PT  - JOURNAL ARTICLE
AU  - Catherine M. Olsen
AU  - Nirmala Pandeya
AU  - Matthew H. Law
AU  - Stuart MacGregor
AU  - Mark M. Iles
AU  - Bridie S. Thompson
AU  - Adele C. Green
AU  - Rachel E. Neale
AU  - David C. Whiteman
AU  - for the QSkin Study
TI  - Ultraviolet radiation exposure and melanoma: evidence for gene-environment interaction in a large prospective cohort
AID  - 10.1101/666123
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 666123
4099  - http://biorxiv.org/content/early/2019/06/14/666123.short
4100  - http://biorxiv.org/content/early/2019/06/14/666123.full
AB  - Melanoma develops as the result of complex interactions between sun exposure and genetic factors. Data on the relationship between sunlight and melanoma from prospective studies are scant, and the combination of ultraviolet exposure data collected before melanoma diagnosis and genetic information is rarer still. We aimed to quantify the association between ambient and personal UV exposure in relation to risk of incident melanoma (invasive; invasive+in situ) in a large population-based prospective study of men and women (n=38,833) residing in a high ambient UV setting, and to examine potential gene-environment interactions. During a median follow-up time of 4.4 years, 782 (1.5%) participants developed cutaneous melanoma (316 invasive, 466 in situ). Country of birth, age at migration and sunburns during all periods of life were significantly associated with melanoma risk. Histories of keratinocyte cancer and of other actinic lesions were both strongly associated with melanoma risk. An interaction with polygenic risk is possible; among people at low risk, markers of cumulative sun exposure were associated with melanoma. In contrast, among people at high polygenic risk, markers of high-level early life ambient exposure were associated with melanoma. Polygenic risk scores can assist in identifying individuals for whom sunlight exposure is most relevant.UVultravioletBCCbasal cell carcinomaSCCsquamous cell carcinomaKCkeratinocyte cancerPRSpolygenic risk scoreGWASgenome-wide association studyMAFminor allele frequencyHRhazard ratioSDstandard deviation