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SIPA1L3 methylation...
SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival : an epigenomic–smoking interaction analysis
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- Zhang, Ruyang (author)
- Harvard University,Nanjing Medical University
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- Lai, Linjing (author)
- Nanjing Medical University
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- Dong, Xuesi (author)
- Nanjing Medical University,Southeast University
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- He, Jieyu (author)
- Nanjing Medical University
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- You, Dongfang (author)
- Nanjing Medical University
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- Chen, Chao (author)
- Nanjing Medical University
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- Lin, Lijuan (author)
- Nanjing Medical University
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- Zhu, Ying (author)
- Nanjing Medical University
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- Huang, Hui (author)
- Nanjing Medical University
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- Shen, Sipeng (author)
- Nanjing Medical University,Harvard University
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- Wei, Liangmin (author)
- Nanjing Medical University
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- Chen, Xin (author)
- Nanjing Medical University
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- Guo, Yichen (author)
- Harvard University
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- Liu, Liya (author)
- Ningbo University
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- Su, Li (author)
- Nanjing Medical University,Harvard University
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- Shafer, Andrea (author)
- Massachusetts General Hospital,Harvard University
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- Moran, Sebastian (author)
- University of Barcelona
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- Fleischer, Thomas (author)
- Oslo university hospital
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- Bjaanæs, Maria Moksnes (author)
- Oslo university hospital
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- Karlsson, Anna (author)
- Lund University,Lunds universitet,Create Health,Annan verksamhet, LTH,Lunds Tekniska Högskola,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Other operations, LTH,Faculty of Engineering, LTH,Research Group Lung Cancer,Lund University Research Groups
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- Planck, Maria (author)
- Lund University,Lunds universitet,Create Health,Annan verksamhet, LTH,Lunds Tekniska Högskola,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Other operations, LTH,Faculty of Engineering, LTH,Research Group Lung Cancer,Lund University Research Groups
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- Staaf, Johan (author)
- Lund University,Lunds universitet,Create Health,Annan verksamhet, LTH,Lunds Tekniska Högskola,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Other operations, LTH,Faculty of Engineering, LTH,Research Group Lung Cancer,Lund University Research Groups
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- Helland, Åslaug (author)
- Oslo university hospital,University of Oslo
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- Esteller, Manel (author)
- University of Barcelona
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- Wei, Yongyue (author)
- Nanjing Medical University,Harvard University
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- Chen, Feng (author)
- Nanjing Medical University
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- Christiani, David C. (author)
- Massachusetts General Hospital,Nanjing Medical University,Harvard University
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(creator_code:org_t)
- 2019-04-17
- 2019
- English 14 s.
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In: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 13:5, s. 1235-1248
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Abstract
Subject headings
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- Smoking cessation prolongs survival and decreases mortality of patients with non-small-cell lung cancer (NSCLC). In addition, epigenetic alterations of some genes are associated with survival. However, potential interactions between smoking cessation and epigenetics have not been assessed. Here, we conducted an epigenome-wide interaction analysis between DNA methylation and smoking cessation on NSCLC survival. We used a two-stage study design to identify DNA methylation–smoking cessation interactions that affect overall survival for early-stage NSCLC. The discovery phase contained NSCLC patients from Harvard, Spain, Norway, and Sweden. A histology-stratified Cox proportional hazards model adjusted for age, sex, clinical stage, and study center was used to test DNA methylation–smoking cessation interaction terms. Interactions with false discovery rate-q ≤ 0.05 were further confirmed in a validation phase using The Cancer Genome Atlas database. Histology-specific interactions were identified by stratification analysis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. We identified one CpG probe (cg02268510 SIPA 1L3 ) that significantly and exclusively modified the effect of smoking cessation on survival in LUAD patients [hazard ratio (HR) interaction = 1.12; 95% confidence interval (CI): 1.07–1.16; P = 4.30 × 10 –7 ]. Further, the effect of smoking cessation on early-stage LUAD survival varied across patients with different methylation levels of cg02268510 SIPA 1L3 . Smoking cessation only benefited LUAD patients with low methylation (HR = 0.53; 95% CI: 0.34–0.82; P = 4.61 × 10 –3 ) rather than medium or high methylation (HR = 1.21; 95% CI: 0.86–1.70; P = 0.266) of cg02268510 SIPA 1L3 . Moreover, there was an antagonistic interaction between elevated methylation of cg02268510 SIPA 1L3 and smoking cessation (HR interaction = 2.1835; 95% CI: 1.27–3.74; P = 4.46 × 10 −3 ). In summary, smoking cessation benefited survival of LUAD patients with low methylation at cg02268510 SIPA 1L3 . The results have implications for not only smoking cessation after diagnosis, but also possible methylation-specific drug targeting.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- DNA methylation
- interaction analysis
- molecular cancer epidemiology
- non-small-cell lung cancer
- overall survival
- smoking cessation
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Zhang, Ruyang
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Lai, Linjing
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Dong, Xuesi
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He, Jieyu
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You, Dongfang
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Chen, Chao
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show more...
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Lin, Lijuan
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Zhu, Ying
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Huang, Hui
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Shen, Sipeng
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Wei, Liangmin
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Chen, Xin
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Guo, Yichen
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Liu, Liya
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Su, Li
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Shafer, Andrea
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Moran, Sebastian
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Fleischer, Thoma ...
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Bjaanæs, Maria M ...
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Karlsson, Anna
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Planck, Maria
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Staaf, Johan
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Helland, Åslaug
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Esteller, Manel
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Wei, Yongyue
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Chen, Feng
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Christiani, Davi ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Molecular Oncolo ...
- By the university
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Lund University