Potentially Functional Variants of ATG16L2 Predict Radiation Pneumonitis and Outcomes in Patients with Non-Small Cell Lung Cancer after Definitive Radiotherapy.
Abstract
INTRODUCTION:Autophagy not only plays an important role in the progression of cancer
but is also involved in tissue inflammatory response. However, few published studies
have investigated associations between functional genetic variants of autophagy-related
genes and radiation pneumonitis (RP) as well as clinical outcomes in patients with
NSCLC after definitive radiotherapy. METHODS:We genotyped nine potentially functional
single-nucleotide polymorphisms (SNPs) in four autophagy-related genes (autophagy
related 2B gene [ATG2B], autophagy related 10 gene [ATG10], autophagy related 12 gene
[ATG12], and autophagy related 16 like 2 gene [ATG16L2]) in 393 North American patients
with NSCLC treated by definitive radiotherapy and assessed their associations with
RP, local recurrence-free survival (LRFS), progression-free survival (PFS), and overall
survival (OS) in multivariable Cox proportional hazard regression analyses. RESULTS:We
found that patients with the ATG16L2 rs10898880 CC variant genotype had a better LRFS,
PFS, and OS (adjusted hazard ratio = 0.59, 0.64, and 0.64; 95% confidence interval:
0.45-0.79, 0.48-0.84, and 0.48-0.86; p = 0.0004, 0.002, and 0.003, respectively),
but a greater risk for development of severe RP (adjusted hazard ratio = 1.80, 95%
confidence interval: 1.04-3.12, p = 0.037) than did patients with AA/AC genotypes.
Further functional analyses suggested that the ATG16L2 rs10898880 C variant allele
modulated expression of the ATG16L2 gene. CONCLUSION:This is the first report that
one potentially functional SNP rs10898880 in ATG16L2 may be a predictor of RP, LRFS,
PFS, and OS in patients with NSCLC after definitive radiotherapy. Additional larger,
prospective studies are needed to confirm these findings.
Type
Journal articleSubject
HumansCarcinoma, Non-Small-Cell Lung
Lung Neoplasms
Radiation Pneumonitis
Genetic Predisposition to Disease
Neoplasm Staging
Polymorphism, Single Nucleotide
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Autophagy-Related Proteins
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https://hdl.handle.net/10161/18511Published Version (Please cite this version)
10.1016/j.jtho.2018.01.028Publication Info
Wen, Juyi; Liu, Hongliang; Wang, Lili; Wang, Xiaomeng; Gu, Ning; Liu, Zhensheng; ...
Wei, Qingyi (2018). Potentially Functional Variants of ATG16L2 Predict Radiation Pneumonitis and Outcomes
in Patients with Non-Small Cell Lung Cancer after Definitive Radiotherapy. Journal of thoracic oncology : official publication of the International Association
for the Study of Lung Cancer, 13(5). pp. 660-675. 10.1016/j.jtho.2018.01.028. Retrieved from https://hdl.handle.net/10161/18511.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Zhensheng Liu
Assistant Professor of Medicine
Qingyi Wei
Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director
for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology
and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally
recognized epidemiologist focused on the molecular and genetic epidemiology of head
and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and
genetic determinants for the DNA repair deficient phenotype and
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