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W% Epidemiology   Study of the frequency and the distribution of health effects in time and space among human populations, and of their determining factors OBJECTIVES Descriptive: - Estimation of the frequency of a pathology, surveillance - Identification of groups of population with excess risk Analytical : - Quantification of the increase of risk with exposure - Modelling the exposure - effect relationship8ZZuZ ZfZs   d  .V iX& History of epidemiologic studies!!4    1950 Radiologists (1900-30) 1950 Radium dial painters (1910-30) 1950 Medical exposures for non malignant illnesses, diagnostic exposures (1920-40) 1950 Hiroshima-Nagasaki survivors (1945) 1960 Miners (uranium) (1940-90) 1970 Population exposed to fallout from atmospheric nuclear weapons (1950-60) 1970 Nuclear workers (1950-) Population exposed to natural background radiation 1990 Population exposed to releases from the Chernobyl accident (1986)PQ0Z<70" Z<K0" Z<Q   f            Y'.Hiroshima and Nagasaki Survivors of the A Bomb//$Z(THiroshima  Nagasaki Distribution of doses++$(    [) \*8Cancer relative risk among Hiroshima-Nagasaki survivors99$  c-2Life Span Study Results - solid cancers (1950-97)$31$ "69335 deaths including 440 in excess (4,5 %) Latency of 15 years Excess beyond 100 mSv Excess of risk persists 50 years later Increase proportional to natural death rate by cancer Dose-effect relationship: excess of relative risk of 40% by Sievert Decrease of risk with age at exposure and with age attained77.                   #                             e..Life Span Study Relative risk of solid cancer// P      f//Life Span Study Relative risk for solid tumors00 D      g0XHiroshima and Nagasaki : Adjustment of a linear model for solid cancer risk at low dosesYPY                    h1JLife Span Study : Effect of Age at exposure and period from the exposureKK  +  l3^Life Span Study Results  leukaemias (1950-90)00$0   4249 deaths by leukemia including 87 in excess (38,1 %) latency of 3 years, pick at 6-8 years 80 % observed before 1970 persistence of excess of 3,5 % on 1985-1990 Linear quadratic dose-effect relationship Excess relative risk of 400% by Sievert Decreasing of risk with age at exposure and with age attained0^0n2n>5$ m I                 m4,Life Span Study Relative risk of leukaemias--$D      n6ELife Span Study : effect of age at exposure and period from exposureFF J    o71Results of the Hiroshima-Nagasaki survivors study22$>   " Risk of radiation induced cancer recognised : leukaemia, breast, lung, thyroid probable : multiple myeloma, liver, digestive, bone, urinary-genital organs, brain, skin above 100 mSv for solid cancers Dose-effect relationship compatible with a non threshold model solid cancers : linear relative risk model leukaemia : linear-quadratic absolute risk model A basis for radiation protection need to extrapolate from high to low doses and dose -rates!0P20P2?0n2\0P2!0n2;0P2! $L'\ ;  FbH   p8BLife Span Study Results : diseases other than cancer (1950-1997) (C6$ $Z       31 881 deaths including 250 in excess (0,8 %) Linear dose-effect relationship: linear excess relative risk of 14% by Sievert Excess statisticaly significant only in recent analyses: large latency or other co-factor ?                                      q9 r:vHiroshima  Nagasaki : diseases other than cancer (1968-97)<<<     s;Hiroshima and Nagasaki $$t<Life span study limits$ Death certificates : under-recording of cancer Particularities of Japaneese population: basic rate of breast and stomach cancer (transposition problem) Exposure rate very high Only external exposure\C W   u5 3Extrapolation distances 6/Power and epidemiological studies at low doses00S#Occupational studies "  Nuclear workers studies : external radiation at low doses and at low annual dose rates Uranium miners studies : inhalation of radon decay products from risk estimation at low cumulative exposures to general public concern HW>Q @                              z=+Main contribution from occupational studies,,$"  Registered individual dosimetry on annual basis Over long working periods ( historical reconstruction) Able to express a long-term risk , by taking in account the protaction of the individual exposure over time2hvir         +           B%Nuclear workers: joint analysis 1995  &$ <      C$Nuclear workers study (Cardis 1995)  %# <     =>Cohort study of nuclear workers in France (CEA-COGEMA group) ??