RGD Reference Report - 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. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

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.

Authors: Li, Peng  Wang, Xiaohong  Liu, Zhensheng  Liu, Hongliang  Xu, Ting  Wang, HuiJuan  Gomez, Daniel R  Nguyen, Quynh-Nhu  Wang, Li-E  Teng, Yuee  Song, Yipeng  Komaki, Ritsuko  Welsh, James W  Wei, Qingyi  Liao, Zhongxing 
Citation: Li P, etal., Clin Lung Cancer. 2016 Jul;17(4):253-262.e5. doi: 10.1016/j.cllc.2015.11.008. Epub 2015 Nov 22.
RGD ID: 150540334
Pubmed: PMID:26732495   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cllc.2015.11.008   (Journal Full-text)


BACKGROUND: 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).
PATIENTS AND METHODS: 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).
RESULTS: 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.
CONCLUSION: 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CBLBHumanlung non-small cell carcinoma treatmentIAGP DNA:SNP and haplotype: :rs2305035(human)RGD 
CblbRatlung non-small cell carcinoma treatmentISOCBLB (Homo sapiens)DNA:SNP and haplotype: :rs2305035(human)RGD 
CblbMouselung non-small cell carcinoma treatmentISOCBLB (Homo sapiens)DNA:SNP and haplotype: :rs2305035(human)RGD 
CBLBHumanRadiation Pneumonitis susceptibilityIAGP associated with lung non-small cell carcinoma more ...RGD 
CblbRatRadiation Pneumonitis susceptibilityISOCBLB (Homo sapiens)associated with lung non-small cell carcinoma more ...RGD 
CblbMouseRadiation Pneumonitis susceptibilityISOCBLB (Homo sapiens)associated with lung non-small cell carcinoma more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cblb  (Cbl proto-oncogene B)

Genes (Mus musculus)
Cblb  (Casitas B-lineage lymphoma b)

Genes (Homo sapiens)
CBLB  (Cbl proto-oncogene B)


Additional Information