RGD Reference Report - Common genetic variants in cell cycle pathway are associated with survival in stage III-IV non-small-cell lung cancer. - Rat Genome Database

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Common genetic variants in cell cycle pathway are associated with survival in stage III-IV non-small-cell lung cancer.

Authors: Yin, Jikai  Lu, Charles  Gu, Jian  Lippman, Scott M  Hildebrandt, Michelle A T  Lin, Jie  Stewart, David  Spitz, Margaret R  Wu, Xifeng 
Citation: Yin J, etal., Carcinogenesis. 2011 Dec;32(12):1867-71. doi: 10.1093/carcin/bgr217. Epub 2011 Sep 28.
RGD ID: 151347589
Pubmed: PMID:21965272   (View Abstract at PubMed)
PMCID: PMC3220611   (View Article at PubMed Central)
DOI: DOI:10.1093/carcin/bgr217   (Journal Full-text)

Cell cycle progression contributes to the cellular response to DNA-damaging factors, such as chemotherapy and radiation. We hypothesized that the genetic variations in cell cycle pathway genes may modulate treatment responses and affect survival in patients with advanced non-small-cell lung cancer (NSCLC). We genotyped 374 single-nucleotide polymorphisms (SNPs) from 49 cell cycle-related genes in 598 patients with stages III-IV NSCLC treated with first-line platinum-based chemotherapy with/without radiation. We analyzed the individual and combined associations of these SNPs with survival and evaluated their gene-gene interactions using survival tree analysis. In the analysis of survival in all the patients, 39 SNPs reached nominal significance (P < 0.05) and 4 SNPs were significant at P <0.01. However, none of these SNPs remained significant after correction for multiple comparisons at a false discovery rate of 10%. In stratified analysis by treatment modality, after adjusting for multiple comparisons, nine SNPs in chemotherapy alone and one SNP in chemoradiation remained significant. The most significant SNP in chemotherapy group was CCNB2:rs1486878 [hazard ratio (HR) = 1.69, 95% confidence interval (CI), 1.25-2.30, P = 0.001]. TP73: rs3765701 was the only significant SNP in chemoradiation group (HR = 1.87; 95% CI = 1.35-2.59, P = 1.8 × 10(-4)). In cumulative analysis, we found a significant gene-dosage effect in patients receiving chemotherapy alone. Survival tree analysis demonstrated potential higher order gene-gene and gene-treatment interactions, which could be used to predict survival status based on distinct genetic signatures. These results suggest that genetic variations in cell cycle pathway genes may affect the survival of patients with stages III-IV NSCLC individually and jointly.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TP73Humanlung non-small cell carcinoma treatmentIAGP DNA:SNP:intron: (rs3765701) (human)RGD 
Tp73Ratlung non-small cell carcinoma treatmentISOTP73 (Homo sapiens)DNA:SNP:intron: (rs3765701) (human)RGD 
Trp73Mouselung non-small cell carcinoma treatmentISOTP73 (Homo sapiens)DNA:SNP:intron: (rs3765701) (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TP73HumanNon-small cell lung carcinoma treatmentIAGP DNA:SNP:intron: (rs3765701)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Tp73  (tumor protein p73)

Genes (Mus musculus)
Trp73  (transformation related protein 73)

Genes (Homo sapiens)
TP73  (tumor protein p73)


Additional Information