<     "Published Results : 50 000 workers All causes mortality lower than in the French male general population (Healthy worker effect) No excess of mortality from leukaemia Elevated mortality risk observed for pleura cancer and skin melanoma (men) and breast and brain cancer (women) Achievements in 2003: Integration in the international joint analysis of nuclear workers (IARC): 17 countries (Germany, Australia, Belgium, Canada, Spain, Finland, France, Hungary, Japan, Slovakia, Sweden, Switzerland, UK, USA, Russia, Lithuania, South Korea) Cohort of 400 000 individuals Analysis of mortality risk associated to cumulated doses : main hypothesis to be tested : potential leukemia risk increasing with exposure Future EC program Analysis of mortality risk associated to multiple exposures #8Z8 " xZ8Z " xZixZ> " xZn#>                   3$ 1    C>)Cohort study of French uranium miners (1)**4     Objectives : Estimation of risk of cancer death associated to cumulated radon exposure Cohort : 5098 uranium miners employed in the CEA-COGEMA group between 1946 and 1990 Reconstruction of individual annual exposure (radon, gamma, ore dust) Low cumulated exposure (37 WLM) Follow-up to December 1994 (mean duration of 26 years) Mortality : 1162 deaths, from which 125 lung cancer deaths Collaborations : Occupational medical service of COGEMA European joint analysis of miners with low levels of exposure (Czech and German cohorts)c(% " I " L %:   ?)Cohort study of French uranium miners (2)**4     Results : Excess risk of death from lung cancer: SMR = 1.5 Linear dose-response relationship with cumulated radon exposure coherent with the literature : ERR = 0.008 / WLM Decrease of the risk with time since exposure (20% / 10 years) No dose rate effect once time since exposure and exposure period are considered Perspectives : 6th EC program Extension of follow-up through end of 1999 (French+ Czech + Wismuth cohorts) Analysis of data collected in the frame of nested case-control studies: tobacco, other occupational factors Risk modelling : time dependant variables, mechanistic modelling; uncertainties linked to organ dose calculations Multiple exposures : Ur + gamma + radon decay in miners  (;( " (, " 9H  ;  ,9  <                        *      0               {>:Uranium miners cohorts with low levels of radon exposure $;9$@        |?4Uranium miners cohorts: Exposure-risk relationship $53$<    }@4Uranium miners cohorts: Exposure-risk relationship $53$<    ~A[Cumulative exposure and duration of exposure to radon in miners cohorts (European program)&\Zt            A@Campaign of measurements of indoor radon concentration in FranceAPA &B@Case-control study of indoor radon and lung cancer in France (1)AA@        C @Case-control study of indoor radon and lung cancer in France (2)AA@      /8JKM^_`ai!j"w$x%y&'h  ` ` ̙33` 333MMM` ff3333f` f` f` 3>?" dd@,|?" dd@   " @ ` n?" dd@   @@``PR    @ ` ` p>>  ,(    6m P  e1Cliquez pour modifier le style du titre du masque2 2:  0Tp   vCliquez pour modifier les styles du texte du masque Deuxime niveau Troisime niveau Quatrime niveau Cinquime niveau4 w  0v ``  X*  00{ `   Z*  0 `   Z*  NHgֳgֳ?" _DRPH/SRBE/LEPID  Z  H   3 A"(H  0޽h ? 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TB ` c $8c?& ,  `  BCDE F8c?@? F NB ` S 8c?  NB ` S 8c?  NB ` S 8c?  NB ` S 8c?  NB ` S 8c? h  `  BCDE F8c?@I  NB ` S 8c?g U NB ` S 8c?  NB ` S 8c?  NB ` S 8c?   NB ` S 8c?  NB ` S 8c?:  `  BCDE F1?@) NB ` S 1?NNNB ` S 1?ddNB ` S 1?ggNB ` S 1?zzNB ` S 1?NB ` S 1? `  BqCDE F1?p_@)  `  BqCDE F1?p_@)  `  BqCDE F1?p_@)  `  BpCDE F1?o^@:   `  BpCDE F1?o^@:   `  BqCDE F1?p]@+ e f  `  BqCDE F1?p]@+ > ?  `  BpCDE F1?o^@:   `  BqCDE F1?p_@)  NB ` S 1?) )  `  `,xaxa1?*   Y0  hh88 `  `xxaxa1?. f   [0.5  hh88 `  `xaxa1?* G  Y1  hh88 `  `!xaxa1?.   [1.5  hh88 `  `|#xaxa1?* ~  Y2  hh88 `  `@2xaxa1?.  M  [2.5  hh88 `  `3xaxa1?*  / Y3  hh88 `  `Bxaxa1? %  [3.5  hh88TB ` c $8c? `  `Dxaxa1? \ kAge < 40 years ATB  hh88TB ` c $ 8c? `  `Mxaxa1?9  lAge > 40 years ATB  hh88 `  BqCDE F1?p_@)  `  BqCDE F1?p_@)  `  BqCDE F1?p_@)  `  BpCDE F1?o^@:   `  BpCDE F1?o^@:   `  BqCDE F1?p]@+ e f  `  BqCDE F1?p]@+ > ?  `  BpCDE F1?o^@:   `  BqCDE F1?p_@)  NB ` S 1?) )  `  BCDE F1?@b NB ` S 1?NB ` S 1?22NB ` S 1?66NB ` S 1?HHNB ` S 1?N N NB ` S 1?b b  `  BrCDE F1?qa@ `  `  BrCDE F1?qa@ `  `  BrCDE F1?qa@ `  `  BmCDE F1?l^@ m  `  BmCDE F1?l^@ m  `  BqCDE F1?pa@n `o  `  BqCDE F1?pa@G `H  `  BmCDE F1?l^@m `  BrCDE F1?qa@`NB ` S 1? `  `(\xaxa1?+ Y0  hh88 `  `dkxaxa1?L Y1  hh88 `  `mxaxa1?c Y2  hh88 `  `|xaxa1?[ Y3  hh88 `  `xaxa1?} Y4  hh88 `  ` xaxa1?  Y5  hh88 `  `xaxa1?   Y6  hh88 `  `xxaxa1?& Y0  hh88 `  `xaxa1?n  [0.5  hh88 `  `dxaxa1?R   Y1  hh88 `  `Xnxaxa1?   [1.5  hh88 `  `xaxa1?   Y2  hh88 `  `$xaxa1?Y  [2.5  hh88 `  `xaxa1?9 Y3  hh88 `  `hxaxa1?{ [3.5  hh88 `  BC;DEF 1?0:   @  `  BC~DE$F,8c? '=}:Ws@H  `  BrCDE F1?qa@ `  `  BrCDE F1?qa@ `  `  BrCDE F1?qa@ `  `  BmCDE F1?l^@ m  `  BmCDE F1?l^@ m  `  BqCDE F1?pa@n `o  `  BqCDE F1?pa@G `H  `  BmCDE F1?l^@m `  BrCDE F1?qa@` `  BC;DEF  8c?0:   @ `2 ` 01?  `2 ` 01?  `2 ` 01?  `2 ` 01?  `2 ` 01?  `2 ` 01? `2 ` 01?q; f `2 ` 01?j  `2 ` 01?E p `2 ` 01?   `  BCDE F(8c?GP44@) b  `2 ` 01? . `2 ` 01? 6 `2 ` 01? | " `2 ` 01?  `2 ` 01?  `2 ` 01?S ~  `  B;CDEF$ 8c?_}`0}:@) I  `2 ` 01?  `2 ` 01?  `2 ` 01?; f `2 ` 01?  `2 ` 01?' O `2 ` 01?z `2 ` 01? ;  `  BCCDE F8c?B/@  NB a S 8c?::NB a S 8c?  NB a S 8c?   a  B@CDE F8c??0@  NB a S 8c?  NB a S 8c? $  a  B7CDE F8c?62@ #  a  B@CDE F8c??.@   a  BACDE F8c?@0@  NB  a S 8c?  NB  a S 8c?S  NB  a S 8c?S S NB  a S 8c?    a  `Hxaxa1? _  Y0  hh88 a  `xaxa1?  Y1  hh88 a  `$xaxa1? Y2  hh88 a  `Xxaxa1? Y3  hh88 a  ` xaxa1? Y4  hh88 a  `xaxa1? Y5  hh88 a  `xaxa1?2 Y6  hh88NB a S 8c?{U U  a  B?CDE F8c?>/@yg h NB a S 8c?"7 ]7 NB a S 8c?>g >8 NB a S 8c?"g Ug NB a S 8c? y 7 NB a S 1?v 7 7 NB a S 8c?b b 2 NB a S 8c?H w NB a S 8c?H 3 { 3 NB a S 1?, V , 0 NB a S 8c? h h NB  a S 8c?x y y NB !a S 8c?  , NB "a S 8c? I ,I NB #a S 1?| G G NB $a S 1?| G G NB %a S 1?| NB &a S 1?^   NB 'a S 8c?^ NB (a S 8c? G NB )a S 8c?| NB *a S 8c?{ G G NB +a S 1?]   NB ,a S 8c?!  NB -a S 8c?! ! NB .a S 8c?  NB /a S 8c?"  NB 0a S 8c?^   NB 1a S 8c?#  NB 2a S 8c? U  3a  BCDE F8c? @  NB 4a S 1? 5a  BCDE F1?@  `2 6a 01?a  `2 7a 01?8 a `2 8a 01?j  NB 9a S 8c?P@ P7 NB :a S 8c? 7 `2 ;a 01? N y `2 a S 8c?  `2 ?a 01?}  NB @a S 8c?u  NB Aa S 8c?  NB Ba S 8c?! ! NB Ca S 8c?x  NB Da S 8c?x  NB Ea S 8c?W W NB Fa S 8c?  NB Ga S 8c?U  NB Ha S 8c?U= = NB Ia S 8c?#= y= NB Ja S 8c?#; y; NB Ka S 8c?^  NB La S 8c?z  NB Ma S 8c?z  NB Na S 8c?  NB Oa S 8c?    Pa  `(xaxa1?r  u*ATB = at the time of bombing  hh88` Qa 01?k~  Ra  `x1xaxa1?k _1950~65 hh88` Sa 01?skC Ta  `9xaxa1?Nko _1966~85 hh88  Ua  fDxaxa1? |~  Risque relatif  hh88 Va  fJ1 ?N~ ^Hiroshima  Nagasaki : no-cancerous death rate 0 Z0H      H ` 0޽h ? a(  pd<(  d~ d s *0UP   p d HA ?US} d Z$W?"^ |(Preston et al 2003) Z  hh88H d 0޽h ? a(d  & %   hx (  hZ h Ngֳgֳ?8H &The Life Span Cohort Study (LSS) : n = 86 000 mortality follow-up from 1950 to 1990 (recent extension up to 1997) incidence follow-up from 1950 to 1987 (recent extension up to 1995) Increased risk (mortality and incidence) of solid cancer and leukaemia associated with dose (Preston 94, Pierce 96, Pierce 2000) Dose-effect relationship for solid cancers and leukaemia varies with attained age (Preston 2002) Significant increase in non-cancer disease death rates with radiation dose (diseases of the circulatory, digestive, respiratory systems) (Shimizu 99) No reduction of life duration associated to radiation dose (Cologne 2000) The Adult Health Study (AHS) : n = 20 000 biannual clinical examinations, medical history, life-style (nutrition, smoking ...) Excess risk for chronic hepatitis, liver cirrhosis, thyroid disease (Wong 93) No dose-response relationship for cardiovascular disease endpoints (Wong 93) In Utero Clinical Study Sample : n = 1 600 Mental retardation linked to dose (Otake 89) Increased mortality risk of solid cancer associated with dose (Delongchamp 97) The Offspring (F1) Cohort Study : n = 31 000 mortality follow-up of children of A bomb survivors from 1946 to 1985 No statistically significant effect of parental radiation dose on cancer mortality (Yoshimoto 91)  Zi xZ Zi xZ, Z~i xZ. ZH Zci xZ/X*+~.j       U N p   -  ?     hh88 h s pgֳgֳ ?`pp   H h 0޽h ? a(  ^Vp(  p p  `@txaxa1 ?P    p  Ztxaxa1 ?Hx   p  `kxaxa1? }  <DStudies in other populations and at various dose rates are necessaryE ZE             hh88p p H?] ~^ H p 0޽h ? a(j  L(  Lr L S ЖP   H L 0޽h ? ̙33b  % Kv(    3 rXgֳgֳ ?y   p K HA?H  0޽h ? a(T    (  x  c $x   d  N?U Single studies are in general limited in size limited statistical power Development of joint analyses: analysis of data of different studies presenting similar protocols advantage: large size (several hundred or thousands individuals) increase of the capability to detect a small excess risk limits: internal variability (methods and quality of data collection, background rates,& ) International collaborations: joint analysis of miners cohort studies (US, NIH and Europe) joint analysis of indoor radon case-control studies in Europe (EC); joint analysis on world level in near future joint analysis of nuclear workers cohort studies (IARC)8 ZB8 Z:8 Z\8 Z 8 Z8 Z[E|\    D         4hh88p  Hf?@ZH  0޽h ? a(\   (  r  S P   r  S   p  H? B"P H  0޽h ? ̙33\   t(  tr t S XP   r t S   p t H?I) H t 0޽h ? ̙33i  @  (     `mexaxa1 ?0p  e d  <1?,  Z^exaxa1?`  ,Data from several cohorts : (Cardis 95) Mortality study on 95 700 workers USA, GB, Canada (15% of women) mean duration of follow-up : 22 ans low mean cumulated exposure : 40 mSv Solid tumor deaths : 3976 (expected > 4000) leukemia deaths :119 (expected < 90) No dose-response relationship for solid tumors for leukemia deaths : ERR at 1 Sv = 2.2 [0.1  5.7] (v0ZZ                                          Z@xaxa1?S  } 80 Z0Z d  <1?5KH  0޽h ? a(  (  d  <1?4$"d  <1?5K  C xPexaxa1 ?0p  e p  HA?TL  Z(e?Jt 8(d aprs Cardis et al. 1995) Z.     hh88H  0޽h ? a(  .