- 學位論文
同半胱胺酸、半胱胺酸及維生素B-6對氧化壓力、抗氧化能力及罹患大腸直腸癌危險性之影響
The effects of homocysteine, cysteine and vitamin B-6 status on oxidative stress, antioxidant capacities and the risk of developing colorectal cancer
摘要
高同半胱胺酸雖然被認為在大腸直腸癌形成中扮演重要角色，但與同半胱胺酸轉硫代謝過程相關的營養素及其抗氧化酵素活性與罹患大腸直腸癌的危險性關係並不清楚。同半胱胺酸進行轉硫作用，由維生素B-6擔任輔酶，催化絲胺酸轉成胱硫醚，水解形成半胱胺酸，半胱胺酸會進而轉換成穀胱甘肽。穀胱甘肽是榖胱甘肽硫轉移酶及榖胱甘肽過氧化酶的重要輔因子，這兩個抗氧化酵素的功能包括去除許多致腫瘤化合物的毒性及保護細胞免於氧化壓力的傷害。本研究的目的為探討同半胱胺酸、半胱胺酸及維生素B-6對氧化壓力、抗氧化能力及罹患大腸直腸癌危險性之影響。本病例對照研究於台中榮民總醫院進行，共招募168位大腸直腸癌患者及188位健康受試者。抽取空腹血液分析同半胱胺酸、半胱胺酸、維生素B-6（血漿磷酸吡哆醛濃度）、氧化壓力指標、總抗氧化能力、穀胱甘肽及其相關酵素活性。大腸直腸癌患者較健康受試者有顯著較高的同半胱胺酸、半胱胺酸、穀胱甘肽及氧化型低密度脂蛋白；但卻有較低的榖胱甘肽硫轉移酶及榖胱甘肽過氧化酶活性。血漿磷酸吡哆醛濃度及總抗氧化能力在兩組間並無顯著差異。調整相關干擾因子後，大腸直腸癌患者的同半胱胺酸及半胱胺酸與氧化壓力指標、總抗氧化能力、榖胱甘肽及相關酵素活性無顯著相關性，但較高血漿磷酸比哆醛濃度會增加榖胱甘肽硫轉移酶活性。羅吉斯迴歸分析結果發現僅有高同半胱胺酸濃度顯著增加罹患大腸直腸癌的危險對比值 (OR, 1.25, p < 0.001)。同半胱胺酸及半胱胺酸不影響大腸直腸癌患者的氧化壓力及抗氧化能力，但高同半胱胺酸是獨立增加罹患大腸直腸癌的重要危險因子。
並列摘要
High homocysteine plays an important role in the progression of colorectal cancer. However the association of transsulfuration of homocysteine metabolism with related nutrients, antioxidant enzyme activities and the risk of colorectal cancer are unclear. During the transsulfuration, homocysteine is irreversibly sulfoconjugated to serine conversion to cystathionine and then cysteine by the pyridoxal 5’-phosphat (PLP) dependent enzymes. Cysteine is an important contributor to glutathione synthesis, which is a key buffer of glutathione S-transferase (GST) and glutathione peroxidase (GPx). There two enzymes involve a fundamental role in protecting the cell from oxidative damage and cellular detoxification. The purpose of this case-control study was to examine the effects of homocysteine, cysteine and vitamin B-6 status on oxidative stress, antioxidant capacities and the risk of developing colorectal cancer. One hundred and sixty-eight patients with colorectal cancer (cases), and 188 healthy participants (controls) were recreated from Taichung Veterans General Hospital, Taichung, Taiwan. Fasting blood samples were drawn to measure homocysteine, cysteine, vitamin B-6 status (plasma PLP), oxidative stress indicators, antioxidant capacities, glutathione and glutathione - dependent enzyme activities patients with colorectal cancer had significantly higher levels of homocysteine, cysteine, glutathione and oxidized low-density lipoprotein (ox-LDL), but had significantly lower levels of GST and GPx when compared to healthy participants. There were no significant differences in plasma PLP and antioxidant capacities between patients with colorectal cancer and healthy participants. After adjusting for confounders, homocysteine and cysteine had no effects on oxidative stress indicators, total antioxidant capacity (TAC), glutathione and glutathione - dependent enzyme activities in patients with colorectal cancer. However, high PLP levels would increase GST activities in patients with colorectal cancer. Logistic regression analysis revealed that high homocysteine levels significantly increased the risk of colorectal cancer (OR,1.25, p<0.001). Homocysteine and cysteine did not affect oxidative stress and antioxidant capacities in patients with colorectal cancer; however, higher homocysteine is an independent contributing factor to increase the risk of colorectal cancer.
參考文獻
延伸閱讀
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