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Article first published online: 17 JUN 2009
Copyright © 2009 American Cancer Society
Volume 115, Issue 18, pages 4176–4185, 15 September 2009
How to Cite
Anderson, W. F., Pfeiffer, R. M., Tucker, M. A. and Rosenberg, P. S. (2009), Divergent cancer pathways for early-onset and late-onset cutaneous malignant melanoma. Cancer, 115: 4176–4185. doi: 10.1002/cncr.24481
We thank the reviewers for helpful comments, which improved the content of this article.
This article is US Government work and, as such, is in the public domain in the United States of America.
- Issue published online: 4 SEP 2009
- Article first published online: 17 JUN 2009
- Manuscript Accepted: 5 FEB 2009
- Manuscript Revised: 2 FEB 2009
- Manuscript Received: 8 DEC 2008
- superficial spreading melanoma;
- lentigo maligna melanoma;
- Poisson regression models;
- 2-component mixture models;
- age-period-cohort models;
- Surveillance, Epidemiology, and End Results
Emerging data suggest that cutaneous malignant melanomas (CMM) may arise through divergent cancer pathways that are linked to intermittent versus accumulated sun exposure. However, numerous questions remain regarding the timing and/or age of exposure.
The authors systematically examined the effect of aging on CMM incidence in data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Standard descriptive epidemiology was supplemented with mathematical models. The impact of advancing age on CMM incidence was assessed by sex, histopathologic classification (superficial spreading melanoma [SSM] or lentigo maligna melanoma [LMM]), and anatomic site (face, head, and neck [FHN] or lower extremity [LE]).
Sex, histopathology, and anatomic site were age-specific effect modifiers for CMM that indicated divergent (bimodal) early-onset and late-onset cancer pathways. Early-onset melanomas were associated predominantly with women, SSM, and LE. Late-onset melanomas were correlated with men, LMM, and FHN. Early- and late-onset melanoma populations were confirmed with age-period-cohort models that were adjusted for period and cohort effects. Two-component mixture models also fit the data better than a single cancer population.
The current results were consistent with a divergent and age-dependent solar hypothesis for CMM. Early-onset melanomas may represent gene-sun exposure interactions that occur early (and/or intermittently) in life among susceptible individuals. Late-onset melanomas may reflect accumulated, lifelong sun exposure in comparatively less susceptible individuals. Future analytical studies should be powered adequately to account for this age-dependent effect modification both for acknowledged melanoma risk factors (sex, histopathology, and anatomic site) and for suspected melanoma risk factors, such as constituent genetic variants. Cancer 2009. Published 2009 by the American Cancer Society.