&(     `<xaxa1 ?@      `,xaxa1 ?`   "H  0޽h ? a( @ % RJ(    3 rgֳgֳ ?px     3 r0gֳgֳ ?b  "H  0޽h ? a(  % <4 (      3 rgֳgֳ ?px      3 r@gֳgֳ ?  H   0޽h ? a(]     x(  x~ x s *l     x B _x OWP1   x 6 (0y s7+ data on gamma, long-lived ore dust, arsenic exposures 87"F PL  x LV Z x s *` Xh Z x s *V2 n ` x 0A ?|l ZB  x s *DoPp p ZB  x s *Do` LPZB  x s *DoV00  x 68 'Working Level Month (WLM): concentration in radon daughters (WL) x duration of work in months (170 h) (1 WLM is equivalent to 3.5 mJ.h.m-3 )\ 2bMB!fnB H x 0޽h ? a(   C ; 0|(  |x | c $x   RF O  | O N P | PZ | s *P | <  Czech cohort S53+N French cohort!x!(    N 8 | 0ZB | s *D3o  Z2  | s *33 `8N 8  | ZB  | s *Do  Z2  | s * `8N O   | O ` | 0A ?O  | <<V  BERR = 0.029 / WLM [0.025  0.033]," "  | <K %  DERR = 0.008 / WLM [0.006  0.015].# #  | B#_x OWP1  H | 0޽h ? ̙33  6.@##(  x  c $(x   RF O   O N P  PZ  s *P  <*  Czech cohort S53+N French cohort!x!(    N 8  0ZB  s *D3o  Z2   s *33 `8N 8   ZB   s *Do  Z2   s * `8N O    O `  0A ?O   <0V  BERR = 0.029 / WLM [0.025  0.033]," "   <5K %  DERR = 0.008 / WLM [0.006  0.015].# #  z L#  L#,$D0IN   Z  s *  <: 9Czech cohort S53+N French expo >= 1956 French expo < 1956:x:  .  T 8 # 0ZB  s *D3o  Z2  s *33 `8 T 8 # ZB  s *Do  Z2  s * `8,T 8 # (h`B  0Do  `2  0 `8N L#  L#Z  s *AL#   <h@V  BERR = 0.029 / WLM [0.025  0.033]," "  ! <0EK  DERR = 0.026 / WLM [0.015  0.039].# #  " <0D #   FERR = 0.003 / WLM [-0.001  0.008].$ $  # BdH_x OWP1  H  0޽h ? ̙33/ ' % //PNN.(  "L } # }B  3 }H  C kI<B  # PnL<B  # PLM<B  # P4 5 <B  # P  <B   # P  <B   # P  <B   # P<B   # P<B   # P<B  # P<B  # Pno<B  # PLM<B  # P2e<B  # P]2^e<B  # P 2e<B  # P 2 e<B  # Pf 2g e<B  # P 2 e<B  # P2e<B  # Pp2qe<B  # P 2!e<B  # P2eZ2  s *i+s0 V Z2  s *i+ / Z2  s *i+`Z2  s *i+ FZ2  s *i+2 X Z2   s *i+S z Z2 ! s *i+  ' Z2 " s *i+5],Z2 # s *i+L t Z2 $ s *i+%LZ2 % s *i+z   & 6xe<ho w0( Z   hh88 ' 6Xo cW  y100( Z   hh88 ( 64x c?  y200( Z   hh88 ) 6k c'  y300( Z   hh88 * 6p c  y400( Z   hh88 + 6c y500( Z   hh88 , 6c y600( Z   hh88 - 6kc y700( Z   hh88 . 6Sc y800( Z   hh88 / 6;c y900( Z   hh88 0 6Ľ w0( Z   hh88 1 6Iu w2( Z   hh88 2 6% w4( Z   hh88 3 6t   w6( Z   hh88 4 6S   w8( Z   hh88 5 6 @  x10( Z   hh88 6 6 x12( Z   hh88 7 6A x14( Z   hh88 8 6I x16( Z   hh88 9 6(  x18( Z   hh88R : 6$ O *Mean duration of exposure to radon (years)*+ Z* N        hh88; ; <"@c  'Mean cumulative exposure to radon (WLM)*( Z' 4     hh88 < 6,- b  Czech Republic0 Z    hh88 = 6( k`   France, Z    hh88H > C vTz J? ; 7 ? ? J; 7,$D 0 @ <x7Jw7 CZ : S52 + N studies (N=5002)&     N  ? ; Y A  ? ; Y~B B NDo? ?  C 68C ; Y y* Z(  hh88 D BE_x OWP1   E 3 rGgֳgֳ ?0   xz  7 F  7,$D 0  G 6I   Germany,  Z  (   hh88 H 6p[  y* Z(  hh88 I 0|]w7 G : Wismut cohort C (N=17935)&    hz  7 J  7,$D 0N   K   L 6`  y* Z(  hh88~B MB NDo?    N Biw7 Fr : extended cohort (N=5098)4     H  0޽h ? a(   [ S ` (  p  HA?=-   ZTp?  r dNumber of departments: 96 Number of measurements: 12641 Crude national arithmetic mean: 90 Bq,m-3 Population weighted national arithmetic mean: 68 Bq,m-3H `#+8#+>@7hh88S  Z,u?^i %IPSN /DPHD-SEGR-LEADS : January 2000*& P%+8   hh88R  Tu?Q  0* 1 Becquerel (Bq) = 1 disintegration per second1 n1# @     hh88u  Z̐gֳgֳ ?T ;Exposure of the French population to natural radiation (2) < Z<N         fgֳgֳ ?`   R   s *H0  0\ 'Departmental arithmetic means in Bq.m-3*(% "   H  0޽h ? a(  pdd 7(      S ~̣xaxa1 ?   d   <1?5}   Txaxa1? Multi-center study 4 regions (+ Ardennes) : Bretagne, Limousin, Auvergne,Languedoc-Roussillon 10 hospitals Subjects in the analysis 486 Cases (diagnosed with lung cancer) 984 Controls (free of respiratory disease) Paired (sex, age, hospital) Risk factors : 2 measurements of radon concentration (6 months) in each house occupied during the last 30 years Questionnaire on other risk factors (occupational exposures smoking, medical history, SPC,,,). /    q    2q          !       p 7 hh88F 2 J     b l   <1?i    BCDEF1?BBstvvnD6#|{p`88;SS{PtBT6R1]^JB8%b+g/hYn]pc|h~ &*08AJMU[`jss@tJ@   s B3CDEF'E1?(().3BC@+.2OROd]R!)22 C[x$**21S?3))QT@ j    ^BC>DEF1?88| uiZSSNsBl2+  [kr|,fesv} **.,*"!8=|9z3}|qt@     BCDEF1?))  ~  # 'GTZ^ _jpo`??:$)r1e"70 - ST@    BCDEtF|1? -G\l~}pF*w\<=*x  ;<@M    BCDEF1?&&n/ zzhYD * 5X8f0lqx (3A@]vMP@O    s XBCDEF'E1?88\[??RSXpUPD vtl"h*e7aCYLJPAQ:Q9 Yg nszld\qt@ x 0   s B"CDEF'E1?--<5,~$ww:1 , !$fCoFqBo!u"56  @AI    ![\@ 2      BCDExF1?@F='[P6'"MOW<:9NO-,D_{=@@$ 8     BCDEF1?((m]FD6!INE0'%$9 JQ Y'~, 'QmmQT@Q >!     