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International Agency for Research on Cancer Lyon, France Global cancer control: an interdisciplinary approach to prevention Dr Christopher P Wild PhD Director.

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Presentation on theme: "International Agency for Research on Cancer Lyon, France Global cancer control: an interdisciplinary approach to prevention Dr Christopher P Wild PhD Director."— Presentation transcript:

1 International Agency for Research on Cancer Lyon, France Global cancer control: an interdisciplinary approach to prevention Dr Christopher P Wild PhD Director

2 Describing occurrence Establishing causes Evaluating prevention Supporting implementation

3 Global cancer control: an interdisciplinary approach to prevention The scale of the cancer problem Implementing what we know Addressing what we don’t know

4 Premature deaths (ages 30 to 69 years) from cancer and other NCDs in 2011 Cancer: 15.8% Total: 1.46 million Cancer: 30.2% Total: million Cancer: 17.0% Total: million Extracted from WHO Global Health Observatory Data Repository

5 Global cancer burden – incidence, mortality and prevalence (2012) Source: GLOBOCAN Globally 1 in 5 men and 1 in 6 women will develop cancer before the age of 75 years …. and 1 in 8 men and 1 in 12 women will die from the disease

6 Incidence: 14.1 million new cases worldwide (both sexes) (6.1 in more developed regions, 8.0 in less developed regions) Global Burden of Cancer (2012) Source: GLOBOCAN 2012

7 Global Burden of Cancer (2012) Mortality: 8.2 million deaths worldwide (both sexes) (2.9 in more developed regions, 5.3 in less developed regions) Source: GLOBOCAN 2012

8 Where does the burden fall – geography? Incidence Mortality 57% of cancer cases and 65% of cancer deaths occur in less developed regions of the world

9 Where does the burden fall – development? HDI> billion 0.54≤HDI< billion 0.71 ≤ HDI< billion HDI< billion

10 Rates of Disability Adjusted Life Years by HDI Globally in million years of healthy life were lost, the majority (>90%) years of life lost (YLLs) rather than years living with disability (YLDs) Soerjomataram I, et al. Disability-adjusted life years: country-specific estimates for 27 cancers in 12 world regions. Lancet 380: (2012). per 100,000

11 Cancer: a global but not uniform problem Men Women Breast cancer: 25% of all female cancers; 20% of all cancer survivors

12 Five most frequent forms of cancer in 2012 by HDI Source: GLOBOCAN 2012, UNDP.

13 Breast cancer (female): estimated incidence and mortality rates by region Source: GLOBOCAN 2012

14 Projected global cancer incidence and mortality burden Millions cases per annum Incidence Mortality

15 Assuming no change in underlying incidence Where will the burden fall – development? million new cases % Increase Bray F et al. Global cancer transitions according to the Human Development Index ( ): a population based study. Lancet Oncol 2012; 13:

16 Age-standardised rates per 100,000, CIV vol. 10 Cancer rates are changing over time and by development: breast and cervix by HDI

17 Cancer rates are changing over time and by development: colorectal cancer by HDI Age-standardised rates per 100,000

18 Cancer transitions by HDI index ( ) High and Very high HDI: breast, lung, colorectum and prostate most common Medium HDI: oesophagus, stomach and liver cancers also common Low HDI: cervical cancer more common than breast and liver Medium and high HDI: decreases in cervical and stomach cancer incidence offset by increases in breast, prostate and colorectum Bray F et al. Global cancer transitions according to the Human Development Index ( ): a population based study. Lancet Oncol 2012; 13:

19 “We cannot treat our way out of the cancer problem” A balanced and integrated approach to prevention and treatment is required

20 Global cancer control: an interdisciplinary approach to prevention The scale of the cancer problem Implementing what we know Addressing what we don’t know

21 Primary cancer prevention Around half of cancers could be prevented by applying the knowledge we have; The majority of cancers have a lifestyle or environmental cause, so the potential for prevention is much higher Vineis P and Wild CP (2014) The Lancet, 383:

22 IARC Monographs Volume 100

23 Major cancer risk factors globally Risk FactorComments Tobacco Implement WHO Framework Convention on Tobacco Control; taxation; bans on advertising; regulations on smoking in public places; counter the introduction into low and middle-income countries Infections HBV and HPV vaccination; H. pylori eradication (?); A void contaminated injections; treatment of HBV and HCV chronic carriers Alcohol Avoid harmful use of alcohol; increase awareness; taxation and regulation Physical inactivity, overweight and obesity Increase physical activity and improve weight control; major area where research is needed

