Polymorphism of Regulatory Region of APEH Gene (c.-521G>C, Rs4855883) As a Relevant Predictive Factor for Radiotherapy Induced Oral Mucositis and Overall Survival in Head Neck Cancer Patients

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Jul 25

PMID 30038710

Citations 6

Authors

Anna Brzozowska

Radoslaw Mlak

Iwona Homa-Mlak

Pawel Golebiowski

Marcin Mazurek

Marzanna Ciesielka

Teresa Malecka-Massalska

Affiliations

Soon will be listed here.

Abstract

Background: The study purpose was to examine the correlation between SNP in the regulatory region (c.-521G>C, rs4855883) of gene as well as the incidence and severity of radiotherapy (RTH) induced oral mucositis (OM) and overall survival (OS) in head and neck cancer (HNC) patients.

Methods: OM in 62 HNC patients subjected to irradiation was assessed using RTOG/EORTC scale. DNA was isolated from whole blood of HNC patients. Mini-sequencing method (SNaPshot PCR) was used to determine the genotype.

Results: The following frequency of occurrence of gene was observed: CC: 37.1%, CG: 43.6% and GG: 19.3%. It was established that the presence of CC genotype reduced the risk of occurrence of grade 2 and 3 OM symptoms: 3-fold in RTH week 2 (in case of CC vs GC or GG it was: 26.8% vs 73.2% patients, respectively, OR = 0.27, 95 CI: 0.09-0.83; = 0.0222), 6-fold in RTH week 3 (in case of CC vs GC or GG it was: 29.4% vs 70.6% patients, respectively, OR = 0.16, 95 CI: 0.04-0.67; = 0.0125) and grade 3 OM symptoms 4-fold in RTH week 6 (in case of CC vs GC or GG it was: 19.2% vs 80.8% patients, respectively, OR = 0.23, 95 CI: 0.07-0.77; = 0.0166). CC genotype was associated with lower OS (CC vs GG or GC: 29 months vs 38 months; HR = 2.48, 95% CI: 0.90-6.85; = 0.0266).

Conclusion: CC genotype of gene was correlated with the risk of more severe radiotherapy-induced OM in HNC patients and lower rates of survival.

Citing Articles

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San Valentin E, Do K, Yeung S, Reyes-Gibby C Int J Mol Sci. 2023; 24(23).

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Predictive Factors for Chemoradiation-Induced Oral Mucositis and Dysphagia in Head and Neck Cancer: A Scoping Review.

Nicol A, Ching J, Tam V, Liu K, Leung V, Cai J Cancers (Basel). 2023; 15(23).

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Sonis S Front Oral Health. 2022; 3:917860.

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References

Cleynen I, Vazeille E, Artieda M, Verspaget H, Szczypiorska M, Bringer M . Genetic and microbial factors modulating the ubiquitin proteasome system in inflammatory bowel disease. Gut. 2013; 63(8):1265-74. DOI: 10.1136/gutjnl-2012-303205. View

Ho A, Atencio D, Peters S, Stock R, Formenti S, Cesaretti J . Genetic predictors of adverse radiotherapy effects: the Gene-PARE project. Int J Radiat Oncol Biol Phys. 2006; 65(3):646-55. DOI: 10.1016/j.ijrobp.2006.03.006. View

Hanasoge S, Magliocca K, Switchenko J, Saba N, Wadsworth J, El-Deiry M . Clinical outcomes in elderly patients with human papillomavirus-positive squamous cell carcinoma of the oropharynx treated with definitive chemoradiation therapy. Head Neck. 2015; 38(6):846-51. PMC: 4959784. DOI: 10.1002/hed.24073. View

Hershko A, Ciechanover A . The ubiquitin system. Annu Rev Biochem. 1998; 67:425-79. DOI: 10.1146/annurev.biochem.67.1.425. View

Sonis S . Oral mucositis in head and neck cancer: risk, biology, and management. Am Soc Clin Oncol Educ Book. 2013; . DOI: 10.14694/EdBook_AM.2013.33.e236. View

Gogliettino M, Riccio A, Balestrieri M, Cocca E, Facchiano A, DArco T . A novel class of bifunctional acylpeptide hydrolases--potential role in the antioxidant defense systems of the Antarctic fish Trematomus bernacchii. FEBS J. 2013; 281(1):401-15. DOI: 10.1111/febs.12610. View

