Heme oxygenase-1

Heme oxygenase-1 和 NAD(P)H ： quinone oxidoreductase 1 基因多形性及砷甲基化代謝 能力與泌尿道上皮癌的相關性研究

The Relationship among Heme oxygenase-1 and NAD(P)H ： quinone oxidoreductase 1 Genetic Polymorphisms 、 Arsenic Methylation Capability and Urothelial Carcinoma

 本研究為探討砷甲基化代謝能力、抗氧化酵素 heme oxygenase-1(HO-1) 和香菸代謝相關 酵素 NAD(P)H:quinone oxidoreductase 1(NQO1) 基因型在泌尿道上皮癌可能扮演的角色

，並評估砷、抽菸和 HO-1 及 NQO1 基因型的交互作用。本研究自民國 91 年 9 月至 93 年 5 月間，於臺大醫院泌尿科門診所收泌尿道上皮癌病人 143 位。對照組為臺大醫院泌 尿科門診尿路結石、前列腺肥大病人，臺北醫學大學附設醫院老人健檢及臺北市立萬芳 醫院成人健檢民眾，排除泌尿道上皮癌者。經年齡性別配對之對照組共收案 143 位。以 標準化問卷訪視研究對象，收集人口學基本資料、抽菸與飲酒習慣、職業暴露及個人與 家族疾病史。取得研究對象同意書後收集其血液尿液檢體。萃取血液 DNA ，利用聚合 酵素連鎖反應 (Polymorphism chain reaction; PCR) 增幅所需片段。用短縱列重複序列 (Sh ort Tandem Repeat Polymorphism, STRP) 鑑定法，分析 HO-1 (GT)n 重複序列次數。利用 限制片段長度多形性 (Restriction fragment length polymorphism) 方法，測量 NQO1 C609 T 基因多形性。利用高效能液相層析儀串聯氫化式原子吸收光譜儀測定尿液三價砷、五 價砷、單甲基砷酸與雙甲基砷酸濃度。結果發現，抽菸與農藥為泌尿道上皮癌重要危險 因子，隨著抽菸年數及累積抽菸量的增加泌尿道上皮癌危險性亦隨之增加，顯示抽菸與 泌尿道上皮癌有劑量效應關係。疾病組單甲基砷酸百分比顯著高於對照組，雙甲基砷酸 百分比與二級甲基化指標顯著低於對照組，顯示疾病組砷甲基化代謝能力比對照組差。

HO-1 (GT)n 重複序列基因多形性及 NQO1 基因多形性與泌尿道上皮癌無關。在調整年 齡、性別與 HO-1 及 NQO1 基因型時，研究對象之砷甲基化代謝能力較差且抽菸及暴露 農藥，泌尿道上皮癌危險性是未暴露任何一個危險因子者之 6.24 倍 (95% 信賴區間 1.84

— 21.22) 。

Effect of Communication Media in Smoke-Free Restaurants Program 2003-2005

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The study to examine the potential role of arsenic methylation capability, antioxidant enzyme (heme oxyge

nase-1, HO-1) and cigarette smoking-related metabolic enzyme (NADPH:quinone oxidoreductase 1, NQO

1) in urothelial carcinoma (UC), and to evaluate the interaction of arsenic methylation capability 、 cigaret

te smoking 、 HO-1 and NQO1 genotypes. Urothelial carcinoma 143 cases were recruited from the Depart

ment of Urology in National Taiwan University Hospital from September 2002 to May 2004. Age-sex mat

ched 143 control subjects excluded urothelial carcinoma were collected from Department of Urology NTU

H, senile health examination from Taipei Medical University Hospital and adult health examination from T

aipei Municipal WanFang Hospital. Interviewers who were well trained on interview techniques and carrie

d out the standardized personal interviews based on structural questionnaire. Information obtained included

the demographic characteristics, cigarette smoking and alcohol drinking habits, occupational exposure hist

ory, personal and family disease history. The study subjects who gave their consent were recruited for bloo

d and urine samples. DNA was extracted from buffy coat, then performed by polymorphism chain reaction

(PCR) to amplify special fragments. Utilizing short tandem repeat polymorphism to analyze the number of

HO-1 (GT)n repeats. Restriction fragment length polymorphism (RFLP) was used to determine NQO1 609

C to T polymorphism. Urine sample of subjects were measured by high performance liquid chromatograph

y to separate arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMA) and dimethylarsinic acid

(DMA), and then quantified by hydride generator combined with atomic absorption spectrometry. Cigarett

e smoking and pesticides exposure are important risk factors for UC, and the risk was increased with cigare

tte smoking duration and cumulative cigarette smoking exposure, with dose-response relationship. UC case

s had a significantly higher percentage of MMA in urine than controls. The HO-1 (GT)n repeats polymorp

hism and NQO1 genotype are not associated with UC. After adjusted for age, sex, HO-1 genotype and NQ

O1 genotype, the study subjects with worse arsenic methylation capability, cigarette smoking and pesticide

exposure, the odds ratio of UC were 6.24 (95% confidence interval 1.84 - 21.22) compared with those did

not expose any risk factor.