Risk factors of incident melanocytic nevi: A longitudinal study in a cohort of 1,232 young German children

Department of Dermatology, Eberhard-Karls-University, Tübingen, Germany.
International Journal of Cancer (Impact Factor: 5.09). 05/2005; 115(1):121-6. DOI: 10.1002/ijc.20812
Source: PubMed


The number of melanocytic nevi is the most important independent risk factor for cutaneous melanoma. Aim of our study was to add information to the controversial discussion on the role of chronic-moderate and intermittent-high sun exposure and sunburns for the development of melanocytic nevi by the use of a large longitudinal study. A longitudinal study with a 3-year follow-up was conducted in 1,232 young children 2-7 years of age attending 78 public nursery schools in Bochum and Stuttgart, Germany. Total body nevus counts, assessment of pigmentary features and nevus counts on arms of parents were carried out. Parents underwent a standardized interview concerning sun exposure, sunburns and sun-protective behavior. Applying multiple linear regression analysis higher numbers of incident nevi were associated with host factors like light skin complexion (skin Type II vs. IV, p = 0.022) and freckling of the face (p < 0.001), with parental factors like nevus counts on mothers' (p < 0.001) and fathers' (p = 0.004) arms and at least one parent being of German descent (p = 0.006), and with environmental factors like intermittent-high sun exposure during holidays (p < 0.001) and chronic-moderate ultraviolet radiation at home (p = 0.007). Sunburns were a significant risk factor for nevus development (p = 0.005). Total cumulative sun exposure seems to be the crucial environmental risk factor for the development of nevi, whether the child is exposed to chronic-moderate or intermittent-high ultraviolet light doses. Public health education should focus primarily on avoiding sun exposure especially in children with fair skin and parents with high nevus counts.

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Available from: Claus Garbe, Sep 30, 2014
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    • "Timing of sunlight exposure was measured using questions on the age at which a blistering sunburn was experienced (≤5, 6–10, 11–15, 16–20, >20 years), the number of moles larger than one quarter of an inch in diameter on the forearms (none, <10, 10–25, >25 moles) and on the entire body (none, <10, 10–25, >25 moles), the age at first tanning bed use (≤15, 16–20, >20 years), and the number of hours of mid-day sunlight exposure on a typical weekday (<1, 1–2, 3–4, 5–6 hours) and weekend day (<1, 1–2, 3–4, 5–6 hours) in the summer during one’s teen years, twenties, thirties, and in the past ten years prior to study enrollment. The presence of moles is considered an indicator of increased sunlight exposure in childhood or adolescence [26-31]. "
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    ABSTRACT: Background Non-melanoma skin cancer (NMSC), comprised of basal (BCC) and squamous (SCC) cell carcinomas, is the most common cancer in Caucasians. Ultraviolet radiation (UVR) exposure is the most important environmental risk factor for NMSC. However, the precise relationship between UVR and the risk of NMSC is complex, and the relationship may differ by skin cancer type. Methods A case–control study was conducted among Florida residents to investigate measures of patterns (intermittent vs. continuous) and timing (childhood vs. adulthood) of sunlight exposure in BCC and SCC. Participants included 218 BCC and 169 SCC cases recruited from a university dermatology clinic and 316 controls with no history of skin or other cancers. Results A history of blistering sunburn (a measure of intermittent sunlight exposure) was associated with both BCC (OR = 1.96, 95% CI = 1.27-3.03) and SCC (OR = 2.02, 95% CI = 1.22-3.33). Additionally, having a job in the sun for ≥3 months for 10 years or longer (a measure of continuous sunlight exposure) was also associated with both BCC and SCC in our study population. With the exception of younger age at first blistering sunburn, measures of younger age at sunlight exposure tended to be associated with SCC, but not BCC risk. Conclusions Results from the current study suggest that sunlight exposure is associated with both BCC and SCC risk regardless of the pattern in which the exposure was received (i.e. intermittent vs. continuous). The data also suggest that sunlight exposure at a younger age may be more important for SCC but not BCC, however additional studies are needed to further characterize sunlight exposure-response relationships in different types of NMSC.
    BMC Cancer 09/2012; 12(1):417. DOI:10.1186/1471-2407-12-417 · 3.36 Impact Factor
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    • "The relationship between the effects of ultraviolet radiation (UV) and BRAF mutations in melanocytic neoplasia is complex. Activating mutations of the BRAF gene have been reported in the majority of melanocytic nevi and cutaneous melanoma (Davies et al., 2002, Pollock et al., 2003, Yazdi et al., 2003, Maldonado et al., 2003), which in turn are associated with UV exposure (most commonly from exposure to sunlight) (Bauer et al., 2005, MacKie and Aitchison, 1982). In contrast, nevi that develop before birth(Bauer et al., 2007) and melanomas on sun-protected anatomic sites (Curtin et al., 2005, Maldonado et al., 2003) rarely harbor BRAF mutations. "
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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.
    Pigment Cell & Melanoma Research 02/2011; 24(2):345-51. DOI:10.1111/j.1755-148X.2011.00837.x · 4.62 Impact Factor
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    • "Activating mutations within the kinase domain of the BRAF gene are a common somatic event in melanoma (Davies et al., 2002) as well as in benign melanocytic nevi (Pollock et al., 2003). Whereas sunlight is an undisputed etiological factor in the development of melanoma (Gandini et al., 2005) and nevi (Bauer et al., 2005), the role of UV exposure in the formation of BRAF mutations is unclear. About 90% of BRAF mutations found in melanoma and melanocytic nevi result in T-to-A transversions at nucleotide 1796 and therefore lack the typical UV radiation signature of CC-to-TT or C-to-T transitions. "
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    ABSTRACT: Most melanocytic nevi develop on sun-exposed skin during childhood and adolescence and commonly harbor BRAF mutations or, less frequently, NRAS mutations. A small subset of nevi is present at birth, and therefore must develop independently of UV light. To assess whether these nevi have a different mutation spectrum than those that develop on sun-exposed skin, we determined the BRAF and NRAS mutation frequencies in 32 truly congenital nevi. We found no BRAF mutations, but 81% (26/32) harbored mutations in NRAS. Consistently, seven of 10 (70%) proliferating nodules that developed early in life in congenital nevi showed mutations in NRAS. A separate set of nevi that displayed histological features frequently found in nevi present at birth ("congenital pattern nevi") but lacked a definitive history of presence at birth showed an inverse mutation pattern with common BRAF mutations (20/28 or 71%) and less frequent NRAS mutations (7/28 or 25%). Thus, nevi that develop in utero are genetically distinct from those that develop later, and histopathologic criteria alone are unable to reliably distinguish the two groups. The results are consistent with the finding in melanoma that BRAF mutations are uncommon in neoplasms that develop in the absence of sun-exposure.
    Journal of Investigative Dermatology 02/2007; 127(1):179-82. DOI:10.1038/sj.jid.5700490 · 7.22 Impact Factor
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