Genomic risk score for melanoma in a prospective study of older individuals
- Author(s)
- Bakshi, A; Yan, M; Riaz, M; Polekhina, G; Orchard, SG; Tiller, J; Wolfe, R; Joshi, A; Cao, Y; McInerney-Leo, AM; Yanes, T; Janda, M; Soyer, HP; Cust, AE; Law, MH; Gibbs, P; McLean, C; Chan, AT; McNeil, JJ; Mar, VJ; Lacaze, P;
- Journal Title
- Journal of the National Cancer Institute
- Publication Type
- epub ahead of print
- Abstract
- BACKGROUND: 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. METHODS: 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 pre-enrolment (self-reported). Multivariable models examined associations between PRS as a continuous variable (per standard deviation [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. RESULTS: 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] = 1.20-1.77) and prevalent melanoma (odds ratio [OR]=1.55 per SD, 95% CI = 1.42-1.69). Participants in the highest-risk PRS group had increased risk compared to the low-risk group for incident (OR = 2.51, 95% CI = 1.28-4.92) and prevalent (OR = 3.66, 95% CI = 2.69-5.05). 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. CONCLUSION: A genomic risk score is associated with melanoma risk in older individuals, and may contribute to targeted surveillance.
- Publisher
- Oxford Academic
- Research Division(s)
- Personalised Oncology
- PubMed ID
- 33837773
- Link To PubMed Central Version
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921762/
- Publisher's Version
- https://doi.org/10.1093/jnci/djab076
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-04-28 08:15:45
Last Modified: 2022-07-25 09:43:39