Monday, September 5, 2011

Prevention - 30 years on


Labor Day weekend 2011 marks thirty years since I ventured from Brisbane, Australia and arrived in Boston to begin my studies towards a Master of Public Health, and hopefully gain admission to the doctoral program at the Harvard School of Public Health. Mentors in the Department of Social and Preventive Medicine at the University of Queensland counseled me to pursue this training and to do so at Harvard as this would give me strong grounding in methods and approaches to prevention at the population level. The population level of health had been a strong influence on my thinking as a medical student with such Australian leaders as Douglas Gordon teaching on principles of community education to advance the uptake of Pap smears. His seminal book was published while I was a medical student and emphasized the need for precision and critical thinking in public health epidemiology. (see: Health, sickness and society: theoretical concepts in social and preventive medicine Gordon, Douglas  St. Lucia, QLD: University of Queensland Press, [1976]) With support from mentors I obtained a Knox Fellowship to study at Harvard and a Fulbright Postgraduate Student Award (covering my air fare).

Summer research projects during medical school allowed me to have hands on experience in data analysis, writing and presenting research findings. Projects included analysis of data on hypertension and response to surgery for renovascular hypertension (Professors Richard Gordon and Gordon Clunie); and analysis of pathology records with Dr J. J. Sullivan to document age and gender trends and incidence of keratoacanthoma in renal transplant patients who show more aggressive forms of this premalignant skin lesion. 1

Medical education was a topic of substantial interest leading to engagement in national and local student politics and curriculum committee activity within the medical school.2-4 I also served on the Committee to Review Future Needs and Medical Education in Queensland, Australia, convened by the Medical Board of Queensland.

Boston 1981 onwards
Early contacts in Boston included Fred Mosteller, who included me in the New England Journal of Medicine related project (Statistics in Medicine) leading to numerous collaborations and an early NEJM paper with John Emerson.5 Subsequent collaboration with Fred Mosteller included studies of design in medical research and the gain of innovation over standard therapy 6-8; meta-analysis (including teaching a course at HSPH)9-12 and our final major contribution, the analysis of BCG vaccine and its efficacy in protecting against tuberculosis (in collaboration with Harvey Fineberg, Mary Wilson, Cathy Berkey, Elizabeth Burdick and Tim Brewer).13,14

Upon arrival in the Epidemiology Department at Harvard School of Public Health, I indicated to my professors that I was interested in the application of epidemiologic data to policy and public health practice. Subsequently, I was referred to a group of health economists in the fall of 1981 and began work applying epidemiologic data to estimating the costs of smoking and benefits of quitting with Nancy Kelly and Gerry Oster.15 Continuing collaborations included analysis of prophylaxis against DVT,16,17 cost effectiveness of nicotine replacement gum as an adjunct to smoking cessation, 18,19 and costs of diabetes20 and subsequently of obesity. 21-24 This research allowed me to apply principles of meta-analysis and of decision sciences taught by Weinstein and Fineberg during my doctoral training.

My doctoral dissertation research focused on cardiovascular disease in women 25 and included participation in the Nurses’ Health Study research group led by Dr. Frank Speizer. This offered opportunities to gain hands on experience in epidemiologic studies, contribute to the study through understanding self-report 26-32, and opened the door to studies of diabetes33,34, stroke 35, fractures 36-38, and cancer 39,40, as well as collaborations with numerous colleagues (including from early on my thesis adviser Walter Willett, colleague and fellow doctoral student Meir Stampfer, and thesis committee member Bernard Rosner) that started the Health Professionals Follow-up Study and Nurses Health Study II.41 Many other colleagues have built on these rich resources and continue to bring new insights to etiology and prevention of chronic diseases through these and related studies.

Cancer prevention has advanced substantially in the 30 years – with the explosion of data from prospective studies relating diet, physical activity, and obesity to cancer incidence and survival (see our Prevention Snapshot). Hormonal drug therapies (oral contraceptives and postmenopausal hormones) as well as aspirin have added to our understanding of the tools available for prevention. 42,43

Doll and Peto in 1979 estimated the proportions of cancer that could be prevented due to lifestyle, largely basing their analysis on international variation, migrant studies, and retrospective data.44 Smoking was the exception where the American Cancer Society Cancer Prevention Study gave strong prospective evidence from the US to support the UK Doctors study.45,46 While the estimates from Doll and Peto were overall strongly supporting lifestyle components as modifiable causes of cancer, the evidence has clearly been enriched over the 30 years with greater insight 47, understanding of and correction for error in measurement 48-50; use of biomarkers, and a parallel increase in understanding strategies to make changes at the population level to reduce the burden of disease. Approaches must include strategies implemented through health care providers, through regulatory change, and through individual and community level changes in behaviors.51-53

