白血球端粒長度與慢性B型肝炎病毒血症和肝細胞癌風險之前瞻性研究

Prospective Study of Leukocyte Telomere Length with Hepatitis B Viremia Levels and Hepatocellular Carcinoma Risk

溫巧尼(Chiao-Ni Wen)

指導教授 ： 于明暉

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/碩士(2011年)

https://doi.org/10.6342/NTU.2011.01784

摘要

背景：端粒長度過短與慢性病毒感染有關，亦會增加各種癌症的風險，而本研究的目的：欲探討在控制病毒量後白血球端粒長度與肝細胞癌之間的相關性。
材料方法：本研究之研究對象為1121名B型肝炎帶原者，其中119名為肝細胞癌於追蹤期間的新發病例。研究對象均從研究世代中隨機抽取。此研究世代為1989年至1992年間在公保中心接受健檢的B型肝炎男性帶原者，年齡於三十歲以上，共計2903人加入，追蹤至2006年。白血球端粒長度是以SYBR-Green Q-PCR方法進行測量。分析方法則以非條件式羅吉斯迴歸控制相關干擾因子後，評估白血球端粒長度與病毒因子和肝細胞癌之間的相關性。
結果：控制年齡、吸菸與喝酒習慣後，均和白血球端粒長度第三三分位組相比，端粒長度第一三分位組與第二三分位和肝細胞癌之OR分別為1.84 (95% 信賴區間=1.14-2.98) 和0.93 (95%信賴區間=0.54-1.58)。HBV基因型為白血球端粒長度與肝細胞癌之間的修飾因子，在調整干擾因子後，以HBV基因型分層，HBV基因型非C型與HBV基因型C型分別來看，均和白血球端粒長度第三三分位組相比，端粒長度第一三分位組其肝細胞癌之OR分別為4.58 (95% 信賴區間=2.14-9.79) 和0.68 (95%信賴區間=0.30-1.57)。然而，本研究沒有發現白血球端粒長度與HBV長期病毒量之間的相關性。
結論：在慢性B型肝炎帶原者中，白血球端粒長度過短為肝細胞癌的危險因子。

關鍵字

白血球端粒長度 ； B型肝炎病毒 ； B型肝炎病毒血症 ； 肝細胞癌 ； 世代研究

並列摘要

Background & Aims: Shorten leukocyte telomere length has been associated with chronic viral infection other than hepatitis B virus (HBV) as well as increased risks for cancers at various anatomic sites. The purposes of this study are to evaluate the role of leukocyte telomere length in control of hepatitis B viral load, and in subsequent development of hepatocellular carcinoma (HCC).
Materials and Methods: Study subjects included a total of 1121 male HBV carriers (of whom 119 HCC cases were ascertained during follow-up) ages≥30 years sampled from a cohort (1989-1992) of 2903 male government employees chronically infected with HBV who have been followed until 2006. Relative telomere length in leukocytes was assessed using a quantitative SYBR-Green real time polymerase chain reaction method. Unconditional logistic regression was used to determine the association between relative leukocyte telomere length and viral factors and HCC after adjustment for potential confounders.
Results: After adjustment for age at recruitment,cigarette smoking, and alcohol consumption, the odds ratios (ORs) of HCC in decreasing tertiles of relative telomere length were 1.00, 0.93 (95% confidence interval [CI]=0.54-1.58), and 1.84 (95% CI= 1.14-2.98), respectively. This association was significantly modified by HBV genotype (P for interaction<0.0001), with the adjusted OR of HCC being larger in carriers of HBV non-C genotype (shortest vs. longest tertile: OR=4.58, 95% CI=2.14-9.79) than in carriers of HBV genotype C (shortest vs. longest tertile: OR=0.68, 95% CI=0.30-1.57). However, there was no convincing evidence of any association between relative
leukocyte telomere length and control of HBV viral load.
Conclusions: Among male HBV carriers, shorter leukocyte telomere length is an independent risk factor for the development of HCC.

並列關鍵字

leukocyte telomere length ； hepatitis B virus ； HBV viremia ； hepatocellular carcinoma ； cohort

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