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  • 學位論文

台灣男性肺腺癌與睪固酮相關基因多形性之基因體流行病學研究

Genetic Epidemiological Study on Association between Polymorphisms in Testosterone-Related Genes and Risk of Male Lung Adenocarcinoma in Taiwan

指導教授 : 陳建仁 楊泮池 簡國龍

摘要


背景:肺癌是台灣癌症的首要死因,本研究探討睪固酮生成和代謝相關基因的基因多形性與台灣男性肺腺癌危險性的相關,包括:CYP17、SRD5A2 和 AR-CAG 重複序列數目的多形性。 方法:本研究是一病例對照研究,自2002年9月至2004年3月,以頻率配對方式選取來自台灣6個醫學中心的男性肺腺癌病例共357名與各醫院健檢中心的健康對照357名。受試者接受問卷訪視和提供血液樣本,以毛細管電泳和TaqMan 即時聚合酵素連鎖反應為基礎的方式分析AR-CAG 重複序列數目和CYP17及SRD5A2 基因的多形性。各基因多形性的危險對比值和95%信賴區間以非條件式羅吉斯迴歸模式進行分析。 結果:調整年齡、教育年數、香菸暴露(吸菸和二手菸暴露)、父親肺癌病史和曾經得過結核病等因子後,CPY17 A1/A1基因型相對於A2/A2和A2/A1基因型有1.46倍的危險性 (95%信賴區間=0.85-2.47);SRD5A2 Val/Val基因型相對於Val/Leu和Leu/Leu基因型有1.79倍的危險性 (95%信賴區間=1.03-3.10 );至於AR-CAG 重複序列數目的多形性和肺腺癌,則無相關。 結論:本研究發現睪固酮生成和代謝相關基因CPY17 A1/A1和SRD5A2 Val/Val多形性和男性肺腺癌的發生有關。

並列摘要


Background: Lung cancer is the leading cause of cancer death in Taiwan. This study aimed to investigate the association of male lung adenocarcinoma and polymorphism of testosterone biosynthetic and metabolic pathway-related genes, including CYP17 and SRD5A2, and the number of CAG repeat length in the androgen receptor (AG) gene. Methods: A total of 357 male patients with lung adenocarcinoma and 357 healthy hospital controls selected by frequency matching were recruited at 6 medical centers in Taiwan from September 2002 to August 2004. These subjects had been interviewed by questionnaires and provided blood samples for analysis. The number of CAG repeat length in the AR gene and genetic polymorphisms of cytochrome17α (CYP17) and 5α-reductase type II (SRD5A2) were determined by capillary electrophoresis and TaqMan assays. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype. Results: After having adjusted for age, schooling year, cigarette smoking exposure, father with lung cancer, and tuberculosis, the ORs of developing lung adenocarcinoma were 1.46 (95% CI=0.85-2.47) for CYP17 A1/A1 genotype compared with A2/A2 and A2/A1 genotype and 1.79 (95% CI=1.03-3.10) for SRD5A2 Val/Val compared with Val/Leu and Leu/Leu genotypes. For AR-CAG repeats length, there was no any association with lung adenocarcinoma. Conclusion: Our result suggest that testosterone-related gene polymorphisms including CYP17 A1/A1 and SRD5A2 Val/Val might contribute to male lung adenocarcinoma in Taiwan.

參考文獻


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