Nordic Summer school in. cancer epidemiology August 2017

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2 Nordic Summer school in Hans H Storm cancer epidemiology August 2017 Host ANCR/DCS Funded by: NCU Introduction: aim; course concept; what is cancer epidemiology an appetiser NordCan a tool

3 Aim To understand the basic principles and methods in cancer epidemiology. To get competence in use of basic tools including registry data. To be capable of exercising critical judgement when assessing results your own and others.

4 Aim cont. To create a good Nordic collaborative and social environment. To give you a memorable and giving experience. To attract some of you to research and in particular epidemiology and cancer. But..---

5 We do not Intend to make you experts in cancer epidemiology. Intend to run a post-graduate course for specialist Intend to stop you from asking stupid? just ask, don t be shy, your neighbour don t have the answer anyway!!

6 We want you to Have a good time, now and later. Use the faculty, tutors and other staff we have collected the best!! Relax and enjoy!! But don t get drunk Alcohol is carcinogenic, Binge drinking is a hazard-

7 Practical remarks! 2 weeks basic THEORY!!! & fun. 1-2 (or more) month practical work with your project. Summer school winter weekend Finland (26/1 28/1 2018) Presentation of results Food, mail and all other arrangements (Marie/Mette+Lissa+Lone). Secretarial assistance (M+L+L).

8 Who is who? 3 min interview of neighbour 1.5 minute presentation Name; country; education (level -). Project at host institute tutor. Private life» Married/kids/engaged/» Sports» Dreams etc.» Music preference etc.» Favourite colour

9 Statistics Indispensable for proper conduct, analysis and interpretation of epidemiological studies. We concentrate more on the interpretation rather than calculations.

10 Statistics Is a good servant but Is a bad master!! Never cured a single patient Quote from Johannes Clemmesen

11 Statistics Is like a bikini!! Reveals a lot But may hide the essential Statement by a Danish GP

12 How would you navigate a super tanker in shallow waters? Without: Charts? Compass? GPS? A Pilot?

13 Cancer a major public health threat (3.6 mill cases/year in Europe) Cancer registries provides: 1. The chart monitoring incidence patterns 2. The compass trends where are we going 3. The GPS where are we now (or yesterday) 4. The pilot Epidemiologist understanding 1-3

14 But isn t mortality data sufficient? (world wide, all countries, WHO classification etc.) 1. Chart the ship has wrecked 2. Compass miss part of the story 3. GPS too late 4. Pilot With so many known carcinogens in the environment, it is a lucky man who manages to get out of this world alive!

15 Florence Nightingale 1875 The ultimate goal is to manage quality. But you cannot manage it until you have a way to measure it, and you cannot measure it until you can monitor it.

16 Epidemiology: Definitions the study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to control of health problems. Primary unit: people/populations not individuals Concerns both the diseased and those not and how these two groups differ.

17 Humans not animals/bacteria etc. Epidemiology is the only source of direct scientific evidence about exposure effects and the preventability of disease within human populations. The laboratory have shown carcinogenic substances but the relevance is first seen when epidemiology demonstrates e.g. that lung cancer occur more frequently among smokers than among non-smokers

18 Goal of epidemiology The ultimate goal of cancer epidemiology is to identify risk factors so as to allow the early introduction of effective preventive measures, To achieve this goal cancer epidemiology requires a multidisciplinary approach bringing together clinicians laboratory and social scientists and public health and other health related professionals.

19 Risk factors affects a person s health Environmental (sunlight, air pollution, occupational exposures) Lifestyle (diet, smoking, physical exercise) Constitutional (blood type, genetic traits)

20 Causality Strenght Consistency Specificity Time order Biological gradient/ dose response Plausibility Coherence Experimental evidence Analogies

21 Causal association? Temporal relationsship Biological plausibility Consistency Strength Exposure-response Specificity Reversibility Coherence (Bradford Hill 1965) The hen before the egg! Animal experiments, biological mechanisms Found in different studies, Using Not explained different by designs bias and confounding The higher exposure, the higher incidence Only certain diseases occur The factor removed incidence decrease The cause-effect does not conflict With natural history or biology

22 Mala Metallorum, St. Joachims Thal "... some mines are so dry that they are entirely devoid of water, and this dryness causes the workmen even greater harm, for the dust which is stirred and beaten up by digging penetrates into the windpipe and lungs, and produces difficulty in breathing, and the disease which the Greeks call (asthma). If the dust has corrosive qualities, it eats away the lungs, and implants consumption in the body; hence in the mines of the Carpathian Mountains women are found who have married seven husbands, all of whom this terrible consumption has carried off to a premature death." De Re Metallica, Georgius Agricola, 1556 pneumoconiosis, tuberculosis or lung cancer

23 RAMAZZINI (1700) - THE FATHER OF OCCUPATIONAL MEDICINE systematic examination of a number of trades and occupations, he observed their conditions of work and their occupational diseases recommendations on welfare, hygiene, posture, ventilation and protective clothing which are still as valid

24 1761 John Hill investigated cancer and declared tobacco snuff to be the cause of cancer of the nose..

