Experimental studies suggest that antioxidants could protect against skin carcinomas. However, epidemiological studies on dietary antioxidant supplement use in relation to risk of basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) yielded inconsistent findings, and very few prospective studies with available sun exposure data have been conducted to date. Our objective was to investigate the relationships between the use of dietary supplements in beta-carotene, and vitamins A, C, and E, and risk of non-melanoma skin cancers (NMSC).

E3N is an ongoing prospective cohort involving 98,995 French women aged 40–65 years at inclusion in 1990. Data on the occurrence of BCC and SCC were collected every 2–3 years through self-administered questionnaires, with skin cancer cases confirmed through pathology reports. Intake of specific antioxidant supplements was collected in 1995. Dietary antioxidant intakes from foods were calculated using data collected via a validated food frequency questionnaire in 1993. We used Cox proportional hazards regression models with age as the time scale to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the risks of BCC and SCC associated with antioxidant supplement use. Models were adjusted for age, birth cohort, pigmentary traits, residential UV exposure at birth and at inclusion, family history of skin cancer, body mass index, physical activity, smoking status, and education.

Over a mean follow-up of 11.6 years, 1245 BCC and 219 SCC cases were diagnosed among the 63,077 included women. We observed a positive association between vitamin A supplement use and risk of NMSCs (HR=1.30, 95% CI: 1.02–1.67), particularly BCC (HR=1.32, 95% CI: 1.01–1.72). There was also a positive association between vitamin E supplement use and NMSC risk (HR=1.28; 95% CI: 1.05–1.56). Moreover, we found an interaction between vitamin A supplement use and dietary intake of retinol (P_interaction=0.04) on the risk of NSMCs: vitamin A supplement use was associated with an increased risk of NMSCs only in women in the highest tertile of dietary retinol intake (HR=1.89; 95% CI: 1.29–2.75), but not in those in the middle (HR=1.05, 95% CI: 0.64–1.74) or lowest tertiles of intake (HR=1.10; 95% CI: 0.70–1.73). However, use of beta-carotene or vitamin C supplements was not associated with NMSC risk.

Our study suggests an increased risk of NMSCs associated with vitamin A (particularly for BCC) and vitamin E supplement use. The increased risk associated with vitamin A supplement use was restricted to women with high intakes of retinol from foods. These findings suggest that high supplementary intakes of some antioxidants could confer a higher risk of NMSCs in women, particularly in the context of high antioxidant intakes in the diet in the case of retinol. More research is warranted in order to replicate these findings and investigate their underlying mechanisms.