title: The Pulmonary Fibrosis Associated MUC5B Promoter Polymorphism Is Prognostic of the Overall Survival in Patients with Non-Small Cell Lung Cancer (NSCLC) Receiving Definitive Radiotherapy.
abstract: BACKGROUND
  MUC5B is glycoprotein secreted by bronchial glands. A promoter variant in MUC5B, rs35705950, was previously found to be strongly associated with the incidence of idiopathic pulmonary fibrosis (IPF) and also the overall survival (OS) of such patients. Patients with IPF and patients with radiation pneumonitis (RP) have the similar pathologic process and clinical symptoms. However, the role of rs35705950 in patients receiving thoracic radiotherapy remains unclear.
  
  
  METHODS
  In total, 664 patients with NSCLC receiving definitive radiotherapy (total dose ≥60 Gy) were included in our study. RP was scored via the Common Terminology Criteria for Adverse Events v3.0. OS was the second end point. MUC5B rs35705950 was genotyped, and Kaplan-Meier and Cox regression analyses were used to evaluate associations between MUC5B rs35705950 and the risk of RP or OS.
  
  
  RESULTS
  The median patient age was 66 years (range 35-88); most (488 [73.2%]) had stage III of the disease. Until the last follow-up, 250 patients developed grade≥2 RP, 82 patients developed grade≥3 RP, and 440 patients died. The median mean lung dose was 17.9 Gy (range 0.15-32.74). No statistically significant associations were observed between genotypes of MUC5B rs35705950 and the incidence of RP≥grade 2 either in univariate analysis (hazard ratio [HR] 1.009, 95% confidence interval [CI] 0.728-1.399, P=.958) or in multivariate analysis (HR 0.921, 95% CI 0.645-1.315, P=.65). Similar results were also observed for RP≥grade 3, while TT/GT genotypes in MUC5B were significantly associated with poor OS in both univariate analysis (HR 1.287, 95% CI 1.009-1.640, P=.042) and multivariate analysis (HR 1.561, 95% CI 1.193-2.042, P=.001).
  
  
  CONCLUSIONS
  MUC5B promoter polymorphism could be prognostic of the OS among NSCLC patients receiving definitive radiotherapy, although no significant associations were found with the risk of RP.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA; The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University &Clinical Cancer Institute of Nanjing University, Nanjing, China. Electronic address: yangjutjh@163.com.
authors.forename: Ju
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. Electronic address: TXu@mdanderson.org.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. Electronic address: DGomez@mdanderson.org.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Gomez
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. Electronic address: mdjeter@mdanderson.org.
authors.forename: Melenda
authors.initials: M
authors.lastname: Jeter
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. Electronic address: lblevy@mdanderson.org.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Levy
authors.affiliation: Department of Radiation Oncology, Yuhuangding Hospital, Zhifu, Yantai, Shandong, China. Electronic address: syp1972@sina.com.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. Electronic address: SHahn@mdanderson.org.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hahn
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. Electronic address: zliao@mdanderson.org.
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
authors.affiliation: Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 40030, China. Electronic address: yxl@medmail.com.cn.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Yuan