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Cancers 2016, 8(2), 23; doi:10.3390/cancers8020023

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

1
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
2
Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
3
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
4
Departement of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Bingliang Fang
Received: 2 September 2015 / Revised: 25 January 2016 / Accepted: 14 February 2016 / Published: 18 February 2016
(This article belongs to the Special Issue Lung Cancer Biomarkers)
View Full-Text   |   Download PDF [232 KB, uploaded 22 February 2016]

Abstract

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. View Full-Text
Keywords: NSCLC; radiation pneumonitis and esophagitis; DNA double-stranded break repair pathway; single nucleotide polymorphism NSCLC; radiation pneumonitis and esophagitis; DNA double-stranded break repair pathway; single nucleotide polymorphism
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Zhao, L.; Pu, X.; Ye, Y.; Lu, C.; Chang, J.Y.; Wu, X. 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. Cancers 2016, 8, 23.

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