Significant association of different preS mutations with hepatitis B-related cirrhosis or hepatocellular carcinoma.
BACKGROUND
The associations of nucleotide substitution mutations in the preS region of hepatitis B virus (HBV) with hepatocellular carcinoma (HCC) and cirrhosis remain unknown. We aimed to determine the associations of preS mutations with HCC or cirrhosis.


METHODS
HBV from 603 asymptomatic hepatitis B surface antigen carriers (ASCs), 219 chronic hepatitis B (CHB) patients, 119 cirrhosis patients, and 231 HCC patients were genotyped and sequenced in the preS region. Nucleotides with the highest frequencies in HBV from the hepatitis B e antigen (HBeAg)-positive ASCs were treated as "wild-type" nucleotides. Twenty-one preS1 mutations and 14 preS2 mutations were evaluated. Multivariate regression analyses were applied to determine factors independently associated with cirrhosis or HCC.


RESULTS
Most (85.7%) preS2 mutations were associated with CHB compared with ASCs, whereas most preS1 mutations were associated with HCC compared with the cirrhosis patients or CHB patients. Compared with the CHB patients, 81.0% preS1 mutations in genotype C were inversely associated with cirrhosis. Multivariate regression analyses showed that C2964A, C3116T, and C7A were novel factors associated with HCC compared with those without HCC, whereas A2964C and T3116C were independently associated with cirrhosis compared with ASCs and the CHB patients. Combined preS1 mutations had specificities greater than 95%, while C3116T and C7A had moderate sensitivities and specificities, for HCC.


CONCLUSIONS
C2964A, C3116T, and C7A are novel markers independently associated with an increased risk of HCC, while A2964C and T3116C are novel markers independently associated with an increased risk of cirrhosis. Combined preS1 mutations are specific for HCC.
Yin
Jianhua
J
Department of Epidemiology, Second Military Medical University, 800 Xiang-yin Rd., Shanghai, China.
Xie
Jiaxin
J
Zhang
Hongwei
H
Shen
Qiuxia
Q
Han
Lei
L
Lu
Wenying
W
Han
Yifang
Y
Li
Chengzhong
C
Ni
Wu
W
Wang
Hongyang
H
Cao
Guangwen
G
D000293:Adolescent; D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000235:genetics; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology*; D008113:Liver Neoplasms / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011498:Protein Precursors / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors; D012680:Sensitivity and Specificity; D055815:Young Adult
D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; C050806:presurface protein 1, hepatitis B surface antigen; C050807:presurface protein 2, hepatitis B surface antigen