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者，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学知之甚少。营养因素可能影响肺癌发生和癌症进展的多个步骤。使用上海妇女健康研究（SWHS）的数据，这是一项在中国进行的大型人群前瞻性队列研究，我们最近报告了膳食钙摄入量与从不吸烟的女性肺癌风险之间的强烈负相关（与最低25%相比，钙摄入量最高的25%的风险降低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。钙可能与维生素D和雌激素在致癌作用中相互作用，但这一假设尚未在非吸烟相关的肺癌中进行研究。我们在这里建议进行一项汇总分析，涉及13个大型前瞻性队列，包括来自美国和欧洲及亚洲国家的约200万男性和女性。这项研究的具体目标是：1）前瞻性研究钙摄入量是否与非吸烟相关或吸烟相关肺癌的风险相关，并评估此类关联是否因性别而异，以及2）评估从不吸烟的女性中钙摄入量与肺癌风险之间的关联是否因种族/民族、维生素D状态的主要决定因素、绝经状态而改变，或激素治疗的使用。这项拟议的研究，其大样本量，广泛的钙摄入量，以及先前收集的详细暴露和协变量数据，是非常具有成本效益的，并提供了一个特殊的机会，全面评估钙摄入量与非吸烟相关肺癌风险的关联。该项目建立的基础设施和网络将为未来肺癌风险和预后方面的国际合作奠定基础。1

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