Anatomic Site, Sun Exposure, and Risk of Cutaneous Melanoma David C. Whiteman, Mark Stickley, Peter Watt, Maria Celia Hughes, Marcia B. Davis, and Adèle C. Green A B S T R A C T Purpose Sunlight is the principal environmental risk factor for cutaneous melanoma. A current hypothesis postulates that the role of sunlight in causing melanoma differs according to anatomic site. We tested this hypothesis in a population-based case-case comparative study of melanoma patients. Methods Patients were sampled from the Queensland cancer registry in three groups: superficial spreading or nodular melanomas of the trunk (n = 154), of the head and neck (HN; n = 76), and lentigo maligna (LM) and lentigo maligna melanoma (LMM; for both LM and LMM, n = 76). Data were collected on school-age sun exposure and occupational and recreational sun exposure in adulthood. Odds ratios (OR) and 95% CIs were calculated using polytomous logistic regression. Results HN melanoma patients were substantially more likely than trunk patients to have higher levels of sun exposure in adulthood (OR, 2.43; 95% CI, 0.98 to 5.99) and specifically, higher levels of occupational exposure (OR, 3.25; 95% CI, 1.32 to 8.00), but lower levels of recreational sun exposure (OR, 0.50; 95% CI, 0.21 to 1.19). LM and LMM patients reported higher occupational exposure and lower recreational sun exposure than trunk melanoma patients, although this was not significant. We found no significant differences between the groups for school-age sun exposures. Conclusion Melanomas developing at different body sites are associated with distinct patterns of sun exposure. Melanomas of the head and neck are associated with chronic patterns of sun exposure whereas trunk melanomas are associated with intermittent patterns of sun exposure, supporting the hypothesis that melanomas may arise through divergent causal pathways. J Clin Oncol 24:3172-3177. © 2006 by American Society of Clinical Oncology INTRODUCTION Several decades of research have confirmed that the relationship between sun exposure and melanoma is complex and is strongly modified by host factors including pigmentation and propensity to develop nevi. 1 The pattern of exposure to sunlight has been hypothesized to be the key determinant in mela- noma development, with intermittent exposure considered to be causal and chronic exposure pro- tective. 2 While epidemiologic evidence has accumu- lated in support of the intermittent exposure hypothesis, 3 several features of the occurrence of melanoma indicate that chronic exposure to sun- light has a causal role. We have previously proposed a divergent path- way model for cutaneous melanoma irrespective of histologic classification which seeks to explain the de- velopment of melanoma by incorporating the role of sunlight, host susceptibility, and anatomic site. 4,5 In support of this model, we found marked differences in the prevalence of nevi and solar keratoses between patients with head and neck melanomas and those with trunk melanomas. 5 Similar findings have been reported by others, 6,7 and coupled with emerging mo- lecular evidence that somatic genetic aberrations in cutaneous melanoma also vary by site, 8,9 suggest that melanomas arising at different anatomic sites may have different causal pathways. 10 Here, we further explore the causation of mel- anoma by sun exposure. Our primary hypothesis was that people with melanomas of the head and neck would be exposed to greater cumulative doses of sunlight than those with melanomas of the trunk. METHODS Methodologic details of patient selection and data col- lection have been described previously. 5 Briefly, we used a case-case study design to test our hypothesis, in From the Queensland Institute of Medi- cal Research, Brisbane, Australia. Submitted February 9, 2006; accepted April 21, 2006. Supported by grants from the Queens- land Cancer Fund and the National Cancer Institute (CA 88363-01A1). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Presented in part during an invited plenary session at the 6th World Congress on Melanoma, Vancouver, British Columbia, Canada, September 8, 2005 (D.C.W.). Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Address reprint requests to David C. Whiteman, MBBS, PhD, Division of Population Studies and Human Genet- ics, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Queensland 4029 Australia; e-mail: david.whiteman@qimr.edu.au. © 2006 by American Society of Clinical Oncology 0732-183X/06/2419-3172/$20.00 DOI: 10.1200/JCO.2006.06.1325 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 24  NUMBER 19  JULY 1 2006 3172 Downloaded from ascopubs.org by University of Queensland on February 9, 2017 from 130.102.082.116 Copyright © 2017 American Society of Clinical Oncology. All rights reserved.