机构：[1]Department of Respiratory and Critical Care Medicine, West China Hospital,Sichuan University, Chengdu 610041, China四川大学华西医院[2]Lung Cancer Research Group,Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, William Henry DuncanBuilding, 6 West Derby Street, Liverpool L7 8TX, UK
Accumulating evidence indicates inherited risk in the aetiology of lung cancer, although smoking exposure is the major attributing factor. Family history is a simple substitute for inherited susceptibility. Previous studies have shown some possible yet conflicting links between family history of cancer and EGFR mutation in lung cancer. As EGFR-mutated lung cancer favours female, never-smoker, adenocarcinoma and Asians, it may be argued that there may be some underlying genetic modifiers responsible for the pathogenesis of EGFR mutation.
We searched four databases for all original articles on family history of malignancy and EGFR mutation status in lung cancer published up to July 2018. We performed a meta-analysis by using a random-effects model and odds ratio estimates. Heterogeneity and sensitivity were also investigated. Then we conducted a second literature research to curate case reports of familial lung cancers who studied both germline cancer predisposing genes and their somatic EGFR mutation status; and explored the possible links between cancer predisposing genes and EGFR mutation.
Eleven studies have been included in the meta-analysis. There is a significantly higher likelihood of EGFR mutation in lung cancer patients with family history of cancer than their counterparts without family history, preferentially in Asians (OR = 1.35[1.06-1.71], P = 0.01), those diagnosed with adenocarcinomas ((OR = 1.47[1.14-1.89], P = 0.003) and those with lung cancer-affected relatives (first and second-degree: OR = 1.53[1.18-1.99], P = 0.001; first-degree: OR = 1.76[1.36-2.28, P < 0.0001]). Familial lung cancers more likely have concurrent EGFR mutations along with mutations in their germline cancer predisposition genes including EGFR T790 M, BRCA2 and TP53. Certain mechanisms may contribute to the combination preferences between inherited mutations and somatic ones.
Potential genetic modifiers may contribute to somatic EGFR mutation in lung cancer, although current data is limited. Further studies on this topic are needed, which may help to unveil lung carcinogenesis pathways. However, caution is warranted in data interpretation due to limited cases available for the current study.
基金：
YIC is funded by China Scholarship Council (CSC201706240094) and West
China-Liverpool Clinician-Scientist Leadership Scholarship. MPAD is funded
by the Roy Castle Lung Cancer Foundation. This work is also partly supported
by the 1.3.5 Project for Disciplines of Excellence, West China Hospital,
Sichuan University (ZYJC18001), the National Key Development Plan for Precision
Medicine Research (2017YFC0910004) and the Transformation Projects
of Sci-Tech Achievements of Sichuan Province (2016CZYD0001). The funding
bodies had no influences on the design of the study and collection, analysis,
and interpretation of data and in writing the manuscript.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|3 区医学
小类|3 区肿瘤学
最新[2023]版：
大类|2 区医学
小类|3 区肿瘤学
第一作者：
第一作者机构：[1]Department of Respiratory and Critical Care Medicine, West China Hospital,Sichuan University, Chengdu 610041, China[2]Lung Cancer Research Group,Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, William Henry DuncanBuilding, 6 West Derby Street, Liverpool L7 8TX, UK
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Cheng Yue I,Gan Yun Cui,Liu Dan,et al.Potential genetic modifiers for somatic EGFR mutation in lung cancer: a meta-analysis and literature review.[J].BMC cancer.2019,19(1):1068.doi:10.1186/s12885-019-6317-6.
APA：
Cheng Yue I,Gan Yun Cui,Liu Dan,Davies Michael P A,Li Wei Min&Field John K.(2019).Potential genetic modifiers for somatic EGFR mutation in lung cancer: a meta-analysis and literature review..BMC cancer,19,(1)
MLA：
Cheng Yue I,et al."Potential genetic modifiers for somatic EGFR mutation in lung cancer: a meta-analysis and literature review.".BMC cancer 19..1(2019):1068
医学