Key Figures and Current Situation. Jacques ESTEVE, UMR CNRS 5558 LBBE UCBL1

Transcription

1 Key Figures and Current Situation Jacques ESTEVE, UMR CNRS 5558 LBBE UCBL1

2 Environmental Hazard? Two different concepts Hazard associated to our behavior (tobacco, alcohol ) Hazard associated to exposures imposed to us through air, water, alimentation contaminated by carcinogenic substances. A worldwide analysis of the current situation is difficult, because in many developing countries we lack adequate data We shall restrict our analysis to developed countries and more specifically to France. It is already difficult to disentangle the true risk from the unwarranted in this simple context 28/11/2013 Jacques Estève 2

3 The current French Paradigm Il est temps d'ouvrir grand les yeux sur la pandémie des maladies modernes qui frappe la France Les diabètes, les cardiopathies, les accidents vasculaires ou encore les affections respiratoires déferlent. Et les cancers bien sûr : nouveaux cas surgissent toutes les 24 heures en France. Une progression de 89% entre 1980 et Source: Le nouvel Observateur d après André Cicolella " Toxique Planète. Le scandale invisible des maladies chroniques" 28/11/2013 Jacques Estève 3

4 and according to INSERM Entre 1995 et 2005, les taux d incidence tous cancers confondus ont augmenté de 14 % chez l homme et de 17 % chez la femme. L augmentation de l espérance de vie et l amélioration du dépistage ne suffisent pas à eux seuls à expliquer ces chiffres. Les modifications de l environnement sont, entre autres, largement suspectées de contribuer à cette augmentation. 28/11/2013 Jacques Estève 4

5 And also, still from INSERM Plus de 400 substances retrouvées dans l environnement sont déjà classées comme cancérigènes sûrs ou probables. Certaines pourraient être mises en cause dans les cancers du sein, du poumon, de la thyroïde, du testicule, dans les hémopathies malignes, le mésothéliome, les tumeurs cérébrales et les cancers de l enfant. Source: 28/11/2013 Jacques Estève 5

6 Fortunately, most of these statements are wrong or at least, the result of wrong interpretation. It is true that incidence of cancer increased in France, but it is trivial that, if the expectation of life increases, cancer incidence in term of number of cases is bound to increase. As noted by INSERM the age standardized rate, which corrects for the size and aging of the population, still increases. However, this increase cannot be link to environmental Hazard 28/11/2013 Jacques Estève 6

7 cancer incidence and mortality trend (MEN) Environment cannot be responsible neither for this recent decrease, nor for the previous increase, Actually this pattern is entirely due to prostate cancer trend Source: Francim, Invs, Inca, Biostat/HCL 28/11/2013 Jacques Estève 7

8 Same as previous slide without prostate cancer Source: Francim, Invs, Inca, Biostat/HCL 28/11/2013 Jacques Estève 8

9 Cancer Incidence and mortality trend WOMEN Breast cancer is largely responsible for this pattern. But because in women lung cancer is strongly increasing the subtraction of breast cancer incidence doest not stabilize the rate Source: Francim, Invs, Inca, Biostat/HCL 28/11/2013 Jacques Estève 9

10 Breast & lung cancer trends in women Age standardized Incidence (ASI) and Mortality (ASM) BREAST LUNG Source: Francim, Invs, Inca, Biostat/HCL 28/11/2013 Jacques Estève 10

11 Cancer in women The increase of other cancers after subtraction of breast cancer is mainly caused by melanoma, thyroid cancer and all cancers linked to alcohol and tobacco. The sex ratio (W/M), omitting breast and prostate, increased from 0.46 to 0.60 between1980 and 2010 Because les femmes sont des hommes comme les autres women will probably reach in some years the same risk of cancer as men if preventing some of their hazardous behavior remains unsuccessful. 28/11/2013 Jacques Estève 11

12 The objective analysis After correction for size and aging of the population there is no cancer epidemic in France. There is only a strong increase of prostate and breast cancer until 2005 and a reversal of this trend since then. Either the environment has changed recently or it is not responsible for this pattern. Obviously that does not mean that cancer hazard is absent in the environment but it means that its impact is not as large as specialists of urban legend pretend. 28/11/2013 Jacques Estève 12

13 Carcinogenic substances in the environment This fact has been known for many years and this knowledge originates mainly from occupational cancer (e.g.: Cancer of the scrotum in chimney sweep): Even collectively, the occupational cancers are not large in number, but they demonstrate how it is often possible to guess the cause of cancer even when there are few cases to go on (quotation from John CAIRNS in CANCER, Science and society ) Actually industry workers have been the segment of the population that has been exposed to environmental carcinogen to higher doses for longer period of exposure. This is also seen in the systematic search undertaken by IARC since the seventies. 28/11/2013 Jacques Estève 13

