Abstract IA09: What's new in melanoma etiology?
Authors: Tucker Margaret A. 
Published: July 2015

Abstract
Melanoma (CM) incidence continues to increase in the US, Europe, and Australia. A concern has been raised whether this is a true increase of CM or a major increase in over diagnosis of CM. Data cited in support of over diagnosis are that mortality rates have not increased proportionately. Another explanation of disproportionate incidence and mortality is that as CM has become more common and both care providers and the general population are more aware of CM, lesions are identified and removed much earlier, leading to better long-term prognosis. In the US, the 5-year relative survival has increased from 81.8% in 1975 to 92.8% in 2006. The distribution of CM differs between men and women; recent data in the U.S. have shown a distinct increase in CM on the trunk of young women, consistent with tanning (Bradford PT et al., CEBP 2010; 19:2410-6). In 2011, there were 960,231 individuals with CM in the US who are at 8.8-fold increased risk of a second primary CM.
The major risk factors for CM include genetic susceptibility (covered in detail by Nick Hayward in this session) and ultraviolet exposure. The major high risk susceptibility genes, CDKN2A and CDK4, were identified in the mid-nineties; mutations in either confer similar risks for CM and similar clinical features. More recently, mutations in POT1 were identified in melanoma-prone families using exome sequencing (Robles-Espinoza CD et al., Nat Genet 2014; 46:478-81; Shi J, et al., Nat Genet 2014; 46:482-6). Other rare high risk susceptibility genes will likely be identified. Genome-wide association studies have identified a number of common variants associated with CM; the causal variants marked by the association signals are in large part still being identified. Nevi, particularly dysplastic nevi, are major host susceptibility factors, but nevus genes have been quite challenging to identify. Using a candidate gene approach, Liang et al. identified variants in CDK6 and XRCC1 that were associated with dysplastic nevi, but not CM (J Invest Derm 2014;134:481-7).
Ultraviolet radiation exposure is causal for CM, whether from the sun or artificial lights. Tanning is a complex behavior, and it is difficult to separate the risks associated with outdoor and indoor tanning since most who tan use both sources. Wehner et al. conducted a systematic review and metaanalysis of the prevalence of indoor tanning and found that 35.7% (95% CI 27.5%-44.0%) of adults, 55.0% (33.0%-77.1%) of university students and 19.3% (14.7%-24.0%) of adolescents had ever used indoor tanning (JAMA Dermatol 2014;150:390-400). The prevalences varied also by geographic area and sex. Due to the high exposure rates, particularly in adolescents, parts of Europe, Australia, and North America have passed legislation limiting access by adolescents to indoor tanning. There is also a growing body of evidence that UV exposure may be addictive (Heckman CJ et al., Am J Health Promo 2014;28:168-174).
The role of screening for CM has been controversial. In 2009, the USPSTF guidelines did not recommend population-based screening for CM. This year, they are reconsidering the issue, in part because of a public health effort in Germany, where screening for skin cancer was made available for adults over 20 (Katalinic A et al., Cancer, 2012; 118:5395-402). In an observational study, melanoma mortality declined by 47% for men and 49% for women in the screened population. Screening may yield higher benefits in recognized at risk groups (Moloney FJ et al. JAMA Dermatol 2014.514). A number of melanoma risk assessment tools could be useful in prioritizing screening, but have not been fully validated (Vuong K et al; JAMA Dermatol 2014;150:434-444).
Citation Format: Margaret A. Tucker. What's new in melanoma etiology? [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr IA09.