Cohort Study of Glucosamine and Chondroitin Supplement Use and Cancer Risk

氨基葡萄糖和软骨素补充剂的使用与癌症风险的队列研究

• 批准号: 7762550
• 负责人: Emily WHITE
• 金额: $ 35.79万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7762550
• 关键词: Adopted; Adverse effects; Age; American; Anti-Inflammatory Agents; Anti-inflammatory; Antineoplastic Agents; Antioxidants; Arthralgia; Arthritis; Aspirin; Benefits and Risks; Biological; Biological Markers; Blood; Breast; C-reactive protein; Cancer Etiology; Cause of Death; Cell Survival; Cessation of life; Characteristics; Chemopreventive Agent; Chondroitin; Chondroitin Sulfates; Chronic; Cohort Studies; Colorectal; Colorectal Cancer; Coronary heart disease; Data Analyses; Databases; Degenerative polyarthritis; Diet; Equipment and supply inventories; Frequencies; Future; Gene Expression; Glucosamine; Glucosamine Sulfate; Health; Health Benefit; Hematopoietic; Home environment; Hormonal; Human; Incidence; Inflammation; Inflammatory; Inflammatory Response; Inhibition of Cell Proliferation; Intake; Interleukin-10; Interleukin-6; Interleukins; Intervention; Interview; Investigation; Laboratory Study; Life Style; Lung; Lymph; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of prostate; Minerals; Modeling; Modification; Multivitamin; NF-kappa B; Obesity; Outcome; Pain; Paper; Participant; Pharmaceutical Preparations; Pilot Projects; Preparation; Preventive; Property; Prospective Studies; Prostate; Questionnaires; Recruitment Activity; Risk; Risk Factors; Risk-Taking; Sample Size; Scientist; Serum; Serum amyloid A protein; Smoking; Stimulus; Stroke; Subgroup; Testing; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Vitamin E; Vitamins; Washington; Woman; base; cancer prevention; cancer risk; cancer type; cardiovascular disorder prevention; cohort; cost; dietary supplements; disorder prevention; disorder risk; follow-up; human TNFRSF1A protein; improved; lifestyle factors; malignant breast neoplasm; medical specialties; men; mortality; neoplasm registry; non-drug; pill; public health relevance; randomized trial; transcription factor; tumor; tumor necrosis factor alpha receptor

DESCRIPTION (provided by applicant): There is a continuing need to identify chemopreventive drugs for cancer, as most identified so far have shown effects on only one type of cancer and/or have been associated with some adverse effects. Glucosamine and chondroitin (G & C), often taken together in a single pill, are the most commonly used specialty (non-vitamin, non-mineral) supplement in the US. Randomized trials support their efficacy for arthritis. Laboratory studies show that G & C both inhibit the transcription factor NF-kappa B, which leads to decreased inflammatory response to stimuli and inhibition of cell proliferation, effects associated with lower cancer risk. Other anti-inflammatory drugs (e.g., aspirin) have been shown in some studies to reduce the risk of colorectal, breast, prostate, lung, and total cancer, but may have adverse effects. However, there are no human studies of G & C in relation to cancer risk. Furthermore, while these supplements are considered to be safe, the small sample sizes (20-952 users of G &/or C) and short durations (<=24 months) of G & C use in prior studies suggests that adverse effects have not been fully assessed. The VITamins And Lifestyle (VITAL) study is a prospective study which targeted supplement users in recruitment. From 2000-2002, 77,738 men and women in western Washington State, age 50-76, entered the cohort, by completing a detailed questionnaire on use of 38 supplements over the past 10 years, diet, and lifestyle factors. Over 15,600 participants used glucosamine, and over 10,400 used chondroitin. Participants are followed for outcomes using cost-effective linkages to databases. In exploratory studies of multiple supplements in relation to three outcomes, G & C were each associated with a 20-35% statistically significant reduced risk of lung cancer, colorectal cancer and total mortality. These are the strongest and most consistent findings across endpoints of a benefit of any supplement examined thus far in this cohort. The aims of this proposed project are to investigate the associations of intake of G & C with risk of breast cancer, prostate cancer, total cancer, and with lung and colorectal cancer in more detail, including examination of frequency/duration of G & C use, effect modification by factors associated with inflammation, and differential effects by cancer characteristics (Aim 1). Additional aims are to investigate the associations of G & C with cancer mortality (Aim 2) and with other cause-specific mortality to identity other major adverse or beneficial effects (Aim 3), and to test in a pilot study biomarkers of the mechanisms by which G & C may reduce risk of disease, including serum IL-1beta, IL-6, IL-10, TNFalpha, sTNF-RI, sTNF-RII, CRP, and SAA (Aim 4). Aims 1-3 will be accomplished by continued follow-up of the VITAL cohort for three additional years to increase study power, and by more detailed and focused data analyses of the outcomes in relation to G & C use. We expect a total of 10,200 cancers and 5700 deaths. 220 men and women who participated in a prior home interview, supplement inventory and blood draw will provide the materials for Aim 4. PUBLIC HEALTH RELEVANCE: This study would provide information to help guide the American public about the benefits and risks of taking glucosamine and chondroitin supplements. In addition, if there are observed protective associations of glucosamine and/or chondroitin with cancer risk and no major adverse effects, then these supplements would deserve further investigation as cancer preventive drugs.

