Calcium intake and lung cancer: effect modification by sex and smoking status

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DESCRIPTION (provided by applicant): 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 and cancer progression. Using data from the Shanghai Women's Health Study (SWHS), 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 and 2) to evaluate whether associations between calcium intake and lung cancer risk among female never smokers are modified by race/ethnicity, major determinants of vitamin D status, 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. The infrastructure and networks established by this project would set the stage for future international collaborations on lung cancer risk and prognosis. 1