Background: Few prospective studies have examined the relationship between sun exposure, other potential risk factors, and risk of different skin cancers [including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma] simultaneously. Methods: We evaluated the association between a number of potential risk factors and skin cancer risk in a cohort of 108,916 US women, the Nurses' Health Study II (1989-2009). Results: During 2.05 million years of follow-up, we identified 6,955, 880, and 779 diagnoses of BCC, SCC, and melanoma, respectively. Compared with participants in the lowest quintile of cumulative ultraviolet flux in adulthood, participants in the highest quintile had multivariable-adjusted relative risks (RR) of 2.35 (Ptrend < 0.0001) for BCC, 2.53 (Ptrend = 0.009) for SCC, and 0.68 (P trend = 0.38) for melanoma. In contrast, the RRs were 1.68 (95% CI, 1.55-1.82) for BCC, 1.68 (95% CI, 1.34-2.11) for SCC, and 1.80 (95% CI, 1.42-2.28) for melanoma for participants with ≥5 blistering sunburns when compared with participants without sunburn between ages 15 and 20 years. We found significant interactions between family history of melanoma, number of blistering sunburns between ages 15 and 20 years and BCC risk, and between sunburn reaction as a child/adolescent and SCC risk (all Pinteraction < 0.05). Conclusion: In a cohort of U.S. women, we found that sun exposures in both early life and adulthood were predictive of BCC and SCC risks, whereas melanoma risk was predominantly associated with sun exposure in early life. Impact: Our results may have potential implications for the prevention of skin cancers.
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