描述（由申请人提供）：持续需要确定癌症的化学预防药物，因为到目前为止，大多数已确定的药物仅对一种癌症有效和/或与一些不良反应有关。葡萄糖胺和软骨素（g&c）通常一起服用，是美国最常用的特种（非维生素，非矿物质）补充剂。随机试验支持它们对关节炎的疗效。实验室研究表明，G和C都能抑制转录因子NF-kappa B，从而降低对刺激的炎症反应和抑制细胞增殖，从而降低癌症风险。其他抗炎药物（如阿司匹林）在一些研究中显示可以降低结直肠癌、乳腺癌、前列腺癌、肺癌和其他癌症的风险，但可能有副作用。然而，目前还没有关于g&c与癌症风险之间关系的人体研究。此外，虽然这些补充剂被认为是安全的，但在先前的研究中，小样本量（20-952名G &/或C使用者）和短持续时间（<=24个月）的G & C使用表明，副作用尚未得到充分评估。维生素和生活方式（VITAL）研究是一项前瞻性研究，针对招募中的补充剂使用者。从2000年到2002年，华盛顿州西部的77,738名年龄在50-76岁的男性和女性通过填写一份详细的问卷调查了过去10年38种补充剂的使用情况、饮食和生活方式因素，进入了研究队列。超过15,600名参与者使用葡萄糖胺，超过10,400名参与者使用软骨素。利用具有成本效益的数据库连接跟踪参与者的结果。在与三个结果相关的多种补充剂的探索性研究中，G和C分别与肺癌、结直肠癌和总死亡率降低20-35%的统计学显著相关。这些是迄今为止在这个队列中检验的任何补充剂益处的最有力和最一致的结果。该项目的目的是更详细地调查G & C的摄入与乳腺癌、前列腺癌、总癌以及肺癌和结直肠癌风险的关系，包括检查G & C使用的频率/持续时间、炎症相关因素对效果的影响以及癌症特征的差异影响（目标1）。其他目的是调查g&c与癌症死亡率（目标2）和其他病因特异性死亡率的关系，以确定其他主要的不利或有利影响（目标3），并在一项试点研究中测试g&c可能降低疾病风险的机制生物标志物，包括血清il -1 β、IL-6、IL-10、TNFalpha、sTNF-RI、sTNF-RII、CRP和SAA（目标4）。目标1-3将通过对VITAL队列进行额外三年的持续随访以增加研究力度，并通过对与G & C使用相关的结果进行更详细和更集中的数据分析来实现。我们预计总共有10 200例癌症和5700例死亡。参加事先家访、补充清单和抽血的220名男性和女性将为目标4提供材料。