24 Risk FactorComments Radiation Avoid excessive sun exposure and indoor tanning; avoid excessive use in medical diagnosis, including in children; awareness and remediation of indoor radon levels Environmental carcinogens Naturally occurring (arsenic, aflatoxins); air pollution: regulatory and other control measures Occupations Occupational health; counter risks of “exporting” at-risk occupational exposures to low and middle- income countries Reproductive factors and hormones Allied to earlier age at menarche, later age at first live birth; fewer children; shorter duration of breast feeding Major cancer risk factors globally

25 Regional variation in cancer risk factors: infection related cancers

26 Opportunities for early detection and treatment Breast cancer*: population-based screening; mammography, clinical breast examination; breast awareness Cervical cancer: cytology; HPV DNA testing; visual inspection with acetic acid; c Colorectal cancer: population-based screening; FOBT, sigmoidoscopy, colonoscopy Oral cancer: in high incidence regions (e.g. east Asia) *IARC Handbook on Cancer Prevention vol. 15 Nov 2014; supported by INCa, France

27 Prevention works but takes time – lung and cervix Lung, men Cervix uteri

28 Prevention works but takes time – HPV vaccination Van de Velde et al., J. Natl. Cancer Inst., 104:

29 Global cancer control: an interdisciplinary approach to prevention The scale of the cancer problem Implementing what we know Addressing what we don’t know

30 Cancers where aetiology is (largely) unknown Organ sitesEstimated annual no. new cases worldwide Percent global cancer burden Prostate1,100, Lymphoma and Leukemia 850, Kidney340, Pancreas340, Thyroid300, Brain260, Colorectal1,400,0009.7

31 Basic Science PopulationPatient Causes and Prevention Personalized treatment Two-way Translational Cancer Research Specific molecular alterations Risk factors Prognosis Laboratory Methodologies genomics, transcriptomics, epigenomics, proteomics, metabolomics Wild CP (2012) Int. J. Epidemiol, 41: Wild CP et al., (2013) Env. Molec. Mutagen.54:

32 ExposureDisease Temporal application of exposure biomarkers in cancer epidemiology Adult cohort Case-control study Timing of exposure measurement Carcinogen metabolites DNA/protein adducts Cytogenetic alterations Mutation spectra Antibodies Peri-natal Childhood Adolescence Adult Birth cohort

33 Laboratory science in population studies – five areas of promise Improved exposure assessmentContributing to biological plausibilityStratifying risks by tumour sub-groupEvaluating interventionsHazard and risk assessment

34 Importance of environmental and lifestyle exposure assessment Most common chronic diseases have an environmental or lifestyle aetiology Currently exposure measurement is problematic in many areas, leading to misclassification Value of prospective cohort studies (e.g. UK Biobank) are predicated on the availability of accurate exposure assessment The requirement for an “exposome” to complement the genome (see Wild CP (2005) CEBP14: ; Wild CP (2012) Int. J. Epi, 41: 24-32)

35 Technological advances applicable to epidemiology Biomarkers (omics) – general or targeted Transcriptomics, Proteomics, Metabolomics, Epigenomics, Adductomics, Lipidomics Sensor technologies (including mobile phones) Environmental pollutants, physical activity, stress, circadian rhythms, location (global positioning systems (GPS)) Imaging (including mobile phones, video cameras) Diet, environment, social interactions Electronic diaries, palm top computers Behaviour and experiences (ecological momentary assessment), stress, diet, physical activity

36 Exposure – clues from transcriptomics A A: Probe sets comparing smokers and nonsmokers: Top right: higher expression in smokers; Top left: lower expression in smokers B: Up-regulated in smokers >1; down-regulated in smokers <1 compared to nonsmokers C: Expressed above average in red, below in blue; each row is one of 375 smoking-responsive genes Tilley et al., PLoS ONE 6: July 2011

37 Exposure – clues from methylomics Hernandez Vargas et al., PLoS One 2010 Methylation of specific gene promoter regions by: Tumour grade Risk factor

38 Exposure - clues from metabolomics Urinary polyphenols in high and low consumers within the EPIC study Edmands W, Scalbert A IARC, unpublished

39 Laboratory science in population studies – what is promised? Improved exposure assessmentContributing to biological plausibilityStratifying risks by tumour sub-groupEvaluating interventionsHazard and risk assessment

40 ©2012 by American Association for Cancer Research Kinetics of N2-ethylidene-DNA adducts in the oral cavity after drinking alcohol Subjects consumed approx. 27 (d1), 39 (d2) or 51 (d3) g ethanol; provided oral mouthwash for DNA extraction Dose response with peak adduct after 4 hours; up to 100-fold above baseline Considerable inter- individual variation Balbo S et al. Cancer Epidemiol Biomarkers Prev 2012; 21:

41 Laboratory science in population studies – what is promised? Improved exposure assessmentContributing to biological plausibilityStratifying risks by tumour sub-groupEvaluating interventionsHazard and risk assessment

