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
Lina ZhaoXifeng Wu

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 reveal...Continue Reading

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Citations

Dec 10, 2020·Environment International·Katalin LumniczkyDörthe Schaue
May 1, 2021·Journal of Biochemical and Molecular Toxicology·Amrita BhatRakesh Kumar

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Methods Mentioned

BETA
Genotyping
chip

Software Mentioned

SNAP
SNPeffect
PolyPhen
STATA
SIFT
SNPs3D
VEGAS
HaploReg

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