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Comparison of Self-Reported Data on infections of the child versus Clinical Records Insights from the UK Childhood Cancer (Case-Control) Study. Terry Dwyer for Tracy Lightfoot. Infection is plausibly involved in the aetiology of Acute Lymphoblastic Leukemia. Stimulates B lymphocytes

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Terry dwyer for tracy lightfoot

Comparison of Self-Reported Data on infections of the child versus Clinical Records Insights from the UK Childhood Cancer (Case-Control) Study

Terry Dwyer for Tracy Lightfoot


Infection is plausibly involved in the aetiology of acute lymphoblastic leukemia
Infection is plausibly involved in the aetiology of Acute Lymphoblastic Leukemia

Stimulates B lymphocytes

to proliferate and produce

antibodies

Infection


Two competing hypotheses
Two competing hypotheses Lymphoblastic

  • Greaves

    Infection in very early life reduces the risk of leukemia

  • Kinlen

    Infection in early life increases risk of leukemia


Day care attendance and risk of childhood leukaemia
Day Lymphoblastic care attendance and risk of childhood leukaemia

McNally. Br J Haematol 2004; 127: 243-263


Childhood infections and risk of childhood leukaemia post 1998
Childhood Infections and risk of childhood leukaemia (post 1998)

Age 0-2 months

Age 3-5 months

McNally Br J Haematol 2004; 127: 243-263


UK Childhood Cancer Study 1998)

UK Childhood cancer Study




Common sources of bias in c ase control studies 1 recall bias
Common sources of bias in c 1998)ase-controlstudies:1) Recall bias

cases

controls

enrolled

Exposed


Case control studies collect most information retrospectively
Case Control studies collect most information retrospectively

Cases

Healthy subjects

some exposed some not

questionnaires


Comparison of maternal report to gp record data
Comparison of maternal report to GP record data retrospectively

Regular social contact outside the home

Mother’s report

OR = 0.6

(CI 0.5-0.9)

GP records

OR = 1.7

1.1-12

History of infection

GP records

OR = 1.12

Mother’s report

OR = 0.94


Uk childhood cancer study
UK Childhood Cancer Study retrospectively

‘This study found that a mother's recollections of past minor illness episodes in her children were unreliable, producing systematic case-control differences.’


Prospective cohort studies
Prospective retrospectivelyCohort studies

cases

Healthy subjects

some exposed some not

serology

epigenetics

Questionnaires

Questionnaires


Common sources of bias in c ase control studies 2 selection bias
Common sources of bias in c retrospectivelyase-controlstudies:2) Selection bias

Cases selected

Controls selected

enrolled

Exposed


The importance of full participation: lessons from a national case-control study

“In conclusion our findings confirm that differential participation is a major source of bias in case control studies…there is a clear need to address this issue in terms of study design ….to overcome this bias”.

Law. Br J Cancer 2002; 86: 350-355


Prospective cohort studies i4c
Prospective national case-control studyCohort studies (I4C)

Healthy subjects

some exposed some not

cases

Selection bias affecting

testing of hypotheses unlikely

at this stage

Possible selection bias

arising from loss to

follow up


How will this provide better evidence for key hypotheses
How will this provide better evidence for key hypotheses? national case-control study

British Childhood Cancer Case-control Study findings: based on

  • mother’s report, infection in the first year of life

  • clinical records, infection in the first year of life

Higher risk of leukemia

Lower risk of leukemia


I4c team
I4C Team national case-control study




Biospecimens
Biospecimens

Biospecimens available in more than 2 cohorts prenatally and at birth


What the future holds

*The estimated numbers of cancer is based on how many would occur over15 years of follow up


Capturing the timing of genetic modifications or environmental exposures appears to be critical
Capturing the timing of genetic modifications or environmental exposures appears to be critical

Greaves Euro J Cancer 1999


Building multidisciplinary teams
Building multidisciplinary teams environmental exposures appears to be critical


Terry environmental exposures appears to be criticalDwyer* Martha Linet** Jean Golding*** Ora Paltiel**** Jorn Olsen***** Camilla Stoltenberg****** Shoji Nakayama ********Zdenko Herceg******* Gabriella Tikellis*

International Childhood Cancer

Cohort Consortium (14C)

