臺灣博碩士論文加值系統

中文摘要
目的：探討血漿睪固酮濃度、第二型類固醇5α還原酵素（steroid 5α-reductase type2, SRD5A2）基因多形性與男性HBsAg帶原者罹患肝細胞癌的關係，及雄性賀爾蒙受體（androgen receptor, AR） CAG重複序列基因多形性與女性肝細胞癌危險性的關係。
方法：110名肝細胞癌病例和110名對照個案選自公保長庚4841名男性HBsAg帶原者的世代研究，以凍存的週邊白血球及血漿檢體進行SRD5A2基因多形性及血漿睪固酮濃度測定。對103名來自醫院的女性肝細胞癌病例和183名選自病例無病的姻親和血親對照個案，以週邊白血球或口腔細胞進行AR CAG重複序列之分析。基因多形性均以聚合酵素鏈鎖反應為基礎的方式進行。
結果：控制其他危險因子後，相較於LL基因型，SRD5A2 VL基因型的危險對比值為2.0（95%信賴區間：1.0-4.0），VV基因型的危險對比值為3.5（95%信賴區間：1.4-8.6），與血漿睪固酮濃度低於4.44ng/ml者比較，血漿睪固酮濃度介於4.45-6.34和＞6.34ng/ml者，罹患肝細胞癌的危險對比值分別為1.4（95%信賴區間：0.6-3.3）和3.1（95%信賴區間：1.4-6.8）。血漿睪固酮濃度和SRD5A2基因型對肝細胞癌危險性具累加模式的協同作用，在調整年齡、氏族及抽菸喝酒習慣後，和具LL基因型且在睪固酮濃度低於4.48ng/ml比較，最高的危險對比值出現在血漿睪固酮濃度＞6.34ng/ml且具有VV基因型者，危險對比值增加至7.6倍（95%信賴區間：1.5-37.9）。血漿睪固酮濃度和SRD5A2 VV基因型的作用，在體質指標較低（≦22.9）、小於50歲、無抽菸習慣、無喝酒習慣及無肝膽疾病史的組別中較顯著。在女性肝細胞癌研究方面，調整其他因子後，個體兩條染色體CAG重複次數皆＞22者相較於≦22者危險性對比值為2.6（95%信賴區間：1.0-6.5）。AR重複次數和肝癌的關係，只有在HBsAg陽性者中才達到統計顯著意義。AR基因多形性和初經、停經年齡生產次數及流產經驗無顯著交互作用存在。
結論：本研究結果發現較高的血漿睪固酮濃度和帶有SRD5A2 V基因增高男性HBsAg帶原者罹患肝細胞癌的危險性；女性帶有較長的AR CAG重複序列基因 （＞22 CAG重複次數）可能增加肝細胞癌危險性。

Abstract
Objective：The specific aims of this study were:1) to assess the risk of hepatocellular carcinoma (HCC) associated with plasma testosterone level and the V89L polymorphism in steroid 5α-reductase type 2 (SRD5A2) gene among HBsAg-positive men in a nested case-control study;and 2) to investigate the association between a microsatellite( (CAG)n) within exon 1 of the androgen receptor(AR) gene and HCC in women by use of case-control study.
Methods：A total of 110 incident cases of HCC and 110 matched controls identified from a cohort of 4841 male HBsAg carriers were tested for plasma testosterone level and SRD5A2 V89L genetic polymorphism. AR-CAG-repeat length was determined for 103 women with HCC and 183 healthy women .Genotyping was performed using polymerase chain reaction based methods on peripheral white blood cells or buccal cells.
Results：Compared with male HBsAg carriers having LL genotype of the V89L polymorphism at SRD5A2, the multivariate-adjusted odds ratio (OR) of HCC for those who had VL and VV genotype was 2.0 (95% confident interval [CI]：1.0-4.0) and 3.5 (95% CI:1.4-8.6), respectively. The multivariate-adjusted ORs of HCC for male HBsAg carriers in increasing tertiles of plasma testosterone were 1.0, 1.4 (95%CI:0.6-3.3) and 3.1 (95%CI:1.4-6.8). Based on additive model, there was a synergistic interaction between the number of carrying the V allele of the V89L polymorphism and elevated testosterone levels in HCC risk. Compared with male HBsAg carriers in the lowest tertile of plasma testosterone who carried the LL genotype, the highest multivariate-adjusted OR was observed among those with both VV genotype and a testosterone level in the highest tertile (OR:7.6;95%CI:1.5-37.9).The association of HCC risk with plasma testosterone level and SRD5A2 was more striking among male HBsAg carriers who were relatively thin (body mass index≦22.9)、were younger(＜50 years)、had no smoking /drinking habit or had no history of hepatobiliary diseases .Long CAG-repeat sequence (＞22 repeats) in both AR alleles was significantly associated with increased risk of HCC in women (multivariate-adjusted OR: 2.6;95%CI: 1.0-6.5). Significantly increased risk associated with the AR genotype was observed only among female HBsAg carriers. There was no significant interaction of AR genotype with age at menarche/menopause、parity or a history of abortions in HCC risk.
Conclusion：These results suggested that male HBsAg carriers who had increased plasma testosterone levels or at least one V allele of the V89L polymorphism in SRD5A2 were at increased risk of HCC. Longer AR-CAG repeats may play a role in the development of HCC among women.

第一章 前言
第二章 文獻探討
第一節 描述流行病學特徵
第二節 危險因子研究
第三節 賀爾蒙與HCC
第四節 雄性賀爾蒙受體
第五節 類固醇5α還原酵素
第三章 材料與方法
第Ⅰ部份
第一節 研究設計
第二節 研究個案
第三節 實驗方法
第Ⅱ部份
第一節 研究設計
第二節 研究個案
第三節 實驗方法
第四節 資料處理及統計分析方法
第四章 結果
第Ⅰ部份
第Ⅱ部份
第五章 討論
文獻探討

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中華民國八十五年癌症登記報告
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