Lung cancer is the leading cause of cancer deaths worldwide and in the United States. Although cigarette smoking is the major cause, up to 25% of lung cancer cases are never smokers and female never smokers have a higher risk of incident lung cancer than male never smokers. The etiology of non-smoking-related lung cancer is poorly understood. Nutritional factors may affect multiple steps in lung carcinogenesis. Using data from the Shanghai Women's Health Study, a large population-based, prospective cohort study in China, we recently reported a strong inverse association between dietary calcium intake and lung cancer risk among female never smokers (34% risk reduction for the top 25% of calcium intake compared with the bottom 25%). Our study is the first prospective study to report this finding, which needs to be confirmed in other populations. Calcium may interact with vitamin D and estrogens in carcinogenesis, but this hypothesis has not been investigated for non-smoking-related lung cancer. We propose here to conduct a pooling analysis involving thirteen large prospective cohorts and including approximately two million men and women from the United States and countries in Europe and Asia.
The specific aims of this study are: 1) to prospectively investigate whether calcium intake is associated with the risk of non-smoking-related or smoking-related lung cancer and to evaluate whether such associations differ by sex, race/ethnicity, or major determinants of vitamin D status and 2) to evaluate whether associations between calcium intake and lung cancer risk among women are modified by menopausal status, or hormone therapy use. This proposed study, with its large sample size, wide range of calcium intake, and previously-collected detailed exposure and covariate data, is extremely cost- efficient and provides an exceptional opportunity to comprehensively evaluate the association of calcium intake with the risk of non-smoking-related lung cancer. Results of this study would be directly translatable to lung cancer prevention. The infrastructure and networks established by this project would set the stage for future international collaborations on lung cancer risk and prognosis.

Public Health Relevance

Up to one quarter of lung cancer is not related to smoking, and modifiable risk factors for lung cancer are poorly understood. The proposed study will pool existing data from cohort studies around the world and comprise about two million men and women for an in-depth evaluation of the role of calcium intake in lung cancer. The study results may help to develop recommendations and guidelines for the prevention of non- smoking-related lung cancer and the infrastructure and networks built will facilitate future international collaborations on lung cancer etiology.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Small Research Grants (R03)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Lam, Tram K
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Vanderbilt University Medical Center
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Yu, Danxia; Zheng, Wei; Johansson, Mattias et al. (2018) Overall and Central Obesity and Risk of Lung Cancer: A Pooled Analysis. J Natl Cancer Inst 110:831-842
Yang, Jae Jeong; Yu, Danxia; Takata, Yumie et al. (2017) Dietary Fat Intake and Lung Cancer Risk: A Pooled Analysis. J Clin Oncol 35:3055-3064
Yu, Danxia; Takata, Yumie; Smith-Warner, Stephanie A et al. (2017) Prediagnostic Calcium Intake and Lung Cancer Survival: A Pooled Analysis of 12 Cohort Studies. Cancer Epidemiol Biomarkers Prev 26:1060-1070
Shen, Tian; Shu, Xiao-Ou; Xiang, Yong-Bing et al. (2015) Association of hypertension and obesity with renal cell carcinoma risk: a report from the Shanghai Men's and Women's Health Studies. Cancer Causes Control 26:1173-80