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Genetic variants of SP‐D confer susceptibility to radiation pneumonitis in lung cancer patients undergoing thoracic radiation therapy

BACKGROUND: Surfactant protein D (SP‐D) is an innate immunity molecule in the alveoli. However, the associations between genetic variants of SP‐D and radiation pneumonitis (RP) have never been investigated. METHODS: The Linkage disequilibrium of SP‐D and tagSNPs were analyzed by using Haploview 4.1....

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Autores principales: Xu, Li, Jiang, Junhong, Li, Yunming, Zhang, Ling, Li, Zhihui, Xian, Jing, Jiang, Chaoyang, Diao, Yong, Su, Xiaomei, Xu, Hongyu, Zhang, Yue, Zhang, Tao, Yang, Zhenzhou, Tan, Bangxian, Li, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536953/
https://www.ncbi.nlm.nih.gov/pubmed/30897289
http://dx.doi.org/10.1002/cam4.2088
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author Xu, Li
Jiang, Junhong
Li, Yunming
Zhang, Ling
Li, Zhihui
Xian, Jing
Jiang, Chaoyang
Diao, Yong
Su, Xiaomei
Xu, Hongyu
Zhang, Yue
Zhang, Tao
Yang, Zhenzhou
Tan, Bangxian
Li, Hua
author_facet Xu, Li
Jiang, Junhong
Li, Yunming
Zhang, Ling
Li, Zhihui
Xian, Jing
Jiang, Chaoyang
Diao, Yong
Su, Xiaomei
Xu, Hongyu
Zhang, Yue
Zhang, Tao
Yang, Zhenzhou
Tan, Bangxian
Li, Hua
author_sort Xu, Li
collection PubMed
description BACKGROUND: Surfactant protein D (SP‐D) is an innate immunity molecule in the alveoli. However, the associations between genetic variants of SP‐D and radiation pneumonitis (RP) have never been investigated. METHODS: The Linkage disequilibrium of SP‐D and tagSNPs were analyzed by using Haploview 4.1. Eight tagSNPs were genotyped among 396 lung cancer patients who received thoracic radiation therapy with follow–up time (median [P25, P75]: 11[6, 18]) using improved multiplex ligation detection reaction (iMLDR). The associations between clinical characteristics, tagSNP alleles, genotypes, haplotypes and onset time of grade ≥2 or ≥3 RP were evaluated by using univariate and multivariate Cox proportional hazard regression model. RESULTS: Three tagSNPs of SP‐D (rs1998374, rs911887 and rs2255326) were significantly associated with grade ≥2 RP in multivariate analysis with multiple testing (Q test). The rs199874 had a protective effect for grade ≥2 RP in the dominant model (Hazard ratio (HR), 0.575; 95% confidence interval (CI), 0.378‐0.875). The homozygous mutant genotype for rs911887 had risk effect for grade ≥2 RP (HR, 2.209; 95% CI, 1.251‐3.902). The A mutant allele of rs2255326 also showed an elevated risk for grade ≥2 RP (HR, 1.777; 95% CI, 1.283‐2.461) and this risk effect was still significant in the recessive genetic model (HR, 3.320; 95% CI, 1.659‐6.644) and dominant genetic model (HR, 1.773; 95% CI, 1.166‐2.696). Compared to the lung cancer patients bearing the most common haplotype C‐G‐T, the patients bearing the haplotype T‐A‐C (rs1998374‐rs2255326‐rs911887) showed a significant risk of both grade ≥2 RP (HR, 1.885; 95% CI, 1.284‐2.765) and grade ≥3 RP (HR, 2.256; 95% CI, 1.248‐4.080). CONCLUSIONS: Genetic variants of SP‐D were associated with risk of RP development in lung cancer patients receiving thoracic radiotherapy.
