B型肝炎病毒基因型與DNA濃度的家族相關分析

Abstract

背景：HBV基因型和DNA濃度與肝細胞癌 (Hepatocellulcar carcinoma; HCC)有關。本研究目的在探討HBV基因型及DNA濃度的家族聚集情形；以及這兩種病毒因子的對HCC家族聚集程度的影響。材料方法：研究對象包括280個HCC病例家族，含766位家族成員，210家為散發病例家族(家中僅有一名HCC病例)，70家為多發病例家族。以real-time PCR同時進行HBV基因型和DNA濃度測定。統計分析：以多變項線性迴歸模式分析各因子和HBV DNA濃度間的關係；利用unconditional logistic regression估計手足間HBV DNA濃度的concordant odds ratio及其95%信賴區間，利用SAGE 5.0版FCOR程式和uniform weighting scheme分析家族成員間HBV DNA濃度的相關係數。結果：88.2 %的研究家族 (247/280) 其家族成員感染的HBV基因型均相同。HBV基因型分析結果顯示，無論在多發或散發病例家族，HCC病例之基因型C的比例均高於未罹病親屬，特別是在多發病例家族具有顯著差異(p=0.050)。相較於散發病例家族親屬，多發病例家族罹病和未罹病親屬之基因型C的比例均顯著較高。性別 (p=0.048)、HBV基因型 (p=0.003) 及HCC罹病狀態 (p=0.020) 和HBV DNA濃度相關。在控制這些影響HBV DNA濃度的因子後，親子間 (r=0.23, p=0.008) 的相關高於手足的相關 (r=0.14, p=0.020)，且以母子間的相關係數最高 (r=0.37, p=0.001)，一等親的相關係數在多發或散發病例家族相似。每家隨機選取一對手足進行HBV DNA濃度的一致性分析。以所有研究個案HBV DNA濃度的最高四分位為分組依據(≧6.46 log10 copies/ml)，則所有手足的concordant OR為2.12 (95% CI=1.12-4.05)，未罹病手足為2.90 (95% CI=1.21-6.93)。結論：HBV基因型具有高度家族聚集，基因型C和HCC家族聚集的程度有關，親子和手足間HBV DNA濃度具顯著相關。

Background Hepatitis B virus (HBV) genotype and DNA levels have been associated with hepatocellular carcinoma (HCC) risk. The aims of this study were to investigate familial correlations for the two viral factors, and to assess whether these factors may influence the degree of familial aggregation of HCC. Materials and Methods A total of 766 HBV surface antigen-positive individuals were included. These individuals were from 280 families ascertained through a HCC proband, including 210 simplex and 70 multiplex families (defined as having an additional patient with HCC among first-degree relatives of the proband). We used real-time polymerase chain reaction assays of plasma DNA samples to quantify HBV DNA levels and determine HBV genotype for all subjects. Multiple linear regression was used to assess correlations between various factors and HBV DNA levels. Unconditional logistic regression was used to estimate sibling concordant odds ratios and their 95% confidence intervals (CIs) for HBV DNA levels. Familial correlation was calculated with use of the uniform weighting scheme as implemented in the FCOR program of SAGE version 5.0. Results For 247 (88.2%) of the 280 families, all family members were infected with the same HBV genotype. The prevalence of genotype C HBV was higher in affected than in unaffected individuals; this difference was statistically significant in multiplex families (P=0.05). Multiplex families had a higher prevalence of genotype C than simplex families. Gender (P=0.048), HBV genotype (P=0.003), and HCC status (P=0.020) were significantly associated with HBV DNA levels. After adjusting for gender, HBV genotype, and HCC status, HBV DNA levels showed higher parent-offspring (r=0.23, P=0.008) and lower sibling correlations (r=0.14, P=0.020). Particularly, the mother-son correlation coefficient reached 0.37 (P=0.001). When 6.46 log copies/mL was used as the cutoff point to classify the data, we obtained a sibling concordant odds ratio of 2.12 (95% CI=1.12-6.93) for all sib pairs (including affected-unaffected discordant pairs), and 2.90 (95% CI=1.21-6.93) for unaffected sib pairs. Conclusions We found strong familial correlation for HBV genotype. There were significant parent-offspring and sibling correlations for HBV DNA levels. Genotype C was associated with the degree of familial aggregation of HCC.