Prof. Leo Kinlen. An infective basis in childhood Leukaemia: the evidence of epidemiology

Transcription

1 Prof. Leo Kinlen An infective basis in childhood Leukaemia: the evidence of epidemiology

2 INFECTION-LINKED CANCERS Primary liver cancer Hepatitis B virus Primary liver cancer Hepatitis C virus Burkitt s lymphoma Epstein-Barr virus Cervix cancer Human Papillomavirus types 16, 18 Penis cancer Human Papillomavirus types 16, 18 Adult T-cell leukaemia Human T-cell leukaemia virus Kaposi s sarcoma Human herpes virus 8 Nasopharynx cancer Epstein-Barr virus Stomach cancer Helicobacter pylori Hodgkin s disease Epstein-Barr virus Post-transplant lymphoma Epstein-Barr virus Oro-pharynx cancer Human Papillomavirus type 16 Bladder cancer Schistosoma haematobium Cholangiocarcinoma Opisthorcis viverrini Squamous cell skin cancer in EV* Human Papillomavirus types 5 & 8 * Epidermodysplasia verruciformis

3 The Infective Hypothesis Childhood leukaemia is a rare response to a common, but unidentified, infection. When appreciable numbers of susceptible and infected individuals first mix, a localised (frequently sub-clinical) epidemic of the underlying infection is promoted. This epidemic leads to an excess of cases of the uncommon complication, childhood leukaemia.

4 POLIOMYELITIS MORTALITY (MALES 20-64) BY SOCIAL CLASS Social Class Observed Deaths Relative Risk V IV III II I

5 Rural-Urban Population Mixing Susceptible individuals are more prevalent in rural areas (less opportunity for exposure). When rural populations mix with urban populations on a large scale, the excess risk of childhood leukaemia might be detected. Variety of ways in which this mixing can occur, but the basic infective hypothesis remains the same.

6

7

8 LEUKAEMIA 0-14 YEARS. RURAL EVACUEE AREAS Mixing Ratio Evacuees:local children Population Observed No. Relative Risk 95% CI < 0.2 : 1 580, : 1 583, (0.91, 1.80) > 0.4 : 1 585, (1.07, 2.06) Trend p <0.05

9

10

11 LEUKAEMIA AT 0-4 YEARS: O/E (O) BY DENSITY OF OIL WORKERS IN RURAL SCOTLAND OIL WORKER DENSITY PRE-MIXING ( ) POST-MIXING ( ) Low 1.09 (19) 0.70 (11) Medium 1.10 (19) 0.93 (15) High 1.05 (17) 1.87 (31)**

12

13 CHILDHOOD LEUKAEMIA IN EARLY GROWTH PERIOD ( ) OF NEW TOWNS: O/E RATIOS Age Rural Overspill 0-4 years 2.75*** (20) 0.95 (22) 5-14 years 0.64 (3) 0.91 (22) 0-14 years 1.92** (23) 0.93 (44) **p<0.01, ***p<0.001

14

15

16

17 LEUKAEMIA IN COHORTS OF ORKNEY AND SHETLAND CHILDREN Age-group Wartime O/E Ratio (Obs) Post-war O/E Ratio (Obs) 0-4 yrs 5.13** (4) 1.28 (2) 5-14 yrs 2.96* (5) 0.64 (1) Total 3.64** (9) 1.06 (3) *p<0.05 **p<0.01

18 EXTREME RURAL POPULATION MIXING AND CHILDHOOD LEUKAEMIA (0-14 YEARS): UK STUDIES Type of Area Observed Expected O/E ratio P-value Rural New Towns * High Rural Oil Areas ** Rural Military Areas ** Growth Local Authority Areas ** High Rural Evacuee Areas * Constructions Projects *** Wartime Orkney and Shetland * Growth Rural Census Tracts * TOTAL ***

19 Childhood Leukaemia (0-14 yrs) in the High Category of Similar Degrees of Urban and Rural Population Mixing URBAN RURAL Study O/E ratio Obs No O/E ratio Observed New Towns * 23 Military Areas ** 71 North Sea Oil Areas ** 48 Evacuee Areas * 90 Total *** 142

20 RURAL POPULATION MIXING (RPM) AND C.L. (0-14 YRS): EXTREME CATEGORY IN STUDIES OUTSIDE UK Country Study Type Observed Expected O/E Ratio CL/ALL 1st Author, Yr France N.Z. Hong Kong (New Terr.) Growth Communes (M) New forestry (M) Rural New Towns CL Laplanche CL Dockerty *** ALL Alexander 1997 Canada (Ontario) France U.S. Growth Census Subdivisions La Manche Dept-La Hague Growth Rural Counties * ALL Koushik * ALL Boutou ** ALL Wartenberg 2004 TOTAL ***

21

22 CASE-CONTROL STUDY OF LEUKAEMIA AT 0-4 YRS BY PATERNAL OCCUPATIONAL CONTACT Occupation Levels Cases Controls OR 95%CI trend Most rural Medium and low High , 1.64 Very high , 7.85 p=0.02 Intermediate rural Medium and low High , 1.12 Very high , 3.03 p=0.79 Most urban Medium and low High , 1.12 Very high , 2.60 p=0.86

23 p for trend <0.001 (Dockerty et al. 2001) RISKS OF A.L.L. (0-14 yrs) BY BIRTH ORDER Birth order Number of cases Adj. Odds Ratio 95% C.I >

24 CASE-CONTROL STUDIES OF EARLY DAY CARE Start of early child care Number Exposed Expected Odds Ratio Reference >3 months at ages 0-1 yrs Petridou et al 1993 Not defined, but duration was greater among 255 cases than 760 controls Rosenbaum et al 2000 <6 months of age Neglia et al 2000 <2 yrs of age Infante-Rivard et al 2000 Not defined Ma et al 2002 <6 months of age Perrillat et al 2002 <3 months of age Jourdan-DaSilva 2004 Not defined, but 97 cases and 303 controls showed no difference Dockerty et al 1999

25 CHILDHOOD LEUKAEMIA IN THE HIGH EXPOSURE CATEGORY OF RURAL POPULATION MIXING IN DIFFERENT STUDIES TYPE OF AREA 2-6 yrs Rem yrs Obs (Exp) Obs (Exp) Rural New Towns 17 (7.49) 6 (7.10) Rural Military Areas 30 (27.62) 41 (15.69) High Rural Oil Areas 23 (17.49) 25 (13.94) Commuting-Increase Areas 43 (29.08) 36 (22.12) High Rural Evacuee Areas 53 (31.15) 37 (36.65) Construction sites 60 (47.66) 70 (47.14) Growth Local Authority Areas 32 (28.73) 49 (29.01) Wartime Orkney and Shetland 3 (1.14) 6 (1.59) TOTAL 265 (190.25) 266 (173.35) Over all O/E ratios 1.39*** 1.53*** *p<0.05, **p<0.01, ***p<0.001

26 RECENTLY IDENTIFIED INFECTIVE AGENTS Disease Peptic ulcer Whipple disease Creutzfeld-Jakob disease Guillain-Barre syndrome Lyme disease Infective Agent Helicobacter Pylori Tropheryma Whippelii Prion-protein Campylobacter jejuni Borrelia burgdorferi

27 Welcome to the International Scientific Conference for Childhood Leukaemia incidence causal mechanisms prevention