Epidemiologic Support for Melanoma Heterogeneity Using the Surveillance, Epidemiology, and End Results Program

Journal of Investigative Dermatology (Impact Factor: 7.22). 06/2008; 128(5):1340-2. DOI: 10.1038/jid.2008.18
Source: PubMed


SEER, Surveillance, Epidemiology, and End Results

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Available from: Marianne Berwick, Jun 02, 2014
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    • "dence from epidemiological and molecular analyses to support this model of etiological heterogeneity of cutaneous melanomas, with anatomical site being an important source of observed heterogeneity (Broekaert et al., 2010; Curtin et al., 2005; Edlundh-Rose et al., 2006; Lachiewicz et al., 2008; Lang & MacKie, 2005; Maldonado et al., 2003; Thomas et al., 2007; Viros et al., 2008). Given that nevus count is significantly more strongly associated with melanomas arising on the trunk than on the head and neck (Whiteman et al., 2003), and given that nevus burden is strongly heritable (Wachsmuth et al., 2001; Zhu et al., 1999), it is plausible to speculate that the risks of melanoma conferred by nevus-associated genotypes might differ according to the anatomical site of the lesion. "
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    ABSTRACT: An evolving hypothesis postulates that melanomas may arise through 'nevus-associated' and 'chronic sun exposure' pathways. We explored this hypothesis by examining associations between nevus-associated loci and melanoma risk across strata of body site and histological subtype. We genotyped 1028 invasive case patients and 1469 controls for variants in methylthioadenosine phosphorylase (MTAP), phospholipase A2, group VI (PLA2G6), and Interferon regulatory factor 4 (IRF4), and compared allelic frequencies globally and by anatomical site and histological subtype of melanoma. Odds-ratios (ORs) and 95% confidence intervals (CIs) were calculated using classical and multinomial logistic regression models. Among controls, MTAP rs10757257, PLA2G6 rs132985 and IRF4 rs12203592 were the variants most significantly associated with number of nevi. In adjusted models, a significant association was found between MTAP rs10757257 and overall melanoma risk (OR = 1.32, 95% CI = 1.14-1.53), with no evidence of heterogeneity across sites (Phomogeneity =.52). In contrast, MTAP rs10757257 was associated with superficial spreading/nodular melanoma (OR = 1.34, 95% CI = 1.15- 1.57), but not with lentigo maligna melanoma (OR = 0.79, 95% CI = 0.46-1.35) (Phomogeneity =.06), the subtype associated with chronic sun exposure. Melanoma was significantly inversely associated with rs12203592 in children (OR = 0.35, 95% CI = 0.16-0.77) and adolescents (OR = 0.61, 95% CI = 0.42-0.91), but not in adults (Phomogeneity =.0008). Our results suggest that the relationship between MTAP and melanoma is subtype-specific, and that the association between IRF4 and melanoma is more evident for cases with a younger age at onset. These findings lend some support to the 'divergent pathways' hypothesis and may provide at least one candidate gene underlying this model. Further studies are warranted to confirm these findings and improve our understanding of these relationships.
    Full-text · Article · Oct 2011 · Twin Research and Human Genetics
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    • "At older ages, the distributions were reversed so that above age 65 yr, the incidence of melanomas on maximally exposed sites was twice that of intermittently exposed sites, and more than 12 times higher than that of minimally exposed sites. Similar observations were made subsequently using registry data from New Zealand (Bulliard, 2000), USA (Lachiewicz et al., 2008), and Australia and Scotland (Whiteman et al., 2007). In all populations, it appeared that melanomas arising at younger ages occurred predominantly on the trunk and limbs, while at older ages, melanomas became more common on habitually sun-exposed sites such as the head and neck. "
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    ABSTRACT: Converging lines of evidence from varied scientific disciplines suggest that cutaneous melanomas comprise biologically distinct subtypes that arise through multiple causal pathways. Understanding the respective relationships of each subtype with etiologic factors such as UV radiation and constitutional factors is the first necessary step toward developing refined prevention strategies for the specific forms of melanoma. Furthermore, classifying this disease precisely into biologically distinct subtypes is the key to developing mechanism-based treatments, as highlighted by recent discoveries. In this review, we outline the historical developments that underpin our understanding of melanoma heterogeneity, and we do this from the perspectives of clinical presentation, histopathology, epidemiology, molecular genetics, and developmental biology. We integrate the evidence from these separate trajectories to catalog the emerging major categories of melanomas and conclude with important unanswered questions relating to the development of melanoma and its cells of origin.
    Full-text · Article · Jun 2011 · Pigment Cell & Melanoma Research
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    • "The frequency of BRAF mutations is also low in melanomas that develop on anatomic sites such as the head and neck, which frequently show histopathologic signs of cumulative sun-damage (CSD) to the skin (solar elastosis) (Maldonado et al., 2003, Curtin et al., 2005). This group of melanomas also differs from those originating on intermittently sun-exposed skin by the infrequent association with melanocytic nevi, frequent association with non-melanoma skin cancers (Whiteman et al., 2003), a 20 year delay in age-specific incidence (Lachiewicz et al., 2008), and the presence of genetic aberrations in the KIT oncogene (Curtin et al., 2006). These observations led to the conclusion that there are different molecular mechanisms leading to melanoma (Maldonado et al., 2003, Rivers, 2004, Whiteman et al., 2003), resulting in genetically distinct subgroups of melanoma (Curtin et al., 2005). "
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    ABSTRACT: Oncogenic BRAF mutations are more frequent in cutaneous melanoma occurring at sites with little or moderate sun-induced damage than at sites with severe cumulative solar ultraviolet (UV) damage. We studied cutaneous melanomas from geographic regions with different levels of ambient UV radiation to delineate the relative effects of cumulative UV damage, age, and anatomic site on the frequency of BRAF mutations. We show that BRAF-mutated melanomas occur in a younger age group on skin without marked solar elastosis and less frequently affect the head and neck area, compared to melanomas without BRAF mutations. The findings indicate that BRAF-mutated melanomas arise early in life at low cumulative UV doses, whereas melanomas without BRAF mutations require accumulation of high UV doses over time. The effect of anatomic site on the mutation spectrum further suggests regional differences among cutaneous melanocytes.
    Full-text · Article · Feb 2011 · Pigment Cell & Melanoma Research
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