維生素B-6及葉酸與大腸直腸息肉患者的基因多型性、抗氧化活性及甲基化作用關係的探討

中山醫學大學機構典藏 CSMUIR > 健康管理學院 > 營養學系暨碩士班 > 研究計劃 > Item 310902500/3955

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/3955

Title:	維生素B-6及葉酸與大腸直腸息肉患者的基因多型性、抗氧化活性及甲基化作用關係的探討 VI Tamin B-6 and Folate in Relation to the Genetic Polymorphism, Antioxidant Function and Dna Methylation in Colorectal Polyps
Authors:	黃怡嘉;林俊哲
Contributors:	中山醫學大學：營養學系
Date:	2010
Issue Date:	2011-06-30T03:52:50Z (UTC)
Abstract:	維生素B-6 及葉酸與大腸直腸息肉患者的基因多型性、抗氧化活性及甲基化作用關係的探討(第3 年) 研究成果報告(完整版) 計畫類別：個別型計畫編號： NSC 97-2320-B-040-031-MY3 執行期間： 99 年08 月01 日至100 年07 月31 日執行單位：中山醫學大學營養學系（所）計畫主持人：黃怡嘉共同主持人：林俊哲、陳丹霞計畫參與人員：碩士級-專任助理人員：朱美慈博士班研究生-兼任助理人員：陳芳霈報告附件：出席國際會議研究心得報告及發表論文處理方式：本計畫可公開查詢中華民國 100 年10 月20 日行政院國家科學委員會補助專題研究計畫 ■成果報告 □期中進度報告維生素B-6 及葉酸與大腸直腸息肉患者的基因多型性、抗氧化活性及甲基化作用關係的探討計畫類別：■個別型計畫 □整合型計畫計畫編號：NSC 97－2320－040－031－MY3 執行期間： 2008 年 8 月 1 日至 2011 年 7 月 31 日執行機構及系所：中山醫學大學營養系計畫主持人：黃怡嘉教授共同主持人：林俊哲醫師、陳丹霞醫師計畫參與人員：陳芳霈博士生成果報告類型(依經費核定清單規定繳交)：□精簡報告 ■完整報告本計畫除繳交成果報告外，另須繳交以下出國心得報告： □赴國外出差或研習心得報告 □赴大陸地區出差或研習心得報告 ■出席國際學術會議心得報告 □國際合作研究計畫國外研究報告處理方式：除列管計畫及下列情形者外，得立即公開查詢 □涉及專利或其他智慧財產權，□一年□二年後可公開查詢中華民國 100 年 10 月 20 日中文摘要大腸直腸癌目前已為台灣十大癌症死亡的第三名。腺瘤性息肉已被認為是發生大腸直腸癌的前身。葉酸與維生素B6 被認為在大腸直腸息肉形成中扮演重要角色。本計劃的主要目的為：1) 觀察及比較大腸直腸增殖性息肉及腺瘤性息肉受試者的維生素B6 及葉酸的營養狀況、抗氧化酵素活性的差異性。2) 探討維生素B6 及葉酸的營養狀況與大腸直腸息肉受試者的抗氧化酵素活性的關係。3) 探討維生素B6 及葉酸的營養狀況與罹患大腸直腸息肉的危險對比值。4) 評估及比較給予大腸直腸腺瘤性息肉受試者單獨維生素B6 或葉酸補充或合併補充後對抗氧化功能及DNA 甲基化程度的差異及影響。本研究設計方法是以醫院為基礎的橫斷面、病例-對照及隨機雙盲的補充劑介入試驗。本研究於中山醫學大學附設醫院肝膽胃腸科募集大腸直腸息肉受試者 (n = 48)及經年齡-性別配對之後的健康受試者 (n = 96)，並進一步詢問息肉受試者是否參加介入研究。介入研究將於受試者接受息肉切除後且經臨床醫師評估同意後進行。最後有24 位受試者接受12 週介入研究，並隨機分成以下三組，：1) 100 mg/d 維生素B6，n = 9；2) 5 mg/d 葉酸，n = 9 及3) 維生素B6 (100 mg/d) 合併葉酸 (5 mg/d)，n = 6。大腸直腸息肉受試者的血液採集將於接受息肉切除後採集。參加介入研究的受試者的空腹血液採集將於第0、4、12 週進行，血液樣本將進行臨床血液生化值 (白蛋白、肌酸酐、鹼性磷酸酶和高敏感度C-反應蛋白) 及生化檢驗值 (血漿與紅血球磷酸比哆醛、血清與紅血球葉酸、血清維生素 B12 及同半胱胺酸) 的分析，萃取DNA 檢測DNA 甲基化作用，及測定氧化壓力程度、脂質過氧化及抗氧化酵素活性。在橫斷面試驗的部分，本研究發現血漿同半胱胺酸濃度對於大腸直腸息肉有顯著影響，在調整相關影響因子之後，影響依然顯著 (OR, 2.23; 95% CI, 1.23-4.03)。而B-維生素營養狀況皆對罹患大腸直腸息肉無顯著影響。在不同型態的腺瘤性息肉或增生性息肉之間，兩組之臨床血液生化值、生化檢驗值、脂質過氧化、維生素B6 營養狀況及抗氧化酵素活性皆無顯著差異。進行12 週的介入試驗後，無論是接受100 mg/d 維生素B6，5 m/dg 葉酸或兩者同時補充的受試者，在臨床生化值，生化檢驗值，脂質過氧化程度及抗氧化酵素活性，三組間皆無顯著差異。可能是因為樣本數太小無法觀察到顯著影響。本研究認為，血漿同半胱胺酸為大腸直腸息肉的獨立危險因子。並且給予5 mg 葉酸介入12 週後，可顯著降低血漿同半胱胺酸濃度。 