砷及胰島素相關酵素基因多形性與腎細胞癌

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題名:	砷及胰島素相關酵素基因多形性與腎細胞癌 Arsenic, Gene Polymorphism of Insulin-related Enzymes and enal Cell Carcinoma
作者:	陳詩珊 Chen, Shih-Shan
貢獻者:	薛玉梅
關鍵詞:	腎細胞癌,砷,喝酒,基因多形性,類胰島素結合蛋白-3,胰島素受器基質-1,磷脂醯肌醇-3 Renal cell carcinoma,Arsenic,Alcohol consumption,Gene polymorphism,IGFBP-3,IRS-1,PI3K
日期:	2013-06-27
上傳時間:	2018-09-27 14:14:45 (UTC+8)
摘要:	背景過去研究發現，不論在砷暴露地區或非砷暴露的台北地區均顯示，尿液總砷與腎細胞癌有顯著的相關性。胰島素相關路徑分別與砷、飲酒、糖尿病、高血壓及肥胖等危險因子相關，但此路徑之基因多形性與腎細胞癌間缺乏綜合性探討。另外，胰島素相關酵素基因多形性是否影響砷對腎細胞癌的風險仍然未知。因此本研究探討尿液總砷、喝酒及胰島素相關酵素基因多形性對腎細胞癌之相關性及其交互作用。方法本研究以年齡 (± 3歲) 與性別匹配之病例對照研究於 2007 年 3 月至 2011 年 11 月間，至臺大醫院、臺北市立萬芳醫院與臺北醫學大學附設醫院泌尿科門診及病房招募 335 位腎細胞癌個案，及 618 位參加健康檢查民眾。向研究對象說明目的並獲得同意書後進行問卷訪視與收集血液及尿液樣本。血液萃取 DNA 並利用聚合酶連鎖反應限制片段長度多形性進行胰島素相關酵素激酶 (類胰島素結合蛋白-3、胰島素受器基質-1、磷脂醯肌醇-3) 之基因多形性分析。尿液三價無機砷、五價無機砷、五價單甲基砷酸及五價雙甲基砷酸等砷物種濃度利用高效能液相層析儀連接氫化器及原子吸收光譜儀進行分析。結果攜帶類胰島素結合蛋白-3 風險雙倍體比未攜帶者腎細胞癌危險對比值與 95% 信賴區間為 2.67 (1.62 - 4.41)。肥胖者中，類胰島素結合蛋白-3 風險雙倍體與喝酒習慣具顯著交互作用 (P＜0.05)，攜帶類胰島素結合蛋白-3 風險雙倍體且無喝酒習慣比未攜帶類胰島素結合蛋白-3 風險雙倍體且有或偶爾有喝酒習慣者，腎細胞癌危險對比值與95% 信賴區間達 11.28 (2.06 - 61.67)。尿液總砷濃度每增加 1 μg/g creatinine 腎細胞癌危險對比值與 95% 信賴區間為 1.02 (1.01 - 1.03)。並且尿液總砷濃度與喝酒具顯著交互作用 (P＜0.05)，尿液總砷濃度＞ 15.19 μg/g creatinine且無喝酒習慣者，比尿液總砷濃度 ≦ 15.19 μg/g creatinine且有喝酒或偶爾有喝酒習慣者腎細胞癌危險對比值與 95% 信賴區間為 3.79 (2.15 - 6.69)。類胰島素結合蛋白-3 風險雙倍體與尿液總砷濃度對腎細胞癌具顯著交互作用 (P＜0.05)，尿液總砷濃度＞ 15.19 μg/g creatinine且為 IGFBP-3 風險雙倍體攜帶者，比尿液總砷濃度 ≦ 15.19 μg/g creatinine且非 IGFBP-3 風險雙倍體攜帶者腎細胞癌危險對比值與 95% 信賴區間為 4.77 (2.43 - 9.40)。結論尿液總砷濃度較高、未有飲酒習慣及類胰島素結合蛋白-3 風險雙倍體與腎細胞癌有關。此外，尿液總砷濃度較高與類胰島素結合蛋白-3 風險雙倍體同時存在時，腎細胞癌的危險對比值大幅增加，而尿液總砷濃度較高及類胰島素結合蛋白-3 風險雙倍體也分別與未有喝酒習慣對腎細胞癌的危險對比值具交互作用。 Background Previous study demonstrated that the relationship between urinary total arsenic level and renal cell carcinoma (RCC) risk was not only found in arsenic exposure area but also in Taipei city where non-obvious arsenic exposure in drinking water. Many studies reported that arsenic exposure, alcohol consumption, type 2 diabetes, hypertension and obesity were associated with insulin-related pathway. However, there was less integrity study mentioned about the association between gene polymorphisms of insulin-related pathway and RCC. In addition, the joint effect of gene polymorphisms of insulin-related pathway and arsenic on the RCC nerver has been confirmed. Therefore, the aim of this study is to explore the relationship between urinary total arsenic, alcohol consumption, gene polymorphisms of insulin-related pathway and the risk of RCC. Materials and Methods Age (± 3 years)- sex- matched case-control study was conducted between March 2007 and November 2011. Three hundred thirty five patients with RCC and six hundred eighteen healthy controls were recruited form out-patient and in-patient of the Department of Urology of National Taiwan University