6/1/17 I HAVE NO DISCLOSURES. Lifestyle Choices and Cancer Risk. Cynthia Buffington PhD DISCLOSURES. Repair. Cellular Suicide (Apoptosis)

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1 Lifestyle Choices and Cancer Risk Cynthia Buffington PhD DISCLOSURES I HAVE NO DISCLOSURES Mutations Repair Uncontrolled Growth & Proliferation Metastasis TUMOR SUPPESSOR GENES Cellular Suicide (Apoptosis) Lifestyle Effectors Body Size Amt. and Type of Foods Physical Activity Sleep Stress/Distress Other 1

2 LIFESTYLE VS. CANCER RISK Body Size Diet/Nutrition Physical Activity Sleep Stress/Distress OBJECTIVES Lifestyle vs. Cancer Risk -General Population -Genetic Mutation OBJECTIVES - Study Findings of Lifestyles of FORCE National Meetings participants with BRCA1,2 mutations 2

3 LIFESTYLE: WEIGHT MANAGEMENT Lean Overweight Obese BODY SIZE VS. CANCER RISK Cancer Risk BMI (kg/m2) OBESITY-CANCER RISK Endometrial Cancer Thyroid Liver Kidney Prostate (aggressive) Esophagus Colorectal Cancer Ovarian Pancreatic Breast Cancer Gallbladder Hematopoietic System Non-Hodgkin s Lymphoma Multiple Myeloma Leukemia WCRF/AICR CUP 2009; 2012; 2016 WHO 2016 AICR Obesity and Cancer 3

4 HORMONES FFA Conditions Insulin IGF1 Androgens Estradiol Leptin Adiponectin Il-6 PAI-1 TNF-a Insulin Resistance Inflammation Oxidative Stress Mitochondrial Function Microbiota, More Mutations Cellular Suicide (Apoptosis) Repair TUMOR SUPPESSOR GENES Uncontrolled Growth & Proliferation Metastasis OBESITY AND CANCER Cancer Diagnosis Obesity Overweight Wt. GAIN -Disease Relapse -Secondary Cancer WCRF/AICR Report (2 nd. Edition 2007) WCRF/AICR CUP Chan DS et al. Ann Oncol 2014 Reeves GK et al. BMJ 2007 Calle EE et al. N Engl J Med 2003 Renehan AG et al. Lancet 2008 Rock CL et al. Cancer J Clin 2012 WEIGHT GAIN POST-DIAGNOSIS Nurses Health Study 5, Median gain 6 lbs. = 35% risk for relapse Median gain 17 lbs. = 64% risk for relapse Kroenke CH et al. J Clin Oncol 2005 North Central Oncology Group 553 early stage, FU = 6.6 y 5.9 kg (13 lb.) 50% relapse Camoriano JK et al. J Clin Oncol

5 WEIGHT GAIN BREAST CANCER 5-14 lb > 20 lb 50-96% Rooney M & A Wald. Clin J Oncol Nurs 2007 Chan DSM & T Norata. Curr Treat Options Oncol 2015 BODY COMPOSITION Adipose Tissue Muscle Mass Vance V et al. Obes Rev 2011 Harvie MN et al. Breast Cancer Res Treat 2004 Keun HC et al. Clin Cancer Res 2009 Demark-Wahnefried W et al. Cancer 2012 Sheean PM et al. Breast Cancer Res Treat 2012 TREATMENT EFFECTS Chemotherapy - Dosage - Duration Radiation Hormones Multi-treatment Makari-Judson G. World J Clin Oncol 2014 Vance V et al. Obes Rev 2011 Rooney M & A Wald. Clin J Oncol Nurs 2007 Chlebowski et al. J Clin Oncol 2002 Sedjo et al. J Cancer Surviv 2014 Chan DSM & T Norata. Curr Treat Options Oncol

6 PHYSICAL EFFECTS - Reduced Physical Activity - Poor Physical Function Neuropathy Pain Anemia Feeling Sick Fatigue OBESITY AND CANCER Overweight Obesity + Cancer Risk Weight Gain + -Disease Relapse -Secondary Cancer - Weight Loss - Chlebowski RT et al. J Natl Cancer Inst 2006 Eliassen AH et al. JAMA 2006 Argenta PA Gynecol Oncol 2017 Zhous X et al. Obes Surg 2016 LINK Obesity Cancer 6

