Clinic-pathologic features and gene fusion pattern of ALK and ROS1 in non-small cell lung cancer show association with household coal combustion.

Clinic-pathologic features and gene fusion pattern of ALK and ROS1 in non-small cell lung cancer show association with household coal combustion.
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非小细胞肺癌的临床病理特征和 ALK 和 ROS1 基因融合模式显示与家庭燃煤相关

DOI:
10.21037/tcr.2019.09.37
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发表时间:
2019-09
影响因子:
0.9
通讯作者:
Ding X
Ding X
中科院分区:
医学4区
文献类型:
--
作者:
Chen Y;Huang Y;Ning H;Chen X;Tan X;Ding X

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背景 由燃煤引起的肺癌在病因学和临床上可能与吸烟引起的肺癌不同。尽管之前的工作有所进展,但受家庭燃煤影响的肺癌患者的基因融合模式仍值得进一步研究。方法从中国云南省农村地区招募家庭用煤(HCU)暴露的非小细胞肺癌(NSCLC)患者,该地区的某些地区是全国肺癌发病率较高的地区。使用逆转录聚合酶链反应 (RT-PCR) 检测 ALK、ROS1、RET 和 NTRK1 重排。总结了 18 项有关 ALK 融合的研究,并与现有工作进行了比较。结果 205例患者中,煤炭使用者112例(54.6%),吸烟者96例(46.8%),联合组145例(70.7%),其中HCU和吸烟双阳性63例(30.7%)。 HCU患者具有年龄年轻、分期晚期的特点。联合组患者年龄跨度较大(40~82岁),早发性明显,且以IIIA~IV期病例为主。双阳性个体以晚期为主,但年龄跨度较大(范围为38~75岁)。此外,18 名患者 (8.8%) 存在 EML4-ALK 重排,变异 3 比率明显高于平均水平 (77.8% vs. 44%)。识别出 5 例 ROS1 融合病例(2.5%),均为 CD74-ROS1(E6/E34),并有 HCU 经验。 ALK 和 ROS1 融合是相互排斥的。 ALK 融合和总基因重排事件(ALK 和 ROS1)均显示与 HCU 和整体暴露(烟草和煤炭)相关。这表明受煤炭使用影响的肺癌患者可能存在独特的基因融合模式。结论 本研究发现 NSCLC 的临床病理特征和基因融合模式与家庭燃煤有关。我们的研究结果可能有助于评估煤炭使用对肺癌发病机制的影响,并强调将不同的暴露史整合到临床和理论研究中的重要性。
Background Lung cancer induced by burning coal can be etiologically and clinically different from lung cancer caused by smoking. Despite previous work, the gene fusion patterns in lung cancer patients affected by household coal combustion still deserve further study. Methods Non-small cell lung cancer (NSCLC) patients exposed to household coal use (HCU) were recruited from rural areas in China’s Yunnan Province, certain areas in this region had notably high lung cancer rate nationwide. Reverse transcription-polymerase chain reaction (RT-PCR) was used for detection of ALK, ROS1, RET and NTRK1 rearrangements. Eighteen studies on ALK fusions were summarized and compared with present work. Results Among the 205 patients, there were 112 (54.6%) coal users and 96 (46.8%) smokers, union set had 145 (70.7%) subjects, in which 63 (30.7%) were double-positive for HCU and smoking. HCU patients featured with younger age and advanced stage. Union set patients covered larger age span (range, 40–82 years old), showed clear early-onset, and made the majority of stage IIIA–IV cases. Double-positive individuals were mainly in later stage, but with wider age span (range, 38–75 years old). In addition, 18 patients (8.8%) had EML4-ALK rearrangement, with apparently higher-than-average variant 3 ratio (77.8% vs. 44%). Five ROS1 fusion cases (2.5%) were identified, all were CD74-ROS1 (E6/E34), and had HCU experience. ALK and ROS1 fusions were mutually exclusive. Both ALK fusions and total gene rearrangement events (ALK and ROS1) showed association with HCU and overall exposure (tobacco and coal). Suggesting there could be unique gene fusion patterns in lung cancer patients affected by coal use. Conclusions Present study found clinic-pathologic features and gene fusion patterns in NSCLC showed association with household coal combustion. Our findings may help evaluate the impact of coal use on the pathogenesis of lung cancer, and also highlight the significance of integrating different exposure histories into clinical and theoretical research.
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