DIET AND GENETIC RISKS FOR LUNG CANCER

描述：（申请人描述）本提案用于调查 饮食和遗传的相互作用 基因多态性与肺癌的风险有关。数据来自18，314名男性， 参加β-胡萝卜素和视黄醇化学预防试验的妇女 （CARET）。平均随访7.4年后，CARET的终点数据为 近800例肺癌。饮食摄入量是用一种食物来测量的 频率问卷血清微量营养素和遗传多态性 分析了388例肺癌病例和753例对照。我们的具体目标 是： 1.为了更好地了解水果和蔬菜摄入量与 降低肺癌的风险。水果和蔬菜的摄入量将被测量为： (i)每天的食用量（总量和按植物化学成分分组），（ii） 与水果和蔬菜有关的微量营养素，包括维生素C和 E、叶酸和类胡萝卜素，和（iii）血清类胡萝卜素和维生素E。 2.研究水果和蔬菜摄入量与肺的关系是否 致癌物代谢酶的基因型改变了癌症风险 (i.e., CYP2D6、CYP2E1、CYP1A1、GSTM1、GSTT1和EH）。我们将进行队列 饮食摄入数据分析和实验室病例对照分析 基于研究。虽然已经收集了基线饮食数据， 实验室分析（血清微量营养素和基因型）已经 完成后，没有具有营养专业知识的CARET调查员 科学家们被资助进行这些分析，并撰写相关的 手稿因此，为了实现上述具体目标，我们要求 支持营养流行病学家，统计学家，分子生物学家， 以及公布调查结果所需的工作人员支持。这项工作涉及 关于肺癌的病因学和预防的重要问题，可以 除了已经完成的项目外， 投入到这个大型的化学预防试验中

DESCRIPTION: (Applicant's Description) This proposal is for an investigation into the associations of diet, and interactions of diet and genetic polymorphisms, with the risk of lung cancer. Data are from 18,314 men and women enrolled in a chemoprevention trial of beta-carotene and retinol (CARET). After a mean of 7.4 years of follow up, CARET has endpoint data on almost 800 cases of lung cancer. Dietary intake was measured with a food frequency questionnaire. Serum micronutrient and genetic polymorphisms have been analyzed for 388 lung cancer cases and 753 controls. Our specific aims are: 1. To better understand the association of fruit and vegetable intake with the reduced risk of lung cancer. Fruit and vegetable intake will be measured as: (i) servings per day (total and grouped by phytochemical content), (ii) micronutrient associated with fruits and vegetables, including vitamins C and E, folate, and carotenoids, and (iii) serum carotenoids and vitamin E. 2. To examine whether the associations of fruit and vegetable intake with lung cancer risk are modified by genotypes of carcinogen metabolizing enzymes (i.e., CYP2D6, CYP2El, CYP1Al, GSTM1, GSTT1, and EH). We will conduct cohort analyses for dietary intake data and case control analyses for laboratory based studies. Although the baseline dietary data have been collected and the laboratory analyses (for serum micronutrients and genotypes) have been completed, there are no CARET investigators with expertise in nutrition science who are funded to conduct these analyses and write the associated manuscripts. Therefore, to meet the specific aims proposed above, we request support for nutritional epidemiologists, a statistician, molecular biologist, and the staff support needed to publish the findings. This work addresses important questions about the etiology and prevention of lung cancer, and can be completed with a modest amount of funding in addition to what has already been invested in this large chemoprevention trial.