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"#$$O6e8hr$fL4³@1i 2$x V]c(@ ib$1JqE b$ $u"&{Br$߀M'$,,Gi _$"$;s5z[:(fb$_js4fL;"yImb$2f;5~m3]2$5̀XPF*4~b$E%Mvrfs2$AL3գ+bSd:#b$@AHB&dO}]2$kXyߌUW@(/c $@4yx ʚ;]#4ʚ;g4BdBdv 0bppp@ <4!d!d` 0b\2b<4dddd` 0b\2b <4BdBdb 0bbg49d9dv 0bp p2___PPT9&  (2? %O =HU$"Results of epidemiological studies##0   {Contribution from occupationally exposed populations to quantification of risk at low doses Margot Tirmarche IRSN France|\ b   !        W% Epidemiology   Study of the frequency and the distribution of health effects in time and space among human populations, and of their determining factors OBJECTIVES Descriptive: - Estimation of the frequency of a pathology, surveillance - Identification of groups of population with excess risk Analytical : - Quantification of the increase of risk with exposure - Modelling the exposure - effect relationship8ZZuZ ZfZs   d  .V iX& History of epidemiologic studies!!4    1950 Radiologists (1900-30) 1950 Radium dial painters (1910-30) 1950 Medical exposures for non malignant illnesses, diagnostic exposures (1920-40) 1950 Hiroshima-Nagasaki survivors (1945) 1960 Miners (uranium) (1940-90) 1970 Population exposed to fallout from atmospheric nuclear weapons (1950-60) 1970 Nuclear workers (1950-) Population exposed to natural background radiation 1990 Population exposed to releases from the Chernobyl accident (1986)PQ0Z<70" Z<K0" Z<Q   f            Y'.Hiroshima and Nagasaki Survivors of the A Bomb//$Z(THiroshima  Nagasaki Distribution of doses++$(    [) \*8Cancer relative risk among Hiroshima-Nagasaki survivors99$  c-2Life Span Study Results - solid cancers (1950-97)$31$ "69335 deaths including 440 in excess (4,5 %) Latency of 15 years Excess beyond 100 mSv Excess of risk persists 50 years later Increase proportional to natural death rate by cancer Dose-effect relationship: excess of relative risk of 40% by Sievert Decrease of risk with age at exposure and with age attained77.                   #                             e..Life Span Study Relative risk of solid cancer// P      f//Life Span Study Relative risk for solid tumors00 D      g0XHiroshima and Nagasaki : Adjustment of a linear model for solid cancer risk at low dosesYPY    !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~Root EntrydO)Wx+ Pictures6Current User)1SummaryInformation(6     S !"#$%&'()*+,-./0123456789;<=>?@ABCDEFGHIRTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|~PowerPoint Document(MDocumentSummaryInformation8 0b( 00DArial Blackmanp1bbv 0b( 0"@DSwitzerlandmanp1bbv 0b( 0PDTimesrlandmanp1bbv 0b( 0  ` .  @n?" dd@  @@`` @e7 !*** L6 7!'& 'e(( ' ),-@E.  / 0 `U>4W" #$$%O9;<ehr$fL4³@1i 2$x V]c(@ ib$1JqE b$ $u"&{Br$߀M'$,,Gi _$"$;s5z[:(fb$_js4fL;"yImb$2f;5~m3]2$5̀XPF*4~b$E%Mvrfs2$AL3գ+bSd:#b$@AHB&dO}]2$kXyߌUW@(/c $@4yx ʚ;]#4ʚ;g4BdBdv 0bppp@ <4!d!d` 0b\2b<4dddd` 0b\2b <4BdBdb 0bbg49d9dv 0bp p2___PPT9&  (2? %O =DU$"Results of epidemiological studies##0   {Contribution from occupationally exposed populations to quantification of risk at low doses Margot Tirmarche IRSN France|\ b   !        W% Epidemiology   Study of the frequency and the distribution of health effects in time and space among human populations, and of their determining factors OBJECTIVES Descriptive: - Estimation of the frequency of a pathology, surveillance - Identification of groups of population with excess risk Analytical : - Quantification of the increase of risk with exposure - Modelling the exposure - effect relationship8ZZuZ ZfZs   d  .V iX& History of epidemiologic studies!!4    1950 Radiologists (1900-30) 1950 Radium dial painters (1910-30) 1950 Medical exposures for non malignant illnesses, diagnostic exposures (1920-40) 1950 Hiroshima-Nagasaki survivors (1945) 1960 Miners (uranium) (1940-90) 1970 Population exposed to fallout from atmospheric nuclear weapons (1950-60) 1970 Nuclear workers (1950-) Population exposed to natural background radiation 1990 Population exposed to releases from the Chernobyl accident (1986)PQ0Z<70" Z<K0" Z<Q   f            Y'.Hiroshima and Nagasaki Survivors of the A Bomb//$Z(THiroshima  Nagasaki Distribution of doses++$(    [) \*8Cancer relative risk among Hiroshima-Nagasaki survivors99$  c-2Life Span Study Results - solid cancers (1950-97)$31$ "69335 deaths including 440 in excess (4,5 %) Latency of 15 years Excess beyond 100 mSv Excess of risk persists 50 years later Increase proportional to natural death rate by cancer Dose-effect relationship: excess of relative risk of 40% by Sievert Decrease of risk with age at exposure and with age attained77.                   #                             e..Life Span Study Relative risk of solid cancer// P      f//Life Span Study Relative risk for solid tumors00 D      g0XHiroshima and Nagasaki : Adjustment of a linear model for solid cancer risk at low dosesYPY                    h1JLife Span Study : Effect of Age at exposure and period from the exposureKK  +  l3^Life Span Study Results  leukaemias (1950-90)00$0   4249 deaths by leukemia including 87 in excess (38,1 %) latency of 3 years, pick at 6-8 years 80 % observed before 1970 persistence of excess of 3,5 % on 1985-1990 Linear quadratic dose-effect relationship Excess relative risk of 400% by Sievert Decreasing of risk with age at exposure and with age attained0^0n2n>5$ m I                 m4,Life Span Study Relative risk of leukaemias--$D      n6ELife Span Study : effect of age at exposure and period from exposureFF J    o71Results of the Hiroshima-Nagasaki survivors study22$>   " Risk of radiation induced cancer recognised : leukaemia, breast, lung, thyroid probable : multiple myeloma, liver, digestive, bone, urinary-genital organs, brain, skin above 100 mSv for solid cancers Dose-effect relationship compatible with a non threshold model solid cancers : linear relative risk model leukaemia : linear-quadratic absolute risk model A basis for radiation protection need to extrapolate from high to low doses and dose -rates!0P20P2?0n2\0P2!0n2;0P2! $L'\ ;  FbH   p8BLife Span Study Results : diseases other than cancer (1950-1997) (C6$ $Z       31 881 deaths including 250 in excess (0,8 %) Linear dose-effect relationship: linear excess relative risk of 14% by Sievert Excess statisticaly significant only in recent analyses: large latency or other co-factor ?                                      q9 r:vHiroshima  Nagasaki : diseases other than cancer (1968-97)<<<     s;Hiroshima and Nagasaki $$t<Life span study limits$ Death certificates : under-recording of cancer Particularities of Japaneese population: basic rate of breast and stomach cancer (transposition problem) Exposure rate very high Only external exposure\C W   u5 3Extrapolation distances 6/Power and epidemiological studies at low doses00S#Occupational studies "  Nuclear workers studies : external radiation at low doses and at low annual dose rates Uranium miners studies : inhalation of radon decay products from risk estimation at low cumulative exposures to general public concern HW>Q @                              z=+Main contribution from occupational studies,,$"  Registered individual dosimetry on annual basis Over long working periods ( historical reconstruction) Able to express a long-term risk , by taking in account the protaction of the individual exposure over time2hvir         +           B%Nuclear workers: joint analysis 1995  &$ <      C$Nuclear workers study (Cardis 1995)  %# <     =>Cohort study of nuclear workers in France (CEA-COGEMA group) ??<     "Published Results : 50 000 workers All causes mortality lower than in the French male general population (Healthy worker effect) No excess of mortality from leukaemia Elevated mortality risk observed for pleura cancer and skin melanoma (men) and breast and brain cancer (women) Achievements in 2003: Integration in the international joint analysis of nuclear workers (IARC): 17 countries (Germany, Australia, Belgium, Canada, Spain, Finland, France, Hungary, Japan, Slovakia, Sweden, Switzerland, UK, USA, Russia, Lithuania, South Korea) Cohort of 400 000 individuals Analysis of mortality risk associated to cumulated doses : main hypothesis to be tested : potential leukemia risk increasing with exposure Future EC program Analysis of mortality risk associated to multiple exposures #8Z8 " xZ8Z " xZixZ> " xZn#>                   3$ 1    C>)Cohort study of French uranium miners (1)**4     Objectives : Estimation of risk of cancer death associated to cumulated radon exposure Cohort : 5098 uranium miners employed in the CEA-COGEMA group between 1946 and 1990 Reconstruction of individual annual exposure (radon, gamma, ore dust) Low cumulated exposure (37 WLM) Follow-up to December 1994 (mean duration of 26 years) Mortality : 1162 deaths, from which 125 lung cancer deaths Collaborations : Occupational medical service of COGEMA European joint analysis of miners with low levels of exposure (Czech and German cohorts)c(% " I " L %:   ?)Cohort study of French uranium miners (2)**4     Results : Excess risk of death from lung cancer: SMR = 1.5 Linear dose-response relationship with cumulated radon exposure coherent with the literature : ERR = 0.008 / WLM Decrease of the risk with time since exposure (20% / 10 years) No dose rate effect once time since exposure and exposure period are considered Perspectives : 6th EC program Extension of follow-up through end of 1999 (French+ Czech + Wismuth cohorts) Analysis of data collected in the frame of nested case-control studies: tobacco, other occupational factors Risk modelling : time dependant variables, mechanistic modelling; uncertainties linked to organ dose calculations Multiple exposures : Ur + gamma + radon decay in miners  (;( " (, " 9H  ;  ,9  <                        *      0               {>:Uranium miners cohorts with low levels of radon exposure $;9$@        |?4Uranium miners cohorts: Exposure-risk relationship $53$<    }@4Uranium miners cohorts: Exposure-risk relationship $53$<    ~A[Cumulative exposure and duration of exposure to radon in miners cohorts (European program)&\Zt            A@Campaign of measurements of indoor radon concentration in FranceAPA &B@Case-control study of indoor radon and lung cancer in France (1)AA@        C @Case-control study of indoor radon and lung cancer in France (2)AA@      /8JKM^_`ai!j"w$x%y&'#  s#k#ad#( : d  <1?4$"d  <1?5K  C xPexaxa1 ?0p  e 4  # 0q4  # kp :B   3 5 p6 :B   3 s pt :B   3 p:B   3 p:B   3 -p.:B  3 kpl4  # kp 4B  # k 4B  #  v 4B  # 5 v6 4B  # s vt 4B  # v4B  # v4B  # -v.4B  # kvl4B  #  p 4B  #  4B  #  4B  #  4B  #  H I 4B  #  4B  #  4B  #  4B   #  674B ! #  pq.B "   A .B #    .B $    .B %    .B &   01 .B '   H .B (   e .B )    .B *   ^_ .B +   Lv .B ,  % ()w .B -  % @& .B .  _ .B /  .B 0  A  .B 1    .B 2    .B 3    .B 4   011 .B 5  1 H2 .B 6  e O .B 7  O P .B 8   ^_ .B 9   Lv .B :  w () .B ;   @ .B <  _ M .B =  M N :B > 3 jJ) 5 :B ? 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Affichage l'cran IPSN/DPHD M& .Times New RomanArialSymbol Arial Black SwitzerlandTimesModle par dfautMicrosoft Excel Chart#Results of epidemiological studies Epidemiology!History of epidemiologic studies/Hiroshima and Nagasaki Survivors of the A Bomb+Hiroshima Nagasaki Distribution of dosesPrsentation PowerPoint9Cancer relative risk among Hiroshima-Nagasaki survivors3Life Span Study Results - solid cancers (1950-97)/Life Span Study Relative risk of solid cancer0Life Span Study Relative risk for solid tumorsYHiroshima and Nagasaki : Adjustment of a linear model for solid cancer risk at low dosesKLife Span Study : Effect of Age at exposure and period from the exposure0Life Span Study Results leukaemias (1950-90)-Life Span Study Relative risk of leukaemiasFLife Span Study : effect of age at exposure and period from exposure2Results of the Hiroshima-Nagasaki survivors studyCLife Span Study Results : diseases other than cancer (1950-1997) Prsentation PowerPoint<Hiroshima Nagasaki : diseases other than cancer (1968-97)Hiroshima and Nagasaki Life span study limitsExtrapolation distances0Power and epidemiological studies at low dosesOccupational studies ,Main contribution from occupational studies&Nuclear workers: joint analysis 1995 %Nuclear workers study (Cardis 1995) ?Cohort study of nuclear workers in France (CEA-COGEMA group) *Cohort study of French uranium miners (1)*Cohort study of French uranium miners (2);Uranium miners cohorts with low levels of radon exposure 5Uranium miners cohorts: Exposure-risk relationship 5Uranium miners cohorts: Exposure-risk relationship \Cumulative exposure and duration of exposure to radon in miners cohorts (European program)ACampaign of measurements of indoor radon concentration in FranceACase-control study of indoor radon and lung cancer in France (1)ACase-control study of indoor radon and lung cancer in France (2) Conclusion Polices utilisesModle de conceptionServeurs OLE incorporsTitres des diapositives&es&)_)^Frdrique ROBERTscenzo                  h1JLife Span Study : Effect of Age at exposure and period from the exposureKK  +  l3^Life Span Study Results  leukaemias (1950-90)00$0   4249 deaths by leukemia including 87 in excess (38,1 %) latency of 3 years, pick at 6-8 years 80 % observed before 1970 persistence of excess of 3,5 % on 1985-1990 Linear quadratic dose-effect relationship Excess relative risk of 400% by Sievert Decreasing of risk with age at exposure and with age attained0^0n2n>5$ m I                 m4,Life Span Study Relative risk of leukaemias--$D      n6ELife Span Study : effect of age at exposure and period from exposureFF J    o71Results of the Hiroshima-Nagasaki survivors study22$>   " Risk of radiation induced cancer recognised : leukaemia, breast, lung, thyroid probable : multiple myeloma, liver, digestive, bone, urinary-genital organs, brain, skin above 100 mSv for solid cancers Dose-effect relationship compatible with a non threshold model solid cancers : linear relative risk model leukaemia : linear-quadratic absolute risk model A basis for radiation protection need to extrapolate from high to low doses and dose -rates!0P20P2?0n2\0P2!0n2;0P2! $L'\ ;  FbH   p8BLife Span Study Results : diseases other than cancer (1950-1997) (C6$ $Z       31 881 deaths including 250 in excess (0,8 %) Linear dose-effect relationship: linear excess relative risk of 14% by Sievert Excess statisticaly significant only in recent analyses: large latency or other co-factor ?                                      