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. 2009 Sep 15;115(18):4176-85.
doi: 10.1002/cncr.24481.

Divergent cancer pathways for early-onset and late-onset cutaneous malignant melanoma

William F Anderson  1 , Ruth M Pfeiffer, Margaret A Tucker, Philip S Rosenberg
Affiliations

Divergent cancer pathways for early-onset and late-onset cutaneous malignant melanoma

William F Anderson et al. Cancer. .

Abstract

Background: 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.

Methods: 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]).

Results: 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.

Conclusions: 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.

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Figures

Figure 1
Figure 1
Age-adjusted (2000 US standard population) incidence trends and age-specific incidence rates among men and women with cutaneous malignant melanoma (CMM), using the National Cancer Institute’s Surveillance, Epidemiology, and End Results program (SEER 9, 1975–2004).
Figure 2
Figure 2
Age distributions at diagnosis for gender, histopathology, and body site, using the National Cancer Institute’s Surveillance, Epidemiology, and End Results program (SEER 9, 1975–2004). The area under each density plot represented 100% of melanoma cases, where density X 100 = percent relative frequency distribution. Abbreviations: SSM, superficial spreading melanoma; LMM, lentigo maligna melanoma; ACM, acral melanoma; UCM, unclassified melanoma; MLF; men + LMM + face, head, and neck; FSLE, females + SSM + lower extremity.
Figure 3
Figure 3
APC “fitted” age-at-onset curve, adjusted for calendar-period and birth-cohort effects (SEER 9, 1975–2004).
See this image and copyright information in PMC

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