Combined pre-S deletion and core promoter mutations related to hepatocellular carcinoma: A nested case-control study in China

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http://onlinelibrary.wiley.com/doi/10.1111/j.1872-034X.2010.00732.x/abstract

Combined pre-S deletion and core promoter mutations related to hepatocellular

carcinoma: A nested case-control study in China

Li-Shuai Qu1,†, Tao-Tao Liu1,†, Fei Jin1, Yan-Mei Guo1, Tao-Yang Chen2,

Zheng-Pin Ni2, Xi-Zhong Shen1,*Article first published online: 25 OCT 2010

DOI: 10.1111/j.1872-034X.2010.00732.x

© 2010 The Japan Society of Hepatology

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Abstract

Aim:  To investigate the roles of biomedical factors, hepatitis B virus (HBV)

DNA levels, genotypes, and specific viral mutation patterns on the progression

of hepatocellular carcinoma (HCC) in Qidong, China.

Methods:  A total of 2387 males (aged 20–65 years) who were seropositive for

the hepatitis B surface antigen (HBsAg), but had not been diagnosed with HCC,

were recruited to a community-based HCC screening study from August, 1996.

Evaluation of virological parameters at recruitment was determined for 196 HCC

patients during 10 years of follow-up and 323 controls.

Results:  After adjustment for age at recruitment, history of cigarette

smoking and alcohol consumption, alanine aminotransferase (ALT) elevation,

alpha-fetoprotein (AFP) levels >20 ng/mL, hepatitis B e antigen positive, HBV

DNA levels ≥4.00 log10 copies/mL, pre-S deletion, T1653 mutation, T1762/A1764

double mutations, and T1766 and/or A1768 mutations were associated with

subsequent risk of HCC. A significant biological gradient of HCC risk by HBV DNA

levels from less than 2.69 log10 copies/mL to 6.00 log10 copies/mL or greater

was observed. HBV with a complex mutation combination pattern (pre-S deletion,

T1762/A1764 double mutations, and T1766 and/or A1768 mutations) rather than a

single mutation was associated with the development of HCC. The longitudinal

observation demonstrated a gradual combination of pre-S deletion, T1762/A1764

double mutations, and T1766 and/or A1768 mutations during the development of

HCC.

Conclusions:  AFP levels >20 ng/mL, high HBV DNA levels, pre-S deletion, and

T1762/A1764 double mutations at recruitment were independent risk factors of

HCC. Combination of pre-S deletion and core promoter mutations increased the

risk of HCC.