Mutant p53 protein is prevalent in Aflatoxin B1 than in Hepatitis B Core antigen associated chronic liver diseases in Southern Nigeria

Jude Ogechukwu Okoye, Success Iwuanyanwu, Goodnews Ubong Nathaniel, O. Agboola, C. Offor, John Kennedy Belonwu
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Abstract

Background: Aflatoxin B1 (AFB1), hepatitis B virus (HBV) and p53 mutation are major risk factors for liver cancer. However, the presence of AFB1 and expression of mutant p53 protein during active HBV replication (nuclear expression of Hepatitis B Core Antigen; HBcAg) and HBV clearance (nuclear expression of HBcAg) is still under-investigated in Africa. Objectives: This study assessed the prevalence, extent of expression, interaction, and risk associated with single and binary expression of AFB1, HBcAg and mutant p53 (mtp53) in liver diseases in relation to age and sex. Materials and Methods: This retrospective study included 14 and 74 cases of liver cancer (LC) and chronic hepatitis, respectively. Tissues were histochemically and immunohistochemically stained, scored and documented as positive (+) or negative (-) for antigen. Result: In this study, the prevalence of AFB1, HBcAg, and mtp53 were 76.1%, 40.9%, and 61.4%, respectively. Higher prevalence and expression of AFB1 was observed in chronic hepatitis than in LC (p= 0.035 and 0.028, respectively). Higher prevalence of AFB1 and mtp53 and lower prevalence of HBcAg were observed in females than in males (p= 0.186, 0.0003 and 0.062, respectively). Cytoplasmic expression of HBcAg was higher in males (58 than in females were 58.6% (17/29) and 14.3% (1/7), respectively (p= 0.088). AFB1+ and HBcAg+ females were more and less likely to develop LC than males (OR: 3.00 and 0.39, 95%CI: 0.10-4.18 and 0.44-12.20, p= 0.012 and 0.003), respectively. AFB1+mtp53- (23.9%), AFB1+mtp53+ (52.3%), HBcAg+mtp53- (13.6%), HBcAg+mtp53+ (27.3%) and AFB1+HBcAg+ (34.1%) increased liver cancer risk (OR: 6.45, 21.50, 2.80, 0.78, and 5.11; 95%CI: 0.89-29.29, 0.95-43.86, 2.96-156.13, 0.60-13.01, and 0.14-4.25; p= 0.057, 0.002, 0.189, 0.772, and 0.067, respectively). Conclusion: This study suggests that women are at a higher risk of AFB1 exposure and p53 mutation, but are at a lower risk of viral replication than men.
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在尼日利亚南部,突变型p53蛋白在黄曲霉毒素B1中比在乙型肝炎核心抗原相关的慢性肝病中更为普遍
背景:黄曲霉毒素B1 (AFB1)、乙型肝炎病毒(HBV)和p53突变是肝癌的主要危险因素。然而,在HBV活跃复制过程中,AFB1的存在和突变型p53蛋白的表达(乙型肝炎核心抗原的核表达;HBcAg)和HBV清除率(HBcAg的核表达)在非洲仍未得到充分研究。目的:本研究评估了AFB1、HBcAg和突变型p53 (mtp53)在肝脏疾病中与年龄和性别相关的单、双表达的患病率、表达程度、相互作用和风险。材料与方法:回顾性研究肝癌(LC) 14例,慢性肝炎74例。对组织进行组织化学和免疫组织化学染色,评分并记录抗原阳性(+)或阴性(-)。结果:本研究中AFB1、HBcAg和mtp53的患病率分别为76.1%、40.9%和61.4%。AFB1在慢性肝炎中的患病率和表达高于LC (p分别= 0.035和0.028)。AFB1和mtp53的女性患病率高于男性,HBcAg的女性患病率低于男性(p分别为0.186、0.0003和0.062)。男性(58)HBcAg细胞质表达高于女性(58.6%(17/29)和14.3%(1/7),差异有统计学意义(p= 0.088)。AFB1+和HBcAg+女性发生LC的可能性分别高于和低于男性(OR: 3.00和0.39,95%CI: 0.10-4.18和0.44-12.20,p= 0.012和0.003)。AFB1+mtp53-(23.9%)、AFB1+mtp53+(52.3%)、HBcAg+mtp53-(13.6%)、HBcAg+mtp53+(27.3%)和AFB1+HBcAg+(34.1%)增加肝癌风险(OR: 6.45、21.50、2.80、0.78、5.11;95%置信区间:0.89 - -29.29,0.95 - -43.86,2.96 - -156.13,0.60 - -13.01,0.14 - -4.25;P = 0.057、0.002、0.189、0.772、0.067)。结论:本研究提示女性AFB1暴露和p53突变的风险较高,但病毒复制的风险低于男性。
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