Infectious proxies and childhood leukaemia

1. Infectious proxies and childhood leukaemia www.UKCCS.org.uk UKCCS Update

2. www.ukccs.org

3. Study population • Children (≤ 15 years) registered for primary care with a General Practitioner (GP) Cases - ascertained from multiple sources:- • Treating/referring hospitals • Cross-checks with cancer registries Controls – selected from primary care population registers and individually matched to cases on:- • date of birth • sex • region of residence

4. U K C C S

7. Most direct Serology Socio-demographic proxies Least direct Measures of exposure to infection Clinical records

10. infectious diagnosis/symptoms N(%) non-infectious diagnosis/symptoms N(%) 0 112 (10.9) 171 (16.6) 1+ 919 (89.1) 860 (83.4) mean (95%CI) 3.9 (3.7– 4.1) 3.0 (2.8 – 3.2) GP consultations in the first year of life(controls N= 1031, 2-5 years old)

11. Controls N=1031 ALL N=425 Infection 3.9(3.7-4.1) 4.5(4.2-4.9) Non-infection 3.0(2.8-3.2) 3.3(2.9-3.6) GP consultations in the first year: mean (95% CI) ages 2-5 years Diagnosis/ symptoms

12. At least one infectious diagnoses in the first month (neonatal)

13. Neonatal infections & age at ALL diagnosis Age at diagnosis (months) Neonatal infections

14. ALL (2-5 yrs) and infection< 1 yr Compared to controls case children had: - • More episodes of infectious illness • Excess apparent from birth • No obvious specificity Within the case series: - • Children with more infections tended to be diagnosed earlier

15. Most direct Serology Socio-demographic proxies Least direct Measures of exposure to infection Clinical records Maternal illness reports

18. Infectious diagnosis first year: UKCCS controls> 15mths old

19. Infectious diagnosis first year: UKCCS cases> 15mths old

20. Infectious diagnosis first year: UKCCS ALL controls & cases>15 mths

21. ALL and prior infectious illness • From birth onwards, children who develop ALL have more infectious illness episodes than those who do not • The difference appears most marked in those exposed to infectious challenge from other children

22. Infections first year: maternalreport of infection with GP visit >15 months

23. Infection (any) in the first year: UKCCS controls

24. Infection (any) in the first year: UKCCS controls

25. Ear infection in the first year: UKCCS controls

26. Ear infection in the first year: UKCCS controls

27. Ear infection in the first year: UKCCS cases

28. Infections recorded in GP notes, birth to diagnosis – control

29. Infections recalled by mother, birth to diagnosis – control

30. Infections recorded in GP notes, birth to diagnosis Oral thrush

31. Infections recalled by mother, birth to diagnosis *mother’s recall: one mouth infection that lasted 5 days Mother also recalled:- Otitis media x1, <3 months Otitis media x1, 3-5 months Chest infection x1, 2 years 7 months

34. UKCCS: primary care record current analysis • Eczema in controls (typically diagnosed in the first two-years of life) in press • Eczema and infection in leukaemia cases and controls in progress • Combined analysis of obstetric and primary care data in progress

35. UKCCS: primary care record current analysis Eczema in controls in press • As expected, compared to children of birth order two or more, those of birth order one were at increased risk of eczema (p<0.018) • But, as has been shown by others, children diagnosed with eczema before the age of two had more prior clinically diagnosed infections recorded than children without eczema - RR = 1.26 (1.18 -1.36) • The difference was apparent from birth and throughout the first two years of life

38. Childhood cancer and deprivation: interviewed cases (3835) and first choice controls (7621)

39. Childhood cancer and deprivation: all cases (4430) and first choice controls (7663)

41. Published UKCCS findings for infection/immunity based on interview data alone are broadly consistent with those of other case control studies

45. www.ukccs.org