14 The IARC Monographs This research program has examined 968 agents suspected to cause cancer. The results are reported in 109 monographs published since Among them 177 agents are proved (group 1) or probable (group 2A) carcinogens. For an other set of 285 agents (group 2B), The evidence is weak but sufficient to encourage further research For a last group of 505 agents The evidence is inadequate Despite the initial selection, the examined agent is a proved carcinogen in only 18% of the evaluations. 28/11/2013 Jacques Estève 14

15 The Carcinogenic agents Besides the carcinogenic agents associated with our behavior, what do we find among the 177 proved carcinogenic agents? Viruses and bacteria (liver cancer, cervical cancer, stomach cancer) Ionizing radiation (all cancers except CLL) Pesticides (proved in animals, limited evidence in human) Pharmaceuticals (in particular anti-cancer drugs) Solvents (Benzene and those used by painters and dry cleaner exposed also to benzidine and others; bladder and pancreatic cancers.) Fiber and dusts (asbestos, wood and leather dust; mesotelioma, lung) Dioxins, PAH (residues of combustion ; lung and bladder cancer) Metals and their Compounds (mainly lung cancer) Products from plastic industry (Vinyl Chloride, liver angiosarcoma) Toxin from fungi (aflatoxin ; liver cancer) 28/11/2013 Jacques Estève 15

16 Remarks on IARC Classification It is important to remember that IARC classification is qualitative, i.e.: answers yes or no evidence for carcinogenicity. It leaves the quantitative evaluation to toxicologists and to some extent, the measure of prevalent exposure to public health scientists, in each country. As a consequence we are left with a large uncertainty about the contribution of these carcinogenic substances to the incidence of cancer 28/11/2013 Jacques Estève 16

17 Remarks on risk quantification (I) Alcohol &tobacco in larynx and oropharynx cancer Source: Tuyns et al 1988 Survival of smoker and non smoker source Doll et all BMJ /11/2013 Jacques Estève 17

18 Risk quantification (II) No such large effects are seen in cohort studies which led to classification of a substance as carcinogenic As an example the best evidence in human for demonstrating that cadmium compounds are carcinogenic comes from cohort studies of workers in the cadmium industry where statistically significant relative risks of lung cancer do not exceed 2. Therefore, from a practical point of view, encouraging people to modify their behavior will have a larger effect than controlling the environment, even if the latter is necessary 28/11/2013 Jacques Estève 18

19 How many cases of cancer due to an exposure? A reasonable question that does not have a simple answer for two reasons: Lack of adequate data Lack of understanding of the concepts in case of multiple exposure The algebra is extremely simple: N ( Re R0) Ne ( Re R Ne R = 0) N N R N RR 1 = RR e e T e e T nombre de cas exposés nombre total de cas The problem is that the relative risk RR= R e / R 0 must be calculated in the same population as the proportion of exposed cases. This is available in cohort study but almost never in the general population 28/11/2013 Jacques Estève 19

20 A classical example: 1. How many cases due to radon? The relative risk of lung cancer due to radon exposure in France is about It is accepted that the risk of lung cancer in non smoker is 7/1000 From previous slide we can calculate the attributable risk to radon among cases as 0.05/1.05 = Among non smoker exposed to radon we expect 1.05*7*100 =735 cases of lung cancer from which 35 are due to radon (4.8%) 28/11/2013 Jacques Estève 20

21 A classical example 2. How many cases due to tobacco? It is accepted that a regular smoker of 10 cigarettes per day has a lung cancer risk of 1/7. Therefore in a population of such smokers we expect cases of lung cancer If we accept that risk of radon and risk of smoking are multiplicative, (i.e.: the relative risk of radon in this population of smokers is still 1.05), we expect cases of lung cancer in this same population if it is exposed to radon, that is 714 due to radon (still 4.8% as expected) but among them are due to the joint exposure (95%) Therefore one may consider more productive to eliminate tobacco rather than radon 28/11/2013 Jacques Estève 21

22 Conclusion Cancer is a frequent disease, which strikes largely at random. Some of us, by their behavior, increase considerably their chance of drawing the bad numbers in this lottery. Carcinogens disseminated in our environment may certainly cause cancer, but their contribution is quantitatively small. The good news is that the incidence of the more lethal cancers is decreasing and the net survival is improving. It would be wise to analyze carefully the hierarchy of the proved hazard, and to avoid To invent hazards that do not exist, To perform crude attributable risk calculation, and To estimate time trends on number of cases 28/11/2013 Jacques Estève 22