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Original Investigation
January 2019

Association of Phenotypic Characteristics and UV Radiation Exposure With Risk of Melanoma on Different Body Sites

Author Affiliations
  • 1Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
  • 2Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway
  • 3Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia
  • 4Cancer Research UK Manchester and Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
  • 5Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
  • 6Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 7Genetic Epidemiology Group, Folkhälsen Research Center, and Faculty of Medicine, University of Helsinki, Helsinki, Finland
JAMA Dermatol. 2019;155(1):39-49. doi:10.1001/jamadermatol.2018.3964
Key Points

Question  Do phenotypic characteristics and pattern of UV radiation exposure differ according to body site of melanoma?

Findings  In this population-based cohort study, associations with large asymmetric nevi, sunbathing vacations, and indoor tanning differed significantly among melanoma sites. Skin color, hair color, small symmetric nevi, residential ambient UV radiation, and sunburns were associated with melanoma risk on all sites.

Meaning  This study adds to the supporting evidence of divergent pathways to melanoma and suggests similar risk profiles for lower limb and trunk melanomas and for upper limb and head and neck melanomas.


Importance  Two pathways have been hypothesized for the development of cutaneous melanoma: one typically affects the head and neck, a site with chronic sun damage, and the other affects the trunk, which is less exposed to the sun. However, the possible cause of limb melanomas is less studied under this hypothesis.

Objective  To investigate the association between phenotypic characteristics, pattern of UV radiation exposure, and risk of melanoma on different body sites.

Design, Setting, and Participants  This study used data on 161 540 women with information on phenotypic characteristics and UV radiation exposure who were part of the Norwegian Women and Cancer study, a population-based prospective study established in 1991 with exposure information collected by questionnaires at baseline and every 4 to 6 years during follow-up through 2015. Data analysis was performed from October 2017 through May 2018.

Exposures  Participants reported hair color, eye color, untanned skin color, number of small symmetric and large asymmetric nevi, and freckling, as well as histories of sunburns, sunbathing vacations, and indoor tanning in childhood, adolescence, and adulthood.

Main Outcomes and Measures  The Norwegian Women and Cancer study was linked to the Cancer Registry of Norway for data on cancer diagnosis and date of death or emigration. Primary melanoma site was categorized as head and neck, trunk, upper limbs, and lower limbs.

Results  During follow-up of the 161 540 women in the study (mean age at study entry, 50 years [range, 34-70 years]; mean age at diagnosis, 60 years [range, 34-87 years]), 1374 incident cases of melanoma were diagnosed. Having large asymmetric nevi was a significant risk factor for all sites and was strongest for the lower limbs (relative risk [RR], 3.38; 95% CI, 2.62-4.38) and weakest for the upper limbs (RR, 1.96; 95% CI, 1.22-3.17; P = .02 for heterogeneity). Mean lifetime number of sunbathing vacations was significantly associated with risk of trunk melanomas (RR, 1.14; 95% CI, 1.07-1.22) and lower limb melanomas (RR, 1.12; 95% CI, 1.05-1.19) but not upper limb melanomas (RR, 0.98; 95% CI, 0.88-1.09) and head and neck melanomas (RR, 0.87; 95% CI, 0.73-1.04; P = .006 for heterogeneity). Indoor tanning was associated only with trunk melanomas (RR for the highest tertile, 1.49; 95% CI, 1.16-1.92) and lower limb melanomas (RR for the highest tertile, 1.33; 95% CI, 1.00-1.76; P = .002 for heterogeneity). Skin color, hair color, small symmetric nevi, and history of sunburns were associated with risk of melanoma on all sites.

Conclusions and Relevance  These results appear to support the hypothesis of divergent pathways to melanoma and that recreational sun exposure and indoor tanning are associated with melanoma on the lower limbs, the most common site of melanoma in women. These findings appear to have important preventive implications.