Examining Special Nutritional Requirements in Disease States. Steven K. Clinton, MD, Ph.D.

Transcription

1 Examining Special Nutritional Requirements in Disease States. Steven K. Clinton, MD, Ph.D. The Ohio State University Comprehensive Cancer Center 1

2 Financial Conflicts of Interest None Opinions Many 2 Research Support NIH, AICR, DOD, ACS, USDA, OSU-Pelotonia, The Cattleman s Association

3 Examples of Complex Disease Cancer 3

4 Current Standards and Public Health Guidelines: Diet, Nutrition, Physical Activity and Cancer Systematic Reviews: Subcontract In partnership with The Ohio State University Comprehensive Cancer Center 4

5 Purposes of the WCRF - AICR Reports The Ohio State University Comprehensive Cancer Center

6 2018 World Cancer Research Fund American Institute for Cancer Research ( WCRF / AICR ) Coming May 24,

7 The 2007 AICR Report International panel of 21 leaders in the field. with over 250 observers, reviewers, contributors Five year project Over 7,000 studies methodically reviewed All relevant types of study admitted as evidence Standard grading of evidence shown in matrices Emphasis always on food and prevention of cancer Comprehensive set of 10 recommendations Integrated with prevention of other chronic diseases Report of 517 pages, plus summary, plus CD The Ohio State University Comprehensive Cancer Center

8 AICR / WCRF Prevention Guidelines The Ohio State University Comprehensive Cancer Center

9 AICR / WCRF Prevention Guidelines Note: No Specific Nutrient Requirement Recommendations The Ohio State University Comprehensive Cancer Center

10 How are the results on diet, nutrition, lifestyle, and cancer risk categorized? Convincing: basis for recommendation Probable: not strong enough Limited but suggestive Limited and no conclusion Substantial effect on risk unlikely The Ohio State University Comprehensive Cancer Center

11 AICR WCRF 2007

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13 Specific Cancers: Endometrial AICR WCRF 2007 The Ohio State University Comprehensive Cancer Center

14 BMI and Endometrial Cancer AICR WCRF CUP v

15 Endometrial Cancer

16 The Continuous Update Program (CUP) 2010: Breast Cancer 2011: Colorectal Cancer 2012: Pancreatic Cancer 2013: Endometrial Cancer 2014: Ovarian Cancer 2014: Prostate 2014: Breast Cancer Survivors 2015: Liver 2015: Gallbladder 2015: Kidney 2015: Bladder 2016: Lung 2016: Esophagus 2016: Stomach

17 WCRF-AICR / WHO Global Impact N = Nutrition label standards and regulations regarding claims and implied claims on foods O = Offer healthy foods and set standards in public institutions and other specific settings U = Use economic tools to address food affordability & purchase incentives R = Restrict food advertising and other forms of commercial promotion I = Improve nutritional quality of the whole food supply S = Set incentives and rules to create a healthy retail and food service environment H = Harness food supply chain & actions across sectors to ensure coherence with health I = Inform people about food & nutrition through public awareness N = Nutrition advice and counselling in health care settings G = Give nutrition education and skills More than 260 implemented government policy actions across 100 countries (by 2016).

18 Note: No Specific Nutrient Requirement Recommendations Regarding Cancer

19 Complexity The Cancer Continuum 19

20 Do nutrient requirements change during the cancer continuum? Screening Diagnosis Surgical Radiation Chemotherapy Hormonal Biological Targeted Pain management Malnutrition Cachexia Sarcopenia End of Life Care Prevention Treatment High Risk Cohorts Genetic Premalignant Lesions Chemical Exposures Viral Exposures UV Radiation Recovery / Survivorship Obesity/Metabolic/Fitness Chemobrain Hearing/Taste Neuropathy GI dysfunction Cardiopulmonary Reproductive Renal The Ohio State University Comprehensive Cancer Center 20

21 Do nutrient requirements change during the cancer continuum? The Ohio State University Comprehensive Cancer Center 21

22 Complexity Host Genetics 22

23 Genetics of the HOST Inherited Cancer Syndromes Cancer Susceptibility Genes The Ohio State University Comprehensive Cancer Center

