广西黄曲霉毒素-乙型肝炎病毒双暴露原发性肝细胞癌亚型的全外显子多态性特征筛查及其功能鉴定

原发性肝细胞癌列广西壮族自治区肿瘤死因谱第一位；食物黄曲霉毒素B1（Aflatoxin B1, AFB1）污染及乙型肝炎病毒（hepatitis B virus, HBV）感染是当地肝癌高发的重要因素。我们的前期研究采用候选基因扫描策略调查广西AFB1-HBV双暴露人群中影响环境致癌物AFB1暴露生物效应的遗传多态性，结果发现达到统计学显著性的基因型信号分布在化学物代谢、DNA损伤修复、肿瘤抑制基因、生长因子、膜蛋白等基因区域。在此基础上，本研究拟进一步采用全外显子多态性扫描策略，调查广西AFB1-HBV双暴露肝癌亚型人群中的全外显子多态性特征，并对其生物学功能进行针对性体外实验验证。其意义在于，利用广西AFB1高暴露的特殊环境背景探索我国与环境致癌物暴露相关的肝癌遗传易感性，有助于针对肝癌高发地区高危人群开发积极的一级和二级预防策略，对探讨肿瘤发病中的环境－基因相互作用机制具有普遍性意义

Hepaocellular carcinoma (HCC) ranks the first mortality of malignant tumors in the Guangxi Zhuang Autonomous Region, where aflatoxin B1 (AFB1) exposure in foods and hepatitis B virus (HBV) infection are important risk factors for the pandemic of HCC. We conducted candidate-gene-screening in our prior study among AFB1-HBV exposed population in identifying genetic polymorphisms influencing bio-effects of AFB1 exposure. We found that significant signals clustered at the region involving chemical metabolism, DNA damage repair, tumor suppressor genes, growth factors and membrane protein genes. Based on these findings, we are going to scan the whole exome for characteristic polymorphisms in the sub-type of AFB1-HBV exposed HCC patients, and validate its biological function in in vitro studies. Taking advantage of AFB1-exposure in the Guangxi region, the investigation of genetic susceptibility relevant to environmental carcinogen exposure might help understanding of the etiology role of gene-environment interaction in carcinogenesis and the development of active prevention strategy in high-risk population in HCC pandemic areas.