Reports by the Surgeon General on the adverse effects of smoking on health have expanded the range of diseases now documented as caused by smoking.54-57 In addition the benefits of quitting smoking have become clearer and the time course for reduction in risk after stopping smoking has been evaluated for a number of diseases. 58-60

For physical activity, we have moved from seminal studies relating higher levels of activity to reduced risk of cardiovascular disease,61 to early studies of occupational exercise and colon cancer mortality 62,63, and ultimately a broader range of epidemiologic approaches showing substantial protection against colon cancer.64-66 Evidence for breast cancer also shows benefits of higher levels of physical activity with reduced risk among premenopausal 67,68 and among postmenopausal women.69 Data for other cancers continues to accumulate and add to the overall benefit of activity to reduce risk of common chronic diseases. 70,71

In the early 1990s, Julius Richmond and Fred Mosteller co-chaired a Working Group on Cancer Prevention that summarized the knowledge base on cancer etiology and the potential strategies for prevention. 72 This working group set the foundation for teaching and research over the next 20 years. In 1992, we successfully competed for NCI funding to start a training program in cancer prevention (this history is summarized in a recent article).73  

The potential for cancer prevention remains substantial. Our insights to the time course of disease risk accumulation and the imperative for interventions to focus on appropriate time periods in life to achieve maximum lifelong benefits gain added support from continuing studies of precursor lesions and prevention programs.74(See related talk: Childhood and Adolescence Exposures as Determinants of Lifetime Cancer Risk). In addition, greater attention to interventions that may reduce risk of recurrence and development of other chronic disease is increasingly important for cancer survivors as cancer treatments improve outcomes. 75 A regular contributor to Cancer News in Context, Dr. Wolin, leads these efforts. Longstanding collaborations with Dr. Cathy Berkey focus on early life exposures and breast cancer risk 76-78. This research is complemented by my collaboration with Dr. Rosner that has given us numerous models of cancer incidence.  These cancer incidence models account for changing risk profiles over time 79-82 and bring us to clinical applications of risk to stratify the population and in the future provide more tailored prevention messages in routine clinical care.

Earlier work bringing prevention messages to the public arose from activities in the Harvard Center for Cancer Prevention, the precursor to our current web site and Cancer News in Context. With encouragement from Dean Fineberg, as a key function of the Harvard Center for Cancer Prevention, we set about summarizing the evidence that lifestyle factors cause the majority of cancer. 83-85 Avoiding meta-analysis which could give a false sense of precision and biased estimates, we use a group consensus approach to identify definite and probable causes of cancer. These were then summarized to convey the message that cancer is preventable, and to provide individual assessments of cancer risk and tailored strategies to reduce risk.86

With substantial input from a longstanding colleague, Hank Dart, and others trained in health communication, we originally developed The Your Disease Risk site as a key communication tool for the Harvard Center for Cancer Prevention. It began as the Harvard Cancer Risk Index, a pen and paper cancer risk assessment tool first put together in the mid-1990s by the Risk Index Working Group at the Harvard School of Public Health.86 In 1999, the Risk Index was adapted to the Web as Your Cancer Risk. Then, to give even greater emphasis to the importance of healthy behaviors, in 2004 we expanded Your Cancer Risk to include assessments for heart disease, stroke, diabetes, and osteoporosis. The expanded site was renamed Your Disease Risk. At the end of 2006, when I was recruited to Washington University School of Medicine and Siteman Cancer Center, Your Disease Risk moved with me so it could continue under my direction with the added resources available through Siteman.

To complement the web tools, we now have key prevention messages available for outreach activities and to focus prevention efforts. These are available on the web site and are the basis for ongoing media outreach (print, radio, and television) throughout the St. Louis region.

Our 8 Ways to Stay Healthy and Prevent Cancer is on our web site and serves as the backbone of numerous community outreach programs from our cancer center. We have extended this approach to survivors given the growing burden of preventable chronic disease in this population. Cancer Survivors' 8 Ways to Stay Healthy After Cancer, includes eight tips that help lay the foundation for the many health-filled years that most survivors enjoy.

