|
|
|
|
The MKK7 p.Glu116Lys Rare Variant Serves as a Predictor for Lung Cancer Risk and Prognosis in Chinese
|
|
|
|
|
|
|
|
نویسنده
|
qiu f. ,yang l. ,lu x. ,chen j. ,wu d. ,wei y. ,nong q. ,zhang l. ,fang w. ,chen x. ,ling x. ,yang b. ,zhang x. ,zhou y. ,lu j.
|
|
منبع
|
plos genetics - 2016 - دوره : 12 - شماره : 3
|
|
چکیده
|
Accumulated evidence indicates that rare variants exert a vital role on predisposition and progression of human diseases,which provides neoteric insights into disease etiology. in the current study,based on three independently retrospective studies of 5,016 lung cancer patients and 5,181 controls,we analyzed the associations between five rare polymorphisms (i.e.,p.glu116lys,p.asn118ser,p.arg138cys,p.ala195thr and p.leu259phe) in mkk7 and lung cancer risk and prognosis. to decipher the precise mechanisms of mkk7 rare variants on lung cancer,a series of biological experiments was further performed. we found that the mkk7 p.glu116lys rare polymorphism was significantly associated with lung cancer risk,progression and prognosis. compared with glu/glu common genotype,the 116lys rare variants (lys/glu/+ lys/lys) presented an adverse effect on lung cancer susceptibility (odds ratio [or] = 3.29,95% confidence interval [ci] = 2.70–4.01). these rare variants strengthened patients’ clinical progression that patients with 116lys variants had a significantly higher metastasis rate and advanced n,m stages at diagnosis. in addition,the patients with 116lys variants also contributed to worse cancer prognosis than those carriers with glu/glu genotype (hazard ratio [hr] = 1.53,95% ci = 1.32–1.78). functional experiments further verified that the mkk7 p.116lys variants altered the expression of several cancer-related genes and thus affected lung cancer cells proliferation,tumor growth and metastasis in vivo and in vitro. taken together,our findings proposed that the mkk7 p.glu116lys rare polymorphism incurred a pernicious impact on lung cancer risk and prognosis through modulating expressions of a serial of cancer-related genes. © 2016 qiu et al.
|
|
|
|
|
آدرس
|
the state key lab of respiratory disease,the institute for chemical carcinogenesis,collaborative innovation center for environmental toxicity,school of public health,guangzhou medical university,guangzhou,china,biomedicine research center and department of surgery,the third affiliated hospital of guangzhou medicine university,guangzhou, China, the state key lab of respiratory disease,the institute for chemical carcinogenesis,collaborative innovation center for environmental toxicity,school of public health,guangzhou medical university,guangzhou, China, school of arts and sciences,colby-sawyer college,new london,nh, United States, the state key lab of respiratory disease,the institute for chemical carcinogenesis,collaborative innovation center for environmental toxicity,school of public health,guangzhou medical university,guangzhou, China, the state key lab of respiratory disease,the institute for chemical carcinogenesis,collaborative innovation center for environmental toxicity,school of public health,guangzhou medical university,guangzhou, China, center of laboratory animal,guangzhou medical university,guangzhou, China, department of environmental health,guangxi medical university,nanning, China, the state key lab of respiratory disease,the institute for chemical carcinogenesis,collaborative innovation center for environmental toxicity,school of public health,guangzhou medical university,guangzhou, China, the state key lab of respiratory disease,the institute for chemical carcinogenesis,collaborative innovation center for environmental toxicity,school of public health,guangzhou medical university,guangzhou, China, the state key lab of respiratory disease,the institute for chemical carcinogenesis,collaborative innovation center for environmental toxicity,school of public health,guangzhou medical university,guangzhou, China, the state key lab of respiratory disease,the institute for chemical carcinogenesis,collaborative innovation center for environmental toxicity,school of public health,guangzhou medical university,guangzhou, China, the state key lab of respiratory disease,the institute for chemical carcinogenesis,collaborative innovation center for environmental toxicity,school of public health,guangzhou medical university,guangzhou, China, department of thoracic surgery,the first affiliated hospital of guangzhou medical university,guangzhou, China, department of genetics,medical college of soochow university,suzhou, China, the state key lab of respiratory disease,the institute for chemical carcinogenesis,collaborative innovation center for environmental toxicity,school of public health,guangzhou medical university,guangzhou, China
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|