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Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.

Publication ,  Journal Article
Wen, J; Liu, H; Wang, Q; Liu, Z; Li, Y; Xiong, H; Xu, T; Li, P; Wang, L-E; Gomez, DR; Mohan, R; Komaki, R; Liao, Z; Wei, Q
Published in: Eur J Cancer
July 2014

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 <65years, males, stage III/IV, ever smokers, having radio-chemotherapy and mean lung dose (MLD) ⩾19.0Gy. 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.

Duke Scholars

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Published In

Eur J Cancer

DOI

EISSN

1879-0852

Publication Date

July 2014

Volume

50

Issue

10

Start / End Page

1706 / 1716

Location

England

Related Subject Headings

  • Treatment Outcome
  • Time Factors
  • Smoking
  • Sex Factors
  • Severity of Illness Index
  • Risk Factors
  • Radiation Pneumonitis
  • Radiation Dosage
  • RNA-Binding Proteins
  • Proportional Hazards Models
 

Citation

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Wen, J., Liu, H., Wang, Q., Liu, Z., Li, Y., Xiong, H., … Wei, Q. (2014). Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy. Eur J Cancer, 50(10), 1706–1716. https://doi.org/10.1016/j.ejca.2014.03.008
Wen, Juyi, Hongliang Liu, Qiming Wang, Zhensheng Liu, Yangkai Li, Huihua Xiong, Ting Xu, et al. “Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.Eur J Cancer 50, no. 10 (July 2014): 1706–16. https://doi.org/10.1016/j.ejca.2014.03.008.
Wen, Juyi, et al. “Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.Eur J Cancer, vol. 50, no. 10, July 2014, pp. 1706–16. Pubmed, doi:10.1016/j.ejca.2014.03.008.
Wen J, Liu H, Wang Q, Liu Z, Li Y, Xiong H, Xu T, Li P, Wang L-E, Gomez DR, Mohan R, Komaki R, Liao Z, Wei Q. Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy. Eur J Cancer. 2014 Jul;50(10):1706–1716.
Journal cover image

Published In

Eur J Cancer

DOI

EISSN

1879-0852

Publication Date

July 2014

Volume

50

Issue

10

Start / End Page

1706 / 1716

Location

England

Related Subject Headings

  • Treatment Outcome
  • Time Factors
  • Smoking
  • Sex Factors
  • Severity of Illness Index
  • Risk Factors
  • Radiation Pneumonitis
  • Radiation Dosage
  • RNA-Binding Proteins
  • Proportional Hazards Models