Two Topics: Tobacco Control and Dietary Chemoprevention Stephen S. Hecht, Ph.D. February 3-5, 2016 Lansdowne Resort, Leesburg, VA

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1 Two Topics: Tobacco Control and Dietary Chemoprevention Stephen S. Hecht, Ph.D. February 3-5, 2016 Lansdowne Resort, Leesburg, VA

2 Outline Tobacco Control Policy Research Dietary Chemoprevention

3 Percentage of Adults Who Were Current Cigarette Smokers U.S., A. Jamal et al, Morbidity and Mortality Weekly Report, CDC, November 13, 2015

4 Rate per 100,000 Age-Adjusted Total U.S. Mortality Rates for Lung and Bronchus Cancer Both sexes Males Females Year of Death Source: SEER data

5 Current Tobacco Use U.S. adults 16.8%; 40,000,000 cigarette smokers Worldwide 1,250,000,000 cigarette smokers xxx, 000,000 smokeless tobacco users Jamal et al, Morbidity and Mortality Weekly Report, CDC, November 13, 2015; The Tobacco Atlas, 3 rd Edition, 2009

6 Lung Cancer Mortality U.S. 158,000 deaths expected in 2016, 90% caused by cigarette smoking Worldwide 1,589,000 deaths in 2012; 80% in males, 50% in females caused by cigarette smoking Primarily shaped by the tobacco epidemic L.A. Torre et al, CEBP, 2016; ACS, Cancer Facts and Figures, 2016; IARC, World Cancer Report, 2014

7 Cancers Caused by Smoking: IARC Monograph Series Volume 38, 1986 Lung Oral cavity Pharynx Larynx Esophagus Pancreas Bladder Volume 83, 2004, added: Nasal Cavity Stomach Liver Kidney Ureter Cervix Myeloid leukemia Volume 100E, 2012, added: Colorectum Ovary (mucinous) International Agency for Research on Cancer, World Health Organization, Lyon

8 Cancers Caused by Smokeless Tobacco: IARC Monograph Series Smokeless tobacco is carcinogenic to humans: Oral cavity Pancreas Esophagus IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 100E, 2012

9 Deaths Due to Smoking Cancer worldwide: 1,420,000 per year; 21% of total cancer Cancer United States: 185,000 per year; 33% of total cancer Total deaths due to smoking worldwide: 6,000,000 per year IARC World Cancer Reports, 2008, 2014

10 Outline Tobacco Control Policy Research Dietary Chemoprevention

11 Reducing Cigarette Smoking and Use of Other Combusted Products Continue to press ahead with efforts on proven tobacco control methods Legislation (e.g. indoor and outdoor smoking bans) Anti-tobacco advertising Taxation Increase age for purchase of tobacco products to 21 years Enforce plain packaging Enforce product standards Decrease nicotine in cigarettes; decrease use of combusted products

12 Indoor Smoke-Free Laws, U.S.

13 Reducing Cigarette Smoking and Use of Other Combusted Products Continue to press ahead with efforts on proven tobacco control methods Legislation (e.g. indoor and outdoor smoking bans) Anti-tobacco advertising Taxation Increase age for purchase of tobacco products to 21 years Enforce plain packaging Enforce product standards Decrease nicotine in cigarettes; decrease use of combusted products

14 Plain Packaging - Australia

15 Reducing Cigarette Smoking and Use of Other Combusted Products Continue to press ahead with efforts on proven tobacco control methods Legislation (e.g. indoor and outdoor smoking bans) Anti-tobacco advertising Taxation Increase age for purchase of tobacco products to 21 years Enforce plain packaging Enforce product standards Decrease nicotine in cigarettes; decrease use of combusted products

16 Reduce Levels of NNN and NNK in Tobacco: Cancer Prev. Res Ashley et al, Nic. Tob. Res by American Association for Cancer Research

17 Reducing Cigarette Smoking and Use of Other Combusted Products Continue to press ahead with efforts on proven tobacco control methods Legislation (e.g. indoor and outdoor smoking bans) Anti-tobacco advertising Taxation Increase age for purchase of tobacco products to 21 years Enforce plain packaging Enforce product standards Decrease nicotine in cigarettes; decrease use of combusted products

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19 Outline Tobacco Control Policy Research Dietary Chemoprevention

20 Goal Understand mechanisms and identify smokers who are susceptible to lung cancer, so they can be targeted for cessation, surveillance, and prevention.

21 Tobacco Carcinogenesis: Biomarkers to Identify Susceptible Smokers Biomarkers Genetics and Metabolites DNA Adducts and Repair Molecular and Biological Changes S.S. Hecht, JNCI, 91: (1999), Nature Rev. Cancer 3: (2003), U.S. Surgeon General Report, 2014

22 Identifying Susceptible Smokers At a young age, before too much damage is done Use a combination of genetic and biomarker data Target for focused cessation therapy Surveillance and early detection Chemoprevention

23 Outline Tobacco Control Policy Research Dietary Chemoprevention

24 Notes from the Field: Green Chemoprevention as Frugal Medicine J.W. Fahey, P. Talalay, TW Kensler : Cancer Prev. Res. 5: 179 (2012) Food centered chemoprevention Relatively inexpensive and applicable in many settings worldwide Generally avoids problems of drug toxicity and expense Can use standardized food products Can be tailored to personal characteristics such as GSTM1 or GSTT1 null Examples Broccoli sprouts and other cruciferous vegetables Freeze-dried black raspberries Tea Garlic preparations Ginger root Pomegranate Challenges Standardization of food products Uniform dosing Placebo in a randomized clinical trial

25 Broccoli Sprout Beverage Clinical Trial Design Collected urine and blood samples 10 samples per subject Two baseline samples Day 1 Weeks 1, 2, 4, 6, 8, 10, and 12 Quantified mercapturic acids in ~2,800 urine samples Egner, PA; Chen, JG; Zarth, AT; Ng, DK; Wang, JB; Kensler, KH; Jacobson, LP; Munoz, A; Johnson, JL; Groopman, JD; Fahey, JW; Talalay, P; Zhu, J; Chen, T-Y; Qian, G-S; Carmella, SG; Hecht, SS; Kensler, TW. Cancer Prev. Res. 7: , 2014

26 Outline Tobacco Control Policy Research Dietary Chemoprevention Funding for our research is from NIH and FDA

27 Results Mercapturic Acids Egner, PA; Chen, JG; Zarth, AT; Ng, DK; Wang, JB; Kensler, KH; Jacobson, LP; Munoz, A; Johnson, JL; Groopman, JD; Fahey, JW; Talalay, P; Zhu, J; Chen, T-Y; Qian, G-S; Carmella, SG; Hecht, SS; Kensler, TW. Cancer Prev. Res. 7: , 2014