Nutrigenetics of cruciferous vegetable intake and breast cancer prognosis

十字花科蔬菜摄入量与乳腺癌预后的营养遗传学

• 批准号: 8334008
• 负责人: LI TANG
• 金额: $ 13.23万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8334008
• 关键词: Accounting; Address; Affect; Animals; Antineoplastic Agents; Apoptotic; Biological Availability; Biological Markers; Biopsy Specimen; Blood specimen; Breast Cancer Cell; Broccoli - dietary; Cancer Patient; Cancer Prognosis; Cancer Survivor; Cell Culture Techniques; Cessation of life; Cleaved cell; Clinical Trials; Cohort Studies; Control Groups; Data; Diagnosis; Diagnostic Neoplasm Staging; Diet; Dietary Isothiocyanate; Disease; Enrollment; Enzymes; Estrogen Receptors; Estrogen receptor positive; Excision; Female; Funding; General Population; Genes; Genetic; Genetic Polymorphism; Glutathione S-Transferase; Goals; Growth; Human; Immunohistochemistry; In Vitro; Individual; Intake; Intervention; Intervention Trial; Investigation; Isothiocyanates; Left; Life Style; Malignant Neoplasms; Mammary Neoplasms; Measures; Metabolic Pathway; Metabolism; Modeling; Molecular; Monitor; Motivation; NAD(P)H dehydrogenase (quinone) 1, human; NQO1 gene; Neoadjuvant Study; Neoplasm Metastasis; Nutritional; Operative Surgical Procedures; Outcome; Participant; Pathway interactions; Patients; Phytochemical; Placebos; Population; Postmenopause; Prospective Studies; Randomized; Reaction; Recruitment Activity; Recurrence; Research; Risk; Role; Source; Specimen; Staging; Testing; Woman; angiogenesis; cancer recurrence; caspase-3; cruciferous vegetable; design; dietary supplements; disorder risk; follow-up; high risk; human NAT2 protein; immune function; improved; in vivo; lifestyle factors; malignant breast neoplasm; neoplastic cell; nutrition related genetics; outcome forecast; patient population; population based; prevent; prospective; urinary

DESCRIPTION (provided by applicant): My long-term goal is to prevent cancer recurrence and improve survival using nutritional/dietary approaches. Breast cancer is my primary focus. Breast cancer is the most commonly diagnosed female malignancy in the US, leaving approximately 2.4 million cancer survivors facing increased risk of disease recurrence and early death. It is increasingly important to identify modifiable lifestyle factors to improve the disease prognosis. Our hypothesis is that higher cruciferous vegetable intake may reduce risk of recurrence and increase survival among breast cancer patients, depending upon their genetic background. The rationale includes: (1) Cruciferous vegetables are rich sources of isothiocyanates (ITCs), a group of promising anti-cancer agents; (2) Polymorphic genes of key enzymes in the pathway of ITC metabolism may affect the bioavailability of ITCs; (3) ITCs potently inhibit the growth of breast cancer cells in vitro and in vivo; (4) ITCs effectively target both estrogen receptor (ER) positive and negative breast cancer cells; (5) ITCs modulate immune function, and inhibit cancer angiogenesis and metastasis; and (6) ITCs potently induce NAD(P)H:quinone oxidoreductase 1 (NQO1), while polymorphisms of NQO1 resulting in low activity strongly predict poor prognosis in breast cancer patients. Two specific aims are proposed: Aim 1 is to examine the effect of cruciferous vegetable intake on breast cancer recurrence and survival. The interactions with functional polymorphisms of key ITC-metabolizing and -inducible genes will be examined. We will use data and specimens from The Pathways Study, a funded prospective cohort study of breast cancer patients. Aim 2 is to evaluate the effect of ITC- rich broccoli sprout extract (ITC-BSE) on breast tumor cells in early stage breast cancer patients in a neoadjuvant study. Biomarkers including Ki-67, cleaved caspase-3, ER, and NQO1 will be examined and the pre-post changes will be compared between treatment and control group. This pilot intervention trial is the mechanistic investigation for the Aim 1 study; it also helps to identify potential biomarkers for monitoring efficacy of dietary ITCs. The proposed study will be the first to address the interactions between cruciferous vegetable intake and individual genetic background in relation to breast cancer prognosis. Due to the wide availability of cruciferous vegetables and the high diet-change motivation of breast cancer patients, the findings from the study may have a significant impact on the lifestyle of breast cancer survivors.

描述（由申请人提供）：我的长期目标是通过营养/饮食方法来防止癌症复发并提高生存率。乳腺癌是我的主要重点。乳腺癌是美国最常见的女性恶性肿瘤，约有240万个癌症幸存者面临疾病复发风险增加和早期死亡的风险增加。识别可修改的生活方式因素以改善疾病预后越来越重要。我们的假设是，较高的十字花科蔬菜摄入量可能会降低乳腺癌患者的复发风险并增加生存率，具体取决于其遗传背景。基本原理包括：（1）十字花科蔬菜是异硫氰酸盐（ITC）的丰富来源，这是一组有前途的抗癌药； （2）ITC代谢途径中关键酶的多态基因可能影响ITC的生物利用度； （3）ITC在体外和体内有效抑制乳腺癌细胞的生长； （4）ITC有效地靶向雌激素受体（ER）阳性和负乳腺癌细胞； （5）ITC调节免疫功能，并抑制癌症的血管生成和转移； （6）ITC有效诱导NAD（P）H：喹酮氧化还原酶1（NQO1），而NQO1的多态性导致活性较低会强烈预测乳腺癌患者的预后不良。提出了两个具体的目的：目标1是检查十字花科蔬菜摄入对乳腺癌复发和生存的影响。将研究与关键ITC代谢和可诱导基因的功能多态性的相互作用。我们将使用途径研究中的数据和标本，这是一项资助的乳腺癌患者的前瞻性队列研究。 AIM 2是在一项新辅助研究中评估富含ITC-富含西兰花发芽提取物（ITC-BSE）对乳腺癌患者乳腺肿瘤细胞的影响。将检查包括KI-67，Cleaved Caspase-3，ER和NQO1在内的生物标志物，并将在治疗组和对照组之间进行比较前的变化。该试验干预试验是AIM 1研究的机械研究；它还有助于鉴定潜在的生物标志物来监测饮食ITC的功效。拟议的研究将是第一个解决十字花科蔬菜摄入与乳腺癌预后有关的个人遗传背景之间相互作用的研究。由于十字花科蔬菜的广泛供应以及乳腺癌患者的饮食变化大量动机，该研究的发现可能会对乳腺癌幸存者的生活方式产生重大影响。