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Inflammation-related genetic variants predict toxicity following definitive radiotherapy for lung cancer.


ABSTRACT: Definitive radiotherapy improves locoregional control and survival in inoperable non-small cell lung cancer patients. However, radiation-induced toxicities (pneumonitis/esophagitis) are common dose-limiting inflammatory conditions. We therefore conducted a pathway-based analysis to identify inflammation-related single-nucleotide polymorphisms associated with radiation-induced pneumonitis or esophagitis. A total of 11,930 single-nucleotide polymorphisms were genotyped in 201 stage I-III non-small cell lung cancer patients treated with definitive radiotherapy. Validation was performed in an additional 220 non-small cell lung cancer cases. After validation, 19 single-nucleotide polymorphisms remained significant. A polygenic risk score was generated to summarize the effect from validated single-nucleotide polymorphisms. Significant improvements in discriminative ability were observed when the polygenic risk score was added into the clinical/epidemiological variable-based model. We then used 277 lymphoblastoid cell lines to assess radiation sensitivity and expression quantitative trait loci (eQTL) relationships of the identified single-nucleotide polymorphisms. Three genes (PRKCE, DDX58, and TNFSF7) were associated with radiation sensitivity. We concluded that inflammation-related genetic variants could contribute to the development of radiation-induced toxicities.

SUBMITTER: Pu X 

PROVIDER: S-EPMC4206576 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Inflammation-related genetic variants predict toxicity following definitive radiotherapy for lung cancer.

Pu X X   Wang L L   Chang J Y JY   Hildebrandt M A T MA   Ye Y Y   Lu C C   Skinner H D HD   Niu N N   Jenkins G D GD   Komaki R R   Minna J D JD   Roth J A JA   Weinshilboum R M RM   Wu X X  

Clinical pharmacology and therapeutics 20140723 5


Definitive radiotherapy improves locoregional control and survival in inoperable non-small cell lung cancer patients. However, radiation-induced toxicities (pneumonitis/esophagitis) are common dose-limiting inflammatory conditions. We therefore conducted a pathway-based analysis to identify inflammation-related single-nucleotide polymorphisms associated with radiation-induced pneumonitis or esophagitis. A total of 11,930 single-nucleotide polymorphisms were genotyped in 201 stage I-III non-small  ...[more]

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