SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic–smoking interaction analysis

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SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival : an epigenomic–smoking interaction analysis. / Zhang, Ruyang; Lai, Linjing; Dong, Xuesi; He, Jieyu; You, Dongfang; Chen, Chao; Lin, Lijuan; Zhu, Ying; Huang, Hui; Shen, Sipeng; Wei, Liangmin; Chen, Xin; Guo, Yichen; Liu, Liya; Su, Li; Shafer, Andrea; Moran, Sebastian; Fleischer, Thomas; Bjaanæs, Maria Moksnes; Karlsson, Anna; Planck, Maria; Staaf, Johan; Helland, Åslaug; Esteller, Manel; Wei, Yongyue; Chen, Feng; Christiani, David C.

I: Molecular Oncology, Vol. 13, Nr. 5, 2019, s. 1235-1248.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Zhang, R, Lai, L, Dong, X, He, J, You, D, Chen, C, Lin, L, Zhu, Y, Huang, H, Shen, S, Wei, L, Chen, X, Guo, Y, Liu, L, Su, L, Shafer, A, Moran, S, Fleischer, T, Bjaanæs, MM, Karlsson, A, Planck, M, Staaf, J, Helland, Å, Esteller, M, Wei, Y, Chen, F & Christiani, DC 2019, 'SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic–smoking interaction analysis', Molecular Oncology, vol. 13, nr. 5, s. 1235-1248. https://doi.org/10.1002/1878-0261.12482

APA

CBE

Zhang R, Lai L, Dong X, He J, You D, Chen C, Lin L, Zhu Y, Huang H, Shen S, Wei L, Chen X, Guo Y, Liu L, Su L, Shafer A, Moran S, Fleischer T, Bjaanæs MM, Karlsson A, Planck M, Staaf J, Helland Å, Esteller M, Wei Y, Chen F, Christiani DC. 2019. SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic–smoking interaction analysis. Molecular Oncology. 13(5):1235-1248. https://doi.org/10.1002/1878-0261.12482

MLA

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Author

Zhang, Ruyang ; Lai, Linjing ; Dong, Xuesi ; He, Jieyu ; You, Dongfang ; Chen, Chao ; Lin, Lijuan ; Zhu, Ying ; Huang, Hui ; Shen, Sipeng ; Wei, Liangmin ; Chen, Xin ; Guo, Yichen ; Liu, Liya ; Su, Li ; Shafer, Andrea ; Moran, Sebastian ; Fleischer, Thomas ; Bjaanæs, Maria Moksnes ; Karlsson, Anna ; Planck, Maria ; Staaf, Johan ; Helland, Åslaug ; Esteller, Manel ; Wei, Yongyue ; Chen, Feng ; Christiani, David C. / SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival : an epigenomic–smoking interaction analysis. I: Molecular Oncology. 2019 ; Vol. 13, Nr. 5. s. 1235-1248.

RIS

TY - JOUR

T1 - SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival

T2 - Molecular Oncology

AU - Zhang, Ruyang

AU - Lai, Linjing

AU - Dong, Xuesi

AU - He, Jieyu

AU - You, Dongfang

AU - Chen, Chao

AU - Lin, Lijuan

AU - Zhu, Ying

AU - Huang, Hui

AU - Shen, Sipeng

AU - Wei, Liangmin

AU - Chen, Xin

AU - Guo, Yichen

AU - Liu, Liya

AU - Su, Li

AU - Shafer, Andrea

AU - Moran, Sebastian

AU - Fleischer, Thomas

AU - Bjaanæs, Maria Moksnes

AU - Karlsson, Anna

AU - Planck, Maria

AU - Staaf, Johan

AU - Helland, Åslaug

AU - Esteller, Manel

AU - Wei, Yongyue

AU - Chen, Feng

AU - Christiani, David C.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - DNA methylation

KW - interaction analysis

KW - molecular cancer epidemiology

KW - non-small-cell lung cancer

KW - overall survival

KW - smoking cessation

U2 - 10.1002/1878-0261.12482

DO - 10.1002/1878-0261.12482

M3 - Article

VL - 13

SP - 1235

EP - 1248

JO - Molecular Oncology

JF - Molecular Oncology

SN - 1574-7891

IS - 5

ER -