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Updated: May 24, 2025
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Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
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Association of Inherited Genetic Variants with Multiple Primary Melanoma.
David C Gibbs1, Brittany M Small2, Isidora Autuori2
1Department of Dermatology, Emory University, Atlanta, Georgia.
Summary
Genetic variants in 11 gene regions are linked to multiple primary melanoma (MPM). A polygenic risk score (PRS) combining these variants significantly increases MPM risk, even for non-individually significant single nucleotide polymorphisms (SNPs).
Area of Science:
- Genetics
- Oncology
- Epidemiology
Background:
- Genome-wide association studies (GWAS) have identified melanoma susceptibility loci.
- The association of these loci with multiple primary melanoma (MPM) remains unclear.
Purpose of the Study:
- To investigate the association of 69 single nucleotide polymorphisms (SNPs) in 39 GWAS-identified loci with the odds of MPM.
- To assess the cumulative effect of these genetic variants on MPM risk using polygenic risk scores (PRS).
Main Methods:
- The study analyzed 1,205 MPM cases and 2,458 single primary melanoma controls from the Genes, Environment, and Melanoma study.
- Multivariable logistic regression was used to estimate odds ratios (ORs) and confidence intervals (CIs) for MPM.
- Polygenic risk scores (PRS) were calculated using 57 independent GWAS SNPs from a 2020 meta-analysis.
Main Results:
- Thirteen SNPs in 11 gene regions showed a statistically significant association with MPM.
- Individuals in the highest PRS quintile had a 2.81-fold increased odds of MPM.
- Even after excluding individually significant SNPs, the PRS remained significantly associated with MPM (OR = 1.75).
Conclusions:
- Inherited genetic variants in 11 gene regions are independently associated with MPM.
- The cumulative effect of multiple SNPs, even those not individually significant, contributes to MPM risk via PRS.
- These findings confirm the association of identified loci with melanoma risk and quantify their impact on subsequent primary melanoma development.
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