European Foundation of Oncology and Environmental Sciences “B. Ramazzini”

1. European Foundation of Oncology and Environmental Sciences “B. Ramazzini” Cesare Maltoni Cancer Research Center Primary prevention in cancer control: the role of the European Ramazzini Foundation and Collegium Ramazzini Dr. Morando Soffritti MTCC, Tunis, Tunisia 15 November 2008

2. Cancer: an environmental disease • According to data from the American Cancer Society: • 1 out of 2 males and 1 out of 3 females will develop cancer over the course of his or her lifetime • the number of people over the age of 70 will double in the next 25 years and the number of tumors will double by 2050 in the US alone

3. Cancer: an environmental disease Factors at the origin of increased cancer incidence in the last 50- 60 years: • Increase in life expectancy of circa 10 years for males and 15 years for females • Increase in the diffusion of agents and situations presenting carcinogenic risks in both the occupational and general environment

4. Cancer: an environmental disease C = f (P x E x A) C = cancer P = predisposition E = environmental exposure A = age

5. Cancer: evidence of environmental risks • Elevated incidence of some types of tumors in geographic areas compared to others. • Studies on immigrants and tumor incidence -breast cancer USA vs Japan • Occupational tumors -workers exposed to asbestos, aromatic amines, vinyl chloride, formaldehyde, etc

6. Cancer: evidence of environmental risks • Transplancental carcinogenesis -case of diethystilbestrol • Behavior and Lifestyle -tobacco use • Results of long term carcinogenicity studies on rodents -50% of agents tested shown to be carcinogenic

7. Cancer: the role of primary prevention • Primary prevention is the identification of potential carcinogenic risks present in the general and occupational environment and the subsequent action to reduce exposure to these risks as much as possible. • Primary prevention has been demonstrated to lower the incidence and mortality of specific types of cancer.

8. Tools to identify environmental carcinogenic risks • Oncologic epidemiological surveys • Short and medium-term studies • Long-term carcinogenesis bioassays on experimental animals

9. Scientific basis for carcinogenesis bioassays • Rodents and humans are mammals which share many basic genetic, pharmacologic, toxicology and carcinogenic responses • All known human carcinogens that have been tested adequately have also been shown to be carcinogenic in animals, and almost always share identical target sites • Nearly 1/3 of human carcinogens were first discovered to induce cancer in animals

10. Chemicals shown to cause cancer first in laboratory animals and then in humans 15. Formaldehyde 1. Aflatoxins 2. 4-Aminobiphenyl 16. Melphalan 3. Asbestos 17. 8-methoxypsoralen + UVA 4. Azothioprine 18. Mustard gas 5. Betel quid with tobacco 19. Myleran 6. 1,3-butadiene 20. Nonsteroidal estrogens 7. Chlorambucil 21. Silica, crystalline 8. Chloranaphazine 22. Solar radiation 9. Chloromethyl methyl ether (technical grade) 23. Steroidal estrogens 10. Ciclosporin 24. 2,3,7,8-TCDD 11. Coal-tar pitches 25. Thiotepa 12. Coal-tars 26. Trichloroethylene 13. Cyclophosphamide 27. Vinyl chloride 14. Diethylstilbestrol Source: Huff 1999

11. 503 53% 14% 31% 2% Results of major international bioassay programs US NTPERF Chemicals/agents studied and published 112 Overall carcinogenicity results • Clear evidence 44% • Equivocal evidence 16% • No evidence 40% • Inadequate bioassays -%

12. Ongoing ERF research projects • Fuels • EMF • Artificial sweeteners • Chemoprevention

13. Concluding remarks 40 years of research and resources (albeit limited) have been dedicated to identifying agents and situations of risk. We have learned the following: • There is wide evidence of the environmental and lifestyle causes of cancer • Primary prevention is crucial to improve results in the strategy of cancer control • Long-term bioassays remain the best tool available to predict and measure occupational and environmental carcinogenic risks

14. Concluding remarks • We are experiencing a period of transition: new energy sources, new technologies, new foods, new pharmaceuticals, new lifestyles • We cannot move forward without taking account of the errors of the past • Today we have more adequate scientific tools for evaluating the safety and risks of the new frontier. We need to use these tools and most of all, take action on the data they provide

15. Primary prevention of environmental and occupational hazards: the role of Collegium Ramazzini

16. Origins The science of occupational medicine emerged during the 17° Century in Italy with the work of Dr. Bernardino Ramazzini. In 1700, Ramazzini published the first edition of his most famous book, “De Morbis Artificum Diatriba” (A Treatise on the Diseases of Workers), the first comprehensive work on occupational diseases.

