Enrichment in selected genotypes, basal core and precore mutations of hepatitis B virus in patients with hepatocellular carcinoma in Cameroon

被引:10
作者
Amougou, Marie Atsama [1 ,2 ]
Marchio, Agnes [3 ]
Bivigou-Mboumba, Berthold [4 ]
Noah, Dominique Noah [5 ]
Banai, Robert [1 ]
Atangana, Paul Jean Adrien [1 ]
Moundipa, Paul Fewou [2 ]
Pineau, Pascal [3 ]
Njouom, Richard [1 ]
机构
[1] Ctr Pasteur Cameroon, Yaounde, Cameroon
[2] Univ Yaounde I, Lab Pharmacol & Toxicol, Yaounde, Cameroon
[3] Inst Pasteur, INSERM U993, Unite Org Nucl & Oncogenese, Paris, France
[4] CIRMF, UMR VIH MIA, Libreville, Gabon
[5] Cent Hosp Yaounde, Yaounde, Cameroon
关键词
basal core promoter; Cameroon; hepatocellular carcinoma; mutation spectra; prescore; quasi-subgenotype A3; RISK-FACTORS; VIRAL LOAD; EARLY AGE; EPIDEMIOLOGY; DIAGNOSIS; SUBGENOTYPE; INFECTION; AFRICA; GENE; HBV;
D O I
10.1111/jvh.13131
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Worldwide, the development of hepatocellular carcinoma (HCC) is known to be influenced by several hepatitis B viral factors. However, the effect of hepatitis B virus (HBV) genotypes and a landscape of nucleotide changes affecting the precore (PC) and basal core promoter (BCP) during infection leading to HCC remain largely unknown in the Central Africa region. Thus, we performed a case-control study on patients with HBV-related HCC and matched controls without HCC but with chronic HBV infection. Genotypes and mutation spectrums were evaluated using a hemi-nested amplification and sequencing analysis focused on the BCP and PC regions. We identified the co-circulation of HBV quasi-subgenotype A3 (QS-A3) and genotype E in both groups. Interestingly, HBV-QS-A3 was significantly more prevalent in patients with HCC (80.0%) than in controls (31.9%, P = 4.5 E-7, OR = 11.5, 95% CI: 3.8-38.5). HBV mutation spectra and nucleotide changes were significantly more polymorphic in patients with HCC. Remarkably, HCC patients infected with HBV-QS-A3 were significantly more mutated compared to patients infected with genotype E (P < 0.0001). In addition, G:C>T:A transversions, generally associated with aflatoxin B1 exposure in tropical regions, were significantly more prevalent in HCC patients infected either with HBV-QS-A3 or HBV genotype E (P = 2.2 E-05) when compared to controls. In conclusion, our results indicate that patients infected with HBV-QS-A3 are at increased risk to develop HCC. In addition, viral genomes isolated for patients with tumour are more heavily altered than those found in controls. Preferential targeting of these patients for antiviral treatment is of paramount importance to reduce future HCC incidence in Cameroon.
引用
收藏
页码:1086 / 1093
页数:8
相关论文
共 33 条
  • [1] A prominent role of Hepatitis D Virus in liver cancers documented in Central Africa
    Amougou, Marie Atsama
    Noah, Dominique Noah
    Moundipa, Paul Fewou
    Pineau, Pascal
    Njouom, Richard
    [J]. BMC INFECTIOUS DISEASES, 2016, 16
  • [2] Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: Possibilities for prevention
    Anwar, Wagida A.
    Khaled, Hussein M.
    Amra, Hassan A.
    El-Nezami, Hani
    Loffredoe, Christopher A.
    [J]. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 2008, 659 (1-2) : 176 - 184
  • [3] Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma
    Arzumanyan, Alla
    Reis, Helena M. G. P. V.
    Feitelson, Mark A.
    [J]. NATURE REVIEWS CANCER, 2013, 13 (02) : 123 - 135
  • [4] Hepatitis B and C Viruses and Hepatocellular Carcinoma
    Bartosch, Birke
    [J]. VIRUSES-BASEL, 2010, 2 (08): : 1504 - 1509
  • [5] Mutation Reporter Tool: An online tool to interrogate loci of interest, with its utility demonstrated using hepatitis B virus
    Bell, Trevor G.
    Kramvis, Anna
    [J]. VIROLOGY JOURNAL, 2013, 10
  • [6] Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma
    Chan, HLY
    Hui, AY
    Wong, ML
    Tse, AML
    Hung, LCT
    Wong, VWS
    Sung, JJY
    [J]. GUT, 2004, 53 (10) : 1494 - 1498
  • [7] Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection
    Chu, CJ
    Hussain, M
    Lok, ASF
    [J]. HEPATOLOGY, 2002, 36 (06) : 1408 - 1415
  • [8] Hepatitis B and Hepatocellular Carcinoma
    Di Bisceglie, Adrian M.
    [J]. HEPATOLOGY, 2009, 49 (05) : S56 - S60
  • [9] High Endemicity and Low Molecular Diversity of Hepatitis B Virus Infections in Pregnant Women in a Rural District of North Cameroon
    Ducancelle, Alexandra
    Abgueguen, Pierre
    Birguel, Jacques
    Mansour, Wael
    Pivert, Adeline
    Le Guillou-Guillemette, Helene
    Sobnangou, Jean-Jacques
    Rameau, Amelie
    Huraux, Jean-Marie
    Lunel-Fabiani, Francoise
    [J]. PLOS ONE, 2013, 8 (11):
  • [10] Epidemiology of hepatocellular carcinoma in USA
    El-Serag, Hashem B.
    [J]. HEPATOLOGY RESEARCH, 2007, 37 : S88 - S94