Classifying Foods as Carcinogenic? A Case Study of Red and Processed Meats.

Transcription

1 Classifying Foods as Carcinogenic? A Case Study of Red and Processed Meats. Andrew Milkowski Feb 23, 2016

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3 Outline What is IARC? How are Carcinogen Classifications Determined 2015 IARC Evaluation of Red and Processed Meat

4 IARC

5 What is IARC? - part of UN World Health Organization - headquartered in Lyon, France - founded member countries and a staff of ~300 from 50 countries biennium budget ~ $47.8 million IARC's mission is to coordinate and conduct research on the causes of human cancer, the mechanisms of carcinogenesis, and to develop scientific strategies for cancer prevention and control. The Agency is involved in both epidemiological and laboratory research and disseminates scientific information through publications, meetings, courses, and fellowships

6 114 published or in preparation, plus 8 supplements Identify environmental factors that can increase the risk of human cancer and include chemicals, complex mixtures, occupational exposures, physical agents, biological agents, and lifestyle factors National health agencies use these for policy and regulatory decisions Since 1971, more >900 agents have been evaluated

7 The IARC Monograph Process Working Group is established by a decision to evaluate an agent A call for applications to participate is placed on the IARC website Members are selected and organized into 4 separate subgroups: Literature is assembled via staff work and submissions by interested parties Final review and discussions are completed in a week long face to face meeting in Lyon Conclusions are made and an outline of the written monograph developed Observers are permitted at the final meeting

8 Monograph Working Groups Evaluate Hazards Not a risk analysis

9 The IARC Monograph Process Working Subgroups 1. Exposure data 2. Studies of cancer in humans 3. Studies of cancer in experimental animals 4. Other data relevant to an evaluation of carcinogenicity and its mechanisms

10 The IARC Monograph Process Conclusions are based on categorized evidence Carcinogenicity in Humans Sufficient Evidence, Limited Evidence, Inadequate Evidence, or Lack of Evidence Carcinogenicity in Experimental Animals Sufficient Evidence, Limited Evidence, Inadequate Evidence, or Lack of Evidence Mechanistic and Other Relevant Data Weak, moderate, strong and likely to operate in humans

11 IARC Classifications Group 1 The agent is carcinogenic to humans There is sufficient evidence of carcinogenicity in humans Exceptionally, an agent may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent acts through a relevant mechanism of carcinogenicity.

12 IARC Classifications Group 2A The agent is probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. Exceptionally, an agent may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans. An agent may be assigned to this category if it clearly belongs, based on mechanistic considerations, to a class of agents for which one or more members have been classified in Group 1 or Group 2A.

13 IARC Classifications Group 2B The agent is possibly carcinogenic to humans This category is used for agents for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent for which there is inadequate evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals together with supporting evidence from mechanistic and other relevant data may be placed in this group. An agent may be classified in this category solely on the basis of strong evidence from mechanistic and other relevant data.

14 IARC Classifications Group 3 The agent is not classifiable as to its carcinogenicity to humans This category is used most commonly for agents for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents that do not fall into any other group are also placed in this category. An evaluation in Group 3 is not a determination of non-carcinogenicity or overall safety. It often means that further research is needed, especially when exposures are widespread or the cancer data are consistent with differing interpretations.

15 IARC Classifications Group 4 The agent is probably not carcinogenic to humans. This category is used for agents for which there is evidence suggesting lack of carcinogenicity in humans and in experimental animals. In some instances, agents for which there is inadequate evidence of carcinogenicity in humans but evidence suggesting lack of carcinogenicity in experimental animals, consistently and strongly supported by a broad range of mechanistic and other relevant data, may be classified in this group.

16 IARC Classifications IARC classifies compounds/exposures using this classification scheme: Classifications in 114 IARC Monographs # Group 1 Carcinogenic to humans 118 Group 2A Probably carcinogenic to humans 75 Group 2B Possibly carcinogenic to humans 288 Group 3 Not classifiable as to its carcinogenicity to humans 503 Group 4 Probably not carcinogenic to humans 1

17 IARC Classifications Notable Agents Group 1 Carcinogenic to humans Tobacco smoke, Asbestos, Coal-tar pitch, Alcoholic beverages, Epstein-Barr virus, Outdoor air pollution, Chinese-style salted fish,, Wood dust Group 2A Probably carcinogenic to humans Hairdresser or barber occupational exposure, Human papillomavirus type 68, Hot Mate, Circadian disruption in shiftwork, Acrylamide Group 2B Possibly carcinogenic to humans Human papillomaviruses, Phenobarbitol, Safrole, Caffeic acid, Lead, Coffee, Butylated hydroxyanisole (BHA), Asian Pickled vegetables (traditional), Carpentry and joinery, Welding fumes Group 3 Not classifiable as to its carcinogenicity to humans Group 4 Probably not carcinogenic to humans Caprolactam Cholesterol, Caffeine, N-Nitrosoproline

