Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jul 16;12(7):1077.
doi: 10.3390/genes12071077.

The Interplay between Nevi and Melanoma Predisposition Unravels Nevi-Related and Nevi-Resistant Familial Melanoma

Affiliations
Review

The Interplay between Nevi and Melanoma Predisposition Unravels Nevi-Related and Nevi-Resistant Familial Melanoma

Stefania Pellegrini et al. Genes (Basel). .

Abstract

Genetic susceptibility to nevi may affect the risk of developing melanoma, since common and atypical nevi are the main host risk factors implicated in the development of cutaneous melanoma. Recent genome-wide studies defined a melanoma polygenic risk score based on variants in genes involved in different pathways, including nevogenesis. Moreover, a predisposition to nevi is a hereditary trait that may account for melanoma clustering in some families characterized by cases with a high nevi density. On the other hand, familial melanoma aggregation may be due to a Mendelian inheritance of high/moderate-penetrance pathogenic variants affecting melanoma risk, regardless of the nevus count. Based on current knowledge, this review analyzes the complex interplay between nevi and melanoma predisposition in a familial context. We review familial melanoma, starting from Whiteman's divergent pathway model to overall melanoma development, distinguishing between nevi-related (cases with a high nevus count and a high polygenic risk score) and nevi-resistant (high/moderate-penetrance variant-carrier cases) familial melanoma. This distinction could better direct future research on genetic factors useful to identify high-risk subjects.

Keywords: familial melanoma; nevi; polygenic risk score; risk factors; susceptibility genes.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Sinclair C., Foley P. Skin cancer prevention in Australia. Br. J. Dermatol. 2009;161(Suppl. 3):116–123. doi: 10.1111/j.1365-2133.2009.09459.x. - DOI - PubMed
    1. Matthews N.H., Li W.Q., Qureshi A.A., Weinstock M.A., Cho E. Epidemiology of melanoma. In: Ward W.H., Farma J.M., editors. Cutaneous Melanoma: Etiology and Therapy. Codon Publications; Brisbane, Australia: 2017. - DOI - PubMed
    1. Holly E.A., Kelly J.W., Shpall S.N., Chiu S.H. Number of melanocytic nevi as a major risk factor for malignant melanoma. J. Am. Acad. Dermatol. 1987;17:459–468. doi: 10.1016/S0190-9622(87)70230-8. - DOI - PubMed
    1. Gandini S., Sera F., Cattaruzza M.S., Pasquini P., Abeni D., Boyle P., Melchi C.F. Meta-analysis of risk factors for cutaneous melanoma: I. Common and atypical naevi. Eur. J. Cancer. 2005;41:28–44. doi: 10.1016/j.ejca.2004.10.015. - DOI - PubMed

Publication types