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- Title
Genomic Risk Score for Melanoma in a Prospective Study of Older Individuals.
- Authors
Bakshi, Andrew; Yan, Mabel; Riaz, Moeen; Polekhina, Galina; Orchard, Suzanne G; Tiller, Jane; Wolfe, Rory; Joshi, Amit; Cao, Yin; McInerney-Leo, Aideen M; Yanes, Tatiane; Janda, Monika; Soyer, H Peter; Cust, Anne E; Law, Matthew H; Gibbs, Peter; McLean, Catriona; Chan, Andrew T; McNeil, John J; Mar, Victoria J
- Abstract
<bold>Background: </bold>Recent genome-wide association meta-analysis for melanoma doubled the number of previously identified variants. We assessed the performance of an updated polygenic risk score (PRS) in a population of older individuals, where melanoma incidence and cumulative ultraviolet radiation exposure is greatest.<bold>Methods: </bold>We assessed a PRS for cutaneous melanoma comprising 55 variants in a prospective study of 12 712 individuals in the ASPirin in Reducing Events in the Elderly Trial. We evaluated incident melanomas diagnosed during the trial and prevalent melanomas diagnosed preenrolment (self-reported). Multivariable models examined associations between PRS as a continuous variable (per SD) and categorical (low-risk [0%-20%], medium-risk [21%-80%], high-risk [81%-100%] groups) with incident melanoma. Logistic regression examined the association between PRS and prevalent melanoma.<bold>Results: </bold>At baseline, mean participant age was 75 years; 55.0% were female, and 528 (4.2%) had prevalent melanomas. During follow-up (median = 4.7 years), 120 (1.0%) incident cutaneous melanomas occurred, 98 of which were in participants with no history. PRS was associated with incident melanoma (hazard ratio = 1.46 per SD, 95% confidence interval [CI] = 1.20 to 1.77) and prevalent melanoma (odds ratio [OR] = 1.55 per SD, 95% CI = 1.42 to 1.69). Participants in the highest-risk PRS group had increased risk compared with the low-risk group for incident melanoma (OR = 2.51, 95% CI = 1.28 to 4.92) and prevalent melanoma (OR = 3.66, 95% CI = 2.69 to 5.05). When stratifying by sex, only males had an association between the PRS and incident melanoma, whereas both sexes had an association between the PRS and prevalent melanoma.<bold>Conclusions: </bold>A genomic risk score is associated with melanoma risk in older individuals and may contribute to targeted surveillance.
- Subjects
GENOME-wide association studies; MELANOMA; LONGITUDINAL method; ULTRAVIOLET radiation; RADIATION exposure; RESEARCH; SEQUENCE analysis; RESEARCH methodology; EVALUATION research; SKIN tumors; COMPARATIVE studies; GENOMICS; RESEARCH funding
- Publication
JNCI: Journal of the National Cancer Institute, 2021, Vol 113, Issue 10, p1379
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djab076