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American Journal of Epidemiology Advance Access published online on November 3, 2009
American Journal of Epidemiology, doi:10.1093/aje/kwp307
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American Journal of Epidemiology © The Author 2009. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Practice of Epidemiology

Population-based, Case-Control-Family Design to Investigate Genetic and Environmental Influences on Melanoma Risk

Australian Melanoma Family Study

Anne E. Cust*, Helen Schmid, Judith A. Maskiell, Jodie Jetann, Megan Ferguson, Elizabeth A. Holland, Chantelle Agha-Hamilton, Mark A. Jenkins, John Kelly, Richard F. Kefford, Graham G. Giles, Bruce K. Armstrong, Joanne F. Aitken, John L. Hopper and Graham J. Mann

* Correspondence to Dr. Anne E. Cust, Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, School of Population Health, The University of Melbourne, Level 1, 723 Swanston Street, Melbourne, Victoria 3010, Australia (e-mail: aecust{at}unimelb.edu.au).

Received for publication February 6, 2009. Accepted for publication August 31, 2009.

Discovering and understanding genetic risk factors for melanoma and their interactions with phenotype, sun exposure, and other risk factors could lead to new strategies for melanoma control. This paper describes the Australian Melanoma Family Study, which uses a multicenter, population-based, case-control-family design. From 2001 to 2005, the authors recruited 1,164 probands including 629 cases with histopathologically confirmed, first-primary cutaneous melanoma diagnosed before age 40 years, 240 population-based controls frequency matched for age, and 295 spouse/friend controls. Information on lifetime sun exposure, phenotype, and residence history was collected for probands and nearly 4,000 living relatives. More than 3,000 subjects donated a blood sample. Proxy-reported information was collected for childhood sun exposure and deceased relatives. Important features of this study include the population-based, family-based design; a focus on early onset disease; probands from 3 major cities differing substantially in solar ultraviolet exposure and melanoma incidence; a population at high risk because of high ultraviolet exposure and susceptible pigmentation phenotypes; population-based, spouse/friend, and sibling controls; systematic recruitment of relatives of case and control probands; self and parent reports of childhood sun exposure; and objective clinical skin examinations. The authors discuss methodological and analytical issues related to the study design and conduct, as well as the potentially novel insights the study can deliver.

case-control studies; environmental exposure; family; genetic predisposition to disease; melanoma; risk factors

Abbreviations: UV, ultraviolet


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