Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer.
Treatment of non-small cell lung cancer (NSCLC) with radiotherapy or chemoradiotherapy is often accompanied by the development of esophagitis and pneumonitis. Identifying patients who might be at increased risk for normal tissue toxicity would help in determination of the optimal radiation dose to a...
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Public Library of Science (PLoS)
2010-08-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0012402&type=printable |
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| author | Michelle A T Hildebrandt Ritsuko Komaki Zhongxing Liao Jian Gu Joe Y Chang Yuanqing Ye Charles Lu David J Stewart John D Minna Jack A Roth Scott M Lippman James D Cox Waun Ki Hong Margaret R Spitz Xifeng Wu |
| author_facet | Michelle A T Hildebrandt Ritsuko Komaki Zhongxing Liao Jian Gu Joe Y Chang Yuanqing Ye Charles Lu David J Stewart John D Minna Jack A Roth Scott M Lippman James D Cox Waun Ki Hong Margaret R Spitz Xifeng Wu |
| author_sort | Michelle A T Hildebrandt |
| collection | DOAJ |
| description | Treatment of non-small cell lung cancer (NSCLC) with radiotherapy or chemoradiotherapy is often accompanied by the development of esophagitis and pneumonitis. Identifying patients who might be at increased risk for normal tissue toxicity would help in determination of the optimal radiation dose to avoid these events. We profiled 59 single nucleotide polymorphisms (SNPs) from 37 inflammation-related genes in 173 NSCLC patients with stage IIIA/IIIB (dry) disease who were treated with definitive radiation or chemoradiation. For esophagitis risk, nine SNPs were associated with a 1.5- to 4-fold increase in risk, including three PTGS2 (COX2) variants: rs20417 (HR:1.93, 95% CI:1.10-3.39), rs5275 (HR:1.58, 95% CI:1.09-2.27), and rs689470 (HR:3.38, 95% CI:1.09-10.49). Significantly increased risk of pneumonitis was observed for patients with genetic variation in the proinflammatory genes IL1A, IL8, TNF, TNFRSF1B, and MIF. In contrast, NOS3:rs1799983 displayed a protective effect with a 45% reduction in pneumonitis risk (HR:0.55, 95% CI:0.31-0.96). Pneumonitis risk was also modulated by polymorphisms in anti-inflammatory genes, including genetic variation in IL13. rs20541 and rs180925 each resulted in increased risk (HR:2.95, 95% CI:1.14-7.63 and HR:3.23, 95% CI:1.03-10.18, respectively). The cumulative effect of these SNPs on risk was dose-dependent, as evidenced by a significantly increased risk of either toxicity with an increasing number of risk genotypes (P<0.001). These results suggest that genetic variations among inflammation pathway genes may modulate the development of radiation-induced toxicity and, ultimately, help in identifying patients who are at an increased likelihood for such events. |
| format | Article |
| id | doaj-art-d1c822ff344a43bca557c9f7f8dd46af |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2010-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-d1c822ff344a43bca557c9f7f8dd46af2025-08-20T03:19:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-08-0158e1240210.1371/journal.pone.0012402Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer.Michelle A T HildebrandtRitsuko KomakiZhongxing LiaoJian GuJoe Y ChangYuanqing YeCharles LuDavid J StewartJohn D MinnaJack A RothScott M LippmanJames D CoxWaun Ki HongMargaret R SpitzXifeng WuTreatment of non-small cell lung cancer (NSCLC) with radiotherapy or chemoradiotherapy is often accompanied by the development of esophagitis and pneumonitis. Identifying patients who might be at increased risk for normal tissue toxicity would help in determination of the optimal radiation dose to avoid these events. We profiled 59 single nucleotide polymorphisms (SNPs) from 37 inflammation-related genes in 173 NSCLC patients with stage IIIA/IIIB (dry) disease who were treated with definitive radiation or chemoradiation. For esophagitis risk, nine SNPs were associated with a 1.5- to 4-fold increase in risk, including three PTGS2 (COX2) variants: rs20417 (HR:1.93, 95% CI:1.10-3.39), rs5275 (HR:1.58, 95% CI:1.09-2.27), and rs689470 (HR:3.38, 95% CI:1.09-10.49). Significantly increased risk of pneumonitis was observed for patients with genetic variation in the proinflammatory genes IL1A, IL8, TNF, TNFRSF1B, and MIF. In contrast, NOS3:rs1799983 displayed a protective effect with a 45% reduction in pneumonitis risk (HR:0.55, 95% CI:0.31-0.96). Pneumonitis risk was also modulated by polymorphisms in anti-inflammatory genes, including genetic variation in IL13. rs20541 and rs180925 each resulted in increased risk (HR:2.95, 95% CI:1.14-7.63 and HR:3.23, 95% CI:1.03-10.18, respectively). The cumulative effect of these SNPs on risk was dose-dependent, as evidenced by a significantly increased risk of either toxicity with an increasing number of risk genotypes (P<0.001). These results suggest that genetic variations among inflammation pathway genes may modulate the development of radiation-induced toxicity and, ultimately, help in identifying patients who are at an increased likelihood for such events.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0012402&type=printable |
| spellingShingle | Michelle A T Hildebrandt Ritsuko Komaki Zhongxing Liao Jian Gu Joe Y Chang Yuanqing Ye Charles Lu David J Stewart John D Minna Jack A Roth Scott M Lippman James D Cox Waun Ki Hong Margaret R Spitz Xifeng Wu Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer. PLoS ONE |
| title | Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer. |
| title_full | Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer. |
| title_fullStr | Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer. |
| title_full_unstemmed | Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer. |
| title_short | Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer. |
| title_sort | genetic variants in inflammation related genes are associated with radiation induced toxicity following treatment for non small cell lung cancer |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0012402&type=printable |
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