Dietary, Nutritional & Metabolic Determinants of Cancer

膳食、营养

• 批准号: 6556288
• 负责人: Regina G Ziegler
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6556288
• 关键词: 1 carbon compound; African American; Asian Americans; Scandinavian; age difference; breast neoplasms; cancer risk; carotenoids; caucasian American; cervix neoplasms; colorectal neoplasms; dietary constituent; esophagus neoplasm; fruit; gender difference; genetic susceptibility; human subject; larynx neoplasms; lung neoplasms; metabolism; nutrition aspect of cancer; nutrition related tag; oral pharyngeal neoplasm; patient oriented research; prostate neoplasms; racial /ethnic difference; soybeans; vegetables

VEGETABLES, FRUITS, AND CAROTENOIDS Previously, we demonstrated that diets high in vegetables, fruits, and carotenoids were strongly associated with reduced risk of lung and upper aerodigestive tract cancers. To explore the individual contributions of the major carotenoids, we conducted nested case-control studies in the Honolulu Heart Program cohort. Low serum levels of several carotenoids were associated with increased risk of lung, oral-pharyngeal, esophageal, and laryngeal cancer, with low alpha-carotene the most predictive. Recently, in the Nurses and Health Professionals cohorts, using repeated dietary measures, we found that high vegetable and fruit intake was associated with only a modestly lower risk of lung cancer in women and no risk reduction in men. Our analyses suggested that the strength of this widely accepted relationship might have been exaggerated because confounding by smoking was not always adequately controlled. Since recent publications have also questioned whether vegetable intake can reduce the risk of colorectal cancer, we are exploring opportunities to continue to evaluate the importance of vegetables and fruits in cancer etiology, with emphasis on prospective studies, range and variety in intake, and accurate assessment of exposure. Initially, we will explore vegetable and fruit intake and blood carotenoid levels with respect to colorectal polyp progression in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort. Lycopene, the major source of which is tomato products, has been linked to prostate cancer in several studies. In a case-control study conducted among U.S. Blacks and Whites, we found that high blood lycopene was protective in both races, and that serum levels were lower in the Blacks, suggesting that low lycopene might contribute to the substantially higher rates of prostate cancer among U.S. Blacks. The protective influence of lycopene-rich diets has been most consistently seen in US studies so we are now exploring its role in a cohort of Finnish men with different dietary patterns. ONE-CARBON METABOLISM Disruption of one-carbon metabolism can interfere with DNA synthesis, repair, and methylation and thus promote carcinogenesis. Efficient one-carbon metabolism requires not only folate but also vitamins B6 and B12 and optimal activity of multiple enzymes, such as methylene tetrahydrofolate reductase and methionine synthase. In a community-based case-control study of invasive cervical cancer in five U.S. areas, we found that low serum and red blood cell folate were only modestly predictive of increased risk. However, elevated serum homocysteine was strongly and significantly predictive (RR's~2-3), suggesting that pervasive problems in one-carbon metabolism might be involved. We are now assessing the contribution of B-vitamin deficiencies and polymorphisms in key one-carbon metabolism genes. In addition, we will be evaluating the importance of one-carbon metabolism in the etiology of brain and colorectal cancer. Dietary and vitamin supplement information are being analyzed in a multicenter case-control study of brain cancer, and will be complemented by assays for genetic polymorphisms. In the PLCO cohort, 2000 men and women have been diagnosed with colorectal adenomatous polyps. The dietary information, serum and DNA collected in this study will allow us to explore the role of one-carbon metabolism in the progression of colorectal cancer. Since folic acid fortification has already been shown to decrease homocysteine levels in populations with a variety of nutritional and genetic impairments, our results may suggest targeted supplementation and/or fortification schemes that can reduce cancer risk. BREAST CANCER International variation in breast cancer incidence and migrant studies indicate that modifiable factors play a major role in breast cancer etiology although the specific lifestyles and environmental exposures remain elusive. We designed a large, population-based case-control study of breast cancer in Asian-American women to take advantage of their diversity in diet and breast cancer risk. Childhood, adolescent, and adult exposures were assessed by interviewing both study participants and their mothers. To complement the extensive interview information, body size and shape were measured, and blood and urine samples were collected. Endogenous hormones, phytoestrogens, growth factors, micronutrients, and fatty acids have been or will be measured in these specimens. We found a 6-fold gradient in breast cancer risk by migration history within our study population, comparable to the international differences in breast cancer incidence rates. Adult exposures substantially influenced risk. Furthermore, there was no evidence of an especially susceptible period during menarche or early reproductive life. Increased adiposity and weight gain in the decade preceding diagnosis were critical determinants of risk. Thus, excess weight may function as a late stage promoter, and weight maintenance or reduction as an adult may have a significant and rapid impact on breast cancer risk. We are currently exploring which endogenous hormones, hormone metabolites, growth factors, and dietary patterns are most correlated with the 6-fold gradient in risk, and predictive of increased breast cancer incidence. Circulating estrogens were only weakly associated with increased risk, while circulating androgens were inversely associated in both pre- and postmenopausal women. Decreased intake of soy was associated with a doubling of breast cancer risk. We now want to examine the broader dietary patterns associated with soy intake; in particular, its relationship vegetable, fruit, and grain consumption; the relative contribution of childhood and adult soy intake; and what specific isoflavones and lignans seem important. Since height was a strong and consistent predictor of risk in these Asian-American women, we are seeking biologic explanations, with emphasis initially on insulin-like growth factors.

