title: Single Nucleotide Polymorphisms in CBLB, a Regulator of T-Cell Response, Predict Radiation Pneumonitis and Outcomes After Definitive Radiotherapy for Non-Small-Cell Lung Cancer.
abstract: The immune system has important roles in tumor development and outcomes after cancer treatment. We evaluated whether single-nucleotide polymorphisms (SNPs) in the gene encoding casitas B-lineage lymphoma b protein (Cbl-b), an E3 ubiquitin ligase that maintains immune tolerance by negatively regulating T-cell activation and function, were associated with outcomes after treatment of non-small-cell lung cancer (NSCLC).
  
  
  
  Samples from 393 patients with NSCLC treated with definitive radiotherapy at a single institution between March 1998 and February 2009 were used to genotype 3 potentially functional SNPs in CBLB (rs1042852 C>T, rs2305035 G>A, and rs7649466 C>G). We evaluated associations between these SNPs and local recurrence-free survival, distant metastasis-free survival, overall survival, and risk of radiation pneumonitis (RP).
  
  
  
  Having the rs2305035 A variant genotypes (AA or AG) was associated with better local recurrence-free survival (median 15.8 vs. 15.3 months; adjusted hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.60-0.98; P = .033), distant metastasis-free survival (median 15.4 vs. 14.0 months; adjusted HR, 0.74; 95% CI, 0.57-0.96; P = .024) and overall survival (median 23.5 vs. 22.8 months; adjusted HR, 0.72; 95% CI, 0.56-0.93; P = .013) after adjustment in a Cox proportional hazard model. Patients with these genotypes were also at greater risk of developing grade 3 or higher RP than were patients with GG genotypes in an adjusted Cox proportional hazard model.
  
  
  
  This is the first report that rs2305035 genotypes in CBLB were associated with clinical and RP risk among patients with NSCLC treated with definitive radiotherapy. These findings could assist in generating hypothesis for further mechanistic studies.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX; Duke Cancer Institute, Duke University Medical Center, Durham, NC.
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX; Duke Cancer Institute, Duke University Medical Center, Durham, NC.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China.
authors.forename: HuiJuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
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.
authors.forename: Quynh-Nhu
authors.initials: QN
authors.lastname: Nguyen
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Yuee
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Department of Radiation Oncology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
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.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: James W
authors.initials: JW
authors.lastname: Welsh
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: zliao@mdanderson.org.
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics*; D017564:Radiation Pneumonitis / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C492211:CBLB protein, human; D050721:Proto-Oncogene Proteins c-cbl
keywords: CBLB; NSCLC; Prognosis; Radiation pneumonitis; Radiotherapy