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

F Sitas; S Yap; S Egger; K Christian; V Hodgkinson; M Barton; E Banks; K Canfell; D L O'Connell; V Nair-Shalliker

doi:10.1016/j.canep.2015.03.006

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

Cancer Epidemiol. 2015 Jun;39(3):414-23. doi: 10.1016/j.canep.2015.03.006. Epub 2015 Apr 16.

Authors

F Sitas¹, S Yap², S Egger², K Christian², V Hodgkinson², M Barton³, E Banks⁴, K Canfell⁵, D L O'Connell⁶, V Nair-Shalliker⁷

Affiliations

¹ 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.
² Cancer Research Division, Cancer Council New South Wales, Woolloomooloo, Australia.
³ Ingham Institute for Applied Medical Research, UNSW Australia, Liverpool, NSW, Australia.
⁴ National Centre for Epidemiology and Population Health, Australian National University, ACT Canberra, Australia; Sax Institute, Sydney, Australia.
⁵ Lowy Cancer Research Centre, University of New South Wales Australia, Kensington, Australia.
⁶ 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.
⁷ Cancer Research Division, Cancer Council New South Wales, Woolloomooloo, Australia; Sydney School of Public Health, University of Sydney, Camperdown, Australia.

PMID: 25892705
DOI: 10.1016/j.canep.2015.03.006

Abstract

Introduction: 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.

Material and 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.

Discussion: 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.

Keywords: Australia; BMI; Biobank; Birthplace; Cancer; Case-spouse control design; Case–control design; Control selection; Family history; Smoking.

Publication types

Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Body Mass Index
Case-Control Studies
Female
Humans
Life Style*
Male
Middle Aged
Neoplasms / epidemiology*
New South Wales / epidemiology
Odds Ratio
Research Design
Risk Factors
Spouses*
Surveys and Questionnaires
Young Adult