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

Abstract

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.

Merkel Cell Carcinoma and Diagnostic Experience in a Reference Hospital: A Case Series

“…e association of gender and upper limbs are described in melanoma studies. Guiasvand et al reported a stronger risk factor for melanoma on lower limbs (RR 3.38; 95% CI, 2.62-4.38) in Norwegian women [12]. Another explanation could be the relationship between positive MCPvV in female patients which is more prevalent than in male patients (66.7% vs 39.6) and MCPyV and MCC are more common in limbs [13].…”

Evolved adaptation to low ultraviolet radiation may be the main cause of malignant melanoma independent of high ultraviolet radiation levels

“…From the perspective of human evolution, the magnitude of heritable depigmentation due to adaptation to low UVR exposure may predispose to melanoma incidence worldwide, while direct individual exposure to sunlight may play some causative role, that is, however, di cult to precisely quantify in population studies [71][72][73][74]. We have applied the modern evolutionary theory in order to interpret how human adaptation had produced the underlying cause for melanoma (C43) over a number of generations.…”

“…A number of genes predisposing to melanoma have been identi ed [95][96][97][98][99][100]. In a large study (N = 100,000) published in 2019, Ghiasvand and colleagues [71] have found that skin colour variation within the range displayed by Norwegian women produced melanoma risk ratios (RR) ranging from 1.53 for the head and neck to 2.32 for trunk, and freckling from 2.50 to 3.30, while sun bathing produced RR from 0.41 to 1.71 and indoor tanning 0.85 -1.18. Clearly, the risk produced by depigmentation was approximately double that resulting from UVR exposure and signi cant for all body regions , not just some.…”

Lifetime Ultraviolet Radiation Exposure and Dna Methylation In Blood Leukocytes: The Norwegian Women And Cancer Study

“…An important strength of our study is the detailed life history of solar and artificial UVR exposure in the population-based NOWAC cohort, which has been consistently associated with risk of cutaneous melanoma (13, [15][16][17] and squamous cell carcinoma (14, 18). Indoor tanning irradiances are high in UVA radiation (45) while UVB is the main cause of sunburns (46).…”