42 Genomic and transcriptomic architecture of breast tumours Analysis of acquired somatic copy number aberrations and gene expression in 2,000 tumours Identified novel molecular sub-groups of breast cancers with distinct clinical outcomes Subgroup-specific gene networks associated with aberration hotspots A basis for stratified medicine (beyond Herceptin) But any implications for breast cancer aetiology? Curtis et al., Nature 2012

43 Standardized protocol for clinical, pathological information and biological specimens Identification of specific endogenous (genetics and genomics) and exogenous factors (biological modifications, behavioral, dietary and cultural factors) with specific subtypes of premenopausal BC, identified based on molecular and pathological phenotypes Provide advanced training, development of the BC research community in Latin America, and influence the public health agenda regarding the management of BC IARC PI: Dr Isabelle Romieu, Section of Nutrition and Metabolism, IARC Molecular subtypes of premenopausal breast cancer in Latin American Women

44 Laboratory science in population studies – what is promised? Improved exposure assessmentContributing to biological plausibilityStratifying risks by tumour sub-groupEvaluating interventionsHazard and risk assessment

45 Widespread exposure through contamination of staple foods (cereals and nuts): Aflatoxicosis Liver cancer Growth impairment Immune modulation? Aflatoxins and human health

46 Exposure to aflatoxin associated with impaired growth Z >0Z 0 to-2Z -2 to -3Z <=-3 AF- alb (pg/mg) Growth Status (Z score) Height for AgeWeight for Age

47 Longitudinal study of aflatoxin exposure and child growth in Benin Quartile of AF-alb adducts over 8 months Mean height increase (cm) 200 children, aged months followed over 8 months Adjusted for age, height, weaning status, mothers SES and village

48 Biomarkers and intervention studies – aflatoxin in subsistence farms in Guinea Sept/OctDec/JanFeb/Mar Survey 1Survey 2Survey 3 20 Villages (10 intervention, 10 control), 30 subjects per village Blood sample collectionGroundnut sample collection Intermediate Survey 1 Intermediate Survey 2

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52 Mean levels of AF-alb are reduced in individuals following intervention Turner et al., (2005) The Lancet, 365,

53 Intervention increases the number of individuals with non-detectable blood AF-alb Turner et al., (2005) The Lancet, 365,

54 Implementation or operational cancer research - a neglected area

55 Gulf of Thailand Andaman Sea CAMBODIA LAOS PDR VIETNAM BURMA THAILAND Bangkok Lampang Province Map showing Lampang Province, Thailand Evaluate the acceptability, feasibility, organization, implementation, monitoring and evaluation of colorectal cancer screening in the general population in Thailand by integrating the programme into the existing public health services Inform and guide the eventual scaling up of CRC screening to cover the entire country In collaboration with the: National Cancer Institute Thailand Goals The Thailand Colorectal Cancer Screening (CRC) Pilot Demonstration Project in Lampang Province

56 The Thailand Colorectal Cancer Screening (CRC) Pilot Demonstration Project in Lampang Province ( ) Stage I = 2 Stage II = 12 Stage III = 7 Unknown = 2 Stage I = 2 Stage II = 12 Stage III = 7 Unknown = 2 Participated n = 80,012 (63%) iFOBT negative n = 79,139 iFOBT negative n = 79,139 Colonoscopy n = 627 (72%) Colonoscopy n = 627 (72%) Invited to participate (50 to 65 years) n = 127,301 Invited to participate (50 to 65 years) n = 127,301 Completed faecal occult blood testing n = 80,012 (63%) Adenoma n = 187 (Advanced adenoma (n = 75)) Adenoma n = 187 (Advanced adenoma (n = 75)) iFOBT positive n = 873 (1.1%) iFOBT positive n = 873 (1.1%) Colorectal cancer n = 23 Colorectal cancer n = 23 Khuhaprema et al, BMJ Open 2014;4:e003671

57 Gambia Hepatitis Intervention Study – randomized trial of HBV vaccine Evaluation of the HBV vaccine to prevent liver disease and liver cancer Begun in mid-1980s including ~120,000 children – expected results in next 5-10 years Identification of cases through the Gambian National Cancer Registry Collaboration between IARC, MRC UK and The Gambian Government

58 AgeHBsAg-HBsAg+PercentageTotal , , , , Total 4, ,613 Impact of routine EPI on chronic HBV infection in The Gambia Peto TJ, Mendy M., Lowe Y., Webb EL., Whittle HC and Hall AJ (2014) BMC Infectious Diseases 14: 7

59 Conclusions The challenge of a rising cancer burden must be met by an integrated approach of prevention, early detection and treatment Recent advances in the molecular (epi)genetics of cancer and related tools offer exciting inter- disciplinary approaches to cancer prevention Implementation research into how prevention measures may best be integrated into health services settings is crucial

60 We have a duty of care to the patients of today and to the populations of tomorrow


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