2018 Iowa Cancer Summit Cancer and Obesity: What We Know Chuck Lynch, MD, PhD

1. 2018 Iowa Cancer SummitCancer and Obesity:What We KnowChuck Lynch, MD, PhD

2. Presentation Objectives • Describe relationship between obesity and cancer risk • Identify specific cancer types linked to obesity • Describe how obesity increases cancer risk at molecular level • Discuss actions that can be taken to reduce obesity

3. Heart Disease Deaths versus Cancer Deaths, Iowa vs US, 1975-2015(Source: SEER*Stat, version 8.3.5)(Rates are age-adjusted to 2000 US population and expressed per 100,000)

4. Heart Disease Deaths versus Cancer Deaths, Iowa, 2010-2015(Source: SEER*Stat, version 8.3.5)(Rates are age-adjusted to 2000 US population and expressed per 100,000)

5. Cancer is primarily a disease of older agesPercent of New Invasive Cancer Cases and Cancer Deaths by Age Group, Iowa, 2010-14(Source: SEER*Stat 8.3.4) 80% of cancers age 55+ 90% of deaths age 55+

8. Leading actual causes of cancer in this country are lifestyle factors. Potential Reduction of Modifiable Factors on Cancer Burden in United States among Adults 30+ Years Old, 2014(Source: Islami F et al. Ca Cancer J Clin68:31-54, 2018 ) Percent reduction (total potential reduction=42.0%) 3.7

9. Presentation Objectives • Describe relationship between obesity and cancer risk • Identify specific cancer types linked to obesity • Describe how obesity increases cancer risk at molecular level • Discuss actions that can be taken to reduce obesity

11. Percent of Obesity-Attributable Cancers in United States among Adults 30+ Years Old by Sex, 2014 (Source: Islami F et al. Ca Cancer J Clin68:31-54, 2018)

12. Presentation Objectives • Describe relationship between obesity and cancer risk • Identify specific cancer types linked to obesity • Describe how obesity increases cancer risk at molecular level • Discuss actions that can be taken to reduce obesity

13. Cancer: A Multistep Process Development of cancer through stepwise accumulation of complementary driver mutations. The order in which various driver mutations occur is usually unknown and may vary from tumor to tumor.

14. Eight cancer hallmarks and two enabling factors (genomic instability and tumor-promoting inflammation)(HanahanD, Weinberg RA: Hallmarks of cancer: the next generation. Cell 144:646, 2011.) Most cancer cells acquire these properties during their development, typically due to mutations in critical genes.

15. p53-encoding tumor suppressor gene, TP53, is the most commonly mutated gene in human cancer (also know as Guardian of the Genome)

16. How does obesity cause cancer?(Perez-Hernandez AI et al. Mechanisms linking excess obesity and carcinogenesis promotion. Frontiers in Endocrinology 2014)

17. Presentation Objectives • Describe relationship between obesity and cancer risk • Identify specific cancer types linked to obesity • Describe how obesity increases cancer risk at molecular level • Discuss actions that can be taken to reduce obesity

18. Population Interests in Cancer Prevention and Control Etiology & Prevention Early Detection Quantity & Quality of Life Risk Factors Negative Influences Genes Environment Birth Cancer Diagnosis Death Protective Factors Positive Influences Stage Distribution Incidence Rates Survival Rates Mortality Rates

19. Obesity and the Economy, U.S.Project Ideas(Ludwig DS et al. JAMA 301(5):533-535, 2009) • Improving food quality • Provide loans/grants to revitalize family farming • Establish local farm to community (and school) food distribution systems • Build community produce gardens • Promoting physical activity • Build sidewalks/pedestrian paths • Build bike paths and lanes • Build indoor and outdoor recreational facilities (e.g., parks) • Establish nature preserves with hiking trails • Build integrated public transportation systems that link bike paths, recreational facilities, farmer’s markers, etc. How many of these ideas do you feel are being pursued in your community?

