title: The potential value of sibling controls compared with population controls for association studies of lifestyle-related risk factors: an example from the Breast Cancer Family Registry.
abstract: BACKGROUND
  A previous Australian population-based breast cancer case-control study found indirect evidence that control participation, although high, was not random. We hypothesized that unaffected sisters may provide a more appropriate comparison group than unrelated population controls.
  
  
  METHODS
  Three population-based case-control-family studies of breast cancer in women of white European origin were carried out by the Australian, Ontario and Northern California sites of the Breast Cancer Family Registry. We compared risk factors between 3643 cases, 2444 of their unaffected sisters and 2877 population controls and conducted separate case-control analyses based on population and sister controls using unconditional multivariable logistic regression.
  
  
  RESULTS
  Compared with sister controls, population controls were more highly educated, had an earlier age at menarche, fewer births, their first birth at a later age and their last birth more recently. The established breast cancer associations detected using sister controls, but not detected using population controls, were decreasing risk with each of later age at menarche, more births, younger age at first birth and greater time since last birth.
  
  
  CONCLUSIONS
  Since participation of population controls might be unintentionally related to some risk factors, we hypothesize that sister controls could provide more valid relative risk estimates and be recruited at lower cost. Given declining study participation by population controls, this contention is highly relevant to epidemiologic research.
authors.affiliation: Genetic and Molecular Epidemiology Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Milne
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.forename: Julia A
authors.initials: JA
authors.lastname: Knight
authors.forename: Gillian S
authors.initials: GS
authors.lastname: Dite
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Carmel
authors.initials: C
authors.lastname: Apicella
authors.forename: Dee W
authors.initials: DW
authors.lastname: West
authors.forename: Irene L
authors.initials: IL
authors.lastname: Andrulis
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001315:Australia / Q000453:epidemiology; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D016022:Case-Control Studies; D005190:Family; D005260:Female; D006801:Humans; D008019:Life Style; D008875:Middle Aged; D015999:Multivariate Analysis; D009864:Ontario / Q000453:epidemiology; D012042:Registries; D035842:Research Subjects; D012307:Risk Factors; D012495:San Francisco / Q000453:epidemiology; D035781:Siblings; D011795:Surveys and Questionnaires; D055815:Young Adult