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. Cancer 2009. Published 2009 by the American Cancer Society.

International trends in the incidence of malignant melanoma 1953–2008—are recent generations at higher or lower risk?

“…The observation lends weight to the hypothesis that a change in generational UV exposure is a key contributor to the recent promising changes in melanoma risk in these higher-risk populations, and that childhood may represent a critical time window for melanoma risk at later ages. 23,31 Although it can be speculated that more recent generations already benefit from public health campaigns of the last decades, particularly introduced in Australia, New Zealand and the U.S. but also in several European countries, 19,53,54 the time lag between the changing prevalence in UV exposure and resulting stabilizations or declines in incidence rates might be too short to be the direct result of such interventions. 22 Nevertheless, in equivalent period terms, declines in the IRRs (Fig.…”

“…The most common (and most rapidly increasing) histological type for melanoma is superficially spreading melanoma, 7-10,18,20 a type which is associated with thinner tumors and intense, intermittent UV exposure. 20,31 The body site distribution and most common type of melanoma among young people lead to the assertion of a high intermittent UV exposure in this age group. This observation contrasts somewhat with the observed trends seen here in young women from both the U.S. and Iceland.…”

Testing the divergent pathway hypothesis for melanoma: recent findings and future challenges

“…Thus, whereas the incidence of melanomas occurring on the trunk peaks in middle-age (younger than for most other cancers), head and neck melanomas become increasingly common with advancing age. A recent analysis of USA cancer registry data used advanced mathematical models and found strong evidence for divergent age-dependent pathways for melanoma development [18]. One interpretation is that younger patients with melanoma represent a distinct subgroup of the population susceptible to melanocytic proliferation.…”

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

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The interesting paper by Anderson et al 1 provides new data about the existence of age-related differing cancer pathways for melanoma, showing that sex, anatomic site, and histopathology are age-dependent effect modifiers of melanoma risk; however, it should consider sex-site interactions.Sex-specific risk patterns of melanoma by site are rarely studied, probably because of the amount of cases required and the assumption that differences in melanoma between sexes are not biologically relevant. We recently reported the striking sex differences observed in age distribution of trunk cutaneous melanoma in Sweden; incidence rates displayed a steady increase with age in men, but plateaued in women from perimenopausal ages.

2 This pattern, only found in trunk ( Fig.

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“…The interesting paper by Anderson et al 1 provides new data about the existence of age-related differing cancer pathways for melanoma, showing that sex, anatomic site, and histopathology are age-dependent effect modifiers of melanoma risk; however, it should consider sex-site interactions.…”