Journal
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
Volume 113, Issue 10, Pages 1379-1385Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/djab076
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Funding
- ASPREE Flagship cluster grant (Commonwealth Scientific and Industrial Research Organisation, Monash University, Menzies Research Institute, Australian National University, University of Melbourne)
- National Institute on Aging [U01AG029824, U19AG062682]
- National Cancer Institute at the National Institutes of Health
- National Health and Medical Research Council of Australia [334047, 1127060]
- Monash University
- Victorian Cancer Agency
- NHMRC Career Development Fellowship [1147843]
- NHMRC MRFF Next Generation Clinical Researchers Program Practitioner Fellowship [APP1137127]
- NHMRC Early Career Fellowship [1160757]
- National Heart Foundation Future Leader Fellowship [102604]
- National Health and Medical Research Council of Australia [1160757] Funding Source: NHMRC
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This study evaluated the performance of a polygenic risk score comprising 55 variants for melanoma risk in older individuals, showing significant associations with both incident and prevalent melanoma, especially in males.
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 preenrolment (selfreported). Multivariable models examined associations between PRS as a continuous variable (per SD) and categorical (lowrisk [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 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. Conclusions: A genomic risk score is associated with melanoma risk in older individuals and may contribute to targeted surveillance.
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