Teaching and mentoring.
With colleagues at Washington University School of Medicine, we have developed a Master of Population Health Sciences. Modeled on comparable programs at our peer institutions, and drawing on our experience teaching over the years, our courses in methods for conduct of research, synthesis and meta-analysis, implementation and prevention, now combine to provide rigorous training for physicians and other clinicians to bring state of the art approaches to understanding health disparities, evaluation of effective therapies, and methods to speed implementation of research findings in real world populations.

Service.
In addition to local service in cancer control working with the State Cancer Control Plan and the chronic disease prevention office of the Massachusetts Department of Public Health, our group led numerous coon cancer awareness effort – from provider information to public advertising.87 Together with the ACS, we also developed a summary for cancer prevention mailed by Mayor Menino (in English and Spanish) to all households in the City of Boston in 1999 as part of his Crusade against Cancer. Again with Hank Dart and colleagues, we developed the original materials for the Komen For the Cure, About Breast Cancer web site.

Many study sections for NIH, site visits for program projects and the NCI cancer center program, other instates, and peer review of journal articles all add experience and insight to how other organizations frame and deliver prevention messages.

The essential ingredients.
Support from family and friends made much of this research and translation to practice possible. Early discussions of education practices with my father (we used the same anatomy text and approach to instruction/learning) led to interest in improving the education process and my engagement in student activities within our medical school. The encouragement of teachers and mentors, in addition to input from colleagues, too many to name, has been enormous and results, in large part, in the high level of citation our research has received over the years. The exceptional dedication and exceptional skills of staff on many projects has been a unique feature of this experience over the years. This past month, as noted by my brother, my own body of research has passed the mark of 100,000 articles citing my papers.

Next steps….Prevention is the future
The future offers growing attention to the potential for prevention to reduce the burden of cancer and other chronic diseases, to integrate prevention more fully into routine care, into policies and practices at our workplaces and in our communities, thus extending high quality life years into older ages, reaping the benefits of the past enormous investment in research. Ninety percent or more of adult onset diabetes could be prevented with strategies to avoid obesity, increase physical activity and improve diet (high in cereal fiber and polyunsaturated fat, low in glycemic load and trans fat, and not smoking cigarettes 88; likewise similar lifestyle changes can reduce coronary heart disease by more than 80 percent 89 and colon cancer by more than this amount too. 90 We have the scientific knowledge base and the social strategies, we need to harness political will to act on what we already know and achieve these population benefits now. It is not too late to increase activity, improve how we eat and get out weight in control. Many tips are included in our disease risk web tools and in this blog.
  
