危地马拉肝细胞癌中黄曲霉毒素特征性突变分析：一项横断面研究（2016 - 2017年）
Analysis of aflatoxin signature mutation in hepatocellular carcinomas from Guatemala: A cross-sectional study (2016-2017).
作者信息
Alvarez Christian S, Ortiz Jeremy, Bendfeldt-Avila Giovanna, Xie Yi, Wang Mingyi, Wu Dongjing, Higson Herbert, Lee Elisa, Teshome Kedest, Barnoya Joaquin, Kleiner David E, Groopman John D, Orozco Roberto, McGlynn Katherine A, Gharzouzi Eduardo, Dean Michael
机构信息
Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Maryland.
Instituto de Cancerología/INCAN Guatemala City Guatemala.
出版信息
Health Sci Rep. 2020 May 6;3(2):e155. doi: 10.1002/hsr2.155. eCollection 2020 Jun.
BACKGROUND AND AIMS
Guatemala has the highest incidence of hepatocellular carcinoma (HCC) in the Western hemisphere. The major risk factors in Guatemala are not well characterized, but the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) appears to be low, while the prevalence of aflatoxin (AFB) exposure appears to be high. To examine whether AFB may contribute to the elevated incidence of HCC in Guatemala, this study examined the frequency of the AFB-signature mutation in the gene (R249S) as well as other somatic mutations. In addition, we assessed whether the frequency of the mutation differed by sex.
METHODS
Formalin-fixed, paraffin-embedded (FFPE) HCC tissues were obtained from three hospitals in Guatemala City between 2016 and 2017. In addition, tumor tissues preserved in RNAlater were also obtained. Sociodemographic and clinical information including HBV and HCV status were collected. Targeted sequencing of was performed in the FFPE samples, and a panel of 253 cancer-related genes was sequenced in the RNAlater samples.
RESULTS
Ninety-one FFPE tissues were examined, from 52 men and 39 women. Median (IQR) age at diagnosis was 62 (51-70). Among those with known HBV and HCV status, two were HBV+ and three were HCV+. Overall, 47% of the HCCs had a mutation. The AFB-signature R249S mutation was present in 24%. No overlap between the R249S mutation and HBV+ was observed in this cohort. Among 18 RNAlater samples examined, 44% had any mutation and 33% had the R249S mutation. Other somatic mutations were identified in known HCC driver genes.
CONCLUSIONS
The presence of the R249S mutation in the samples studied suggests that AFB may contribute to the high incidence of HCC in Guatemala. The proportion of HBV+ tumors was low, suggesting that AFB may be associated with HCC in the absence of concomitant HBV infection. Further investigation of AFB and other risk factors for HCC in Guatemala is warranted.
背景与目的
危地马拉的肝细胞癌（HCC）发病率在西半球最高。危地马拉的主要风险因素尚未得到充分描述，但乙肝病毒（HBV）和丙肝病毒（HCV）的流行率似乎较低，而黄曲霉毒素（AFB）暴露的流行率似乎较高。为了研究AFB是否可能导致危地马拉HCC发病率升高，本研究检测了 基因（R249S）中AFB特征性突变以及其他体细胞突变的频率。此外，我们评估了该突变的频率是否因性别而异。
方法
2016年至2017年间，从危地马拉城的三家医院获取福尔马林固定、石蜡包埋（FFPE）的HCC组织。此外，还获取了保存在RNA保护剂中的肿瘤组织。收集了包括HBV和HCV状态在内的社会人口统计学和临床信息。对FFPE样本进行 靶向测序，并对保存在RNA保护剂中的样本进行一组253个癌症相关基因的测序。
结果
共检查了91个FFPE组织，其中男性52例，女性39例。诊断时的中位（IQR）年龄为62岁（51 - 70岁）。在已知HBV和HCV状态的患者中，2例为HBV阳性，3例为HCV阳性。总体而言，47%的HCC有 突变。AFB特征性R249S突变存在于24%的病例中。在该队列中未观察到R249S突变与HBV阳性之间有重叠。在检测的18个保存在RNA保护剂中的样本中，44%有任何 突变，33%有R249S突变。在已知的HCC驱动基因中鉴定出其他体细胞突变。
结论
所研究样本中存在 R249S突变表明AFB可能导致危地马拉HCC的高发病率。HBV阳性肿瘤的比例较低，这表明在没有伴随HBV感染的情况下，AFB可能与HCC相关。有必要对危地马拉的AFB和其他HCC风险因素进行进一步研究。
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