Genetic Variants of SP-D Confer Susceptibility to Radiation Pneumonitis in Lung Cancer Patients Undergoing Thoracic Radiation Therapy

Overview

Journal Cancer Med

Specialty Oncology

Date 2019 Mar 22

PMID 30897289

Citations 6

Authors

Li Xu

Junhong Jiang

Yunming Li

Ling Zhang

Zhihui Li

Jing Xian

Chaoyang Jiang

Yong Diao

Xiaomei Su

Hongyu Xu

Yue Zhang

Tao Zhang

ZhenZhou Yang

Bangxian Tan

Hua Li

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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References

Ikegami M, Na C, Korfhagen T, Whitsett J . Surfactant protein D influences surfactant ultrastructure and uptake by alveolar type II cells. Am J Physiol Lung Cell Mol Physiol. 2004; 288(3):L552-61. DOI: 10.1152/ajplung.00142.2004. View

Sapkota M, Kharbanda K, Wyatt T . Malondialdehyde-Acetaldehyde-Adducted Surfactant Protein Alters Macrophage Functions Through Scavenger Receptor A. Alcohol Clin Exp Res. 2016; 40(12):2563-2572. PMC: 5133169. DOI: 10.1111/acer.13248. View

Yin M, Liao Z, Liu Z, Wang L, OReilly M, Gomez D . Genetic variants of the nonhomologous end joining gene LIG4 and severe radiation pneumonitis in nonsmall cell lung cancer patients treated with definitive radiotherapy. Cancer. 2011; 118(2):528-35. PMC: 3184314. DOI: 10.1002/cncr.26214. View

Ishii T, Hagiwara K, Ikeda S, Arai T, Mieno M, Kumasaka T . Association between genetic variations in surfactant protein d and emphysema, interstitial pneumonia, and lung cancer in a Japanese population. COPD. 2012; 9(4):409-16. DOI: 10.3109/15412555.2012.676110. View

Zhang L, Yang M, Bi N, Fang M, Sun T, Ji W . ATM polymorphisms are associated with risk of radiation-induced pneumonitis. Int J Radiat Oncol Biol Phys. 2010; 77(5):1360-8. DOI: 10.1016/j.ijrobp.2009.07.1675. View

Yin M, Liao Z, Yuan X, Guan X, OReilly M, Welsh J . Polymorphisms of the vascular endothelial growth factor gene and severe radiation pneumonitis in non-small cell lung cancer patients treated with definitive radiotherapy. Cancer Sci. 2012; 103(5):945-50. PMC: 3337362. DOI: 10.1111/j.1349-7006.2012.02229.x. View

Korfhagen T, Sheftelyevich V, Burhans M, Bruno M, Ross G, Wert S . Surfactant protein-D regulates surfactant phospholipid homeostasis in vivo. J Biol Chem. 1998; 273(43):28438-43. DOI: 10.1074/jbc.273.43.28438. View

Fleming C, Cagney D, OKeeffe S, Brennan S, Armstrong J, McClean B . Normal tissue considerations and dose-volume constraints in the moderately hypofractionated treatment of non-small cell lung cancer. Radiother Oncol. 2016; 119(3):423-31. DOI: 10.1016/j.radonc.2016.03.013. View

Hildebrandt M, Komaki R, Liao Z, Gu J, Chang J, Ye Y . Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer. PLoS One. 2010; 5(8):e12402. PMC: 2928273. DOI: 10.1371/journal.pone.0012402. View

10.

Thomas N, DiAngelo S, Hess J, Fan R, Ball M, Geskey J . Transmission of surfactant protein variants and haplotypes in children hospitalized with respiratory syncytial virus. Pediatr Res. 2009; 66(1):70-3. PMC: 2710771. DOI: 10.1203/PDR.0b013e3181a1d768. View

11.

Nayak A, Dodagatta-Marri E, Tsolaki A, Kishore U . An Insight into the Diverse Roles of Surfactant Proteins, SP-A and SP-D in Innate and Adaptive Immunity. Front Immunol. 2012; 3:131. PMC: 3369187. DOI: 10.3389/fimmu.2012.00131. View

12.

Yin M, Liao Z, Liu Z, Wang L, Gomez D, Komaki R . Functional polymorphisms of base excision repair genes XRCC1 and APEX1 predict risk of radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy. Int J Radiat Oncol Biol Phys. 2011; 81(3):e67-73. PMC: 3136565. DOI: 10.1016/j.ijrobp.2010.11.079. View

13.

Yang M, Zhang L, Bi N, Ji W, Tan W, Zhao L . Association of P53 and ATM polymorphisms with risk of radiation-induced pneumonitis in lung cancer patients treated with radiotherapy. Int J Radiat Oncol Biol Phys. 2010; 79(5):1402-7. DOI: 10.1016/j.ijrobp.2009.12.042. View

14.

Sasaki R, Soejima T, Matsumoto A, Maruta T, Yamada K, Ota Y . Clinical significance of serum pulmonary surfactant proteins a and d for the early detection of radiation pneumonitis. Int J Radiat Oncol Biol Phys. 2001; 50(2):301-7. DOI: 10.1016/s0360-3016(00)01591-1. View

15.

Zhou F, He X, Liu H, Zhu Y, Jin T, Chen C . Functional polymorphisms of circadian positive feedback regulation genes and clinical outcome of Chinese patients with resected colorectal cancer. Cancer. 2011; 118(4):937-46. DOI: 10.1002/cncr.26348. View

16.

Mak R, Alexander B, Asomaning K, Heist R, Liu C, Su L . A single-nucleotide polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy. Cancer. 2011; 118(14):3654-65. PMC: 3312983. DOI: 10.1002/cncr.26667. View

17.

Kelsey C, Rosenstein B, Marks L . Predicting toxicity from radiation therapy--it's genetic, right?. Cancer. 2011; 118(14):3450-4. PMC: 4287226. DOI: 10.1002/cncr.26670. View

18.

Ikegami M, Whitsett J, Jobe A, Ross G, Fisher J, Korfhagen T . Surfactant metabolism in SP-D gene-targeted mice. Am J Physiol Lung Cell Mol Physiol. 2000; 279(3):L468-76. DOI: 10.1152/ajplung.2000.279.3.L468. View

19.

Tanabe S, Myojin M, Shimizu S, Fujino M, Takahashi H, Shirato H . Dose-volume analysis for respiratory toxicity in intrathoracic esophageal cancer patients treated with definitive chemoradiotherapy using extended fields. J Radiat Res. 2013; 54(6):1085-94. PMC: 3823774. DOI: 10.1093/jrr/rrt047. View

20.

Palma D, Senan S, Tsujino K, Barriger R, Rengan R, Moreno M . Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys. 2012; 85(2):444-50. PMC: 3448004. DOI: 10.1016/j.ijrobp.2012.04.043. View