Related web resources



Literature Cited
2.         Colditz GA, McGarvey C, Wainwright L. Voluntary vacation attachments to rural general practitioners: experience with pre-clinical medical students. Aust Fam Physician. May 1978;7(5):577-579.
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4.         Colditz GA. My student elective: an Australian in Southampton. Br Med J. Feb 16 1980;280(6212):466-467.
5.         Emerson JD, Colditz GA. Use of statistical analysis in the New England Journal of Medicine. N Engl J Med. Sep 22 1983;309(12):709-713.
6.         Colditz G, Miller J, Mosteller F. The effect of study design on gain in evaluations of new treatments in Medicine and Surgery. Drug Information Journal. 1988;22:343-352.
7.         Colditz G, Miller J, Mosteller F. Measuring gain in the evaluation of medical technology: the probability of a better outcome. Int J Technology Assessment in Health Care. 1988;4:637-642.
8.         Colditz G, Miller J, Mosteller F. How study design affects outcomes in comparisons of therapy.  1 Medical. Stat Med. 1989;8:441-454.
9.         Mosteller F, Colditz G. Understanding Research Synthesis (meta-analysis). Ann Rev Public Health. 1996;17:1-32.
10.         Colditz G, Burdick E, Mosteller F. Heterogeneity in meta-analysis of data from epidemiologic studies: A commentary. Am J Epidemiol. 1995;142:371-382.
11.         Berkey CS, Hoaglin D, Mosteller F, Colditz GA. A random-effects regression model for meta-analysis. Statistics in Medicine. 1995;14:395-411.
12.         Berkey CS, Hoaglin DC, Antczak-Bouckoms A, Mosteller F, Colditz GA. Meta-analysis of multiple outcomes by regression with random effects. Stat Med. Nov 30 1998;17(22):2537-2550.
13.         Colditz GA, Berkey CS, Mosteller F, et al. The efficacy of bacillus Calmette-Guerin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature. Pediatrics. Jul 1995;96(1 Pt 1):29-35.
14.         Colditz GA, Brewer TF, Berkey CS, et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA. Mar 2 1994;271(9):698-702.
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16.         Oster G, Tuden R, Colditz G. A cost-effectiveness analysis of prophylaxis against deep-vein thrombosis in major orthopedic surgery. JAMA. 1987;257:203-208.
17.         Colditz G, Tuden R, Oster G. Rates of venous thrombosis after general surgery:  Combined results of randomized clinical trials. Lancet. 1986;ii:143-146.
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23.         Colditz G. Economic costs of obesity. Am J Clin Nutr. 1992;55:503S-507S.
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25.         Colditz GA, Willett WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH. Menopause and risk of coronary heart disease in women. N Engl J Med. 1987;316:1105-1110.
26.         Colditz GA, Martin P, Stampfer MJ, et al. Validation of questionnaire information on risk factors and disease outcomes in a prospective cohort study of women. Am J Epidemiol. 1986;123:894-900.
27.         Colditz GA, Stampfer MJ, Willett WC, et al. Reproducibility and validity of self-reported menopausal status in a prospective cohort study. Am J Epidemiol. 1987;126:319-325.
28.         Colditz GA, Willett WC, Stampfer MJ, et al. The influence of age, relative weight, smoking, and alcohol intake on the reproducibility of a dietary questionnaire. Int J Epidemiol. 1987;16:392-398.
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31.         Rockett HR, Wolf AM, Colditz GA. Development and reproducibility of a food frequency questionnaire to assess diets of older children and adolescents. J Am Diet Assoc. 1995;95:336-340.
32.         Wolf A, Hunter D, Colditz GA, et al. Reproducibility and validity of a self-administered physical activity questionnaire. Int J Epidemiol. 1994;23:991-999.
33.         Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes in women. Ann Intern Med. 1995;122:481-486.
34.         Salmeron J, Manson JE, Stampfer MJ, Colditz GA, Wing AL, Willett WC. Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women. JAMA. 1997;277:472-477.
35.         Colditz GA, Bonita R, Stampfer MJ, et al. Cigarette smoking and risk of stroke in middle-aged women. N Engl J Med. 1988;318(15):937-941.
36.         Feskanich D, Willett WC, Stampfer MJ, Colditz GA. Milk, dietary calcium, bone fractures in women: A 12-year prospective study. Am J Public Health. 1997;87:992-997.
37.         Feskanich D, Willett W, Colditz G. Walking and leisure-time activity and risk of hip fracture in postmenopausal women. Jama. Nov 13 2002;288(18):2300-2306.
38.         Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz GA. Vitamin K intake and hip fractures in women: a prospective study. American Journal of Clinical Nutrition. 1999;69(1):74-79.
39.         Bain C, Feskanich D, Speizer FE, et al. Lung cancer rates in men and women with comparable histories of smoking. J Natl Cancer Inst. Jun 2 2004;96(11):826-834.
40.         Colditz GA, Willett WC, Speizer FE. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women  (Letter to the Editor, errata). N Engl J Med. 1995;333:1357-1358.
41.         Colditz GA, Hankinson SE. The Nurses' Health Study: lifestyle and health among women. Nat Rev Cancer. May 2005;5(5):388-396.
42.         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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47.         Colditz GA, Sellers TA, Trapido E. Epidemiology - identifying the causes and preventability of cancer? Nat Rev Cancer. Jan 2006;6(1):75-83.
48.         Rosner B. Measurement error models for ordinal exposure variables measured with error. Statistics Med. 1996;15(3):293-303.
