Cohort Study of Glucosamine and Chondroitin Supplement Use and Cancer Risk

有一个持续的需要，以确定化学预防药物的癌症，因为大多数确定 到目前为止仅显示出对一种类型的癌症的作用和/或与某些副作用有关。 氨基葡萄糖和软骨素（G & C），通常在一个单一的药丸一起服用，是最常用的 特殊（非维生素，非矿物质）补充剂。随机试验支持其对关节炎的疗效。 实验室研究表明，G & C都抑制转录因子NF-κ B B，这导致减少 炎症反应的刺激和抑制细胞增殖，与较低的癌症风险的影响。 其他抗炎药（例如，阿司匹林）在一些研究中显示可以降低结肠直肠癌的风险， 乳腺癌、前列腺癌、肺癌和总癌，但可能有副作用。然而，目前还没有人体研究 G & C与癌症风险的关系此外，虽然这些补充剂被认为是安全的，但小剂量 样本量（20-952名G &/或C用户）和G & C在先前研究中使用的短持续时间（<=24个月） 表明不良影响尚未得到充分评估。 维生素与生活方式（VITAL）研究是一项前瞻性研究，针对以下人群的补充剂使用者： 招聘从2000年到2002年，华盛顿州西部有77,738名年龄在50-76岁之间的男性和女性进入了 队列，通过完成一份关于过去10年中使用38种补充剂的详细问卷，饮食， 生活方式因素。超过15，600名参与者使用葡萄糖胺，超过10，400人使用软骨素。参与者 利用与数据库的成本效益高的联系，在对多种 补充剂与三种结果相关，G & C分别与20-35%的统计学显著性相关， 降低肺癌、结直肠癌和总死亡率的风险。这些都是最强的和最一致的 迄今为止在该队列中检查的任何补充剂的益处的终点发现。 本项目的目的是调查G & C摄入量与乳腺癌风险之间的关系 癌症，前列腺癌，总癌，并与肺癌和结直肠癌更详细，包括检查 G & C使用的频率/持续时间，与炎症相关的因素对效果的影响，以及 癌症特征（目标1）。其他目的是调查G & C与癌症的关系 死亡率（目标2）和其他原因导致的特定死亡率，以确定其他主要不良或有益影响 (Aim 3），并在试点研究中测试G & C可能降低疾病风险的机制的生物标志物， 包括血清IL-1 β、IL-6、IL-10、TNF α、sTNF-RI、sTNF-RII、CRP和SAA（目的4）。 将通过对VITAL队列继续随访3年来实现目标1-3， 增加研究能力，并通过对与G & C相关的结果进行更详细和更有针对性的数据分析 使用.我们预计总共有10,200例癌症和5700例死亡。220名男性和女性参加了一个先前的 家庭访谈、补充库存和抽血将为目标4提供材料。

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.