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

描述（由申请人提供）：肺癌是全球和美国癌症死亡的主要原因。虽然吸烟是主要原因，但高达25%的肺癌病例是从不吸烟的，而从不吸烟的女性患肺癌的风险高于从不吸烟的男性。非吸烟相关肺癌的病因尚不清楚。营养因素可能影响肺癌发生的多个步骤。根据上海妇女健康研究（一项基于中国人群的大型前瞻性队列研究）的数据，我们最近报道了从不吸烟的女性饮食钙摄入量与肺癌风险之间的强烈负相关（钙摄入量最高的25%与最低的25%相比，风险降低34%）。我们的研究是第一个报告这一发现的前瞻性研究，这需要在其他人群中得到证实。钙可能在致癌过程中与维生素D和雌激素相互作用，但这一假设尚未对非吸烟相关的肺癌进行研究。我们在此建议进行一项涉及13个大型前瞻性队列的汇总分析，其中包括来自美国、欧洲和亚洲国家的约200万男性和女性。本研究的具体目的是：1)前瞻性调查钙摄入量是否与非吸烟相关或吸烟相关肺癌的风险相关，并评估这种关联是否因性别、种族/民族或维生素D水平的主要决定因素而异；2)评估钙摄入量与女性肺癌风险之间的关联是否因绝经状态或激素治疗的使用而改变。本研究样本量大，钙摄入量范围广，先前收集的详细暴露和协变量数据极具成本效益，为全面评估钙摄入量与非吸烟相关肺癌风险之间的关系提供了难得的机会。这项研究的结果将直接转化为肺癌的预防。该项目建立的基础设施和网络将为今后的国际合作奠定基础

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. 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.