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spelling pubmed-65369532019-06-03 Genetic variants of SP‐D confer susceptibility to radiation pneumonitis in lung cancer patients undergoing thoracic radiation therapy Xu, Li Jiang, Junhong Li, Yunming Zhang, Ling Li, Zhihui Xian, Jing Jiang, Chaoyang Diao, Yong Su, Xiaomei Xu, Hongyu Zhang, Yue Zhang, Tao Yang, Zhenzhou Tan, Bangxian Li, Hua Cancer Med Cancer Prevention BACKGROUND: Surfactant protein D (SP‐D) is an innate immunity molecule in the alveoli. However, the associations between genetic variants of SP‐D and radiation pneumonitis (RP) have never been investigated. METHODS: The Linkage disequilibrium of SP‐D and tagSNPs were analyzed by using Haploview 4.1. Eight tagSNPs were genotyped among 396 lung cancer patients who received thoracic radiation therapy with follow–up time (median [P25, P75]: 11[6, 18]) using improved multiplex ligation detection reaction (iMLDR). The associations between clinical characteristics, tagSNP alleles, genotypes, haplotypes and onset time of grade ≥2 or ≥3 RP were evaluated by using univariate and multivariate Cox proportional hazard regression model. RESULTS: Three tagSNPs of SP‐D (rs1998374, rs911887 and rs2255326) were significantly associated with grade ≥2 RP in multivariate analysis with multiple testing (Q test). The rs199874 had a protective effect for grade ≥2 RP in the dominant model (Hazard ratio (HR), 0.575; 95% confidence interval (CI), 0.378‐0.875). The homozygous mutant genotype for rs911887 had risk effect for grade ≥2 RP (HR, 2.209; 95% CI, 1.251‐3.902). The A mutant allele of rs2255326 also showed an elevated risk for grade ≥2 RP (HR, 1.777; 95% CI, 1.283‐2.461) and this risk effect was still significant in the recessive genetic model (HR, 3.320; 95% CI, 1.659‐6.644) and dominant genetic model (HR, 1.773; 95% CI, 1.166‐2.696). Compared to the lung cancer patients bearing the most common haplotype C‐G‐T, the patients bearing the haplotype T‐A‐C (rs1998374‐rs2255326‐rs911887) showed a significant risk of both grade ≥2 RP (HR, 1.885; 95% CI, 1.284‐2.765) and grade ≥3 RP (HR, 2.256; 95% CI, 1.248‐4.080). CONCLUSIONS: Genetic variants of SP‐D were associated with risk of RP development in lung cancer patients receiving thoracic radiotherapy. John Wiley and Sons Inc. 2019-03-21 /pmc/articles/PMC6536953/ /pubmed/30897289 http://dx.doi.org/10.1002/cam4.2088 Text en © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Prevention
Xu, Li
Jiang, Junhong
Li, Yunming
Zhang, Ling
Li, Zhihui
Xian, Jing
Jiang, Chaoyang
Diao, Yong
Su, Xiaomei
Xu, Hongyu
Zhang, Yue
Zhang, Tao
Yang, Zhenzhou
Tan, Bangxian
Li, Hua
Genetic variants of SP‐D confer susceptibility to radiation pneumonitis in lung cancer patients undergoing thoracic radiation therapy
title Genetic variants of SP‐D confer susceptibility to radiation pneumonitis in lung cancer patients undergoing thoracic radiation therapy
title_full Genetic variants of SP‐D confer susceptibility to radiation pneumonitis in lung cancer patients undergoing thoracic radiation therapy
title_fullStr Genetic variants of SP‐D confer susceptibility to radiation pneumonitis in lung cancer patients undergoing thoracic radiation therapy
title_full_unstemmed Genetic variants of SP‐D confer susceptibility to radiation pneumonitis in lung cancer patients undergoing thoracic radiation therapy
title_short Genetic variants of SP‐D confer susceptibility to radiation pneumonitis in lung cancer patients undergoing thoracic radiation therapy
title_sort genetic variants of sp‐d confer susceptibility to radiation pneumonitis in lung cancer patients undergoing thoracic radiation therapy
topic Cancer Prevention
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536953/
https://www.ncbi.nlm.nih.gov/pubmed/30897289
http://dx.doi.org/10.1002/cam4.2088
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