title: The Cancer, Lifestyle and Evaluation of Risk Study (CLEAR): Rationale and design of an unmatched "case-spouse control" study of over 10,000 participants in New South Wales, Australia.
abstract: BACKGROUND
  The New South Wales (NSW) Cancer, Lifestyle and Evaluation of Risk Study (CLEAR) is an open epidemiological bioresource, using an all cancer unmatched case-spouse control design. Participant characteristics and selected confirmed associations are compared to published estimates: current smoking and lung cancer; country of birth and melanoma; body mass index (BMI) and bowel cancer; and paternal history of prostate cancer and prostate cancer, to illustrate the validity of this design.
  
  
  METHODS
  Cases are NSW residents, ≥18 years, with an incident cancer of any type. Controls are cancer-free spouses of cases. Participants complete a consent form, a questionnaire, and provide an optional blood sample. For analyses, odds ratios for males and females are calculated for cancers and exposures of interest, by sex-matching controls to cases.
  
  
  RESULTS
  10,816 participants (8569 cases, 2247 controls, 54% female) recruited to-date, median age: 61.6 y cases, 61.3 y controls. The top five cancer types are female breast (n=1691), prostate (n=1102), bowel (n=888), melanoma (n=608), and lung (n=265). Adjusted odds ratios (OR) were: 20.65 (95% CI: 13.25-32.19) for lung cancer in current versus never smokers; 1.16 (1.05-1.28) for bowel cancer per 5 kg/m(2) increment in BMI; 1.41 (1.01-1.96) for melanoma in Australian-born compared to those born in UK/Ireland; and 2.47 (1.82-3.37) for prostate cancer in men with versus without a paternal history of prostate cancer.
  
  
  CONCLUSIONS
  This study design, where controls are the spouses of cases diagnosed with a variety of cancers and which are analysed unmatched, avoids potential biases due to overmatching, considered problematic in standard case-spouse control studies, and illustrates that risk estimates analysed are consistent with the published literature. CLEAR methodology provides a practical design to advance local knowledge on the causes of various leading and emerging cancers.
authors.affiliation: Cancer Research Division, Cancer Council New South Wales, Woolloomooloo, Australia; Sydney School of Public Health, University of Sydney, Camperdown, Australia; School of Population Health and Community Medicine, University of New South Wales Australia, Kensington, Australia. Electronic address: Frederick.sitas@Sydney.edu.au.
authors.forename: F
authors.initials: F
authors.lastname: Sitas
authors.affiliation: Cancer Research Division, Cancer Council New South Wales, Woolloomooloo, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Yap
authors.affiliation: Cancer Research Division, Cancer Council New South Wales, Woolloomooloo, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Egger
authors.affiliation: Cancer Research Division, Cancer Council New South Wales, Woolloomooloo, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Christian
authors.affiliation: Cancer Research Division, Cancer Council New South Wales, Woolloomooloo, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Hodgkinson
authors.affiliation: Ingham Institute for Applied Medical Research, UNSW Australia, Liverpool, NSW, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Barton
authors.affiliation: National Centre for Epidemiology and Population Health, Australian National University, ACT Canberra, Australia; Sax Institute, Sydney, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Banks
authors.affiliation: Lowy Cancer Research Centre, University of New South Wales Australia, Kensington, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Canfell
authors.affiliation: Cancer Research Division, Cancer Council New South Wales, Woolloomooloo, Australia; Sydney School of Public Health, University of Sydney, Camperdown, Australia; School of Population Health and Community Medicine, University of New South Wales Australia, Kensington, Australia; School of Medicine and Public Health, University of Newcastle, NSW, Australia.
authors.forename: D L
authors.initials: DL
authors.lastname: O'Connell
authors.affiliation: Cancer Research Division, Cancer Council New South Wales, Woolloomooloo, Australia; Sydney School of Public Health, University of Sydney, Camperdown, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Nair-Shalliker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology*; D009517:New South Wales / Q000453:epidemiology; D016017:Odds Ratio; D012107:Research Design; D012307:Risk Factors; D018454:Spouses; D011795:Surveys and Questionnaires; D055815:Young Adult
keywords: Australia; BMI; Biobank; Birthplace; Cancer; Case-spouse control design; Case–control design; Control selection; Family history; Smoking