Independent evaluation of melanoma polygenic risk scores in UK and Australian prospective cohorts*

J Steinberg; MM Iles; JY Lee; X Wang; MH Law; AK Smit; T Nguyen-Dumont; GG Giles; MC Southey; RL Milne; GJ Mann; DT Bishop; RJ MacInnis; AE Cust

Conference Proceedings

Independent evaluation of melanoma polygenic risk scores in UK and Australian prospective cohorts*

J Steinberg, MM Iles, JY Lee, X Wang, MH Law, AK Smit, T Nguyen-Dumont, GG Giles, MC Southey, RL Milne, GJ Mann, DT Bishop, RJ MacInnis, AE Cust

British Journal of Dermatology | Published : 2022

DOI: 10.1111/bjd.20956

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Abstract

Background: Previous studies suggest that polygenic risk scores (PRSs) may improve melanoma risk stratification. However, there has been limited independent validation of PRS-based risk prediction, particularly assessment of calibration (comparing predicted to observed risks). Objectives: To evaluate PRS-based melanoma risk prediction in prospective UK and Australian cohorts with European ancestry. Methods: We analysed invasive melanoma incidence in the UK Biobank (UKB; n = 395 647, 1651 cases) and a case-cohort nested within the Melbourne Collaborative Cohort Study (MCCS, Australia; n = 4765, 303 cases). Three PRSs were evaluated: 68 single-nucleotide polymorphisms (SNPs) at 54 loci from a ..

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University of Melbourne Researchers

Tu Nguyen Author

Graham Giles Author

Melissa Southey Author

Roger Milne Author

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Awarded by Cancer Council Victoria

Funding Acknowledgements

Financial support was provided by a National Health and Medical Research Council (NHMRC) Program Grant (1093017). A.E.C. received an NHMRC Career Development Fellowship (1147843). T.N.-D. received a National Breast Cancer Foundation (Australia) Career Development Fellowship (ECF-17-001). Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further augmented by NHMRC grants 209057, 396414 and 1074383, with genotyping funded by an NHMRC Project Grant (1129136, principal investigator R.J.M.), and Cancer Council Victoria.infrastructure provided by Cancer Council Victoria. MCCS cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. Funding and acknowledgements for the melanoma genome-wide association study meta-analysis can be found in Landi et al. Nat Genet 2020; 52:494-504. The funders had no role in the study design, data collection, data analysis, manuscript preparation or publication decisions.