Evidence map›Paper›PMID 36064556›Full record

SynthesisJournal of translational medicine2022

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

Mathias Seviiri, Richard A Scolyer, D Timothy Bishop, Julia A Newton-Bishop, Mark M Iles, Serigne N Lo, Johnathan R Stretch, Robyn P M Saw, Omgo E Nieweg, Kerwin F Shannon and 9 more

Open access · goldAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 6 institutions in 3 countries.

Mathias SeviiriStatistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, 4006, Australia. Mathias.Seviiri@qimrberghofer.edu.au.ORCID 0000-0002-8610-3283
Richard A ScolyerMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.ORCID 0000-0002-8991-0013
D Timothy BishopDivision 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-BishopDivision of Haematology and Immunology, Leeds Institute of Medical Research at St James', University of Leeds, Leeds, UK.ORCID 0000-0001-9147-6802
Mark M IlesSt James's Institute of Medical Research, University of Leeds, Leeds, UK.ORCID 0000-0002-2603-6509
Serigne N LoMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.ORCID 0000-0001-5092-5544
Johnathan R StretchMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Robyn P M SawMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Omgo E NiewegMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Kerwin F ShannonMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Andrew J SpillaneMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Scott D GordonGenetic Epidemiology Lab, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.ORCID 0000-0001-7623-328X
Catherine M OlsenCancer Control Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.ORCID 0000-0003-4483-1888
David C WhitemanCancer Control Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.ORCID 0000-0003-2563-9559
Maria Teresa LandiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-4507-329X
John F ThompsonMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.ORCID 0000-0002-2816-2496
Georgina V LongMelanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.ORCID 0000-0001-8894-3545
Stuart MacGregorStatistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, 4006, Australia.ORCID 0000-0001-6731-8142
Matthew H LawStatistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, 4006, Australia. matthew.law@qimrberghofer.edu.au.ORCID 0000-0002-4303-8821
The University of Sydney · AUQueensland University of Technology · AUUniversity of Leeds · GBQIMR Berghofer Medical Research Institute · AUNational Institutes of Health · USThe University of Queensland · AU

Funding

Genetic Epidermiology of MelanomaR01CA083115 · NCI · UNIVERSITY OF PENNSYLVANIA · PI BISHOP, DAVID TIMOTHY, ELDER, DAVID ERIC · 2001 to 2017
$13.0M
Cancer Research UK 19167Cancer Research UK C588/A19167Cancer Research UK C8216/A6129Medical Research Council MC_PC_17228Medical Research Council MC_QA137853NCI NIH HHS R01 CA083115
6 · The paper itself

Abstract

backgroundThe role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood.

objectiveTo 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.

methodsWe 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.

resultsTwo 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).

conclusionWe found two loci potentially associated with MSS. Increased genetic susceptibility to develop CM is associated with improved MSS in a high UV setting.

Indexed as

MelanomaSkin NeoplasmsCutaneous Malignant MelanomaGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideUltraviolet RaysGenome-wide association studyMelanomaMelanoma-specific survivalPolygenic risk scoreSkin cancer

Identifiers

PMID36064556
PMCPMC9446843
OpenAlexW4294653791

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.