly, shortening accumulates across the life course. The growing biologic understanding of this measure of DNA stability turns our focus and priority to prevention.

A second presentation by Dr. Eisenhauer (http://www.queensu.ca/news/articles/profiles/elizabeth-eisenhauer), an internationally recognized gynecologic oncologist pointed to the complexity of mutations in tumors and the long way we are from providing real time genomic medicine to guide cancer treatment. Supporting this position is the documented heterogeneity within tumors (http://www.nejm.org/doi/full/10.1056/NEJMoa1113205) and the evidence of more than 7000 mutations in 103 breast cancer samples  (http://www.nature.com/nature/journal/v486/n7403/full/nature11154.html). 

These two juxtaposed insights point to the priority for prevention and the imperative of working to apply the prevention knowledge we already have.

Many of our strategies are summarized in a recent paper (see http://dx.doi.org/10.1007/s10552-012-9924-y) or details on our blog.

(Video) 8 Ways to Prevent Cancer (and A Bunch of Other Diseases)

"8 Ways to Prevent Cancer" - Talk at Sydney University

Preventing colon cancer: Screening works – mortality down 30% nationwide from 1992 through 2009.

The evidence on screening as an effective strategy to reduce colorectal cancer mortality has its roots in studies of fecal occult blood testing (FOBT) that showed a reduction in colorectal cancer mortality^1-3. These three independent trials were conducted in the US, England and Scandinavia. Completing the clinical trials of fecal occult blood testing case-control sampling frames were also used to analyze prospective data from the Kaiser Permanente Health Plan ^4,5, showing significant reductions in colorectal cancer mortality. In 1997, the combined efforts of gastroenterologists and others led to the seminal paper recommending colorectal cancer screening ⁶ and ACS also adopted a guideline recommending screening for colorectal cancer ⁷. Congress subsequently approved screening for colorectal cancer to be covered by Medicare, providing coverage for Americans over age 65. Many other activities at the local and national level to promote colon screening have led to increase in screening and reduction in colorectal cancer mortality.

In the figure below, we see that there is a steady decline in mortality from colorectal cancer form 1992 through 2009. 

The goals of the American Cancer Society included a target of 55% of the population being screened and up to date for CRC screening by 2015 ⁸. We have already met this national goal. Data from CDC indicate that in 2010 we already have met this goal, in fact the national average was 64.5% of adults 50 to 75 years of age were up to date ⁹. Variability is substantial – in Massachusetts screening increased to 75% of the population.

Does screening reduce colon cancer? – yes.

Randomized trial evidence now builds on the evidence available in 1997 and confirms the value of screening to reduce mortality. In 2010, Atkin and colleagues published a randomized trial of once-only flexible sigmoidoscopy conducted in the United Kingdom ¹⁰. Both incidence and mortality from colorectal cancer were reduced among those randomized screening compared to the control arm. Most recently, data from the PLCO randomized trial also show a reduction in incidence and mortality ¹¹.

Despite national access to screening through Medicare, rates of screening vary substantially between states. Massachusetts has the highest uptake of screening as of 2010. Rates of screening by 2010 varied from 54 to 59% in the bottom quartile of States to 70 to 75% in New England, Maryland and Washington State ⁹. Likewise the drop in colorectal cancer mortality varies substantially over the past 20 years.  New England states and New York have had the highest drop in colorectal cancer mortality – rates declining by 30 to 37% from 1994 to 2007 ¹².

Promoting population health through reduction in colorectal cancer mortality requires successfully moving from knowledge through translation to implementation in widespread practice. Preventive action usually lags behind the science. Colorectal cancer is the second ranked leading cause of cancer mortality. Yet screening within the US has substantial variation in the rate of uptake and the associated decline in mortality. However, the overall national average of 64% exceeds the ACS challenge goals of 55% up to date by 2010 ⁸.

National changes in access through Medicare coverage and in professional awareness through publication of prevention guidelines recommending screening alone do not speed translation to practice ¹³. Components of implementation, for example within health systems ¹⁴, show how changes can be made to speed implementation of new guidelines such as screening for colorectal cancer. But much of the colorectal prevention and screening effort promoted over the past 15 years extends beyond individual provider systems and insurance providers.

To be effective public health programs must engage providers but also build community support for the preventive efforts. This requires education and awareness beyond the clinical care setting. Massachusetts led many education and outreach efforts that spread across New England from a partnership of academics, the ACS, and the Massachusetts Medical Society. Alas, to this day CDC still only funds about half of all states to promote colorectal cancer screening ¹⁵.

One might contrast the substantial decline in mortality across New England, New York, New Jersey, and Maryland (all greater than 30% decline in mortality) with states such as Mississippi, Wyoming and Alabama where in the same time period mortality has declined by less than 10% ¹². 

Why do we have such variation in the implementation of a program that can almost halve mortality from colorectal cancer? The Richmond model of health policy and prevention offers a unifying approach to this and many cancer prevention issues ^16,17. In the model, Richmond sets forth the interplay of three interrelated forces: the scientific knowledge base; political will to allocate resources towards a prevention program; and a social strategy to implement the prevention activity and reduce the burden of illness. This model developed in part through the design of Healthy People, 1979 ¹⁸, offers a structure to evaluate the strategies that have been employed to promote screening over more than 15 years. A social strategy includes a multilevel approach promoting health through healthcare providers, through regulatory changes, and through individual and community changes. A multilevel set of issues must be addressed to implement a comprehensive social strategy.  Particularly in Massachusetts where a broad coalition came together to promote awareness and work to implement screening such an approach appears to have paid off. 

Our priority going forward is to understand how other states can emulate the success in prevention achieved in New England. Where do you think our priorities for prevention should be now?

Related posts

More than half of cancer is preventable now

Web resources

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Literature cited

  

1.      Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med. May 13 1993;328(19):1365-1371.

2.      Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet. Nov 30 1996;348(9040):1472-1477.

3.      Kronborg O, Fenger C, Olsen J, Jorgensen OD, Sondergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet. Nov 30 1996;348(9040):1467-1471.

4.      Selby JV, Friedman GD, Quesenberry CP, Jr., Weiss NS. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med. Mar 5 1992;326(10):653-657.

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6.      Winawer SJ, Fletcher RH, Miller L, et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology. Feb 1997;112(2):594-642.

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16.    Richmond J, Kotelchuck M. Coordination and development of strategies and policy for public health promotion in the United States. In: Holland W, Detel R, Know G, eds. Oxford Textbook of Public Health. Vol 1. Oxford: Oxford University Press; 1991.

17.    Atwood K, Colditz GA, Kawachi I. From public health science to prevention policy: placing science in its social and political contexts. Am J Public Health. Oct 1997;87(10):1603-1606.

18.    U. S. Department of Health E, and Welfare,. Healhty People. The Suregeon General's report on health promotion and disease prevention, 1979. Washington, DC: Office of the Assistant Secretary for Health and Surgeon General;1979.