7 BRCA: BODY SIZE/WT. LOSS VS. ONSET King et al. Science 2003 Lean vs. Overwt. at menarche and 21 y delays age of Onset Kotsopoulos J et al. Breast Cancer Res 2005 Wt. Loss 10 lbs (18 to 30 y) has protective effect for early onset BRCA: WT. GAIN/OBESITY VS. CANCER RISK/ONSET? YES NO Kotsopoulos J et al. Breast Cancer Res 2005 Nkondjock A et al. Breast Cancer Res Treat 2006 Chang-Claude J et al. J Cancer Res Clin Oncol 1997 McGee J et al. Obesity 2012 Manders P et al. Breast Cancer Res Treat 2011 For review see Pettapiece-Phillips R et al. Cancer Casues Control 2015 NUTRITION 7

8 Anti-Cancer Foods AICR Foods that Fight Cancer Anti-cancer Foods Reduce development of cancer Reduce progression of cancer AICR Anti-cancer Foods AICR Cancer Fighters in Your Food Anti-Cancer Foods Cruciferous Vegetables Green Leafy Vegetables Alliums Legumes Whole Grains Seeds, Nuts Colorful Fruits & Vegetables Berries, Grapes Anti-Cancer Foods Coffee, Tea Protein Healthy Fat 8

9 Processed Meats (carcinogens, smoked, salted) Red Meats (> 18 oz/wk) (beef, lamb, pork) Saturated Fat For review see: Xia H et al. Medicine 2015 Cao et al. Int J Cancer 2016 Wu et al. Nutrients 2016 Alcohol Sugar Processed Grains Dong et al. Breast Cancer Res Treat 2011 Jiang Y et al. Cancer Res 2016 HIGH RISK: BRCA Nkondjock A et al. Breast Cancer Res Treat 2006 Nkondjock A, Ghadirian P. Breast Cancer Res Treat 2007 Nkondjock A et al. Int J Cancer 2006 Dennis J et al. Breast 2010,

10 RECOMMENDATIONS PHYSICAL ACTIVITY WCRF/AICR, ACS, ACSM: -Engage in regular physical activity -Engage in activity at diagnosis and long-term follow-up -Avoid inactivity even in patients undergoing difficult treatment EXERCISE AND CANCER PREVENTION Number of studies find physical activity reduces cancer occurrence/recurrence (20 to 50%). 180 minutes per week 50% Reduction Recurrence Nurses Health Study Holmes MD et al. JAMA 2005 Lahart IM et al. Acta Oncol 2015 Schmid D & MF Leitzmann. Ann Oncol 2014 Ibrahim et al. Med Oncol 2011 Loprinzi PD & HLee Oncol Nurs Forum 2014 Kruk J & U Czerniak. Asian Pac J Cancer Prev 2013 Behrens G et al. Eur J Epidemiol 2014 BENEFITS DURING TREATMENT Physical Function Body Composition Cramp F & Byron-Daniel J. Cochrane Database Syst Rev 2012 Van Vulpen JK et al. Maturitas 2016 Jones et al. Cancer Prev Res 2013 Leach HJ et al. Support Cancer Care

11 EXERCISE DURING CHEMO May Improve Efficiency of Chemo Exercise during chemotherapy improves breast cancer disease-free survival Courneya KS et al. Med Sci Sports Exerc 2014 BENEFITS Reduce cancer fatigue Improves body composition Improves physical function Reduces risk weight gain Reduces anxiety, stress, depression Improves sleep duration/quality Mishra SE et al. Cochrane Database Syst Rev 2012 Cramp F & Byron-Daniel J. Cochrane Database Syst Rev 2012 HORMONES Conditions Insulin, IGF1, E2 Oxidative Stress Insulin Resistance Inflammation Mutations Repair Cellular Suicide (Apoptosis) TUMOR SUPPESSOR GENES Decrease Growth, Proliferation, Metastasis 11

12 BRCA: PHYSICAL ACTIVITY King et al. Science 2003 YES. Teenage years = Delayed onset Pijpe A et al. Breast Cancer Res Treat 2010 YES. Activity 30 y reduced risk Nkondjock A et al. Breast Cancer Res Treat 2006 NO. BC risk vs. levels of physical activity For review see Pettapiece-Phillips R et al. Cancer Causes Control 2015 SLEEP Need: 7 to 9 hours SLEEP LOSS AND CANCER Sleep Loss Risk Breast Cancer Occurrence/Recurrence Breast Cancer Aggressiveness Shift Workers Night Workers Poor Sleep Quality Short Duration Malina et al. Gynecol Obstet Fertil 2013 Wang et al. Scand J Work Environ Health 2012 Thompson CL et al. Breast Cancer Res Treat 2012 He C et al. Int Arch Occup Environ Health 2015 Soucise A et al. Breast Cancer Res Treat

