TY - JOUR
T1 - Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy
AU - Wen, Juyi
AU - Liu, Hongliang
AU - Wang, Qiming
AU - Liu, Zhensheng
AU - Li, Yangkai
AU - Xiong, Huihua
AU - Xu, Ting
AU - Li, Peng
AU - Wang, Li E.
AU - Gomez, Daniel R.
AU - Mohan, Radhe
AU - Komaki, Ritsuko
AU - Liao, Zhongxing
AU - Wei, Qingyi
N1 - Funding Information:
This study was supported in part by National Institutes of Health Grants R01 ES 11740 and R01 CA 131274 (to Q. W.) and by Cancer Center Core Grant P30 CA016672 to The University of Texas M.D. Anderson Cancer Center.
PY - 2014/7
Y1 - 2014/7
N2 - Background LIN28 is an RNA-binding protein that not only plays key roles in multiple cellular developmental processes and tumourigenesis, but also is involved in tissue inflammatory response. However, no published study has investigated associations between genetic variants in LIN28 and radiation-induced pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy. Methods We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of LIN28A (rs11247946 T>C, rs3811464 C>T, rs11581746 T>C, and rs12728900 G>A) and LIN28B (rs314280 G>A, rs12194974 G>A, rs17065417 A>C and rs314276 C>A) in 362 patients with NSCLC, who received definitive radio(chemo)therapy. The associations between RP risk and genotypes were assessed by hazards ratio (HR) in Cox proportional hazards regression analysis with time to event considered with and without adjustment for potential confounders. Results Multivariate analyses found that patients carrying LIN28B rs314280 AG and AA/AG or rs314276 AC and AA/AC genotypes had a higher risk of grade ≥3 RP (for rs314280 AG and AA/AG versus GG, adjusted HR = 2.97 and 2.23, 95% confidence interval (CI) = 1.32-6.72 and 1.01-4.94, P = 0.009 and 0.048, respectively; for rs314276 AC and AA/AC versus CC, adjusted HR = 2.30 and 2.00, 95% CI = 1.24-4.28 and 1.11-3.62, and P = 0.008 and 0.022, respectively). Further stratified analyses showed a more consistent and profound risk in the subgroups of age <65 years, males, stage III/IV, ever smokers, having radio-chemotherapy and mean lung dose (MLD) ≥19.0 Gy. Conclusion Genetic variants of LIN28B, but not LIN28A, may be biomarkers for susceptibility to severe RP in NSCLC patients. Large, prospective studies are needed to confirm our findings.
AB - Background LIN28 is an RNA-binding protein that not only plays key roles in multiple cellular developmental processes and tumourigenesis, but also is involved in tissue inflammatory response. However, no published study has investigated associations between genetic variants in LIN28 and radiation-induced pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy. Methods We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of LIN28A (rs11247946 T>C, rs3811464 C>T, rs11581746 T>C, and rs12728900 G>A) and LIN28B (rs314280 G>A, rs12194974 G>A, rs17065417 A>C and rs314276 C>A) in 362 patients with NSCLC, who received definitive radio(chemo)therapy. The associations between RP risk and genotypes were assessed by hazards ratio (HR) in Cox proportional hazards regression analysis with time to event considered with and without adjustment for potential confounders. Results Multivariate analyses found that patients carrying LIN28B rs314280 AG and AA/AG or rs314276 AC and AA/AC genotypes had a higher risk of grade ≥3 RP (for rs314280 AG and AA/AG versus GG, adjusted HR = 2.97 and 2.23, 95% confidence interval (CI) = 1.32-6.72 and 1.01-4.94, P = 0.009 and 0.048, respectively; for rs314276 AC and AA/AC versus CC, adjusted HR = 2.30 and 2.00, 95% CI = 1.24-4.28 and 1.11-3.62, and P = 0.008 and 0.022, respectively). Further stratified analyses showed a more consistent and profound risk in the subgroups of age <65 years, males, stage III/IV, ever smokers, having radio-chemotherapy and mean lung dose (MLD) ≥19.0 Gy. Conclusion Genetic variants of LIN28B, but not LIN28A, may be biomarkers for susceptibility to severe RP in NSCLC patients. Large, prospective studies are needed to confirm our findings.
KW - Hazards ratio
KW - Inflammation
KW - LIN28
KW - Non-small cell lung cancer
KW - Polymorphisms
KW - Radiation pneumonitis
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U2 - 10.1016/j.ejca.2014.03.008
DO - 10.1016/j.ejca.2014.03.008
M3 - Article
C2 - 24780874
AN - SCOPUS:84901748432
SN - 0959-8049
VL - 50
SP - 1706
EP - 1716
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 10
ER -