Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting.

Genetic Predisposition to Disease Genome-Wide Association Study Humans Melanoma / genetics Polymorphism, Single Nucleotide / genetics Skin Neoplasms / genetics Ultraviolet Rays Melanoma, Cutaneous Malignant
Genome-wide association study Melanoma Melanoma-specific survival Polygenic risk score Skin cancer

Journal

Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741

Informations de publication

Date de publication:
05 09 2022
Historique:
received: 01 08 2022
accepted: 24 08 2022
entrez: 5 9 2022
pubmed: 6 9 2022
medline: 9 9 2022
Statut: epublish

Résumé

The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood. To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS. We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis. Significant (P < 5 × 10-8) results were investigated in the Leeds Melanoma Cohort (LMC; 1,947 patients with melanoma; 370 melanoma deaths). We also developed a CM-susceptibility PRS using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls). The PRS was tested for an association with MSS in the MIA and UKB cohorts. Two loci were significantly associated with MSS in the meta-analysis of MIA and UKB with lead SNPs rs41309643 (G allele frequency 1.6%, HR = 2.09, 95%CI = 1.61-2.71, P = 2.08 × 10-8) on chromosome 1, and rs75682113 (C allele frequency 1.8%, HR = 2.38, 95%CI = 1.77-3.21, P = 1.07 × 10-8) on chromosome 7. While neither SNP replicated in the LMC, rs75682113 was significantly associated in the combined discovery and replication sets. After adjusting for age at diagnosis, sex and the first ten principal components, a one standard deviation increase in the CM-susceptibility PRS was associated with improved MSS in the discovery meta-analysis (HR = 0.88, 95% CI = 0.83-0.94, P = 6.93 × 10-5; I2 = 88%). However, this was only driven by the high UV setting cohort (MIA HR = 0.84, 95% CI = 0.78-0.90). We found two loci potentially associated with MSS. Increased genetic susceptibility to develop CM is associated with improved MSS in a high UV setting.

Sections du résumé

BACKGROUND
The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood.
OBJECTIVE
To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS.
METHODS
We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis. Significant (P < 5 × 10-8) results were investigated in the Leeds Melanoma Cohort (LMC; 1,947 patients with melanoma; 370 melanoma deaths). We also developed a CM-susceptibility PRS using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls). The PRS was tested for an association with MSS in the MIA and UKB cohorts.
RESULTS
Two loci were significantly associated with MSS in the meta-analysis of MIA and UKB with lead SNPs rs41309643 (G allele frequency 1.6%, HR = 2.09, 95%CI = 1.61-2.71, P = 2.08 × 10-8) on chromosome 1, and rs75682113 (C allele frequency 1.8%, HR = 2.38, 95%CI = 1.77-3.21, P = 1.07 × 10-8) on chromosome 7. While neither SNP replicated in the LMC, rs75682113 was significantly associated in the combined discovery and replication sets. After adjusting for age at diagnosis, sex and the first ten principal components, a one standard deviation increase in the CM-susceptibility PRS was associated with improved MSS in the discovery meta-analysis (HR = 0.88, 95% CI = 0.83-0.94, P = 6.93 × 10-5; I2 = 88%). However, this was only driven by the high UV setting cohort (MIA HR = 0.84, 95% CI = 0.78-0.90).
CONCLUSION
We found two loci potentially associated with MSS. Increased genetic susceptibility to develop CM is associated with improved MSS in a high UV setting.

Identifiants

DOI: 10.1186/s12967-022-03613-2 PMID: 36064556 PMC: PMC9446843
pubmed: 36064556
doi: 10.1186/s12967-022-03613-2
pii: 10.1186/s12967-022-03613-2
pmc: PMC9446843
doi:

Types de publication

Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

403

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C588/A19167
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C8216/A6129
Pays : United Kingdom
Organisme : National Institutes of Health (US)
ID : R01 CA83115
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

