SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic–smoking interaction analysis
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...
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Wiley
2019-05-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.12482 |
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| author | Ruyang Zhang Linjing Lai Xuesi Dong Jieyu He Dongfang You Chao Chen Lijuan Lin Ying Zhu Hui Huang Sipeng Shen Liangmin Wei Xin Chen Yichen Guo Liya Liu Li Su Andrea Shafer Sebastian Moran Thomas Fleischer Maria Moksnes Bjaanæs Anna Karlsson Maria Planck Johan Staaf Åslaug Helland Manel Esteller Yongyue Wei Feng Chen David C. Christiani |
| author_facet | Ruyang Zhang Linjing Lai Xuesi Dong Jieyu He Dongfang You Chao Chen Lijuan Lin Ying Zhu Hui Huang Sipeng Shen Liangmin Wei Xin Chen Yichen Guo Liya Liu Li Su Andrea Shafer Sebastian Moran Thomas Fleischer Maria Moksnes Bjaanæs Anna Karlsson Maria Planck Johan Staaf Åslaug Helland Manel Esteller Yongyue Wei Feng Chen David C. Christiani |
| author_sort | Ruyang Zhang |
| collection | DOAJ |
| description | 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 (cg02268510SIPA1L3) 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 cg02268510SIPA1L3. 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 cg02268510SIPA1L3. Moreover, there was an antagonistic interaction between elevated methylation of cg02268510SIPA1L3 and smoking cessation (HRinteraction = 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 cg02268510SIPA1L3. The results have implications for not only smoking cessation after diagnosis, but also possible methylation‐specific drug targeting. |
| format | Article |
| id | doaj-art-62833bd18f1b47aba4295519fc343056 |
| institution | OA Journals |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2019-05-01 |
| publisher | Wiley |
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| series | Molecular Oncology |
| spelling | doaj-art-62833bd18f1b47aba4295519fc3430562025-08-20T02:07:05ZengWileyMolecular Oncology1574-78911878-02612019-05-011351235124810.1002/1878-0261.12482SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic–smoking interaction analysisRuyang Zhang0Linjing Lai1Xuesi Dong2Jieyu He3Dongfang You4Chao Chen5Lijuan Lin6Ying Zhu7Hui Huang8Sipeng Shen9Liangmin Wei10Xin Chen11Yichen Guo12Liya Liu13Li Su14Andrea Shafer15Sebastian Moran16Thomas Fleischer17Maria Moksnes Bjaanæs18Anna Karlsson19Maria Planck20Johan Staaf21Åslaug Helland22Manel Esteller23Yongyue Wei24Feng Chen25David C. Christiani26Department of Biostatistics Center for Global Health School of Public Health Nanjing Medical University ChinaDepartment of Biostatistics Center for Global Health School of Public Health Nanjing Medical University ChinaDepartment of Biostatistics Center for Global Health School of Public Health Nanjing Medical University ChinaDepartment of Biostatistics Center for Global Health School of Public Health Nanjing Medical University ChinaDepartment of Biostatistics Center for Global Health School of Public Health Nanjing Medical University ChinaDepartment of Biostatistics Center for Global Health School of Public Health Nanjing Medical University ChinaDepartment of Biostatistics Center for Global Health School of Public Health Nanjing Medical University ChinaDepartment of Biostatistics Center for Global Health School of Public Health Nanjing Medical University ChinaDepartment of Biostatistics Center for Global Health School of Public Health Nanjing Medical University ChinaDepartment of Biostatistics Center for Global Health School of Public Health Nanjing Medical University ChinaDepartment of Biostatistics Center for Global Health School of Public Health Nanjing Medical University ChinaDepartment of Biostatistics Center for Global Health School of Public Health Nanjing Medical University ChinaDepartment of Environmental Health Harvard T.H. Chan School of Public Health Boston MA USADepartment of Preventive Medicine Medical School of Ningbo University ChinaDepartment of Environmental Health Harvard T.H. Chan School of Public Health Boston MA USAPulmonary and Critical Care Division Department of Medicine Massachusetts General Hospital Harvard Medical School Boston MAUSABellvitge Biomedical Research Institute Institucio Catalana de Recerca i Estudis Avançats University of Barcelona Barcelona SpainDepartment of Cancer Genetics Institute for Cancer Research Oslo University Hospital NorwayDepartment of Cancer Genetics Institute for Cancer Research Oslo University Hospital NorwayDivision of Oncology and Pathology Department of Clinical Sciences Lund CREATE Health Strategic Center for Translational Cancer Research Lund University SwedenDivision of Oncology and Pathology Department of Clinical Sciences Lund CREATE Health Strategic Center for Translational Cancer Research Lund University SwedenDivision of Oncology and Pathology Department of Clinical Sciences Lund CREATE Health Strategic Center for Translational Cancer Research Lund University SwedenDepartment of Cancer Genetics Institute for Cancer Research Oslo University Hospital NorwayBellvitge Biomedical Research Institute Institucio Catalana de Recerca i Estudis Avançats University of Barcelona Barcelona SpainDepartment of Biostatistics Center for Global Health School of Public Health Nanjing Medical University ChinaDepartment of Biostatistics Center for Global Health School of Public Health Nanjing Medical University ChinaDepartment of Environmental Health Harvard T.H. Chan School of Public Health Boston MA USASmoking 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 (cg02268510SIPA1L3) 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 cg02268510SIPA1L3. 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 cg02268510SIPA1L3. Moreover, there was an antagonistic interaction between elevated methylation of cg02268510SIPA1L3 and smoking cessation (HRinteraction = 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 cg02268510SIPA1L3. The results have implications for not only smoking cessation after diagnosis, but also possible methylation‐specific drug targeting.https://doi.org/10.1002/1878-0261.12482DNA methylationinteraction analysismolecular cancer epidemiologynon‐small‐cell lung canceroverall survivalsmoking cessation |
| spellingShingle | Ruyang Zhang Linjing Lai Xuesi Dong Jieyu He Dongfang You Chao Chen Lijuan Lin Ying Zhu Hui Huang Sipeng Shen Liangmin Wei Xin Chen Yichen Guo Liya Liu Li Su Andrea Shafer Sebastian Moran Thomas Fleischer Maria Moksnes Bjaanæs Anna Karlsson Maria Planck Johan Staaf Åslaug Helland Manel Esteller Yongyue Wei Feng Chen David C. Christiani SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic–smoking interaction analysis Molecular Oncology DNA methylation interaction analysis molecular cancer epidemiology non‐small‐cell lung cancer overall survival smoking cessation |
| title | SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic–smoking interaction analysis |
| title_full | SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic–smoking interaction analysis |
| title_fullStr | SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic–smoking interaction analysis |
| title_full_unstemmed | SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic–smoking interaction analysis |
| title_short | SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic–smoking interaction analysis |
| title_sort | sipa1l3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival an epigenomic smoking interaction analysis |
| topic | DNA methylation interaction analysis molecular cancer epidemiology non‐small‐cell lung cancer overall survival smoking cessation |
| url | https://doi.org/10.1002/1878-0261.12482 |
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