Vitamin D intake and lung cancer risk in the Women's Health Initiative

Background: Prior research suggests that vitamin D protects against lung cancer only among certain subgroups. Objectives: We investigated whether vitamin D intake was associated with lung cancer and explored whether vitamin A intake modified the association. Design: Prospective cohort data from 128,779 postmenopausal women, including 1771 incident lung cancers in the Women's Health Initiative (Clinical Trials and Observational Study) 1993-2010, were analyzed. Twelve percent of women received active intervention (1 g Ca + 400 IU vitamin D-3/d) in the Calcium/Vitamin D Trial. Baseline total intake included both dietary intake (from food-frequency questionnaires) and supplement intake (from bottle labels). HRs were estimated by Cox proportional hazard models. Results: No significant association was observed overall. Among never smokers, a total vitamin D intake >= 400 IU/d was significantly associated with lower risks of lung cancer (HR: 0.37; 95% CI: 0.18, 0.77 for >= 800 compared with,100 IU/d; P-trend = 0.01). No significant effect modification of total vitamin A intake on the association between total vitamin D intake and lung cancer was found. However, the Calcium/Vitamin D Trial active intervention was significantly associated with a lower lung cancer risk only among women with a vitamin A intake <1000 mu g/d retinol activity equivalents (HR: 0.69; 95% CI: 0.50, 0.96; P-interaction = 0.09). Conclusions: Vitamin D intake was associated with a lower lung cancer risk in never-smoking, postmenopausal women. Lower vitamin A intake may be important for a beneficial association of 1 g Ca + 400 IU vitamin D-3 supplementation with lung cancer. This trial was registered at clinicaltrials.gov as NCT00000611.