Références

Cancer Res. 2018 Nov 1;78(21):6329-6338
pubmed: 30385609
Eur J Epidemiol. 2011 Apr;26(4):261-4
pubmed: 21431839
J Invest Dermatol. 2018 Dec;138(12):2617-2624
pubmed: 29890168
Nat Genet. 2009 Aug;41(8):920-5
pubmed: 19578364
Am J Hum Genet. 1999 Aug;65(2):483-92
pubmed: 10417291
Int J Cancer. 2015 Oct 1;137(7):1691-8
pubmed: 25809795
J Invest Dermatol. 2001 Aug;117(2):348-52
pubmed: 11511314
Med J Aust. 2020 Aug;213(4):189-189.e1
pubmed: 32277474
J Clin Oncol. 2004 Sep 15;22(18):3651-3
pubmed: 15302907
An Bras Dermatol. 2018 Jan-Feb;93(1):19-26
pubmed: 29641692
Cancer Prev Res (Phila). 2010 Feb;3(2):233-45
pubmed: 20086181
Sci Rep. 2018 Jul 19;8(1):10947
pubmed: 30026606
Hum Mol Genet. 2020 May 28;29(8):1388-1395
pubmed: 32219344
Cancer Epidemiol. 2020 Apr;65:101688
pubmed: 32092486
Circulation. 2020 Feb 25;141(8):616-623
pubmed: 31707849
Eur J Cancer. 2005 Jan;41(1):28-44
pubmed: 15617989
J Natl Cancer Inst. 2005 Feb 2;97(3):195-9
pubmed: 15687362
Cancer Res. 2002 Mar 1;62(5):1246-50
pubmed: 11888884
J Clin Aesthet Dermatol. 2013 Sep;6(9):18-26
pubmed: 24062870
Medicine (Baltimore). 2016 Oct;95(40):e4975
pubmed: 27749552
Evid Based Ment Health. 2019 Nov;22(4):153-160
pubmed: 31563865
JAMA Netw Open. 2021 Oct 1;4(10):e2127784
pubmed: 34613403
JAMA Dermatol. 2021 Dec 01;157(12):1425-1436
pubmed: 34730781
Eur J Cancer. 2008 Jun;44(9):1275-81
pubmed: 18406602
Am J Hum Genet. 2008 Nov;83(5):604-9
pubmed: 18926513
J Invest Dermatol. 2022 Jun;142(6):1607-1616
pubmed: 34813871
Gigascience. 2015 Feb 25;4:7
pubmed: 25722852
Cancer Epidemiol Biomarkers Prev. 2010 Aug;19(8):2043-54
pubmed: 20647408
Int J Cancer. 2015 Jun 15;136(12):2890-9
pubmed: 25403087
J Clin Oncol. 2014 Aug 10;32(23):2479-85
pubmed: 25002727
Nat Commun. 2018 Nov 14;9(1):4774
pubmed: 30429480
Eur J Cancer. 2017 Feb;72:210-214
pubmed: 28042992
Nature. 2012 Nov 15;491(7424):449-53
pubmed: 23123854
Appl Health Econ Health Policy. 2017 Dec;15(6):805-816
pubmed: 28756584
Int J Cancer. 2015 Dec 15;137(12):3006-7
pubmed: 26095813
PLoS One. 2013 Aug 19;8(8):e71121
pubmed: 23990928
Int J Epidemiol. 2012 Aug;41(4):929-929i
pubmed: 22933644
Nat Commun. 2017 Nov 28;8(1):1826
pubmed: 29184056
Eur J Cancer. 2005 Sep;41(14):2040-59
pubmed: 16125929
Circulation. 2020 Feb 25;141(8):624-636
pubmed: 31707832
Bioinformatics. 2010 Sep 1;26(17):2190-1
pubmed: 20616382
Nat Commun. 2019 Apr 5;10(1):1561
pubmed: 30952951
Int J Epidemiol. 2009 Jun;38(3):814-30
pubmed: 19359257
Wellcome Open Res. 2020 Oct 22;5:252
pubmed: 33381656
Am J Surg. 2016 Jan;211(1):89-94
pubmed: 26275921
Nature. 2018 Oct;562(7726):203-209
pubmed: 30305743
Br J Dermatol. 2011 Aug;165(2):342-8
pubmed: 21457213
Cancer Epidemiol Biomarkers Prev. 2010 Jan;19(1):111-20
pubmed: 20056629
Hum Mol Genet. 2019 Nov 21;28(R2):R133-R142
pubmed: 31363735
Nat Genet. 2020 May;52(5):494-504
pubmed: 32341527
Nat Genet. 2016 Nov;48(11):1443-1448
pubmed: 27694958
PLoS Med. 2015 Mar 31;12(3):e1001779
pubmed: 25826379
Am J Hum Genet. 2020 Sep 3;107(3):418-431
pubmed: 32758451
Am J Hum Genet. 2015 Oct 1;97(4):576-92
pubmed: 26430803
N Engl J Med. 2021 Jan 7;384(1):72-79
pubmed: 33406334
J Clin Oncol. 2016 Jan 20;34(3):251-8
pubmed: 26628467

