Lung cancer family history and exposure to occupational/domestic coal combustion contribute to variations in clinicopathologic features and gene fusion patterns in non-small cell lung cancer
Lung cancer family history and exposure to occupational/domestic coal combustion contribute to variations in clinicopathologic features and gene fusion patterns in non-small cell lung cancer
复制标题
肺癌家族史和职业/家庭燃煤暴露导致非小细胞肺癌临床病理特征和基因融合模式的变化
DOI：
10.1111/1759-7714.12987
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发表时间：
2019-04-01
期刊：
影响因子：
2.9
通讯作者：
Huang, Yunchao
中科院分区：
文献类型：
--
作者：
Chen, Ying;Li, Guangjian;Huang, Yunchao
研究背景遗传和环境因素共同作用于肿瘤及其突变谱的发生发展。肺癌具有家族聚集性。非烟草因素引起的肺癌具有独特的病理和分子特征。遗传性肺癌易感性与燃煤致癌物之间的相互作用仍然复杂且未充分研究MethodsWe选择了410例非小细胞肺癌（NSCLC）患者，他们有肺癌（FLC）家族史，并在2014年至2017年期间暴露于燃煤。分析临床病理参数。逆转录-PCR检测ALK，ROS 1，RET，NTRK 1重排。结果在410例NSCLC患者中，192人有FLC和204（49.8%）暴露于职业或家庭燃煤。无论性别和煤炭暴露如何，FLC患者具有相同的特征：年龄较小，女性比例高，腺癌，转移增加，诊断时分期较晚，基因融合频率较高。67例患者（16.3%）发生基因重排：51例（12.4%）携带EML 4-ALK融合，16例（3.9%）携带ROS 1融合。FLC和高烟煤暴露患者的基因融合率最高（35.1%，33/94）。ALK融合和总基因重排与女性、从不吸烟者、年龄较小、FLC和燃煤暴露密切相关。结论FLC和燃煤暴露对NSCLC的临床病理特征和基因融合模式有重要影响，尤其是在致癌物水平较高的情况下，遗传易感性影响更大。我们的研究结果可能有助于评估FLC和煤炭暴露在肺癌发病机制中的作用。
BackgroundBoth genetic and environmental factors contribute to the development of cancer and its mutant spectrum. Lung cancer has familial aggregation. Lung cancer caused by non-tobacco factors has unique pathological and molecular characteristics. The interaction between genetic lung cancer susceptibility and carcinogens from coal burning remains complex and understudied.MethodsWe selected 410 non-small cell lung cancer (NSCLC) patients with a family history of lung cancer (FLC) and exposure to coal combustion between 2014 and 2017. Clinicopathologic parameters were analyzed. Reverse transcription-PCR was performed to detect ALK, ROS1, RET, and NTRK1 rearrangement.ResultsAmong the 410 NSCLC patients, 192 had FLC and 204 (49.8%) were exposed to occupational or domestic coal combustion. FLC patients had the same characteristics regardless of gender and coal exposure: younger age, high female ratio, adenocarcinoma, increased metastasis, later stage at diagnosis, and higher frequency of gene fusion. Sixty-seven patients (16.3%) had gene rearrangement: 51 (12.4%) harbored EML4-ALK fusions and 16 ROS1 fusions (3.9%). The highest gene fusion rate (35.1%, 33/94) occurred in patients with both FLC and high tobacco and coal exposure. ALK fusions and total gene rearrangement were closely associated with women, never smokers, younger age, FLC, and coal exposure.ConclusionFLC and exposure to coal combustion have an important impact on the clinicopathological characteristics and gene fusion mode of NSCLC, particularly in cases of higher levels of carcinogens, and genetic susceptibility has a greater impact. Our findings may help evaluate the effect of FLC and coal exposure on the pathogenesis of lung cancer.