25 1775 Dr. Percival Pott noted the high incidence of scrotal cancers in chimney sweeps, linking cancer to soot

26 Cholera mortality in South London by water company supply & houses Deaths per Cholera 10,000 Water company Houses deaths houses Southwark & Vauxhall 40,046 1, Lambeth 26, Other companies 256,423 1, South London 322,576 2, John Snow, On the mode of communication of cholera, 1855

27 IACR September 2012

28 John Snow - intervention Removal of the handle of the pump in Broad street. Not cancer but indeed translational!

29 1942 Cancer card index show the way to cure Is cancer increasing due to ageing of the pop Every 6 hour a citizen of Copenhagen die fro In 1980 this will be 1 every hour unless a cur Reports from hospitals is the backbone. Accurate death certificates of outmost impor GP s have difficulties in assessing the diagno Breast cancer is very frequent. Stomach cancer predominates in rural areas. The cancer pattern is different among worke academics. Ageing due better social and personal hygie people into cancer ages cancer incidence in Why do some get more than 1 cancer. Is there a link between cancer of the ovary a Could it be due to hormonal factors?

30 Breast cancer -Clemmesens Hook 5 year age groups vs 10 year Clemmesen J: Carcinoma of the breast. Br J Radiol 21(252): , 1948 IACR September 2012 Menopau se ~ hormones

31 Breast cancer -Clemmesens Hook? Screening effect IACR September 2012

32 Evolution of Cancer registration and cancer epidemiology a visit to Clemmensen production and to days! Foundation and history Scientific IACR September production

33 Epidemiology - philosophy of public health... philosophers have merely interpreted the world... ; the point... is to change it.» Karl Marx, 1888

34 Prevention "Hee is a better physician that keepes diseases off us, than hee that cures them being on us; prevention is so much better than healing because it saves the labour of being sick." (Sir Thomas Adams 1618) Forebyggelsesafdelingen

35 Epidemiology Descriptive Analytical

36 Study types Case series Cohort Case-control Intervention

37 What is this?

38 So what is this?

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40 Marc D Espine William Farr Father of vital statistics,

41 Breast cancer in Denmark , rates (crude, WSP & Esp), average annual number. Actual data , prediction per Thousands Year 0 DCS, DCE (Storm 1994) Based on Engeland et al 1993

42 Post-mortem diagnosis - a difficult job "Clinical observation suggests death was caused by pneumonitis or a bad cold" Medical examiner's report "Death was due to multiple gunshot wounds to the head" Autopsy Passaic Herald, New Jersey, USA, reported in Guardian, November 1995

43 Initiation Latency Progression Normal cell Cancer Induction Modification: Genetic factors repair process primary prevention Influenced by: Promoters sekundary prevention Hormone balance Local response Immune response

44 Carcinogenesis Initiation irreversible DNA change Promotion reversible DNA change Progression development to cancer Initiator (polycycl.carbon) Promotor (eks. Forbolester) Local interaction Immunological reaction Hormone sensitivity Genetic sensitivity

45 Cancer genes Oncogenes - protooncogene activation - Amplification - Translocation Supressorgenes (growth inhibition) Apoptosis genes Mismatch repairgenes

46 Tumour size weight Cells 10 kg kg Letal niveau 1 g 10 9 Diagnostic level 1 mg ug ng Time - years

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52 Age-specific incidence boys & girls

53 Non Melanoma Skin Cancer cases Males Females year

54 NMSC. Age-specific incidence rates in cohorts born (Males) Head & Neck

55 NMSC. Age-specific incidence rates in cohorts born (Males) Trunk

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59 NordCan A PC based tool for key cancer data for regions in the Nordic countries & Web-based application Sponsored by Powered by ANCR

