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

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Presentation on theme: "Infectious proxies and childhood leukaemia UKCCS Update www.UKCCS.org.uk."— Presentation transcript:

1 Infectious proxies and childhood leukaemia UKCCS Update

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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 UKCCS

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7 Measures of exposure to infection Most direct Least direct SerologySocio-demographicproxies Clinical records

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

11 GP consultations in the first year: mean (95% CI) ages 2-5 years 3.3( )3.0( )Non-infection 4.5( )3.9( )InfectionALLN=425ControlsN=1031Diagnosis/symptoms

12 At least one infectious diagnoses in the first month (neonatal) Controls(%)Cases(%) OR(95% CI) Any ( ) Conjunctivitis ( ) URTI ( ) Fungal ( ) Gastrointestinal ( )

13 Neonatal infections & age at ALL diagnosis Number Mean(95% CI) ( ) ( ) ( ) Neonatal infections Age at diagnosis (months)

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 Measures of exposure to infection Most direct Least direct SerologySocio-demographicproxies Clinical records Maternal illness reports

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18 Infectious diagnosis first year: UKCCS controls > 15mths old Number Mean (95% CI) Infectious diagnosis ( ) - Birth order ( ) ( ) - Regular social contact outside the home no6062.9( ) yes6822.9( ) - Deprivation at birth low/med ( ) high1923.3( )

19 Infectious diagnosis first year: UKCCS cases > 15mths old Number Mean (95% CI) Infectious diagnosis ( ) - Birth order ( ) ( ) - Regular social contact outside the home no3873.1( ) yes3163.3( ) - Deprivation at birth low/med5653.0( ) high1363.8( )

20 Infectious diagnosis first year: UKCCS ALL controls & cases >15 mths Odds ratio (95% CI) - Birth order 10.9( ) 2+1.6( ) - Regular social contact outside the home no1.0( ) yes1.7( ) - Deprivation at birth low/med1.1( ) high2.7( )

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: maternal report of infection with GP visit >15 months Odds ratio (95% CI) - Birth order 10.7( ) 2+0.8( ) - Regular social contact outside the home no0.9( ) yes0.6( ) - Deprivation at birth low/med0.7( ) high0.8( )

23 Infection (any) in the first year: UKCCS controls Mother’sreport GP infection record YesNo Total (%) yes (68) no (32) 1055(82)233(18)1288(100)

24 Infection (any) in the first year: UKCCS controls Mother’sreport GP infection record YesNo Total (%) yes (68) no (32) 1055(82)233(18)1288(100)

25 Ear infection in the first year: UKCCS controls Mother’sreport Otitis media GP record YesNo Total (%) yes (18) no (82) 238(19)1050(81)1288(100)

26 Ear infection in the first year: UKCCS controls Mother’sreport Otitis media GP record YesNo Total (%) yes (18) no (82) 238(19)1050(81)1288(100)

27 Ear infection in the first year: UKCCS cases Mother’sreport Otitis media GP record YesNo Total (%) yes (17) no (83) 163(20)648(80)811(100)

28 Age 3 days conjunctivitis 9 months URTI, ?otitis media 12 months Cold 13 months Cough 15 months Cough 16 months Conjunctivitis 19 months Chesty cough 2 years 7 months Pharyngitis 2 years 8 months Chesty, wheeze Infections recorded in GP notes, birth to diagnosis – control

29 Age 3 days conjunctivitis 9 months URTI, ?otitis media 12 months Cold 13 months Cough 15 months Cough 16 months Conjunctivitis 19 months Chesty cough 2 years 7 months Pharyngitis 2 years 8 months Chesty, wheeze Infections recalled by mother, birth to diagnosis – control

30 Age 2 weeks Severe oral thrush 3 weeks URTI, oral thrush, thrush nappy rash 6 weeks Severe oral thrush 7 weeks Conjunctivitis 8 weeks Conjunctivitis persists 7 months Cold 9 months Otitis media 10 months Viral infection 11 months Conjunctivitis 15 months Ringworm 16 months Diarrhoea 18 months Viral encephalitis  hospitalised 19 months Cough 20 months Nasal congestion, ?chronic tonsillitis 21 months Smelly nasal discharge, ?sinusitis 2 years URTI, conjunctivitis, otitis media 2 years 1 month Otitis media 2 years 6 months Otitis media 2 years 8 months Unwell for 10 days, yellow tinge, blue lips, loose motions, leg pains, won’t walk  ALL Oral thrush Infections recorded in GP notes, birth to diagnosis

31 Age 2 weeks Severe oral thrush* 3 weeks URTI, oral thrush, thrush nappy rash 6 weeks Severe oral thrush 7 weeks Conjunctivitis 8 weeks Conjunctivitis persists 7 months Cold 9 months Otitis media 10 months Viral infection Cold 11 months Conjunctivitis 15 months Ringworm 16 months Diarrhoea 18 months Viral encephalitis  hospitalised 19 months Cough 20 months Nasal congestion, ?chronic tonsillitis 21 months Smelly nasal discharge, ?sinusitis 2 years URTI, conjunctivitis, otitis media 2 years 1 month Otitis media 2 years 6 months Otitis media 2 years 8 months Unwell for 10 days, yellow tinge, blue lips, loose motions, leg pains, won’t walk  ALL 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

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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  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 ( )  The difference was apparent from birth and throughout the first two years of life Eczema in controls in press

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38 Childhood cancer and deprivation: interviewed cases (3835) and first choice controls (7621) BirthDiagnosis Affluent ( )1.10( ) 31.00( )1.06( ) 41.09( )1.15( ) Deprived51.12( )1.22( )

39 Childhood cancer and deprivation: all cases (4430) and first choice controls (7663) BirthDiagnosis Affluent ( )1.08( ) 30.99( )0.99( ) 41.03( )1.04( ) Deprived50.95( )0.98( )

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

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