History of Keratinocyte Carcinoma and Risk of Melanoma: A Prospective Cohort Study

The association between history of keratinocyte carcinoma (KC, also known as nonmelanoma skin cancer) and risk of developing invasive melanoma has not been assessed comprehensively using prospective data.

We followed 91 846 women in the Nurses' Health Study (NHS; 1984-2010), 114 918 women in the NHSII (1989-2011), and 48 946 men in the Health Professionals Follow-up Study (1986-2010) for diagnoses of KC and melanoma biennially. Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) of melanoma associated with history of KC, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). All statistical tests were two-sided.

We documented 1949 melanomas, 38 842 BCCs, and 7462 SCCs over 6.4 million person-years of follow-up. After adjustment for other risk factors, a personal history of KC was associated with an increased risk of melanoma (meta-analysis HR = 2.22, 95% CI = 1.73 to 2.85). The association was more apparent among participants with a history of both BCC and SCC (HR = 3.40, 95% CI = 1.60 to 7.19) than among participants with a history of BCC only (HR = 2.20, 95% CI = 1.80 to 2.70) or SCC only (HR = 1.56, 95% CI = 0.98 to 2.46), and there was a strong risk-increasing trend associated with a higher number of reported KCs removed by surgery ( P trend < .001). In women, KC history was more strongly associated with head/neck melanomas (HR = 4.17, 95% CI = 2.77 to 6.27) than with trunk or limb melanomas (both HRs < 2.50, P heterogeneity = .04).

Our results provide novel insights for the relationship between KC history and risk of developing melanoma, which may be important for melanoma prevention.