The deadliest common skin cancer, and the one most tied to sun exposure acting on a genetically susceptible person. A meta-analysis of almost 16,000 melanoma cases confirmed 13 known risk loci and found five new ones, in genes tied to how melanocytes are regulated.
Cutaneous malignant melanoma starts in melanocytes, the pigment-producing cells of the skin, and it is the deadliest of the common skin cancers — far less common than basal or squamous cell carcinoma, but with a much greater tendency to spread. This site's sun sensitivity and skin cancer risk page covers the pigmentation traits — how easily someone burns or freckles — that raise skin cancer risk broadly. This page is a different, more direct question: a genome-wide study of people who actually developed melanoma, not of the pigmentation traits that predispose to it.
By the time the study behind this page was done, 13 loci had already been reproducibly linked to melanoma risk in earlier work. The authors combined 11 genome-wide association studies — five of them previously unpublished — with three further stage-2 datasets, reaching 15,990 melanoma cases and 26,409 controls in total, the largest melanoma genetic study to that point.
The result: all 13 previously established loci were confirmed, two earlier loci that had not been independently replicated were now confirmed too, and five entirely new loci reached genome-wide significance, among them rs498136 near CCND1, a gene that controls the cell cycle and is already well known in cancer biology more broadly. The newly associated positions sit in regions the study's own bioinformatic analysis flags as likely regulatory elements in melanocytes — the cells melanoma actually starts in — and one of the highlighted candidate genes is involved in telomere biology, the mechanism cells use to count their own divisions.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 15 more positions to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Landi MT et al. 2020, Nature genetics rs408825 (MX2), rs143190905 (RTEL1), rs2853667 (TERT), rs3217986 (CDKN2B), rs75883022 (CDKN2B-AS1), rs79356439 (UBA52P6), rs72834823 (RP1-309H15.2), rs12523094 (CTD-2266L18.1), rs117648907 (SNORD77) — PMID:32341527
Liyanage UE et al. 2022, The Journal of investigative dermatology rs7943603 (near NOX4), rs1888621 (near RPS15AP27), rs112761681 (MED13L), rs9322309 (AKAP12) — PMID:34813871
Rashkin SR et al. 2020, Nature communications rs112584165 (near CBFA2T3), rs35026726 (ZNF276) — PMID:32887889
The two things with the strongest, most direct evidence for melanoma are not genetic: limiting UV exposure (sunlight and tanning beds alike) and knowing your own skin well enough to notice a new or changing mole. Regular skin self-examination, and a dermatologist's examination for anyone with many moles, a family history, or a fair-skinned, easily-burning complexion, is what actually catches melanoma early, when it is most treatable.
The ABCDE rule. A mole worth having checked is Asymmetric, has an irregular Border, uneven Color, a Diameter over 6mm, or is Evolving — changing in size, shape or color. None of the variants on this page changes that advice.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Cutaneous Malignant Melanoma comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 1 of 17 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
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Cutaneous Malignant Melanoma. MyGeneLog™. https://www.mygenelog.com/conditions/cutaneous-malignant-melanoma
No. It is one of at least 18 common variants that each modestly shift risk in a large population. UV exposure remains the strongest known modifiable risk factor, and regular skin checks — not this or any single genotype — are what actually catch melanoma early.
That page covers pigmentation traits — how easily you burn or freckle — as risk factors for skin cancer broadly. This page is from a study of people who actually developed melanoma specifically, looking directly at what distinguishes melanoma cases from controls.
A new mole, or an existing one that is Asymmetric, has an irregular Border, uneven Color, a Diameter over 6mm, or is Evolving (changing) — the ABCDE rule. That advice holds regardless of genotype.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.