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50.         Rosner B, Spiegelman D, Willett WC. Correction of logistic regression relative risk estimates and confidence intervals for measurement error: the case of multiple covariates measured with error. Am J Epidemiol. 1990;132:734-745.
51.         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.
52.         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.
53.         Colditz G. Cancer culture: epidemics, human behavior, and the dubious search for new risk factors. Am J Public Health. 2001;91:357-359.
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58.         Kenfield SA, Stampfer MJ, Rosner BA, Colditz GA. Smoking and smoking cessation in relation to mortality in women. Jama. May 7 2008;299(17):2037-2047.
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60.         Kenfield SA, Wei EK, Stampfer MJ, Rosner BA, Colditz GA. Comparison of aspects of smoking among the four histological types of lung cancer. Tob Control. Jun 2008;17(3):198-204.
61.         Morris JN, Kagan A, Patterson DC, Gardner MJ, Raffle PAB. Incidence and prediction of ischaemic heart-disease in London busmen. Lancet. 1966(September 10):553-559.
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63.         Vena JE, Graham S, Zielezny M, Swanson MK, Barnes RE, Nolan J. Lifetime occupational exercise and colon cancer. Am J Epidemiol. 1985;122:357-365.
64.         Colditz G, Cannuscio C, Frazier A. Physical activity and colon cancer. Cancer Causes Control. 1997;8.
65.         Wolin KY, Yan Y, Colditz GA. Physical activity and risk of colon adenoma: a meta-analysis. Br J Cancer. Mar 1 2011;104(5):882-885.
66.         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.
67.         Bernstein L, Henderson BE, Hanisch R, Sullivan-Halley J, Ross RK. Physical exercise and reduced risk of breast cancer in young women. J Natl Cancer Inst. 1994;86:1403-1408.
68.         Maruti SS, Willett WC, Feskanich D, Rosner B, Colditz GA. A Prospective Study of Age-Specific Physical Activity and Premenopausal Breast Cancer. J Natl Cancer Inst. May 13 2008.
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70.         Hu F, Sigal R, Rich-Edwards J, et al. Walking compared with vigorous physical activity and risk of type 2 diabetes in women: a prospective study. JAMA. 1999;282:1433-1439.
71.         Hu F, Stampfer M, Colditz G, et al. Physical activity and risk of stroke in women. JAMA. 2000;283:2961-2967.
72.         Colditz G, Gortmaker S. Cancer prevention strategies for the future: risk identification and prevention intervention. Millbank Q. 1995;73:621-651.
73.         Colditz GA, Wolin KY. Transdisciplinary training in cancer prevention: reflections on two decades of training. J Cancer Educ. Sep 2011;26(3):586-590.
74.         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.
75.         Wolin KY, Colditz GA, Proctor EK. Maximizing benefits for effective cancer survivorship programming: defining a dissemination and implementation plan. Oncologist. 2011;16(8):1189-1196.
76.         Berkey CS, Colditz GA, Rockett HR, Frazier AL, Willett WC. Dairy consumption and female height growth: prospective cohort study. Cancer Epidemiol Biomarkers Prev. Jun 2009;18(6):1881-1887.
77.         Berkey CS, Willett WC, Frazier AL, Rosner B, Tamimi RM, Colditz GA. Prospective study of growth and development in older girls and risk of benign breast disease in young women. Cancer. Apr 15 2011;117(8):1612-1620.
78.         Berkey CS, Willett WC, Frazier AL, et al. Prospective study of adolescent alcohol consumption and risk of benign breast disease in young women. Pediatrics. May 2010;125(5):e1081-1087.
79.         Colditz G, Rosner B. Cumulative risk of breast cancer to age 70 years according to risk factor status: data from the Nurses' Health Study. Am J Epidemiol. 2000;152(10):950-964.
80.         Rosner B, Colditz GA, Iglehart JD, Hankinson SE. Risk prediction models with incomplete data with application to prediction of estrogen receptor-positive breast cancer: prospective data from the Nurses' Health Study. Breast Cancer Res. Jul 3 2008;10(4):R55.
81.         Rosner B, Colditz GA. Nurses' health study: log-incidence mathematical model of breast cancer incidence. J Natl Cancer Inst. Mar 20 1996;88(6):359-364.
82.         Rosner B, Colditz G, Webb P, Hankinson S. Mathematical models of Ovarian Cancer incidence in the Nurses' Health Study. Epidemiology. 2004;16:508-515.
83.         Colditz GA, DeJong D, Hunter DJ, Trichopoulos D, Willett WC. Harvard Report on Cancer Prevention. Volume 1. Causes of Human Cancer. Cancer Causes Control. 1996;7(Suppl 1):1-59.
84.         Colditz GA, DeJong D, Emmons K, Hunter DJ, Mueller N, Sorensen G. Harvard Report on Cancer Prevention. Volume 2. Prevention of Human Cancer. Cancer Causes Control. 1997;8.
85.         Willett W, Colditz G, Mueller N. Strategies for minimizing cancer risk. Scientific American. 1996;275(3):88-95.
86.         Colditz GA, Atwood KA, Emmons K, et al. Harvard report on cancer prevention volume 4: Harvard Cancer Risk Index. Risk Index Working Group, Harvard Center for Cancer Prevention. Cancer Causes Control. Jul 2000;11(6):477-488.
87.         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.
88.         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.
89.         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.
90.         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.


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