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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. Stimulates B lymphocytes

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Terry Dwyer for Tracy Lightfoot

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  1. 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

  2. Infection is plausibly involved in the aetiology of Acute Lymphoblastic Leukemia Stimulates B lymphocytes to proliferate and produce antibodies Infection

  3. Two competing hypotheses • Greaves Infection in very early life reduces the risk of leukemia • Kinlen Infection in early life increases risk of leukemia

  4. Day care attendance and risk of childhood leukaemia McNally. Br J Haematol 2004; 127: 243-263

  5. 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

  6. UK Childhood Cancer Study UK Childhood cancer Study

  7. Study subjects

  8. Putting the data to be presented into context for 14C

  9. Common sources of bias in case-controlstudies:1) Recall bias cases controls enrolled Exposed

  10. Case Control studies collect most information retrospectively Cases Healthy subjects some exposed some not questionnaires

  11. Comparison of maternal report to GP record data 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

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

  13. Prospective Cohort studies cases Healthy subjects some exposed some not serology epigenetics Questionnaires Questionnaires

  14. Common sources of bias in case-controlstudies:2) Selection bias Cases selected Controls selected enrolled Exposed

  15. 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

  16. Prospective Cohort 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

  17. How will this provide better evidence for key hypotheses? 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

  18. I4C Team

  19. Where we will be in 5 years, with current cohorts in the I4C

  20. New or Planned Cohorts

  21. Biospecimens Biospecimens available in more than 2 cohorts prenatally and at birth

  22. What the future holds *The estimated numbers of cancer is based on how many would occur over15 years of follow up

  23. Capturing the timing of genetic modifications or environmental exposures appears to be critical Greaves Euro J Cancer 1999

  24. Building multidisciplinary teams

  25. Terry Dwyer* 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

  26. Study of biological intermediates in humans?

  27. 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

  28. Pesticide exposure and Childhood cancer 1) Parental occupational exposure to pesticides: farming ?Childhood cancer

  29. 2) Exposure to pesticides: Residential proximity to agricultural areas Land cover map identifying crop type Proximity of residence to areas of pesticide use Satellite image map

  30. 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

  31. There has been little progress In finding out how to prevent childhood cancer!

  32. Total Live Births 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

  33. Total Live Births 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

  34. Total Live Births 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

  35. Total Live Births 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

  36. Total Live Births 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

  37. Total Live Births 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

  38. Cohorts that are in discussion with the I4C 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

  39. Case-controlstudies Compare a group of patients or ‘cases’ with ‘controls’ free of disease cases controls exposed Exposed

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