20. The Community Guide – Recommended Task Force Findings(https://www.thecommunityguide.org/topic/nutrition?field_recommendation_tid=All&items_per_page=5&page=1) • Diabetes: Combined diet and physical activity promotion programs to prevent type 2 diabetes among people at increased risk • Obesity: Worksite programs • Nutrition: Gardening interventions to increase use of vegetable consumption among children • Obesity: Meal and fruit and vegetable snack interventions to increase Healthier foods and beverages provided by schools

21. Comprehensive Cancer Control Plans, 2018 https://www.cdc.gov/cancer/ncccp/ccc_plans.htm

22. Iowa Cancer Plan – Obesity and Physical Activity Actions • Increase access to and availability of healthy food and beverage choices in public locations and private businesses, including grocery stores, convenience stores, schools, restaurants and workplaces. • Implement policies that increase access to healthy food and decrease access to unhealthy food. • Require public and private venues including restaurants to label all food and drink products with nutritional information. • Increase awareness and educate policy makers about food swamps and food deserts and their contribution to obesity. • Establish workplace and community policies that support breastfeeding. • Improve community design and infrastructure to create environments that support increased physical activity. • Support initiatives that increase opportunities for physical activity in schools and workplaces. • Increase access to overweight and obesity screening and educate providers on the associated risk factors. • Engage providers and patients in healthy weight management and best practices, including the role of nutrition and physical activity as part of cancer prevention, treatment and care. • Support third-party reimbursement for primary care treatment of overweight and obesity from medical providers, registered dieticians and other qualified health care providers.

23. Wisconsin Cancer Control Plan to Reduce Obesity • Strategy A: Increase physical activity - Action steps • Improve safe, built environments to encourage physical activity • Improve access to and utilization of programs that promote physical activity within targeted populations in communities, workplaces and schools • Develop and promote planning, zoning and transportation policies that build physical activity into daily routines • Develop a social marketing campaign that emphasizes the benefits of sustained physical activity • Adopt, implement and enforce standards for physical activity in childcare, after school care and schools • Strategy B: Increase healthy balanced diets – action items • Increase availability and affordability of safe, healthy food & beverages in communities, workplaces and schools • Adopt, implement and enforce nutrition and nutrition education standards to promote healthy food and beverages in childcare, after school care and schools • Limit advertising of less healthy foods and beverages • Develop a social marketing campaign that emphasizes the benefits of healthy foods and beverages • Support policies and programs that increase breastfeeding initiation, duration and exclusivity • Strategy C: Increase screening of and treatment for obesity - action steps • Train health care providers on how to use a lifestyle assessment protocol with patients annually and accurately screen for obesity • Promote reimbursement of nutrition and physical activity counseling and interventions • Provide patients with tools for self-assessment and tracking of eating and physical activity habits.

24. Pharmaceutical SolutionO’Neil PM et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet 2018 (Aug 25);392:637-49 • Background Obesity is a major public health issue, and new pharmaceuticals for weight management are needed. Therefore, we evaluated the efficacy and safety of the glucagon-like peptide-1 (GLP-1) analogue semaglutide in comparison with liraglutide and a placebo in promoting weight loss. • Methods A randomised, double-blind, placebo and active controlled, multicentre, dose-ranging, phase 2 trial. The study was done in eight countries involving 71 clinical sites. Eligible participants were adults (≥18 years) without diabetes and with a body-mass index (BMI) of 30 kg/m² or more. • FindingsBetween Oct 1, 2015, and Feb 11, 2016, 957 individuals were randomly assigned. All semaglutide groups versus placebo were significant. Estimated weight loss of 10% or more occurred in 10% of participants receiving placebo compared with 37–65% receiving 0·1 mg or more of semaglutide. All semaglutide doses were generally well tolerated, with no new safety concerns. The most common adverse events were dose-related gastrointestinal symptoms, primarily nausea. • InterpretationIn combination with dietary and physical activity counselling, semaglutide was well tolerated over 52 weeks and showed clinically relevant weight loss compared with placebo at all doses.

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