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Soo Park, MD
Soo Park, MD
Posted: Friday, November 8, 2024
The risk of developing an in situ or invasive cutaneous melanoma may be influenced by germline genetic variation, according to Matthew H. Law, PhD, of QI QIMR Berghofer Medical Research Institute, Brisbane, Australia, and colleagues. Although both melanoma subtypes appeared to be highly genetically related, polygenetic risk scores were higher in invasive melanoma groups. The findings of these three genome-wide association study meta-analyses were published in JAMA Dermatology.
“Despite indistinguishable heritability estimates between the melanoma classifications, polygenic risk scores suggest germline genetics may influence whether a person gets in situ melanoma or invasive melanoma,” stated the study investigators. “Polygenic risk scores could potentially help stratify populations based on invasive melanoma risk, informing future screening programs without exacerbating the current burden of melanoma overdiagnosis.”
Meta-analyses were conducted to identify heritable components when comparing in situ melanoma to controls, invasive melanoma to controls, as well as in situ to invasive melanoma using four population-based genetic cohorts in Australia. Genetic effect estimates were calculated for single-nucleotide variants throughout the genome for each group. Heritability of single-nucleotide variants was estimated along with the genetic correlation across subtypes. The investigators used a leave-one-out cohort approach, and polygenic risk scores were calculated by comparing invasive and in situ melanoma genetic risk.
Genome-wide loci associated with in situ melanoma (n = 6) and loci with invasive melanoma were identified (n = 18), which were found to be genetically correlated (genetic r = 0.96). Loci near IRF4, KLF4, and HULC were found to be more highly associated with in situ vs invasive melanoma, whereas MC1R seemed to have a greater effect on invasive melanoma. In situ melanoma heritability was 6.7%, and invasive melanoma heritability was 4.9%. Polygenic risk scores were found to be higher for invasive melanoma, with an odds ratio per 1-standard deviation increase of 1.43.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
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