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Novel point mutations and mutational complexes in the enhancer II, core promoter and precore regions of hepatitis B virus genotype D1 associated with hepatocellular carcinoma in Saudi Arabia
Author(s) -
Khan Anis,
Al Balwi Mohammed A.,
Tanaka Yasuhito,
Hajeer Ali,
Sanai Faisal M.,
Al Abdulkarim Ibrahim,
Al Ayyar Latifah,
Badri Motasim,
Saudi Dib,
Tamimi Waleed,
Mizokami Masashi,
Al Knawy Bandar
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28307
Subject(s) - hepatocellular carcinoma , hepatitis b virus , genotype , medicine , odds ratio , hbeag , gastroenterology , virology , hepatitis b , virus , biology , gene , genetics , hbsag
In this study, a cohort of 182 patients [55 hepatocellular carcinoma (HCC) and 127 non‐HCC] infected with hepatitis B virus (HBV) in Saudi Arabia was investigated to study the relationship between sequence variation in the enhancer II (EnhII), basal core promoter (BCP) and precore regions of HBV genotype D (HBV/D) and the risk of HCC. HBV genotypes were determined by sequencing analysis and/or enzyme‐linked immunosorbent assay. Variations in the EnhII, BCP and precore regions were compared between 107 non‐HCC and 45 HCC patients infected with HBV/D, followed by age‐matched analysis of 40 cases versus equal number of controls. Age and male gender were significantly associated with HCC ( p = 0.0001 and p = 0.03, respectively). Serological markers such as aspartate aminotransferase, albumin and anti‐HBe were significantly associated with HCC ( p = 0.0001 for all), whereas HBeAg positivity was associated with non‐HCC ( p = 0.0001). The most prevalent HBV genotype was HBV/D (94%), followed by HBV/E (4%), HBV/A (1.6%) and HBV/C (0.5%). For HBV/D1, genomic mutations associated with HCC were T1673/G1679, G1727, C1741, C1761, A1757/T1764/G1766, T1773, T1773/G1775 and C1909. Age‐ and gender‐adjusted stepwise logistic regression analysis indicated that mutations G1727 [odds ratio (OR) = 18.3; 95% confidence interval (CI) = 2.8–118.4; p = 0.002], A1757/T1764/G1766 (OR = 4.7; 95% CI = 1.3–17.2; p = 0.01) and T1773 (OR = 14.06; 95% CI = 2.3–84.8; p = 0.004) are independent predictors of HCC development. These results implicate novel individual and combination patterns of mutations in the X /precore region of HBV/D1 as predictors of HCC. Risk stratification based on these mutation complexes would be useful in determining high‐risk patients and improving diagnostic and treatment strategies for HBV/D1.