q9 r:vHiroshima  Nagasaki : diseases other than cancer (1968-97)<<<     s;Hiroshima and Nagasaki $$t<Life span study limits$ Death certificates : under-recording of cancer Particularities of Japaneese population: basic rate of breast and stomach cancer (transposition problem) Exposure rate very high Only external exposure\C W   3Extrapolation distances 6/Power and epidemiological studies at low doses00S#Occupational studies  $"  Nuclear workers studies : external radiation at low doses and at low annual dose rates Uranium miners studies : inhalation of radon decay products from risk estimation at low cumulative exposures to general public concern HW>Q &                           z=+Main contribution from occupational studies,,$"  Registered individual dosimetry on annual basis Over long working periods ( historical reconstruction) Able to express a long-term risk , by taking in account the protaction of the individual exposure over time2hvir         +           B%Nuclear workers: joint analysis 1995  &$ <      C$Nuclear workers study (Cardis 1995)  %# <     =>Cohort study of nuclear workers in France (CEA-COGEMA group) ??<     "Published Results : 50 000 workers All causes mortality lower than in the French male general population (Healthy worker effect) No excess of mortality from leukaemia Elevated mortality risk observed for pleura cancer and skin melanoma (men) and breast and brain cancer (women) Achievements in 2003: Integration in the international joint analysis of nuclear workers (IARC): 17 countries (Germany, Australia, Belgium, Canada, Spain, Finland, France, Hungary, Japan, Slovakia, Sweden, Switzerland, UK, USA, Russia, Lithuania, South Korea) Cohort of 400 000 individuals Analysis of mortality risk associated to cumulated doses : main hypothesis to be tested : potential leukemia risk increasing with exposure Future EC program Analysis of mortality risk associated to multiple exposures #8Z8 " xZ8Z " xZixZ> " xZn#>                   3$ 1    C>)Cohort study of French uranium miners (1)**4     Objectives : Estimation of risk of cancer death associated to cumulated radon exposure Cohort : 5098 uranium miners employed in the CEA-COGEMA group between 1946 and 1990 Reconstruction of individual annual exposure (radon, gamma, ore dust) Low cumulated exposure (37 WLM) Follow-up to December 1994 (mean duration of 26 years) Mortality : 1162 deaths, from which 125 lung cancer deaths Collaborations : Occupational medical service of COGEMA European joint analysis of miners with low levels of exposure (Czech and German cohorts)c(% " I " L %:   ?)Cohort study of French uranium miners (2)**4     Results : Excess risk of death from lung cancer: SMR = 1.5 Linear dose-response relationship with cumulated radon exposure coherent with the literature : ERR = 0.008 / WLM Decrease of the risk with time since exposure (20% / 10 years) No dose rate effect once time since exposure and exposure period are considered Perspectives : 6th EC program Extension of follow-up through end of 1999 (French+ Czech + Wismuth cohorts) Analysis of data collected in the frame of nested case-control studies: tobacco, other occupational factors Risk modelling : time dependant variables, mechanistic modelling; uncertainties linked to organ dose calculations Multiple exposures : Ur + gamma + radon decay in miners  (;( " (, " 9H  ;  ,9  <                        *      0               {>:Uranium miners cohorts with low levels of radon exposure $;9$@        |?4Uranium miners cohorts: Exposure-risk relationship $53$<    }@4Uranium miners cohorts: Exposure-risk relationship $53$<    ~A[Cumulative exposure and duration of exposure to radon in miners cohorts (European program)&\Zt            A@Campaign of measurements of indoor radon concentration in FranceAPA &B@Case-control study of indoor radon and lung cancer in France (1)AA@        C @Case-control study of indoor radon and lung cancer in France (2)AA@      D Conclusion    Epidemiological studies results are closely related to quality of past exposure data, Analytical studies need individual information on the main risk factor (radiation) and on potential co-factors (occupational and others) At low doses : interaction with other co-carcinogenic factors : mechanistic models Good quality of health indicator is absolutely necessary (incidence versus mortality studies) Z         #                              )    /8JKM^_`ai!j"w$x%y&'\   (  r  S  8P  8 r  S < 8 8 p  H? B"P H  0޽h ? ̙33  $(  r  S @K P   r  S O    H  0޽h ? ̙33r{S& y{ Root EntrydO)Pt0 Pictures6Current User)MSummaryInformation(6:R     S !"#$%&'()*+,-./0123456789;<=>?@ABCDEFGHITUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|~  !"#$%&'(*tives&es&'_)Lucie D'AscenzoLucie D'Ascenzo