Ερευνητικό υλικό ΕΚΠΑ

Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility

Αγγλικά

Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10−8) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis. © 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

2020

Landi, M.T.
Bishop, D.T.
MacGregor, S.
Machiela, M.J.
Stratigos, A.J.
Ghiorzo, P.
Brossard, M.
Calista, D.
Choi, J.
Fargnoli, M.C.
Zhang, T.
Rodolfo, M.
Trower, A.J.
Menin, C.
Martinez, J.
Hadjisavvas, A.
Song, L.
Stefanaki, I.
Scolyer, R.
Yang, R.
Goldstein, A.M.
Potrony, M.
Kypreou, K.P.
Pastorino, L.
Queirolo, P.
Pellegrini, C.
Cattaneo, L.
Zawistowski, M.
Gimenez-Xavier, P.
Rodriguez, A.
Elefanti, L.
Manoukian, S.
Rivoltini, L.
Smith, B.H.
Loizidou, M.A.
Del Regno, L.
Massi, D.
Mandala, M.
Khosrotehrani, K.
Akslen, L.A.
Amos, C.I.
Andresen, P.A.
Avril, M.-F.
Azizi, E.
Soyer, H.P.
Bataille, V.
Dalmasso, B.
Bowdler, L.M.
Burdon, K.P.
Chen, W.V.
Codd, V.
Craig, J.E.
Dębniak, T.
Falchi, M.
Fang, S.
Friedman, E.
Simi, S.
Galan, P.
Garcia-Casado, Z.
Gillanders, E.M.
Gordon, S.
Green, A.
Gruis, N.A.
Hansson, J.
Harland, M.
Harris, J.
Helsing, P.
Henders, A.
Hočevar, M.
Höiom, V.
Hunter, D.
Ingvar, C.
Kumar, R.
Lang, J.
Lathrop, G.M.
Lee, J.E.
Li, X.
Lubiński, J.
Mackie, R.M.
Malt, M.
Malvehy, J.
McAloney, K.
Mohamdi, H.
Molven, A.
Moses, E.K.
Neale, R.E.
Novaković, S.
Nyholt, D.R.
Olsson, H.
Orr, N.
Fritsche, L.G.
Puig-Butille, J.A.
Qureshi, A.A.
Radford-Smith, G.L.
Randerson-Moor, J.
Requena, C.
Rowe, C.
Samani, N.J.
Sanna, M.
Schadendorf, D.
Schulze, H.-J.
Simms, L.A.
Smithers, M.
Song, F.
Swerdlow, A.J.
van der Stoep, N.
Kukutsch, N.A.
Visconti, A.
Wallace, L.
Ward, S.V.
Wheeler, L.
Sturm, R.A.
Hutchinson, A.
Jones, K.
Malasky, M.
Vogt, A.
Zhou, W.
Pooley, K.A.
Elder, D.E.
Han, J.
Hicks, B.
Hayward, N.K.
Kanetsky, P.A.
Brummett, C.
Montgomery, G.W.
Olsen, C.M.
Hayward, C.
Dunning, A.M.
Martin, N.G.
Evangelou, E.
Mann, G.J.
Long, G.
Pharoah, P.D.P.
Easton, D.F.
Barrett, J.H.
Cust, A.E.
Abecasis, G.
Duffy, D.L.
Whiteman, D.C.
Gogas, H.
De Nicolo, A.
Tucker, M.A.
Newton-Bishop, J.A.
Peris, K.
Chanock, S.J.
Demenais, F.
Brown, K.M.
Puig, S.
Nagore, E.
Shi, J.
Iles, M.M.
Law, M.H.
GenoMEL Consortium
Q-MEGA
QTWIN Investigators
ATHENS Melanoma Study Group
23andMe
The SDH Study Group
IBD Investigators
Essen-Heidelberg Investigators
AMFS Investigators
MelaNostrum Consortium

Nature Genetics

Lithuanian Nature Research Centre

52

5

494-504

adam15 protein; alpha ketoglutarate dependent dioxygenase FTO; dstyk protein; dtnb protein; foxd3 protein; gba protein; hdgfl1 protein; histone deacetylase 4; HLA antigen class 2; HLA DQB2 antigen; host factor; interferon regulatory factor 4; kiaa0930 protein; kruppel like factor 4; mfsd12 protein; microphthalmia associated transcription factor; Notch2 receptor; peptides and proteins; peroxisome proliferator activated receptor gamma coactivator 1beta; plxnb2 protein; pot1 protein; protein p53; rapgef5 protein; retl1 protein; terc protein; transcription factor Sox6; transcriptome; tumor marker; unclassified drug; uvomorulin; zbtb7b protein, acral lentiginous melanoma; Article; cancer genetics; cancer risk; cancer susceptibility; case control study; cohort analysis; controlled study; cutaneous melanoma; female; gene locus; gene structure; genetic association; genetic risk; genetic susceptibility; genome-wide association study; genotype; hair color; human; major clinical study; male; malignant lentigo; medical geography; melanoma; nevus; phenotype; priority journal; risk assessment; single nucleotide polymorphism; skin pigmentation; superficial spreading melanoma; telomere homeostasis; transcriptomics; genetic predisposition; genetics; melanoma; meta analysis; pigmentation; procedures; single nucleotide polymorphism; skin tumor, Female; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Male; Melanoma; Phenotype; Pigmentation; Polymorphism, Single Nucleotide; Skin Neoplasms

https://doi.org/10.1038/s41588-020-0611-8

10.1038/s41588-020-0611-8

https://pergamos.lib.uoa.gr/uoa/dl/object/3077491