Association of Patient Risk Factors and Frequency of Nevus-Associated Cutaneous Melanomas

Haenssle, Holger A.; Mograby, Nerjes; Ngassa, Anni; Buhl, Timo; Emmert, Steffen; Schön, Michael P.; Rosenberger, Albert; Bertsch, Hans Peter

doi:10.1001/jamadermatol.2015.3775

Cited by 82 publications

(99 citation statements)

References 34 publications

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“…17,19 One study 20 found that patients with multiple primary melanomas or a family history of melanoma had fewer nevusassociated melanomas than patients with high nevus counts. For these reasons, people with many nevi may be most likely to benefit from sequential digital dermoscopy and total body photography for ongoing surveillance.…”

Section: Discussionmentioning

confidence: 99%

Clinical Features Associated With Individuals at Higher Risk of Melanoma

et al. 2017

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IMPORTANCEThe identification of a subgroup at higher risk of melanoma may assist in early diagnosis.OBJECTIVE To characterize melanoma patients and the clinical features associated with their melanomas according to patient risk factors: many nevi, history of previous melanoma, and family history of melanoma, to assist with improving the identification and treatment of a higher-risk subgroup. DESIGN, SETTING, AND PARTICIPANTSThe Melanoma Patterns of Care study was a population-based observational study of physicians' reported treatment of 2727 patients diagnosed with an in situ or invasive primary melanoma over a 12-month period from October 2006 to 2007 conducted in New South Wales. Our analysis of these data took place from 2015 to 2016. MAIN OUTCOMES AND MEASURESAge at diagnosis and body site of melanoma. RESULTSOf the 2727 patients with melanoma included, 1052 (39%) were defined as higher risk owing to a family history of melanoma, multiple primary melanomas, or many nevi. Compared with patients with melanoma who were at lower risk (ie, without any of these risk factors), the higher-risk group had a younger mean age at diagnosis (62 vs 65 years, P < .001), but this differed by risk factor (56 years for patients with a family history, 59 years for those with many nevi, and 69 years for those with a previous melanoma). These age differences were consistent across all body sites. Among higher-risk patients, those with many nevi were more likely to have melanoma on the trunk (41% vs 29%, P < .001), those with a family history of melanoma were more likely to have melanomas on the limbs (57% vs 42%, P < .001), and those with a personal history were more likely to have melanoma on the head and neck (21% vs 15%, P = .003). CONCLUSIONS AND RELEVANCEThese findings suggest that a person's risk factor status could be used to tailor surveillance programs and education about skin self-examination.

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Section: Discussionmentioning

confidence: 99%

Clinical Features Associated With Individuals at Higher Risk of Melanoma

et al. 2017

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“…An individual with a single clinically dysplastic naevus has a twofold increased risk for melanoma, whereas having greater than 10 clinically dysplastic naevi is associated with a 12-fold increased risk [104] . For each additional naevus on the body, relative risk of CMM increases by 3% [105] and newly published work indicates that over 50% of CMM arise from naevi [106] , but this remains to be confirmed in larger studies. Dysplastic naevi are more common in patients with melanoma, and a personal and family history of melanoma can significantly increase the incidence of finding dysplastic naevi in a patient.…”

Section: Naevi and Melanomamentioning

confidence: 95%

Skin Pigmentation Genetics for the Clinic

Ainger

Jagirdar²,

Lee³

et al. 2017

Dermatology

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Human pigmentation characteristics play an important role in the effects of sun exposure, skin cancer induction and disease outcomes. Several of the genes most important for this diversity are involved in the regulation and distribution of melanin pigmentation or enzymes involved in melanogenesis itself within the melanocyte cell present in the skin, hair and eyes. The single nucleotide polymorphisms and extended haplotypes within or surrounding these genes have been identified as risk factors for skin cancer, in particular, melanoma. These same polymorphisms have been under selective pressure leading towards lighter pigmentation in Europeans in the last 5,000-20,000 years that have driven the increase in frequency in modern populations. Although pigmentation is a polygenic trait, due to interactive and quantitative gene effects, strong phenotypic associations are readily apparent for these major genes. However, predictive value and utility are increased when considering gene polymorphism interactions. In melanoma, an increased penetrance is found in cases when pigmentation gene risk alleles such as MC1R variants are coincident with mutation of higher-risk melanoma genes including CDKN2A, CDK4 and MITF E318K, demonstrating an interface between the pathways for pigmentation, naevogenesis and melanoma. The clinical phenotypes associated with germline changes in pigmentation and naevogenic genes must be understood by clinicians, and will be of increasing relevance to dermatologists, as genomics is incorporated into the delivery of personalised medicine.

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“…Melanoma often arises from melanocytic nevi (i.e. moles) (4), which frequently are found on sun-exposed areas (5). Ultraviolet (UV) radiation in sunlight (6) or from tanning beds (7) is the major environmental risk factor for melanoma.…”

Section: Introductionmentioning

confidence: 99%

A Phase II Randomized Placebo-Controlled Trial of OralN-acetylcysteine for Protection of Melanocytic Nevi against UV-Induced Oxidative StressIn Vivo

Cassidy

Liu

Florell

et al. 2017

Cancer Prevention Research

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Oxidative stress plays a role in UV-induced melanoma, which may arise from melanocytic nevi. We investigated whether oral administration of the antioxidant N-acetylcysteine (NAC) could protect nevi from oxidative stress in vivo in the setting of acute UV exposure. The minimal erythemal dose (MED) was determined for 100 patients at increased risk for melanoma. Patients were randomized to receive a single dose (1200 mg) of NAC or placebo, in double-blind fashion, and then one nevus was irradiated (1–2 MED) using a solar simulator. One day later, the MED was re-determined and the irradiated nevus and a control un-irradiated nevus were removed for histologic analysis and examination of biomarkers of NAC metabolism and UV-induced oxidative stress. Increased expression of 8-oxoguanine, thioredoxin reductase-1, and γ-glutamylcysteine synthase modifier subunit were consistently seen in UV-treated compared to unirradiated nevi. However, no significant differences were observed in these UV-induced changes or in the pre- and post-intervention MED between those patients receiving NAC vs. placebo. Similarly, no significant differences were observed in UV-induced changes between subjects with germline wild-type vs. loss of function mutations in the melanocortin-1 receptor. Nevi showed similar changes of UV-induced oxidative stress in an open-label post-trial study in 10 patients who received NAC 3 h before nevus irradiation. Thus a single oral dose of NAC did not effectively protect nevi from UV-induced oxidative stress under the conditions examined.

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Association of Patient Risk Factors and Frequency of Nevus-Associated Cutaneous Melanomas

Cited by 82 publications

References 34 publications

Clinical Features Associated With Individuals at Higher Risk of Melanoma

Clinical Features Associated With Individuals at Higher Risk of Melanoma

Skin Pigmentation Genetics for the Clinic

A Phase II Randomized Placebo-Controlled Trial of OralN-acetylcysteine for Protection of Melanocytic Nevi against UV-Induced Oxidative StressIn Vivo

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