Journal article
Inflammation-related genetic variants predict toxicities following definitive-radiotherapy for lung cancer
Clinical pharmacology and therapeutics, Vol.96(5), pp.609-615
07/23/2014
DOI: 10.1038/clpt.2014.154
PMCID: PMC4206576
PMID: 25054431
Abstract
Definitive radiotherapy improves locoregional control and survival in inoperable non-small cell lung cancer (NSCLC) patients. However, radiation-induced toxicities (pneumonitis/esophagitis) are common dose-limiting inflammatory conditions. We therefore conducted a pathway-based analysis to identify inflammation-related SNPs associated with radiation-induced pneumonitis or esophagitis. 11,930 SNPs were genotyped in 201 stage I-III NSCLC patients treated with definitive radiotherapy. Validation was performed in an additional 220 NSCLC cases. After validation, 19 SNPs remained significant. A polygenic risk score (PRS) was generated to summarize the effect from validated SNPs. Significant improvements in discriminative ability were observed by adding the PRS into the clinical/epidemiological variable-based model. We then used 277 lymphoblastoid cell-lines to assess radiation sensitivity and eQTL relationships of the identified SNPs. 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. These loci could assist in predicting those unfavorable events.
Details
- Title: Subtitle
- Inflammation-related genetic variants predict toxicities following definitive-radiotherapy for lung cancer
- Creators
- Xia PuLiewei Wang - Mayo ClinicJoe Y. Chang - The University of Texas MD Anderson Cancer CenterMichelle A.T. Hildebrandt - The University of Texas MD Anderson Cancer CenterYuanqing Ye - The University of Texas MD Anderson Cancer CenterCharles Lu - The University of Texas MD Anderson Cancer CenterHeath D. Skinner - The University of Texas MD Anderson Cancer CenterNifang Niu - Mayo ClinicGregory D. Jenkins - Mayo Clinic in FloridaRitsuko Komaki - The University of Texas MD Anderson Cancer CenterJohn D. Minna - The University of Texas Southwestern Medical CenterJack A. Roth - The University of Texas MD Anderson Cancer CenterRichard M. Weinshilboum - Mayo ClinicXifeng Wu
- Resource Type
- Journal article
- Publication Details
- Clinical pharmacology and therapeutics, Vol.96(5), pp.609-615
- Publisher
- WILEY-BLACKWELL; HOBOKEN
- DOI
- 10.1038/clpt.2014.154
- PMID
- 25054431
- PMCID
- PMC4206576
- ISSN
- 0009-9236
- eISSN
- 1532-6535
- Grant note
- US National Institutes of Health: R01-CA111646, P50CA070907, R01-CA127615, CPRIT RP130502, U19-GM61388, R01-CA138461
This study was supported by US National Institutes of Health grants R01-CA111646 (X.W.), P50CA070907 (J.D.M., J.A.R., and X.W.), R01-CA127615 (X.W.), CPRIT RP130502 (X.W.), U19-GM61388 (LW.) and R01-CA138461 (L.W.). Additional support was provided by the Center for Translational and Public Health Genomics of the Duncan Family Institute for Cancer Prevention and Risk Assessment, The University of Texas MD Anderson Cancer Center (X.W.).
- Language
- English
- Date published
- 07/23/2014
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984701548402771
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