Association of Vitamin A Intake with Cutaneous Squamous Cell Carcinoma Risk in the United States

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Importance: Retinoids are bioactive forms of vitamin A that are essential in the maintenance of epithelial maturation and differentiation. Synthetic retinoids are used in chemoprevention of skin cancer among high-risk populations with potential adverse effects. Epidemiologic data on vitamin A intake and risk of cutaneous squamous cell carcinoma (SCC) are limited. Objective: To examine whether vitamin A intake is associated with a reduction in SCC risk. Design, Settings, and Participants: This cohort study prospectively examined intake of vitamin A and carotenoids and SCC risk in the Nurses' Health Study (1984-2012) and the Health Professionals Follow-up Study (1986-2012). Diet was assessed repeatedly. Incident SCC was confirmed by pathologic reports. Data analysis was performed from June 21, 2017, to December 4, 2018. Exposures: Intakes of vitamin A, retinol, and carotenoids. Main Outcomes and Measures: Incident SCC. Cox proportional hazards regression models were used to compute cohort-specific hazard ratios (HRs) and 95% CIs. Pooled HRs of the cohort-specific results were calculated. Results: A total of 3978 SCC cases in 75170 women in the Nurses' Health Study (mean [SD] age, 50.4 [7.2] years) and 48400 men in the Health Professionals Follow-up Study (mean [SD] age, 54.3 [9.9] years) were documented. Higher total vitamin A was associated with a reduction in SCC risk; with quintile 1 as the reference, the pooled multivariate HRs for the increasing quintiles of vitamin A intake were 0.97 (95% CI, 0.87-1.07) for quintile 2, 0.97 (95% CI, 0.80-1.17) for quintile 3, 0.93 (95% CI, 0.84-1.03) for quintile 4, and 0.83 (95% CI, 0.75-0.93) for quintile 5 (P <.001 for trend). Higher intakes of retinol and some carotenoids were also associated with a reduction in SCC risk; the pooled HRs for the highest quintiles of intake compared with the lowest quintiles were 0.88 (95% CI, 0.79-0.97; P =.001 for trend) for total retinol, 0.86 (95% CI, 0.76-0.96; P =.001 for trend) for beta cryptoxanthin, 0.87 (95% CI, 0.78-0.96; P <.001 for trend) for lycopene, and 0.89 (95% CI, 0.81-0.99; P =.02 for trend) for lutein and zeaxanthin. The results were generally consistent by sex and other SCC risk factors. Conclusions and Relevance: This study suggests that increased intake of dietary vitamin A is associated with decreased risk of incident SCC. Future studies are needed to determine whether vitamin A supplementation has a role in chemoprevention of SCC.




Kim, J., Park, M. K., Li, W. Q., Qureshi, A. A., & Cho, E. (2019). Association of Vitamin A Intake with Cutaneous Squamous Cell Carcinoma Risk in the United States. JAMA Dermatology, 155(11), 1260–1268.

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