18 The IARC Monograph - Red and Processed Meats Selection and Priority for Review

19 The IARC Monograph - Red and Processed Meats

20 IARC - Red and Processed Meats Working Group 1. Exposure data 4 members, 2 staff 2. Studies in humans 8 members, 8 staff 3. Studies in animals 3 members, 1 staff 4. Mechanisms - 7 members, 4 staff Additionally there were 8 Observers ( 6 US, 1 France, 1 Uruguay

21 Red and Processed Meats Working Group Focal points Human Epidemiology Weak Associations for Colorectal Cancer Red meat 1.17 inc. risk/100g/d (C.I ) Processed meat 1.18 inc. risk/50g/d (C.I ) Other associations with pancreas and prostate (red meat) and stomach (processed meat)

22 Red and Processed Meats Working Group Focal points Other data relevant to an evaluation of carcinogenicity and its mechanisms N-nitroso compounds Involvement of heme in their formation in he colon High temperature cooking Formation of polycyclic aromatic hydrocarbons Formation of heterocyclic amines DNA adduct formation

23 Red and Processed Meats Classification

24 Media Controversy

25 WHO Clarifies IARC s Press Classification

26 Published in Lancet Oncology online October 26, 2015, Bouvard et. al.. Vol 16, Dec 2015 pp Data on the association of red meat consumption with colorectal cancer were available from 14 cohort studies. Positive associations were seen with high versus low consumption of red meat in half of those studies, including Of the15 informative case-control studies considered, seven reported positive associations of colorectal cancer with high versus low consumption of red meat. On the basis of the large amount of data and the consistent associations of colorectal cancer with consumption of processed meat across studies in different populations, which make chance, bias, and confounding unlikely as explanations Positive associations of colorectal cancer with consumption of processed meat were reported in 12 of the 18 cohort studies that provided relevant data Supporting evidence came from six of nine informative case-control studies

27 Published in Lancet Oncology online October 26, 2015, Bouvard et. al.. Vol 16 Dec 2015 pp Substantial supporting mechanistic evidence was available for multiple meat components (NOC, haem iron, and HAA). Consumption of red meat and processed meat by man induces NOC formation in the digestive tract. High red meat consumption (300 or 420 g/day) increased levels of DNA adducts putatively derived from NOC in exfoliated colonocytes or rectal biopsies in two intervention studies. 19,20 Few human data, especially from intervention studies, were available for processed meat. Haem iron mediates formation of NOC, and of lipid oxidation products in the digestive tract of human beings and rodents.

28 Questions Around the IARC Classification Human Epidemiology Red meat 1.17 inc. risk/100g/d (C.I ) Processed meat 1.18 inc. risk/50g/d (C.I ) Why is one sufficient evidence for Group 1 and the other for Group 2A when they are essentially the same (and both weak) associations?

29 Red and Processed Meats Working Group Mechanisms NOC s Data presented is focused on red meat Microbiome and other interactions ignored Cured meats minor source of nitrate/nitrite in human physiology High temperature cooking PAH s and HCA s Also formed in cooking poultry and fish to sometimes higher levels RTE Processed meats heated at temperatures too low to form HCA s DNA adduct formation Selective use of data null data in significant experiments ignored

30 What s Next? Publication of the full Monograph Expected in August - September 2017 Will provide further details about the logic behind the determinations Part of US Dietary Guidelines 2020 deliberations World Cancer Research Fund Expected 2017 update of Cancer Prevention Document

31 Final Thoughts

32 Context Study in rats reignites debate over cell phones and cancer Liz Szabo, USA TODAY4:58 p.m. EDT May 27, 2016 (Photo: HOW HWEE YOUNG, EPA) A study released Friday found an increased risk of certain cancers in animals exposed to cell phone radiation, a conclusion that could reignite concerns over the safety of the widely used devices. However, some scientists expressed serious concerns about the study, noting inconsistencies in its results. Even officials at the National Toxicology Program, which conducted the research, said the report fails to provide the clear answers many seek... "If cell phones cause tumors, they don't cause a lot of them," Brawley said. "If the risk exists, it is really, really small. It's more like the cancer risk from eating red meat than from smoking cigarettes."

33 Source: J. Heller Green Bay Gazette with permission