Hospital, Taipei Municipal Wan Fang Hospital and Taipei Medical University Hospital. Personel interview were conducted and urine and serum samples werw collected from participants after well trained interviewers mentioned the study purpose and received their informed consents. After DNA was extracted from blood specimens, and used polymerase chain reaction - restriction fragment length polymorphism to determine the gene polymorphisms of insulin-related growth factors (IGFBP-3, IRS-1, PI3K). Concentrations of urinary arsenic species, including inorganic arsenic (arsenite (As [III]) and arsenate (As[V])), monomethylarsonic acid (MMA[V]) and dimethylarsinic acid (DMA[V]), were determined by a high performance liquid chromatography - linked hydride generator and atomic absorption spectrometry. Result Compared with non-carried IGFBP-3 risk diplotype, the odds ratio (OR) and 95% confident of interval (CI) of RCC among those carried IGFBP-3 risk diplotype was 2.67 (1.62 - 4.41). Among obese participants, there was an addictive interaction on RCC between IGFBP-3 risk diplotype and alcohol consumption habits (p < 0.05) , the OR and 95% CI of RCC among who wthout alcohol consumption habits and carried IGFBP-3 risk diplotype compared with those had alcohol consumption habits and without IGFBP-3 risk diplotype carrier was 11.28 (2.06 - 61.67). The OR of RCC was increased 1.02 times (1.01 - 1.03) with a 1 μg/g creatinine of total urinary arsenic level increment. There was a significant interaction on RCC between total urinary arsenic level and alcohol consumption habits (p < 0.05), the OR and 95% CI of RCC among who without alcohol consumption habits and total urinary arsenic level > 15.19 μg/g creatinine compared with those had alcohol consumption habits and total urinary arsenic level ?T 15.19 μg/g creatinine was 3.79 (2.15 - 6.69). The interaction on RCC between IGFBP-3 risk diplotype and total urinary arsenic level was also significant (p < 0.05), the OR and 95% CI of RCC among who had total urinary arsenic level > 15.19 μg/g creatinine and carried IGFBP-3 risk diplotype compared with those who had total urinary arsenic level ?T 15.19 μg/g creatinine and without IGFBP-3 risk diplotype carrier was 4.77 (2.43 - 9.40). Conslusions High total urinary arsenic level and without alcohol consumption was associated with RCC. In addition, both high total urinary arsenic level and risk diplotype of IGFBP-3 substantially elevated the odds ratio of RCC. There was an interaction between total urinary arsenic level and alcohol consumption habits, or between the risk diplotype of IGFBP-3 and alcohol consumption habits on the OR of RCC respectively.
描述:	碩士論文指導教授-薛玉梅委員-蒲永孝委員-陳彥州
資料類型:	thesis
顯示於類別:	[公共衛生學系暨研究所] 碩博論文

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