title: TP53 R249S mutation, genetic variations in HBX and risk of hepatocellular carcinoma in The Gambia.
abstract: In regions with high prevalence of chronic hepatitis B virus (HBV) infection and dietary aflatoxin B(1) (AFB(1)) exposure, hepatocellular carcinomas (HCCs) often contain TP53 mutation at codon 249 (R249S). Furthermore, a C-terminal truncated HBx protein expressed from hepatocyte integrated HBV is associated with HCC development. This study evaluates the association between R249S and HBX status in relation to HCC in West African population. HBX (complete or 3'-truncated) and HBS genes were assessed by PCR in cell-free DNA (CFDNA) from plasma of subjects recruited in a hospital-based case-control study (325 controls, 78 cirrhotic patients and 198 HCC cases) conducted in The Gambia. These samples had been previously analyzed for R249S and HBV serological status. Complete HBX sequence was frequently detected in CFDNA of HCC-R249S positive (77%, 43/56) compared with HCC-R249S-negative cases (44%, 22/50). Conversely, the proportion of 3'-truncated HBX gene was significantly higher in HCC-R249S negative than positive cases (34%, 17/50, compared with 12%, 7/56) (χ(2) = 12.12; P = 0.002; distribution of R249S negative and positive according to HBX status). Occult HBV infection (detected by PCR) was present in 24% of HCC previously considered as negative by HBV serology. Moreover, HBV mutation analysis revealed that double mutation at nucleotides 1762(T)/1764(A) was associated with diagnosis of cirrhosis or HCC {cirrhosis: odds ratio (OR): 9.50 [95% confidence interval (CI) 1.50-60.11]; HCC: OR: 11.29 [95% CI 2.07-61.47]}. These findings suggest that in HCC from The Gambia, complete HBX sequences are often associated with the presence of TP53 R249S mutation.
authors: International Agency for Research on Cancer, Molecular Carcinogenesis Group, Lyon, France.
authors: Doriane A
authors: DA
authors: Gouas
authors: Stphanie
authors: S
authors: Villar
authors: Sandra
authors: S
authors: Ortiz-Cuaran
authors: Pénélope
authors: P
authors: Legros
authors: Gilles
authors: G
authors: Ferro
authors: Gregory D
authors: GD
authors: Kirk
authors: Olufunmilayo A
authors: OA
authors: Lesi
authors: Maimuna
authors: M
authors: Mendy
authors: Ebrima
authors: E
authors: Bah
authors: Marlin D
authors: MD
authors: Friesen
authors: John
authors: J
authors: Groopman
authors: Isabelle
authors: I
authors: Chemin
authors: Pierre
authors: P
authors: Hainaut
mesh_terms: D000328:Adult; D016604:Aflatoxin B1 / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics* / Q000821:virology*; D016022:Case-Control Studies; D005260:Female; D005714:Gambia / Q000453:epidemiology; D016158:Genes, p53; D014644:Genetic Variation; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000821:virology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D015534:Trans-Activators / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D006514:Hepatitis B Surface Antigens; C495901:TP53 protein, human; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D016604:Aflatoxin B1