Auteurs

Mathias Seviiri (M)

Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, 4006, Australia. Mathias.Seviiri@qimrberghofer.edu.au.
School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia. Mathias.Seviiri@qimrberghofer.edu.au.
Center for Genomics and Personalised Health, Queensland University of Technology, Brisbane, QLD, Australia. Mathias.Seviiri@qimrberghofer.edu.au.
ORCID: 0000-0002-8610-3283

Richard A Scolyer (RA)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Department of Tissue Oncology and Diagnostic Pathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
NSW Health Pathology, Sydney, NSW, Australia.
ORCID: 0000-0002-8991-0013

D Timothy Bishop (DT)

Division of Haematology and Immunology, Leeds Institute of Medical Research at St James', University of Leeds, Leeds, UK.
ORCID: 0000-0002-8752-8785

Julia A Newton-Bishop (JA)

Division of Haematology and Immunology, Leeds Institute of Medical Research at St James', University of Leeds, Leeds, UK.
ORCID: 0000-0001-9147-6802

Mark M Iles (MM)

St James's Institute of Medical Research, University of Leeds, Leeds, UK.
Leeds Institute of Data Analytics, University of Leeds, Leeds, UK.
ORCID: 0000-0002-2603-6509

Serigne N Lo (SN)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
ORCID: 0000-0001-5092-5544

Johnathan R Stretch (JR)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.

Robyn P M Saw (RPM)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.

Omgo E Nieweg (OE)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.

Kerwin F Shannon (KF)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Sydney Head & Neck Cancer Institute, Chris O'Brien Lifehouse Cancer Center, Sydney, NSW, Australia.

Andrew J Spillane (AJ)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Department of Breast and Melanoma Surgery, Royal North Shore Hospital, Sydney, NSW, Australia.

Scott D Gordon (SD)

Genetic Epidemiology Lab, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
ORCID: 0000-0001-7623-328X

Catherine M Olsen (CM)

Cancer Control Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
ORCID: 0000-0003-4483-1888

David C Whiteman (DC)

Cancer Control Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
ORCID: 0000-0003-2563-9559

Maria Teresa Landi (MT)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0003-4507-329X

John F Thompson (JF)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
ORCID: 0000-0002-2816-2496

Georgina V Long (GV)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Department of Medical Oncology, Mater Hospital, North Sydney, NSW, Australia.
Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia.
ORCID: 0000-0001-8894-3545

Stuart MacGregor (S)

Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, 4006, Australia.
School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.
ORCID: 0000-0001-6731-8142

Matthew H Law (MH)

Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, 4006, Australia. matthew.law@qimrberghofer.edu.au.
School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia. matthew.law@qimrberghofer.edu.au.
ORCID: 0000-0002-4303-8821

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

Recherchemedicale.com › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Higher polygenic risk for melanoma is...
Recherchemedicale.com › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Higher polygenic risk for melanoma is...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Higher polygenic risk for melanoma is...
Recherchemedicale.com › Tumeurs › Tumeurs par type histologique › Naevus et mélanomes › Mélanome › Higher polygenic risk for melanoma is...
Recherchemedicale.com › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Higher polygenic risk for melanoma is...
Recherchemedicale.com › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Tumeurs cutanées › Higher polygenic risk for melanoma is...
Recherchemedicale.com › Environnement et santé publique › Environnement › Concepts météorologiques › Atmosphère › Temps (météorologie) › Lumière du soleil › Rayons ultraviolets › Higher polygenic risk for melanoma is...