Abstract
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. To examine whether vitamin A intake is associated with a reduction in SCC risk. 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. Intakes of vitamin A, retinol, and carotenoids. 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. A total of 3978 SCC cases in 75 170 women in the Nurses' Health Study (mean [SD] age, 50.4 [7.2] years) and 48 400 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. 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.
Highlights
MethodsStudy Population This cohort study used data from the Nurses’ Health Study (NHS), which was established in 1976 with 121 700 US female registered nurses aged 30 to 55 years, and the Health Professionals Follow-up Study (HPFS), which was established in 1986 with 51 529 US male health professionals aged 40 to 75 years
Higher total vitamin A level was associated with a reduction in squamous cell carcinoma (SCC) risk; with quintile 1 as the reference, the pooled multivariate hazard ratios (HRs) for the increasing quintiles of vitamin A intake were 1.00, 0.97 for quintile 2, 0.97
Forest Plot of Pooled Multivariable Hazard Ratios (HRs) and 95% CIs of Squamous Cell Carcinoma by Energy-Adjusted Vitamin A and Carotenoid Intake (Quintile 5 vs Quintile 1) in the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS). In this large prospective study of US women and men, we found that higher intake of total vitamin A, retinol, and several individual carotenoids, including beta cryptoxanthin, lycopene, and lutein and zeaxanthin, was associated with lower risk of SCC
Summary
Study Population This cohort study used data from the NHS, which was established in 1976 with 121 700 US female registered nurses aged 30 to 55 years, and the HPFS, which was established in 1986 with 51 529 US male health professionals aged 40 to 75 years. Participants in both cohorts completed a questionnaire on their medical history and lifestyle and have been followed up biennially, with follow-up rates generally exceeding 90%.
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