TY - JOUR
T1 - Association between genetic variants in DNA double-strand break repair pathways and risk of radiation therapy-induced pneumonitis and esophagitis in non-small cell lung cancer
AU - Zhao, Lina
AU - Pu, Xia
AU - Ye, Yuanqing
AU - Lu, Charles
AU - Chang, Joe Y.
AU - Wu, Xifeng
N1 - Publisher Copyright:
© 2016 by the authors; licensee MDPI, Basel, Switzerland.
PY - 2016/2/18
Y1 - 2016/2/18
N2 - Radiation therapy (RT)-induced pneumonitis and esophagitis are commonly developed side effects in non-small cell lung cancer (NSCLC) patients treated with definitive RT. Identifying patients who are at increased risk for these toxicities would help to maximize treatment efficacy while minimizing toxicities. Here, we systematically investigated single nucleotide polymorphisms (SNPs) within double-strand break (DSB) repair pathway as potential predictive markers for radiation-induced esophagitis and pneumonitis. We genotyped 440 SNPs from 45 genes in DSB repair pathways in 250 stage I-III NSCLC patients who received definitive radiation or chemoradiation therapy, followed by internal validation in 170 additional patients. We found that 11 SNPs for esophagitis and 8 SNPs for pneumonitis showed consistent effects between discovery and validation populations (same direction of OR and reached significance in meta-analysis). Among them, rs7165790 in the BLM gene was significantly associated with decreased risk of esophagitis in both discovery (OR = 0.59, 95% CI: 0.37-0.97, p = 0.037) and validation subgroups (OR = 0.45, 95% CI: 0.22-0.94, p = 0.032). A strong cumulative effect was observed for the top SNPs, and gene-based tests revealed 12 genes significantly associated with esophagitis or pneumonitis. Our results support the notion that genetic variations within DSB repair pathway could influence the risk of developing toxicities following definitive RT in NSCLC.
AB - Radiation therapy (RT)-induced pneumonitis and esophagitis are commonly developed side effects in non-small cell lung cancer (NSCLC) patients treated with definitive RT. Identifying patients who are at increased risk for these toxicities would help to maximize treatment efficacy while minimizing toxicities. Here, we systematically investigated single nucleotide polymorphisms (SNPs) within double-strand break (DSB) repair pathway as potential predictive markers for radiation-induced esophagitis and pneumonitis. We genotyped 440 SNPs from 45 genes in DSB repair pathways in 250 stage I-III NSCLC patients who received definitive radiation or chemoradiation therapy, followed by internal validation in 170 additional patients. We found that 11 SNPs for esophagitis and 8 SNPs for pneumonitis showed consistent effects between discovery and validation populations (same direction of OR and reached significance in meta-analysis). Among them, rs7165790 in the BLM gene was significantly associated with decreased risk of esophagitis in both discovery (OR = 0.59, 95% CI: 0.37-0.97, p = 0.037) and validation subgroups (OR = 0.45, 95% CI: 0.22-0.94, p = 0.032). A strong cumulative effect was observed for the top SNPs, and gene-based tests revealed 12 genes significantly associated with esophagitis or pneumonitis. Our results support the notion that genetic variations within DSB repair pathway could influence the risk of developing toxicities following definitive RT in NSCLC.
KW - DNA double-stranded break repair
KW - NSCLC
KW - Pathway
KW - Radiation pneumonitis and esophagitis
KW - Single nucleotide polymorphism
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U2 - 10.3390/cancers8020023
DO - 10.3390/cancers8020023
M3 - Article
C2 - 26901225
AN - SCOPUS:84958774455
SN - 2072-6694
VL - 8
JO - Cancers
JF - Cancers
IS - 2
M1 - 05
ER -