Andrew Bakshi1, Mabel Yan1, Moeen Riaz1, Galina Polekhina1, Suzanne G Orchard1, Jane Tiller1, Rory Wolfe1, Amit Joshi2, Yin Cao3, Aideen M McInerney-Leo4, Tatiane Yanes4, Monika Janda4,5, H Peter Soyer4, Anne E Cust6, Matthew H Law7,8, Peter Gibbs9, Catriona McLean9, Andrew T Chan2, John J McNeil1, Victoria J Mar1,10, Paul Lacaze1. 1. Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. 2. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; MGH Cancer Center, Boston, MA, USA. 3. Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, USA. 4. The University of Queensland Diamantina Institute, The University of Queensland, Dermatology Research Centre, Brisbane, QLD, USA. 5. Centre of Health Services Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia. 6. Sydney School of Public Health and Melanoma Institute Australia, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia. 7. Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. 8. School of Biomedical Sciences, Faculty of Health, and Institute of health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia, Personalised Oncology Division, Walter and Eliza Hall Institute Medical Research and Faculty of Medicine University of Melbourne, Australia. 9. Department of Anatomical Pathology, Alfred Hospital, Melbourne, Victoria, Australia. 10. Victorian Melanoma Service, Alfred Health, Melbourne, Australia.
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 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. 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.
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 (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. 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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