24 Inherited Cancer Syndromes (>50 described) Gene BRCA (breast/ovary) APC (polyposis coli) RB (retinoblastoma) Gene prevalence Gene type Study setting Strength of association Absolute risk Population attributable risk Gene-environment interaction p53 (Li-Fraumeni Syndrome) Low Mutation Family Very high High (high penetrance) Low 2 and variable Role of environmental exposure 2 and variable

25 Host SUSCEPTIBILITY GENES IN CANCER RISK Genes CYP1A1 (lung) CYP2D6 (lung) Gene prevalence Gene type Study setting Strength of association Absolute risk Population attributable risk Gene-environment interaction Role of environmental exposure GST-M1 (lung, bladder) Often high Polymorphism or mutation General population / Epi. studies Low to moderate Low High 1 and implicit Crucial

26 Li-Fraumeni Syndrome Li-Fraumeni Syndrome (LFS) is a rare genetic condition characterized by increased risk to develop multiple types of cancer. The cancers that occur in LFS can be diagnosed during childhood, adolescence or adulthood. Cancers include sarcoma, breast, leukemia, lung, brain, adrenal

27 Li-Fraumeni Syndrome and mutant p53: The Guardian of the Genome Also the most common acquired mutation in cancer The Ohio State University Comprehensive Cancer Center 27

28 Lessons Learned from Murine Models The Ohio State University Comprehensive Cancer Center

29 Does nutritional status alter the biology of inherited cancer syndromes in mice?

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31 Energy balance and many nutrients alter inherited cancer in diverse murine models? Human studies are needed to define DRIs relevant to inherited cancer syndromes?

32 Complexity Genetics of the Cancer 32

33 The Cancer Genome Atlas: Molecular Map The Ohio State University Comprehensive Cancer Center

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35 The Cancer Genome Atlas (TCGA) The mutational landscape of cancer is large? Important cancer subtypes are emerging within histopathologic Types. Yet, a more limited array of driver mutations dominate. The Ohio State University Comprehensive Cancer Center

36 The Cancer Phenotype Cell 144, March 4, 2011

37 Driver Mutations and The Hallmarks of Cancer. The Ohio State University Comprehensive Cancer Center

38 Omega-3 Fatty Acids and HER-2/neu (Driver Mutation) Breast Cancer J Nutr Am J Clin Nutr The inhibition of early stages of HER-2/neu-mediated mammary carcinogenesis by dietary n-3 PUFAs Lisa D. Yee, Deepak Agarwal, Thomas J. Rosol, Amy Lehman, Min Tian, Jennifer Hatton, Jessica Heestand, Martha A. Belury, Steven K. Clinton Mol Nutr Food Res. 2013

39 Drugs or Food Components May Reduce Disease Risk and Progression (Women with HER-2 mutations and HER-2 transgenic mice) Human Murine Slide adapted from J. A. Milner

40 Complexity If that is not enough The Genetics of Metastatic and Treated Cancer 40

41 Cancer Genetics is Very Complex (and Frightening) The Ohio State University Comprehensive Cancer Center

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43 We lack an understanding of how diet and nutrition can impact the evolution of cancer at distant sites and during therapy. The Ohio State University Comprehensive Cancer Center 43

44 44 Cancer is a Complex Disease

45 Thoughts on Examining Special Nutritional Requirements in Disease States Cancer DRIs for cancer prevention using the public health approach will continue. The complexity of cancer and the unique aspect of each individuals experience will drive efforts towards personalized nutritional therapy Technology to define nutritional status more precisely Research to define efficacy and safety of interventions Health care reform Access to nutritional support services Reimbursement and integration into care Training of RDs, RDNs, and RD-PhDs The future. DRIs for nutrients remains an essential strategy Formally establish the category of Bioactive Food Components Greater emphasis on Dietary Patterns The Ohio State University Comprehensive Cancer Center 45

46 Thank You The Ohio State University Comprehensive Cancer Center 46

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