title: Divergent cancer pathways for early-onset and late-onset cutaneous malignant melanoma.
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.
authors.affiliation: Biostatistics Branch, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Bethesda, Maryland 20892-7244, USA. wanderso@mail.nih.gov
authors.forename: William F
authors.initials: WF
authors.lastname: Anderson
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tucker
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000209:etiology*; D008875:Middle Aged; D015233:Models, Statistical; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology*; D012307:Risk Factors; D018426:SEER Program; D012737:Sex Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000209:etiology*; D013472:Sunlight / Q000009:adverse effects*