Evidence map›Paper›PMID 36879448›Full record

ArticleThe British journal of dermatology2023

The MC1R r allele does not increase melanoma risk in MITF E318K carriers.

Courtney K Wallingford, Anastassia Demeshko, Asha Krishnankutty Krishnakripa, Darren J Smit, David L Duffy, Brigid Betz-Stablein, Annette Pflugfelder, Kasturee Jagirdar, Elizabeth Holland, Graham J Mann and 17 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The British journal of dermatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 9 institutions in 4 countries.

Courtney K WallingfordFrazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Australia.ORCID 0000-0001-6529-7528
Anastassia DemeshkoFrazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Australia.
Asha Krishnankutty KrishnakripaFrazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Australia.
Darren J SmitFrazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Australia.ORCID 0000-0002-3288-3659
David L DuffyFrazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Australia.ORCID 0000-0001-7227-632X
Brigid Betz-StableinFrazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Australia.
Annette PflugfelderCenter of Dermato-Oncology, Department of Dermatology, University of Tübingen, Tübingen, Germany.ORCID 0000-0001-7858-0453
Kasturee JagirdarFrazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Australia.ORCID 0000-0001-8761-132X
Elizabeth HollandThe Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, Australia.
Graham J MannThe Melanoma Institute Australia, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Clare A PrimieroFrazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Australia.
Tatiane YanesFrazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Australia.ORCID 0000-0002-3905-3025
Josep MalvehyDermatology Department, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
Cèlia BadenasCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain.
Cristina CarreraDermatology Department, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
Paula AguileraDermatology Department, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
Catherine M OlsenFrazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Australia.ORCID 0000-0003-4483-1888
Sarah V WardSchool of Population and Global Health, The University of Western Australia, Perth, WA, Australia.
Nikolas K HaassFrazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Australia.ORCID 0000-0002-3928-5360
Richard A SturmFrazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Australia.ORCID 0000-0003-1301-0294
Susana PuigDermatology Department, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
David C WhitemanQIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland, Australia.ORCID 0000-0003-2563-9559
Matthew H LawStatistical Genetics, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, QLD, 4006, Australia.ORCID 0000-0002-4303-8821
Anne E CustThe Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, Australia.ORCID 0000-0002-5331-6370
Miriam PotronyCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain.
H Peter SoyerFrazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Australia.ORCID 0000-0002-4770-561X
Aideen M McInerney-LeoFrazer Institute, University of Queensland, Dermatology Research Centre, Brisbane, Australia.ORCID 0000-0002-0059-5732
The University of Queensland · AUCentre for Biomedical Network Research on Rare Diseases · ESAustralian National University · AUThe University of Sydney · AUJohns Hopkins University · USQIMR Berghofer Medical Research Institute · AUQueensland University of Technology · AUThe University of Western Australia · AUUniversity of Tübingen · DE

Funding

NIH HHS
6 · The paper itself

Abstract

backgroundPopulation-wide screening for melanoma is not cost-effective, but genetic characterization could facilitate risk stratification and targeted screening. Common Melanocortin-1 receptor (MC1R) red hair colour (RHC) variants and Microphthalmia-associated transcription factor (MITF) E318K separately confer moderate melanoma susceptibility, but their interactive effects are relatively unexplored.

objectivesTo evaluate whether MC1R genotypes differentially affect melanoma risk in MITF E318K+ vs. E318K- individuals. MATERIALS AND

methodsMelanoma status (affected or unaffected) and genotype data (MC1R and MITF E318K) were collated from research cohorts (five Australian and two European). In addition, RHC genotypes from E318K+ individuals with and without melanoma were extracted from databases (The Cancer Genome Atlas and Medical Genome Research Bank, respectively). χ2 and logistic regression were used to evaluate RHC allele and genotype frequencies within E318K+/- cohorts depending on melanoma status. Replication analysis was conducted on 200 000 general-population exomes (UK Biobank).

resultsThe cohort comprised 1165 MITF E318K- and 322 E318K+ individuals. In E318K- cases MC1R R and r alleles increased melanoma risk relative to wild type (wt), P < 0.001 for both. Similarly, each MC1R RHC genotype (R/R, R/r, R/wt, r/r and r/wt) increased melanoma risk relative to wt/wt (P < 0.001 for all). In E318K+ cases, R alleles increased melanoma risk relative to the wt allele [odds ratio (OR) 2.04 (95% confidence interval 1.67-2.49); P = 0.01], while the r allele risk was comparable with the wt allele [OR 0.78 (0.54-1.14) vs. 1.00, respectively]. E318K+ cases with the r/r genotype had a lower but not significant melanoma risk relative to wt/wt [OR 0.52 (0.20-1.38)]. Within the E318K+ cohort, R genotypes (R/R, R/r and R/wt) conferred a significantly higher risk compared with non-R genotypes (r/r, r/wt and wt/wt) (P < 0.001). UK Biobank data supported our findings that r did not increase melanoma risk in E318K+ individuals.

conclusionsRHC alleles/genotypes modify melanoma risk differently in MITF E318K- and E318K+ individuals. Specifically, although all RHC alleles increase risk relative to wt in E318K- individuals, only MC1R R increases melanoma risk in E318K+ individuals. Importantly, in the E318K+ cohort the MC1R r allele risk is comparable with wt. These findings could inform counselling and management for MITF E318K+ individuals.

Indexed as

MelanomaSkin NeoplasmsAllelesAustraliaGenetic Predisposition to DiseaseGenotypeHumansMicrophthalmia-Associated Transcription FactorReceptor, Melanocortin, Type 1Microphthalmia-Associated Transcription FactorMITF protein, humanReceptor, Melanocortin, Type 1

Identifiers

PMID36879448
PMCPMC10230961
OpenAlexW4323347694

What OpenQuestion holds

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LicenceCC BY-NC
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 OpenQuestion graph.