Combined Mutations in Pre-S/Surface and Core Promoter/Precore Regions of Hepatitis B Virus Increase the Risk of Hepatocellular Carcinoma: A Case-Control Study

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http://www.journals.uchicago.edu/doi/abs/10.1086/592990

http://www.mdlinx.com/IDLinx/newsl-article.cfm/2476124/ZZ680655367925639220014/?\

news_id=497 & subspec_id=130

The Journal of Infectious Diseases 2008;198:1634–1642

0022-1899/2008/19811-0009$15.00

DOI: 10.1086/592990

MAJOR ARTICLE

Combined Mutations in Pre-S/Surface and Core Promoter/Precore Regions of

Hepatitis B Virus Increase the Risk of Hepatocellular Carcinoma: A Case-Control

Study

Chien-Hung Chen,1,2

Chi-Sin Changchien,1

Chuan-Mo Lee,1

Chao-Hung Hung,1

Tsung-Hui Hu,1

Jing-Houng Wang,1

Jyh-Chwan Wang,1 and

Sheng-Nan Lu1

1Division of Hepatogastroenterology, Department of Internal Medicine, and

2Graduate Institute of Clinical Medical Sciences, Chang Gung Memorial

Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine,

Kaohsiung, Taiwan

Background. We sought to investigate the role of sequence variations in

pre-S/surface and basal core promoter (BCP)/precore regions of the hepatitis B

virus (HBV) in hepatocellular carcinoma (HCC).

Chen CH et al. – Pre-S deletions, I68T in surface gene, T1762/A1764, and A1899

were independent risk factors for hepatocellular carcinoma (HCC); the

combination of these viral mutations appeared to increase HCC risk.

Methods

Study of the role of sequence variations in pre-S/surface and basal core

promoter (BCP)/precore regions of the hepatitis B virus (HBV) in HCC

Direct sequencing in pre-S/surface and BCP/precore regions of HBV for 80 HCC pts

and 160 controls with HBV infection

Results

Compared with controls, HCC pts had higher frequencies of pre-S deletions and

amino acid substitutions at codon 4, 7, and 81 in pre-S1 genes; at the start

codon in pre-S2 genes; and at codon 68 in surface genes

These pts also had a lower frequency of amino acid substitution at codon 2 in

pre-S2 genes, compared with controls

In BCP/precore regions, HCC pts had higher frequencies of C or G1753,

A1762/T1764, T1846, and A1899

On multivariate analysis that pre-S deletions, I68T surface gene, T1762/A1764,

and A1899 were independent factors associated with development of HCC

HCC risks increased for pts with these factors in combination

HBV strain with complex rather than single mutation was associated with HCC

Conclusions. Pre-S deletions, I68T in surface gene, T1762/A1764, and A1899 were

independent risk factors for HCC. Combination of these viral mutations appeared

to increase the risk of HCC.

Received 25 November 2007; accepted 12 June 2008; electronically published 21

October 2008.

Reprints or correspondence: Dr. Chuan-Mo Lee, Div. of Hepatogastroenterology,

Dept. of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei

Rd., Kaohsiung, Taiwan (chmolee@...).

Potential conflicts of interest: none reported.

Financial support: Chang Gung Memorial Hospital and National Council of Science,

Taiwan (grants NMRPG T60011 [NSC 96–2314-B-182A-086] and NMRPD 150081 [NSC

95–2314-B-182–017]).

[Guest guest]

http://www.journals.uchicago.edu/doi/abs/10.1086/592990

http://www.mdlinx.com/IDLinx/newsl-article.cfm/2476124/ZZ680655367925639220014/?\

news_id=497 & subspec_id=130

The Journal of Infectious Diseases 2008;198:1634–1642

0022-1899/2008/19811-0009$15.00

DOI: 10.1086/592990

MAJOR ARTICLE

Combined Mutations in Pre-S/Surface and Core Promoter/Precore Regions of

Hepatitis B Virus Increase the Risk of Hepatocellular Carcinoma: A Case-Control

Study

Chien-Hung Chen,1,2

Chi-Sin Changchien,1

Chuan-Mo Lee,1

Chao-Hung Hung,1

Tsung-Hui Hu,1

Jing-Houng Wang,1

Jyh-Chwan Wang,1 and

Sheng-Nan Lu1

1Division of Hepatogastroenterology, Department of Internal Medicine, and

2Graduate Institute of Clinical Medical Sciences, Chang Gung Memorial

Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine,

Kaohsiung, Taiwan

Background. We sought to investigate the role of sequence variations in

pre-S/surface and basal core promoter (BCP)/precore regions of the hepatitis B

virus (HBV) in hepatocellular carcinoma (HCC).

Chen CH et al. – Pre-S deletions, I68T in surface gene, T1762/A1764, and A1899

were independent risk factors for hepatocellular carcinoma (HCC); the

combination of these viral mutations appeared to increase HCC risk.

Methods

Study of the role of sequence variations in pre-S/surface and basal core

promoter (BCP)/precore regions of the hepatitis B virus (HBV) in HCC

Direct sequencing in pre-S/surface and BCP/precore regions of HBV for 80 HCC pts

and 160 controls with HBV infection

Results

Compared with controls, HCC pts had higher frequencies of pre-S deletions and

amino acid substitutions at codon 4, 7, and 81 in pre-S1 genes; at the start

codon in pre-S2 genes; and at codon 68 in surface genes

These pts also had a lower frequency of amino acid substitution at codon 2 in

pre-S2 genes, compared with controls

In BCP/precore regions, HCC pts had higher frequencies of C or G1753,

A1762/T1764, T1846, and A1899

On multivariate analysis that pre-S deletions, I68T surface gene, T1762/A1764,

and A1899 were independent factors associated with development of HCC

HCC risks increased for pts with these factors in combination

HBV strain with complex rather than single mutation was associated with HCC

Conclusions. Pre-S deletions, I68T in surface gene, T1762/A1764, and A1899 were

independent risk factors for HCC. Combination of these viral mutations appeared

to increase the risk of HCC.

Received 25 November 2007; accepted 12 June 2008; electronically published 21

October 2008.

Reprints or correspondence: Dr. Chuan-Mo Lee, Div. of Hepatogastroenterology,

Dept. of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei

Rd., Kaohsiung, Taiwan (chmolee@...).

Potential conflicts of interest: none reported.

Financial support: Chang Gung Memorial Hospital and National Council of Science,

Taiwan (grants NMRPG T60011 [NSC 96–2314-B-182A-086] and NMRPD 150081 [NSC

95–2314-B-182–017]).