RGD Reference Report - Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer. - Rat Genome Database

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Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer.

Authors: Hildebrandt, MA  Komaki, R  Liao, Z  Gu, J  Chang, JY  Ye, Y  Lu, C  Stewart, DJ  Minna, JD  Roth, JA  Lippman, SM  Cox, JD  Hong, WK  Spitz, MR  Wu, X 
Citation: Hildebrandt MA, etal., PLoS One. 2010 Aug 25;5(8):e12402.
RGD ID: 5131286
Pubmed: PMID:20811626   (View Abstract at PubMed)
PMCID: PMC2928273   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0012402   (Journal Full-text)

Treatment of non-small cell lung cancer (NSCLC) with radiotherapy or chemoradiotherapy is often accompanied by the development of esophagitis and pneumonitis. Identifying patients who might be at increased risk for normal tissue toxicity would help in determination of the optimal radiation dose to avoid these events. We profiled 59 single nucleotide polymorphisms (SNPs) from 37 inflammation-related genes in 173 NSCLC patients with stage IIIA/IIIB (dry) disease who were treated with definitive radiation or chemoradiation. For esophagitis risk, nine SNPs were associated with a 1.5- to 4-fold increase in risk, including three PTGS2 (COX2) variants: rs20417 (HR:1.93, 95% CI:1.10-3.39), rs5275 (HR:1.58, 95% CI:1.09-2.27), and rs689470 (HR:3.38, 95% CI:1.09-10.49). Significantly increased risk of pneumonitis was observed for patients with genetic variation in the proinflammatory genes IL1A, IL8, TNF, TNFRSF1B, and MIF. In contrast, NOS3:rs1799983 displayed a protective effect with a 45% reduction in pneumonitis risk (HR:0.55, 95% CI:0.31-0.96). Pneumonitis risk was also modulated by polymorphisms in anti-inflammatory genes, including genetic variation in IL13. rs20541 and rs180925 each resulted in increased risk (HR:2.95, 95% CI:1.14-7.63 and HR:3.23, 95% CI:1.03-10.18, respectively). The cumulative effect of these SNPs on risk was dose-dependent, as evidenced by a significantly increased risk of either toxicity with an increasing number of risk genotypes (P<0.001). These results suggest that genetic variations among inflammation pathway genes may modulate the development of radiation-induced toxicity and, ultimately, help in identifying patients who are at an increased likelihood for such events.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL4RHumanesophagitis susceptibilityIAGP associated with carcinoma more ...RGD 
Il4rRatesophagitis susceptibilityISOIL4R (Homo sapiens)associated with carcinoma more ...RGD 
Il4raMouseesophagitis susceptibilityISOIL4R (Homo sapiens)associated with carcinoma more ...RGD 
PTGS2Humanesophagitis  IAGP associated with carcinoma and non-small-cell lungRGD 
Ptgs2Ratesophagitis  ISOPTGS2 (Homo sapiens)associated with carcinoma and non-small-cell lungRGD 
Ptgs2Mouseesophagitis  ISOPTGS2 (Homo sapiens)associated with carcinoma and non-small-cell lungRGD 
TNFHumanesophagitis susceptibilityIAGP associated with carcinoma and non-small-cell lung: DNA:SNPs: :rs1799724(human)RGD 
TnfRatesophagitis susceptibilityISOTNF (Homo sapiens)associated with carcinoma and non-small-cell lung: DNA:SNPs: :rs1799724(human)RGD 
TnfMouseesophagitis susceptibilityISOTNF (Homo sapiens)associated with carcinoma and non-small-cell lung: DNA:SNPs: :rs1799724(human)RGD 
TNFRSF1BHumanpneumonia susceptibilityIAGP associated with Carcinoma more ...RGD 
Tnfrsf1bRatpneumonia susceptibilityISOTNFRSF1B (Homo sapiens)associated with Carcinoma more ...RGD 
Tnfrsf1bMousepneumonia susceptibilityISOTNFRSF1B (Homo sapiens)associated with Carcinoma more ...RGD 
IL13HumanRadiation Pneumonitis susceptibilityIAGP associated with carcinoma more ...RGD 
IL1AHumanRadiation Pneumonitis susceptibilityIAGP associated with carcinoma more ...RGD 
Il13RatRadiation Pneumonitis susceptibilityISOIL13 (Homo sapiens)associated with carcinoma more ...RGD 
Il13MouseRadiation Pneumonitis susceptibilityISOIL13 (Homo sapiens)associated with carcinoma more ...RGD 
Il1aRatRadiation Pneumonitis susceptibilityISOIL1A (Homo sapiens)associated with carcinoma more ...RGD 
Il1aMouseRadiation Pneumonitis susceptibilityISOIL1A (Homo sapiens)associated with carcinoma more ...RGD 
MIFHumanRadiation Pneumonitis susceptibilityIAGP associated with carcinoma more ...RGD 
MifRatRadiation Pneumonitis susceptibilityISOMIF (Homo sapiens)associated with carcinoma more ...RGD 
MifMouseRadiation Pneumonitis susceptibilityISOMIF (Homo sapiens)associated with carcinoma more ...RGD 
NOS3HumanRadiation Pneumonitis susceptibilityIAGP associated with carcinoma more ...RGD 
Nos3RatRadiation Pneumonitis susceptibilityISONOS3 (Homo sapiens)associated with carcinoma more ...RGD 
Nos3MouseRadiation Pneumonitis susceptibilityISONOS3 (Homo sapiens)associated with carcinoma more ...RGD 
TNFHumanRadiation Pneumonitis susceptibilityIAGP associated with carcinoma and non-small-cell lung: DNA:SNPs: :rs1799724(human)RGD 
TnfRatRadiation Pneumonitis susceptibilityISOTNF (Homo sapiens)associated with carcinoma and non-small-cell lung: DNA:SNPs: :rs1799724(human)RGD 
TnfMouseRadiation Pneumonitis susceptibilityISOTNF (Homo sapiens)associated with carcinoma and non-small-cell lung: DNA:SNPs: :rs1799724(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il13  (interleukin 13)
Il1a  (interleukin 1 alpha)
Il4r  (interleukin 4 receptor)
Mif  (macrophage migration inhibitory factor)
Nos3  (nitric oxide synthase 3)
Ptgs2  (prostaglandin-endoperoxide synthase 2)
Tnf  (tumor necrosis factor)
Tnfrsf1b  (TNF receptor superfamily member 1B)

Genes (Mus musculus)
Il13  (interleukin 13)
Il1a  (interleukin 1 alpha)
Il4ra  (interleukin 4 receptor, alpha)
Mif  (macrophage migration inhibitory factor (glycosylation-inhibiting factor))
Nos3  (nitric oxide synthase 3, endothelial cell)
Ptgs2  (prostaglandin-endoperoxide synthase 2)
Tnf  (tumor necrosis factor)
Tnfrsf1b  (tumor necrosis factor receptor superfamily, member 1b)

Genes (Homo sapiens)
IL13  (interleukin 13)
IL1A  (interleukin 1 alpha)
IL4R  (interleukin 4 receptor)
MIF  (macrophage migration inhibitory factor)
NOS3  (nitric oxide synthase 3)
PTGS2  (prostaglandin-endoperoxide synthase 2)
TNF  (tumor necrosis factor)
TNFRSF1B  (TNF receptor superfamily member 1B)


Additional Information