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

9079 Background: Emerging data suggest that cutaneous malignant melanomas (CMM) may arise through divergent cancer pathways, linked to intermittent versus accumulated sun exposure. However, numerous questions remain regarding the timing and/or age of exposure.


METHODS
We, therefore, systematically examined the effect of aging upon CMM incidence in 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 upon CMM incidence was assessed by gender, histopathological subtype (superficial spreading melanoma (SSM) or lentigo maligna melanoma [LMM]), and anatomic site (face, head, and neck [FHN] or lower extremity [LE]).


RESULTS
Gender, histopathological and anatomic site were age-specific effect modifiers for CMM, showing divergent (or bimodal) early- and late-onset cancer pathways. Early-onset melanomas were predominantly associated with female gender, SSM, and LE. Late- onset melanomas were correlated with male gender, LMM, and FHN. Early- and late-onset melanoma populations were confirmed with age-period-cohort models (adjusted for period and cohort effects) and two-component mixture models.


CONCLUSIONS
These results are consistent with a divergent and age-dependent solar hypothesis for CMM. Early-onset melanomas may represent gene-sun exposure interactions occurring early (and/or intermittently) in life among susceptible individuals. Late-onset melanomas possibly reflect accumulated lifelong sun exposure in comparatively less susceptible individuals. Future analytical studies should be adequately powered to account for this age-dependent effect modification for acknowledged (gender, histopathology, and anatomic site) as well as suspected melanoma risk factors such as constituent genetic variants. No significant financial relationships to disclose.