[新聞][轉載]Ｂ肝病毒ＤＮＡ濃度高 肝癌風險大
http://www.libertytimes.com.tw/2008/new/aug/14/today-life1.htm
Ｂ肝病毒ＤＮＡ濃度高 肝癌風險大
前衛生署長、中研院基因體研究中心特聘研究員陳建仁率領研究團隊，長期進行Ｂ肝病毒
研究獲得重大突破，將成為全球Ｂ型肝炎臨床治療重要指引﹛]記者劉力仁攝）
陳建仁研究團隊成果 國際重視
〔記者劉力仁／台北報導〕前衛生署長、中研院基因體研究中心特聘研究員陳建仁率領研
究團隊，長期進行Ｂ肝病毒研究獲得重大突破，確認Ｂ肝病毒「基因型」及「突變型」基
因特質不同，誘發肝癌的風險也不相同，刊登在最新一期《美國國家癌症研究所期刊》，
預期將成為全球Ｂ型肝炎臨床治療重要指引。
陳建仁的研究團隊，從一九九一年起在台灣七個鄉鎮追蹤二千七百六十二名Ｂ肝病毒ＤＮ
Ａ陽性帶原者，累積了三萬三千八百四十七人年為分析背景，平均每人追蹤十二年，雖其
中一百五十三人發生肝癌，但累積了珍貴資料。
ｅ抗原呈陽性罹癌 是陰性六倍
分析資料後，研究團隊確認Ｂ肝病毒基因特質不同，誘發肝癌風險也不相同。陳建仁說，
研究已經證實「ｅ抗原呈陽性」者得到肝癌的機會，是「ｅ抗原呈陰性」者的六倍，Ｂ肝
病毒ＤＮＡ濃度越高，得到肝癌的風險也越大。
這次研究團隊進一步證實，如果帶原者感染的是Ｃ基因型Ｂ肝病毒，比起感染Ｂ基因型Ｂ
肝病毒，有兩倍得到肝癌的風險。
此外，帶原者體內的Ｂ肝病毒，如果在基礎核心促進子（basal core promoter, BCP）發
生突變，得到肝癌的可能性會增加兩倍；如果是在前核心區（precore region）產生突變
，反而會大幅降低得到肝癌的可能性到三分之一。顯示Ｂ肝病毒的基因型與突變型和肝癌
之間仍然呈現顯著相關。
有助醫生判斷 是否要用干擾素
陳建仁表示，全球四億、台灣三百萬人口是Ｂ肝慢性帶原者，全球每年有五十萬人死於肝
癌，他兩年前發表帶原者血液中的「Ｂ肝病毒量」，已經成為預測帶原者罹患肝癌的重要
指標，這項研究，未來對於臨床治療應會有幫助，可協助醫生判斷要不要用干擾素或超音
波治療，甚至未來健保都可能給付。
paper摘要(全文免費pdf連結如下)
http://jnci.oxfordjournals.org/cgi/content/full/djn243
Journal of the National Cancer Institute Advance Access published online on
August 11, 2008 JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn243
Associations Between Hepatitis B Virus Genotype and Mutants and the Risk of
Hepatocellular Carcinoma
Hwai-I Yang, Shiou-Hwei Yeh, Pei-Jer Chen, Uchenna H. Iloeje, Chin-Lan Jen,
Jun Su, Li-Yu Wang, Sheng-Nan Lu, San-Lin You, Ding-Shinn Chen, Yun-Fan Liaw,
Chien-Jen Chen, For the REVEAL-HBV Study Group
Affiliations of authors: Genomics Research Center, Academia Sinica and
Graduate Institute of Epidemiology, National Taiwan University, Taipei,
Taiwan (HIY, CLJ, SLY, CJC); Department of Microbiology, National Taiwan
University College of Medicine, Taipei, Taiwan (SHY); Division of
Gastroenterology, Department of Internal Medicine, National Taiwan University
Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
(PJC, DSC); Pharmaceutical Research Institute, Bristol-Myers Squibb Company,
Wallingford, CT (UHI, JS); Graduate Institute of Aboriginal Health, Tzu Chi
University, Hualien, Taiwan (LYW); Department of Gastroenterology, Kaohsiung
Chang-Gung Memorial Hospital, Kaohsiung, Taiwan (SNL); Chang-Gung Memorial
Hospital and Chang-Gung University, Taoyuan, Taiwan (YFL)
Correspondence to: Chien-Jen Chen, ScD, Genomics Research Center, Academia
Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan (e-mail:
cjchen@ntu.edu.tw).
ABSTRACT
Background: The risk of hepatocellular carcinoma (HCC) increases with
increasing level of hepatitis B virus (HBV) in serum (viral load). However,
it is unclear whether genetic characteristics of HBV, including HBV genotype
and specific genetic mutations, contribute to the risk of HCC. We examined
the HCC risk associated with HBV genotypes and common variants in the precore
and basal core promoter (BCP) regions.
Methods: From January 5, 1991, to December 21, 1992, baseline blood samples
were collected from 2762 Taiwanese men and women who were seropositive for
HBV surface antigen but had not been diagnosed with HCC; the samples were
tested for HBV viral load by real-time polymerase chain reaction and
genotyped by melting curve analysis. Participants who had a baseline serum
HBV DNA level greater than 104 copies/mL (n = 1526) were tested for the
precore G1896A and BCP A1762T/G1764A mutants by direct sequencing. Incident
cases of HCC were ascertained through follow-up examinations and computerized
linkage to the National Cancer Registry and death certification profiles. A
Cox proportional hazards model was used to estimate the risk of HCC
associated with HBV genotype and precore and BCP mutants after adjustment for
other risk factors. All statistical tests were two-sided.
Results: A total of 153 HCC cases occurred during 33 847 person-years of
follow-up. The HCC incidence rates per 100 000 person-years for participants
infected with HBV genotype B or C were 305.6 (95% confidence interval [CI] =
236.9 to 388.1) and 785.8 (95% CI = 626.8 to 972.9), respectively. Among
participants with a baseline HBV DNA level of at least 104 copies/mL, HCC
incidence per 100 000 person-years was higher for those with the precore
G1896 (wild-type) variant than for those with the G1896A variant (955.5 [95%
CI = 749.0 to 1201.4] vs 269.4 [95% CI = 172.6 to 400.9]) and for those with
the BCP A1762T/G1764A double mutant than for those with BCP A1762/G1764
(wild-type) variant (1149.2 [95% CI = 872.6 to 1485.6] vs 358.7 [95% CI =
255.1 to 490.4]). The multivariable-adjusted hazard ratio of developing HCC
was 1.76 (95% CI = 1.19 to 2.61) for genotype C vs genotype B, 0.34 (95% CI =
0.21 to 0.57) for precore G1896A vs wild type, and 1.73 (95% CI = 1.13 to
2.67) for BCP A1762T/G1764A vs wild type. Risk was highest among participants
infected with genotype C HBV and wild type for the precore 1896 variant and
mutant for the BCP 1762/1764 variant (adjusted hazard ratio = 2.99, 95% CI =
1.57 to 5.70, P < .001).
Conclusions: HBV genotype C and specific alleles of BCP and precore were
associated with risk of HCC. These associations were independent of serum HBV
DNA level.
同期EDITORIALS導讀文章(也是免費, 連結在此)
http://jnci.oxfordjournals.org/cgi/content/full/djn261
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