13 SLEEP LOSS Indirect Causes Weight Gain/Obesity/Fat Accumulation Appetite Fat Accumulation Fat Utilization Decrease Physical Activity Leger D et al. Mol Cell Endocrinol 2015 Khalyfa A et al. Sleep 2014 Cedernaes J et al. Diabetes 2015 Chaput JP et al. Obesity 2014 Nedeltcheva A et al. Ann Intern Med 2010 SLEEP LOSS Impaired sleep quality occurs among most cancer patients and studies find 30 to 50% of individuals with cancer suffer from insomnia O-Donnell JF Clin Cornerstone 2004; Davidson JR et al. Soc Sci Med 2002; Theobald DE Clin Cornerstone 2004; Kozachik SL et al. Cancer Nurs 2008; Breen SJ et al. Med J Aust 2009 BRCA (previvors) Poor Sleep Quality (PSQI) Sleep Disturbance related distress, cancer-related worry, fatigue Shochat, E Dagan. J Sleep Res 2010 PSYCHOLOGICAL DISTRESS Stress and Stress Catecholamines, Cortisol Hormones Initiation, Growth/ Progression Shin KJ et al. Curr Pharm Des 2016 Powell ND et al. Brain Behav Immun 2013 Yuan A et al. Exp Ther Med

14 STRESS/DISTRESS Indirect Causes Appetite Food Cravings Fat Accumulation Physical Activity HIGH RISK PATIENTS Distress Stress Anxiety BRCA Affected and Non-affected Early Months Intermediate Long-term See Review: Ringwald J et al. J Genet Counsel 2016 SUMMARY Poor lifestyle (overweight and obesity, poor nutrition, inactivity, insufficient sleep, psychological distress) increases the risk for CANCER. 14

15 SUMMARY A healthy lifestyle may help to reduce cancer risk in individuals with/without genetic mutations. Lifestyle STUDY FORCE 2013 How healthy is your lifestyle? STUDY POPULATION Study Population: FORCE Attendees National Meetings BRCA mutation carriers Survivors 44% Previvors 52% Controls Matched for age, body size No family history breast/ ovarian cancer 15

16 MEASUREMENTS General Questionnaire Measurements: -Anthropometrics (wt., ht., BMI, Fat, Lean tissue, waist circumference) -Diet (3-day food records) -Physical Activity (General Practice) -Physical Function (RAND Quality of Life) -Sleep Quality (Self-reported) -Psychological Distress Anxiety (BAI) and Emotional Quality of Life (RAND) Findings? Anthropometrics Group Wt. (lbs) BMI (kg/m 2 ) Fat (%) Lean: Fat Controls Previvors Survivors a 1.81 a a p<0.05 = NS Survivors vs. Previvors or Controls 16

17 3 Lean-to- Fat Mass *γ * γ.5 0 CONTROLS PREVIVORS SURVIVORS p<0.02 Controls vs. Survivors p<0.003 Previvors vs. Survivors Physical Effectors: Physical QoL Lean:Fat Mass (-) Physical Function Pain *p<0.05 Lean:Fat Mass vs. Measures of Physical QoL Found: Body composition associated with poor physical function Physical Effectors: Physical Activity Lean-to-Fat Mass ACTIVE INACTIVE *p<0.01 Active vs. Inactive Poor body composition associated with inactive lifestyle 17

18 % Physically Active 68% 77% 45% Survivors Controls Previvors Quality Sleep 65% 42% 25% Controls Previvors Survivors PSYCHOLOGICAL DISTRESS Anxiety a a BAI Score Controls Previvors Survivors Emotional QoL a a Score a p=0.01 Control Values 30 Controls Previvors Survivors 18

19 DIET Measure Controls Previvors Survivors Tot Kcal % Fat % Carbs % Protein Fiber g Sugar g Alcohol/wk No Significant Differences OVERVIEW q Wt. BMI ü Body Composition (Survivors) ü Physical Activity, Function (Survivors) ü Sleep Quality (Previvors, Survivors) ü Anxiety, Emotional Issues (Previvors, Survivors) q Diet (?) CONCLUSION -For individuals who inherit mutations that increase cancer risk, preventative strategies are of utmost importance. -Evidence suggests that a healthy lifestyle may help to prevent or delay cancer onset in mutation carriers. 19