中文摘要：

目的探讨广西肝癌高发区乙型肝炎病毒（HBV）基因组基本核心启动子（BCP）区A1762T/G1764A双突变对肝癌家族聚集的影响。方法收集2007年7月—2012年7月广西肝癌高发区39个肝癌高发家族中103例成员作为试验组,在相同地区59个无癌家族中选择与试验组年龄、性别、生活环境匹配的103例成员作为对照组,将试验组按家族患肝癌例数分为2~3例亚组（45例）和≥4例亚组（58例）;按亲属分级分为一级亲属组（48例）,二级亲属组（32例）,三级及以上亲属组（23例）。提取所有研究对象HBV DNA,PCR扩增并测序检测BCP区A1762T/G1764A双突变情况。结果试验组A1762T/G1764A双突变率高于对照组〔χ^2=12.518,P〈0.001;OR=2.788,95%CI（1.569,4.955）〕。试验组男性A1762T/G1764A双突变率高于对照组〔χ^2=11.377,P=0.001;OR=3.450,95%CI（1.659,7.176）〕;两组女性A1762T/G1764A双突变率比较,差异无统计学意义〔χ^2=1.983,P=0.159;OR=1.950,95%CI（0.766,4.965）〕。试验组≥30岁年龄段A1762T/G1764A双突变率高于对照组〔χ^2=10.743,P=0.001;OR=3.444,95%CI（1.622,7.314）〕;两组〈30岁年龄段A1762T/G1764A双突变率比较,差异无统计学意义〔χ^2=2.489,P=0.115;OR=2.053,95%CI（0.836,5.041）〕。试验组患肝癌2-3例亚组与≥4例亚组A1762T/G1764A双突变率比较,差异有统计学意义〔（χ^2=6.639,P=0.01;OR=3.122,95%CI（1.290,7.555）〕。3组A1762T/G1764A双突变率比较,差异有统计学意义（P〈0.05）。一级亲属亚组双突变率高于二级亲属亚组（P〈0.05）。试验组HBe Ag阴性者突变率高于HBe Ag阳性者（χ^2=6.361,P=0.012）。试验组A1762T/G1764A双突变者HBV DNA水平低于无双突变者（Z=-3.957,P〈0.01）。结论广西肝癌高发区HBV BCP区A1762T/G1764A双突变与肝癌家族聚集密切相关,A1762T/G1764A双突变可能对肝癌的发生具有重要的预测价值。

英文摘要：

Objective To investigate the effect of double mutation of basal core promoter（ BCP） A1762T/G1764 A of hepatitis B virus（ HBV） genome on familial aggregation of primary liver cancer（ PLC） in area of Guangxi with high PLC incidence. Methods 103 cases from 39 families with high PLC incidence in area of Guangxi with high PLC incidence were selected as experiment group from July 2007 to July 2012,and another 103 cases with matched age,sex and living environment from families without PLC history in the same area were selected as control group. Based on the number of PLC cases in the family,the experiment group was further divided into 2- 3 cases subgroup（ n = 45） and ≥4 cases subgroup（ n = 58）; based on the classification of relatives,the experiment group was divided into first- level relatives group（ n = 48）,second- level relatives group（ n = 32） and third- level and ≥ relatives group（ n = 23）. The HBV DNA of all the subjects was extracted,and polymerase chain reaction（ PCR） was used to amplify and sequence as well as to detect the double mutation of BCP A1762 T /G1764 A. Results The experiment group had a significantly higher double mutation rate of A1762 T / G1764 A 〔χ2= 12. 518,P 0. 001; OR = 2. 788,95% CI（ 1. 569, 4. 955） 〕. Compared with the males in the control group, the males in the experiment group had a significantly higher double mutation rate of A1762 T / G1764 A 〔χ2= 11. 377,P = 0. 001; OR = 3. 450,95% CI（ 1. 659,7. 176） 〕, while the double mutation rate of females in the two groups showed no statistically significant differences〔χ2= 1. 983,P = 0. 159; OR = 1. 950,95% CI（ 0. 766,4. 965） 〕. Compared with the control group,the cases≥30 years old had a significantly higher double mutation rate of A1762T/G1764 A 〔χ2= 10. 743,P = 0. 001; OR = 3. 444,95% CI（ 1. 622,7. 314） 〕,while the double mutation rate of the cases 30 years old in the two groups showed no statistically significant differences〔χ2= 2. 489,P = 0. 115; OR = 2. 053,9