17. History Three hundred years later, in 1982, Irving J. Selikoff, Cesare Maltoni and other eminent scientists from nations around the world formed an independent academy in honor of the father of occupational medicine, the Collegium Ramazzini.

18. Mission The mission of the Collegium Ramazzini is to advance the study of occupational and environmental health issues and to be a bridge between the world of scientific discovery and the social and political centers which must act on the discoveries of science to protect public health.

19. Secretariat The Secretariat of the Collegium Ramazzini is headquartered in the Castle of Bentivoglio, near Bologna, Italy. The Castle is also home to the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation.

20. Membership The 180 elected Fellows of the Collegium are internationally distinguished, intellectually independent physicians, scientists and advocates who have devoted their professional lives to the improvement of occupational and environmental health and who have embraced the habit of truth.

21. Geographic distribution The Collegium Ramazzini is composed of 208 members, of whom 176 are active Fellows and 32 are Emeritus. Fellows and Emeritus Fellows currently represent 40 countries across 5 continents.

22. Institutional Relations The Collegium Ramazzini is a non-profit organization and is not associated with or supported by a single government body or interest group. In May 2006, the Collegium Ramazzini was admitted as member of special list of International Non-Governmental Organizations of the International Labour Organization.

23. Activities The Collegium Ramazzini disseminates information about primary prevention via the following activities: 1. Conferences and symposia, in particular in the developing world 2. Collegium Ramazzini Statements 3. Annual Ramazzini Days of Carpi 4. Advocacy work with national and international regulatory agencies

24. Conferences Beginning in 1985 and following in ten-year intervals, the Collegium Ramazzini has organized large international scientific conferences on the topic of “Living in a Chemical World”. 1985 Living in a Chemical World, Bologna, Italy 1995 Preventive Strategies for Living in a Chemical World, Washington DC, USA 2005 Framing the Future in Light of the Past: Living in a Chemical World, Bologna, Italy The conference proceedings of all three events were published inAnnals of the New York Academy of Sciences.

25. Symposia Recent symposia in the developing world include: 2006: Quito, Ecuador “Occupational and Environmental Health: Emerging Issues in the Developing World” 2007: Bangkok, Thailand “Occupational and Environmental Health in the Asia/Pacific Region” 2009: New Delhi, India “Preventing emerging occupational and environmental risks in South Asia and beyond"

26. Statements Statements reflect the official orientation of the Collegium on topics of major interest and are used as reference points for governments and international agencies as well as by physicians in occupational medicine. Statements are adopted in full independence and are exclusively based on scientific knowledge and ethical principles.

27. Statements

28. Statements

29. Statements The 2008 statement on “Cancer Prevention, Screening and Early Diagnosis, the Neglected Side of Cancer Control: A Call for Action” is the result of an ad hoc working group chaired by Collegium Ramazzini Fellow Prof. Massimo Crespi. The statement was published in American Journal of Industrial Medicine, the European Journal of Oncology and is available on the CR website. A future MTCC event is being planned to locally address the themes discussed in the statement.

30. Annual Ramazzini Days Every year on the last weekend of October, the Collegium Ramazzini hosts the Ramazzini Days in Carpi, Italy where Fellows and guests participate in workshops on scientific topics and present new data from their respective institutions. During this event the Mayor of Carpi confers the Ramazzini Award on scientists deemed by the Collegium to have made outstanding contributions to furthering the aims of Bernardino Ramazzini in safeguarding public health.

31. Advocacy Work An emphasis on reducing industrial exposure to asbestos and benzene have been among the Collegium’s main topics of interest and intervention since its founding. Recent activities include: July 2008: Filing a position with the US EPA expressing strong disagreement with new asbestos risk assessment methodology. October 2008: An appeal to the delegates to the 4th conference of the parties to the Rotterdam convention re: chrysotile asbestos, endosulfan and tributyl tin.

32. Longe praestantius est quam curare È meglio prevenire che curare It is better to prevent than to cure Bernardino Ramazzini (1633-1714)