60 NordCan Programmed by: Jacques Ferlay, DEP IARC, France Based on: EUCan and Cancer Incidence in Five Continents

61 Nordic Cancer Incidence Publications Ringertz (APMIS 1971): Finland, Iceland, Norway, Sweden Hakulinen (APMIS 1986): All Nordic countries trends Jensen (NCU 1988) Atlas of cancer incidence Tulinius (APMIS 1992): Urban/rural differences trends Engeland (APMIS 1993): Trends & predictions ANCR (Teppo) 1999: Small and colorfull, summary

62 Electronic Cancer Incidence Publications Cancer Incidence in Five Continents Vol 5: (ICD- 9 whole countries) Vol 6: (ICD- 9 whole countries) Vol 7: (ICD- 9, incl. Some morphology) EuroCIM (excl. Norway whole countries) EUCan 1990, 1995 (whole countries single year) NordCIM (Nordic countries/regions/morphology) Baltic Atlas NordCan July-2005

63 Features. NordCan Maps, Bar charts, age-specific curves, cohort specific graphs, pie chart, population pyramids. Reports incidence & mortality summary rates, age-specific rates Predictions Survival and prevalence

64 Mapping

65 Smoothing and moving, time Periods. Administrative borders

66 1 Bangalore 2 Torshavn 3 Edinburgh Hvilket postkort kom hurtigst til Danmark?

67 Statistics? Unique Prognosis depends on internal and external factors

68 Age Standardized relative survival % Eurocare II cases Austria* Denmark England Estonia Finland France* Germany* Iceland Italy* 1 year 5 year Netherlands Poland* Scotland Slovakia Slovenia Spain Sweden* Switzerland* Eurocare * < 20% of population covered

69 Survival after breast cancer in Denmark, by stage 100% 80% 60% 40% 20% 0% Years since diagnosis in Localised Regional spread Distant metast. Forebyggelsesafdelingen

70 5-year relative survical after breastcancer for women in the Nordic countries 80% 60% 40% 20% 0% Year DK SF IS N S From Engeland et al. APMIS 1995

71 Survival following lung cancer in Denmark % Men Women Forebyggelsesafdelingen Years since diagnosis in

72 Age adjusted 5 year relative cancer survival in the Nordic countries Prostate - men Relative survival % Denmark Finland Iceland Norway Sweden Engeland et al. APMIS suppl 49, vol 103, 1995

73 Cancer mortality in the Nordic countries predictions, males, prostate Age adjusted rates per Denmark Finland Iceland Norway Sweden

74 5 year relative survival after cancer in the Nordic countries Denmark versus the others - selected cancers Cancer Last Period Denmark equal other Nordic Denmark distance (%) from best survival in Oesophagus Stomach Colon Lung Breast Ovary < Kidney

75 "Something is rotten in the State of Denmark" Life style Patient delay - poor knowledge about cancer symptoms? Doctors delay - ignorance, poor education, poor diagnostics Hospital delay - poor organization, poor education Poor equipment - diagnostics, therapy machines Poor economy - lack of resources, no "science" Poor follow-up and after care Lack of a comprehensive cancer plan!!!!!!!!!!

76 Ref: SCIENCE 2000

77 Cancer Registry Cause of Death Register Hospital Patient Register Congenital Malformation Register Natl. Pathology Register tissue+blocs 22 dept. Central Register of Cytogenetic Anomalities Medical Birth Register Register for Induced Abortions Central Population Register DMCG 20 Clinical DB s Natl. Biobank Statistics Denmark Prescription DB

78 Lung cancer and tobacco & asbestos Exposure Mortality per Risk Tobacco + asbestos Asbestos only Tobak only Neither tobacco nor asbestos Fra Hammond et al 1979

79 Risiko for spiserørskræft ved alkohol og Alkohol g/dag tobaksforbrug Tobaksforbrug (g/dag) From Tuyns et al 1977

80 RR of bladder cancer by cigarette consumption RR 6 3 Tyrrel 1971 Howe 1980 Wynder 1977 Clavel Years of cigarette consumption

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83 Emigrant studier (generationer) Tyktarmskræft Japan 1:A 2:A 3:A USA

84 Avoidable cancers in Denmark year if.. * Environment & lifestyle factor Preventable cancers Tobacco Alcohol 445 Occupation 480 Sun ((melanoma) 935 # ( ) * Diet & phys.exersize Infection 600 Total > From den Nationale Kræftplan - Forebyggelsespontentialet * APMIS suppl 75, 105, 1997; # World Can Res Fund 1997