* Murdoch Childrens Research Institute, Australia** National Cancer Institute, NIH USA*** United Kingdom: ALSPAC **** Jerusalem ***** Denmark

******Norwegian MoBa

*******IARC

******* JECS


Study of biological intermediates in humans
Study of biological intermediates in humans? environmental exposures appears to be critical


Minimum number needed to study leukemia acute lymphoblastic leukemia acute myeloid leukemia
Minimum number needed to study leukemia (Acute Lymphoblastic Leukemia & Acute Myeloid Leukemia)

Garcia-Closas M, Lubin JH. Am J Epidemiol. 1999

Age-adjusted SEER cancer incidence rates USA 1975-2002


Pesticide exposure and childhood cancer
Pesticide exposure and Childhood cancer Leukemia & Acute Myeloid Leukemia)

1) Parental occupational exposure to pesticides: farming

?Childhood cancer


2) Exposure to pesticides: Leukemia & Acute Myeloid Leukemia)

Residential proximity to agricultural areas

Land cover map identifying crop type

Proximity of residence to areas of pesticide use

Satellite image map


Birth weight and determinants of birth weight and childhood cancer
Birth weight and determinants of birth weight and childhood cancer

BIRTH WEIGHT

  • Maternal /Paternal factors

  • Age

  • Education

  • Birth order

  • Race/ethnicity

  • Exposures

  • X-ray during pregnancy

  • Pregnancy weight gain

  • Smoking

  • Pesticide exposure

  • Occupation

Pooling prospective data on 175,000 mothers and babies amongst which there are 230 cases of childhood cancer


There has been little progress cancer

In finding out how to prevent

childhood cancer!


Total Live Births cancer

Where are we now

388,100

Total Cancer Cases

528

MoBa - Norway 109,981

DNBC - Denmark 101,042

ALSPAC - UK 14,042

CPP - USA

60,000

JPS - Israel

92,408

TIHS

10,627


Total Live Births cancer

388,100

Total Cancer Cases

762

MoBa - Norway 109,981

DNBC - Denmark 101,042

ALSPAC - UK 14,042

CPP - USA

60,000

JPS - Israel

92,408

TIHS

10,627


Total Live Births cancer

635,931

Total Cancer Cases

1,339

MoBa - Norway 109,981

DNBC - Denmark 101,042

ALSPAC - UK 14,042

CPP - USA

60,000

JPS - Israel

92,408

BDSS – China 247,831

TIHS

10,627


Total Live Births cancer

735,931

Total Cancer Cases

1,572

MoBa - Norway 109,981

DNBC - Denmark 101,042

ALSPAC - UK 14,042

CPP - USA

60,000

JPS - Israel

92,408

JECS – Japan 100,000

BDSS – China 247,831

TIHS

10,627


Total Live Births cancer

835,931

Total Cancer Cases

1,805

MoBa - Norway 109,981

DNBC - Denmark 101,042

ALSPAC - UK 14,042

CPP - USA

60,000

JPS - Israel

92,408

JECS - Japan 100,000

BDSS - China 247,831

NCS - USA 100,000

TIHS

10,627


Total Live Births cancer

1,135,931

Total Cancer Cases

2,504

MoBa - Norway 109,981

DNBC - Denmark 101,042

ALSPAC - UK 14,042

CFCS – China 300,000

CPP - USA

60,000

JPS - Israel

92,408

JECS - Japan 100,000

BDSS - China 247,831

NCS - USA 100,000

TIHS

10,627


Cohorts that are in discussion with the I4C cancer

Total Live Births

1,793,431

Total Cancer Cases

4,036

MoBa - Norway 109,981

DNBC - Denmark 101,042

GEHBC – Germany 200,000

ALSPAC - UK 14,042

ELFE – France 20,000

BCS - UK 100,000

CFCS – China 300,000

Bradford - UK 10,000

CPP - USA

60,000

JPS - Israel

92,408

JECS - Japan 100,000

NINFEA – Italy 7,500

Wuhan - China 120,000

BDSS - China 247,831

NCS - USA 100,000

CIHS - Brazil 100,000

MCRI - VIC 100,000

TIHS

10,627


C ase control studies
C cancerase-controlstudies

Compare a group of patients or ‘cases’ with ‘controls’ free of disease

cases

controls

exposed

Exposed


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