{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:59:28Z","timestamp":1791352768086,"version":"4.3.1"},"reference-count":35,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2009,6,17]],"date-time":"2009-06-17T00:00:00Z","timestamp":1245196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2009,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>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]).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>Sex, histopathology, and anatomic site were age\u2010specific effect modifiers for CMM that indicated divergent (bimodal) early\u2010onset and late\u2010onset cancer pathways. Early\u2010onset melanomas were associated predominantly with women, SSM, and LE. Late\u2010onset melanomas were correlated with men, LMM, and FHN. Early\u2010 and late\u2010onset melanoma populations were confirmed with age\u2010period\u2010cohort models that were adjusted for period and cohort effects. Two\u2010component mixture models also fit the data better than a single cancer population.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>The current results were consistent with a divergent and age\u2010dependent solar hypothesis for CMM. Early\u2010onset melanomas may represent gene\u2010sun exposure interactions that occur early (and\/or intermittently) in life among susceptible individuals. Late\u2010onset melanomas may reflect accumulated, lifelong sun exposure in comparatively less susceptible individuals. Future analytical studies should be powered adequately to account for this age\u2010dependent 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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.24481","type":"journal-article","created":{"date-parts":[[2009,6,17]],"date-time":"2009-06-17T18:27:01Z","timestamp":1245263221000},"page":"4176-4185","source":"Crossref","is-referenced-by-count":73,"title":["Divergent cancer pathways for early\u2010onset and late\u2010onset cutaneous malignant melanoma"],"prefix":"10.1002","volume":"115","author":[{"given":"William F.","family":"Anderson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth M.","family":"Pfeiffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A.","family":"Tucker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip S.","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,6,17]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.2984"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.0442"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/3.4.325"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00054301"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19971009)73:2<198::AID-IJC6>3.0.CO;2-R"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-200109000-00015"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(20000301)85:5<627::AID-IJC5>3.0.CO;2-Y"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a112400"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-004-4325-5"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-07-2743"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0895-4356(91)90033-6"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djn411"},{"key":"e_1_2_6_14_2","unstructured":"National Cancer Institute Surveillance Epidemiology and End Results (SEER) Program. SEER Program SEER*Stat Database: Incidence\u2010SEER 9 Registries limited\u2010use based on the November 2006 submission (1992\u20102004). Bethesda Md: National Cancer Institute DCCPS Surveillance Research Program Cancer Statistics Branch; 2007. 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