Melanoma risk prediction using a multilocus genetic risk score in the Women's Health Initiative cohort - 18/06/18
Abstract |
Background |
Single-nucleotide polymorphisms (SNPs) associated with melanoma have been identified though genome-wide association studies. However, the combined impact of these SNPs on melanoma development remains unclear, particularly in postmenopausal women who carry a lower melanoma risk.
Objective |
We examine the contribution of a combined polygenic risk score on melanoma development in postmenopausal women.
Methods |
Genetic risk scores were calculated using 21 genome-wide association study–significant SNPs. Their combined effect on melanoma development was evaluated in 19,102 postmenopausal white women in the clinical trial and observational study arms of the Women's Health Initiative dataset.
Results |
Compared to the tertile of weighted genetic risk score with the lowest genetic risk, the women in the tertile with the highest genetic risk were 1.9 times more likely to develop melanoma (95% confidence interval 1.50-2.42). The incremental change in c-index from adding genetic risk scores to age were 0.075 (95% confidence interval 0.041-0.109) for incident melanoma.
Limitations |
Limitations include a lack of information on nevi count, Fitzpatrick skin type, family history of melanoma, and potential reporting and selection bias in the Women's Health Initiative cohort.
Conclusion |
Higher genetic risk is associated with increased melanoma prevalence and incidence in postmenopausal women, but current genetic information may have a limited role in risk prediction when phenotypic information is available.
Le texte complet de cet article est disponible en PDF.Key words : genetic risk score, melanoma, postmenopausal, single-nucleotide polymorphism, women, Women's Health Initiative
Plan
Supported by a Dermatology Foundation Grant (Dr Sarin) and the Stanford Medical Scholars Research Program (Ms Cho). The Women's Health Initiative is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, and the US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. |
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Conflicts of interest: None disclosed. |
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Reprints not available from the authors. |
Vol 79 - N° 1
P. 36 - juillet 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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