蔬菜，水果和类胡萝卜素以前，我们证明了蔬菜，水果和类胡萝卜素高的饮食与肺部和上层气管癌的风险降低密切相关。为了探索主要类胡萝卜素的个人贡献，我们在檀香山心脏计划队列中进行了嵌套的病例对照研究。几种类胡萝卜素的低血清水平与肺，口腔 - 咽，食管和喉癌的风险增加有关，而α-胡萝卜素低的风险最为预测性。最近，在护士和卫生专业人员队列中，使用反复的饮食措施，我们发现，高蔬菜和水果摄入量仅与女性肺癌的较低风险相关，而男性则没有降低风险。我们的分析表明，这种广泛接受的关系的强度可能被夸大了，因为吸烟混淆并不总是得到充分控制。由于最近的出版物还质疑蔬菜摄入是否可以降低结直肠癌的风险，因此我们正在探索机会继续评估蔬菜和水果在癌症病因中的重要性，重点是前瞻性研究，范围和摄入量的范围，并准确评估暴露。最初，我们将探索有关前列腺，肺，结直肠癌和卵巢癌筛查试验的结直肠息肉进展的蔬菜和水果摄入量以及血类胡萝卜素水平。 番茄红素是番茄产品的主要来源，在几项研究中与前列腺癌有联系。在美国黑人和白人之间进行的一项病例对照研究中，我们发现高血番茄红素在两种种族中都是保护性的，黑人的血清水平较低，这表明低番茄红素可能导致美国黑人中前列腺癌的较高率。在美国研究中，最持续的浓度富含番茄红素的饮食的保护作用是最始终如一的，因此我们现在正在探索其在饮食方式不同的芬兰男性中的作用。 一碳代谢的一碳代谢破坏会干扰DNA的合成，修复和甲基化，从而促进致癌作用。有效的一碳代谢不仅需要叶酸，还需要维生素B6和B12，以及多种酶的最佳活性，例如甲基四氢叶酸酸酯还原酶和蛋氨酸合酶。在美国五个地区的侵入性宫颈癌的基于社区的病例对照研究中，我们发现低血清和红细胞叶酸仅适度地预测了风险增加。然而，升高的血清同型半胱氨酸具有强烈和显着的预测性（RR 〜2-3），表明可能涉及一种碳代谢的普遍性问题。我们现在正在评估关键的单碳代谢基因中B-维生素缺乏症和多态性的贡献。此外，我们将评估单碳代谢在大脑和大肠癌病因中的重要性。在多中心病例对照研究中，正在分析饮食和维生素补充剂的信息，并通过遗传多态性的测定来补充。在PLCO队列中，有2000名男女被诊断为结直肠腺瘤息肉。这项研究中收集的饮食信息，血清和DNA将使我们能够探索单碳代谢在结直肠癌进展中的作用。由于已经显示出叶酸强化可以降低具有多种营养和遗传障碍的人群中的同型半胱氨酸水平，因此我们的结果可能表明有针对性的补充和/或防御力可以降低癌症风险。 乳腺癌 乳腺癌发病率和移民研究的国际变异表明，可修改因素在乳腺癌病因中起着重要作用，尽管特定的生活方式和环境暴露仍然难以捉摸。我们设计了一项基于人群的大型病例对照研究，对亚裔妇女的乳腺癌研究，以利用其在饮食和乳腺癌风险方面的多样性。通过采访研究参与者及其母亲来评估童年，青少年和成人的暴露。为了补充广泛的访谈信息，测量了身体的大小和形状，并收集了血液和尿液样本。内源激素，植物雌激素，生长因子，微量营养素和脂肪酸已在这些标本中进行或将测量。我们发现研究人群中的移民历史上发现了乳腺癌风险的6倍，与乳腺癌发病率的国际差异相当。成人暴露会极大地影响风险。此外，没有证据表明在初潮或早期生殖生活期间特别容易受到影响。在诊断之前的十年中，肥胖和体重增加的增加是风险的关键决定因素。因此，多余的体重可能是后期促进剂，成年人的体重维持或减少可能会对乳腺癌风险产生重大而快速的影响。我们目前正在探索哪些内源激素，激素代谢产物，生长因子和饮食模式与风险的6倍梯度最相关，并预测了乳腺癌发病率增加。循环雌激素仅与风险增加相关，而循环雄激素在绝经前和绝经后妇女中均与循环中均相关。大豆摄入量的降低与乳腺癌风险增加一倍。我们现在想检查与大豆摄入相关的更广泛的饮食模式。特别是它的关系蔬菜，水果和谷物消费；儿童和成人大豆摄入的相对贡献；以及哪些特定的异黄酮和木兰似乎很重要。由于身高是这些亚裔妇女的强烈且一致的风险预测指标，因此我们正在寻求生物学解释，最初强调了胰岛素样生长因子。