• Department of Biostatistics and Epidemiology, University of North Texas Health Science Center, Fort Worth, TX 76107, United States. Electronic address: menghua.tao@unthsc.edu.
• Vanderbilt Epidemiology Center, University of Vanderbilt, Nashville, TN 37203, United States.
• Department of Biostatistics and Epidemiology, University of North Texas Health Science Center, Fort Worth, TX 76107, United States.
• Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY 14214, United States.
• Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, United States.
• Department of Medicine, Stanford University Medical Center, Stanford, CA, United States.
• Department of Nutrition Science, Purdue University, West Lafayette, IN, United States.

BACKGROUND: Magnesium and calcium are antagonistic in many physiologic processes. However, few studies have investigated the associations of supplemental calcium with lung cancer risk taking this antagonism into account. We evaluated the effect of calcium and vitamin D supplementation on lung cancer incidence and explored whether the ratio of baseline calcium to magnesium (Ca:Mg) intake modifies the association in the Women's Health Initiative (WHI) calcium plus vitamin D supplementation (CaD) trial.

METHODS: The intervention phase of the WHI CaD was a double-blinded, randomized, placebo-controlled trial in 36,382 postmenopausal women aged 50-79 years, recruited at 40U.S. centers. Post-intervention follow-up continued among 29,862 (86%) of the surviving participants. Risk of lung cancer in association with CaD supplementation was evaluated using proportional hazard regression models.

RESULTS: After 11 years' cumulative follow-up, there were 207 lung cancers (incidence 0.11% per year) in the supplement arm and 241 (0.12%) in the placebo arm (hazard ratio (HR) for the intervention, 0.91; 95% confidence interval (CI), 0.71-1.17). Subgroup analyses suggested that the HR for lung cancer varied by baseline Ca:Mg intake ratio among women who were current smokers at enrollment (p=0.04 for interaction).

CONCLUSIONS: Over the entire follow-up period, calcium and vitamin D supplementation did not reduce lung cancer incidence among postmenopausal women. In exploratory analyses, an interaction was found for the baseline Ca:Mg intake ratio on lung cancer among current smokers at the trial entry. This findings need to be further studied for the role of calcium with magnesium in lung carcinogenesis in current smokers.