Colorectal cancer is now the third leading cause of cancer mortality among men and women in Taiwan. Colorectal adenomas are considered precursors of colorectal cancer, prevention of colorectal adenomas may decrease the occurrence of colorectal cancer. Vitamin B6 and folate may play a critical role in the colorectal polyps progression. The specific aims of this proposal are: 1) to compare folate and vitamin B6 status between colorectal hyperplastic polyps adenomatous polyps; 2) to compare and evaluate folate and vitamin B6 status in relation to oxidative stress, antioxidant activities; 3) to evaluate the effect of vitamin B6 and folate status on the risk of colorectal polyps; 4) to evaluate whether folic acid and/or pyridoxine supplementation had a beneficial effect on reducing oxidative stress, increasing antioxidant function and DNAmethylation in patients with colorectal adenomas. This study was an observational case-control design. Forty-eight participants with colorectal polyps [29 adenomatous polyps , 19 hyperplastic polyps (HP)] and 96 age-, sex-matched healthy participants who met the inclusion criteria were recruited from Chung Shan Medical University Hospital and Taichung General Veterans Hospital. Fasting blood was drawn from each participant to measure hematological and biochemical parameters (plasma and erythrocytes pyridoxal 5’-phosphate (PLP), serum and erythrocytes folate, serum vitamin B12, and plasma homocysteine). Subjects with polyps were blinded and randomly assigned to either the 1) 100 mg/d vitamin B6 (n = 9) ; 2) 5 mg/d folic acid group (n=9); or 3) vitamin B6 (100 mg/d) plus folic acid (5 mg/d)(n=6) for 12 weeks. Participants with AP and HP had significantly higher plasma homocysteine levels than did healthy participants. There was no significant difference in serum folate and vitamin B12 and plasma PLP among the three groups. B-vitamins had no significant effect on the risk of developing colorectal polyps. However, participants with higher plasma homocysteine (OR, 2.23; 95% CI, 1.23-4.03) level exhibited significantly increased risk of developing colorectal polyps after adjusting for body mass index, diastolic blood pressure, total cholesterol and B-vitamins. There were no significant effect on DNA methylation, oxidative stress, antioxidant enzymatic activities, TBARS and oxidized low density lipoprotein levels among three groups after treated either vitamin B6 or folic acid supplements. However, plasma homocysteine level has reduced by 14.2% in the folic acid group. In conclusion, plasma homocysteine was a strong predictor for risk of developing colorectal polyps in subjects with adequate B-vitamins status. Treatment with 5 mg/d folic acid 12 weeks could significantly decrease plasma homocysteine level.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/3955
Appears in Collections:	[營養學系暨碩士班] 研究計劃

Files in This Item:

File	Description	Size	Format
972320B040031MY3.pdf		325Kb	Adobe PDF	577	View/Open

Loading...