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. Issue 12 (9th July 2013)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: International journal of cancer. Volume 133:Issue 12(2013:Dec. 15)
• Page Start: 2864
• Page End: 2871
• Publication Date: 2013-07-09
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28307
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>versus</italic> equal number of controls. Age and male gender were significantly associated with HCC (<italic>p</italic> = 0.0001 and <italic>p</italic> = 0.03, respectively). Serological markers such as aspartate aminotransferase, albumin and anti‐HBe were significantly associated with HCC (<italic>p</italic> = 0.0001 for all), whereas HBeAg positivity was associated with non‐HCC (<italic>p</italic> = 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; <italic>p</italic> = 0.002], A1757/T1764/G1766 (OR = 4.7; 95% CI = 1.3–17.2; <italic>p</italic> = 0.01) and T1773 (OR = 14.06; 95% CI = 2.3–84.8; <italic>p</italic> = 0.004) are independent predictors of HCC development. These results implicate novel individual and combination patterns of mutations in the <italic>X</italic>/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.</p> </abstract>