Trotti A, Bellm L, Epstein J, Frame D, Fuchs H, Gwede C . Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiother Oncol. 2003; 66(3):253-62. DOI: 10.1016/s0167-8140(02)00404-8. View

Werbrouck J, De Ruyck K, Duprez F, Veldeman L, Claes K, van Eijkeren M . Acute normal tissue reactions in head-and-neck cancer patients treated with IMRT: influence of dose and association with genetic polymorphisms in DNA DSB repair genes. Int J Radiat Oncol Biol Phys. 2009; 73(4):1187-95. DOI: 10.1016/j.ijrobp.2008.08.073. View

Hu K, Harrison L . Impact of anemia in patients with head and neck cancer treated with radiation therapy. Curr Treat Options Oncol. 2004; 6(1):31-45. DOI: 10.1007/s11864-005-0011-4. View

10.

Azria D, Ozsahin M, Kramar A, Peters S, Atencio D, Crompton N . Single nucleotide polymorphisms, apoptosis, and the development of severe late adverse effects after radiotherapy. Clin Cancer Res. 2008; 14(19):6284-8. PMC: 2771757. DOI: 10.1158/1078-0432.CCR-08-0700. View

11.

Wu W, Cho C, Lee C, Wu K, Fan D, Yu J . Proteasome inhibition: a new therapeutic strategy to cancer treatment. Cancer Lett. 2010; 293(1):15-22. DOI: 10.1016/j.canlet.2009.12.002. View

12.

Siegel R, Miller K, Jemal A . Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67(1):7-30. DOI: 10.3322/caac.21387. View

13.

Song Y, Han F, Liu M, Xia C, Shi W, Dong L . Association between Single Nucleotide Polymorphisms in XRCC3 and Radiation-Induced Adverse Effects on Normal Tissue: A Meta-Analysis. PLoS One. 2015; 10(6):e0130388. PMC: 4474802. DOI: 10.1371/journal.pone.0130388. View

14.

Le Z, Niu X, Chen Y, Ou X, Zhao G, Liu Q . Predictive single nucleotide polymorphism markers for acute oral mucositis in patients with nasopharyngeal carcinoma treated with radiotherapy. Oncotarget. 2017; 8(38):63026-63037. PMC: 5609900. DOI: 10.18632/oncotarget.18450. View

15.

Wen Z, Fan S, Du C, Yin T, Zhou B, Peng Z . Influence of acylpeptide hydrolase polymorphisms on valproic acid level in Chinese epilepsy patients. Pharmacogenomics. 2016; 17(11):1219-1225. DOI: 10.2217/pgs-2016-0030. View

16.

Komatsu T, Yoshioka K, Hanaoka K, Terai T, Ueno T, Nagano T . Identification of Lung Inflammation-Related Elevation of Acylamino Acid Releasing Enzyme (APEH) Activity Using an Enzymomics Approach. Chem Pharm Bull (Tokyo). 2016; 64(11):1533-1538. DOI: 10.1248/cpb.c16-00540. View

17.

Nakai A, Yamauchi Y, Sumi S, Tanaka K . Role of acylamino acid-releasing enzyme/oxidized protein hydrolase in sustaining homeostasis of the cytoplasmic antioxidative system. Planta. 2012; 236(2):427-36. DOI: 10.1007/s00425-012-1614-1. View

18.

Becker-Schiebe M, Sperling M, Pinkert U, Hoffmann W . Impact of p16 Alterations and Pretreatment Anemia on Toxicity in Head and Neck Cancer Patients Undergoing Definitive Radiochemotherapy. Oncol Res Treat. 2015; 38(11):570-6. DOI: 10.1159/000441344. View

19.

Gautam A, Fernandes D, Vidyasagar M, Maiya A, Vadhiraja B . Low level laser therapy for concurrent chemoradiotherapy induced oral mucositis in head and neck cancer patients - a triple blinded randomized controlled trial. Radiother Oncol. 2012; 104(3):349-54. DOI: 10.1016/j.radonc.2012.06.011. View

20.

Ren J, Dai X, Yan G, Jin M, Liu C, Yang K . Acute oral mucositis in nasopharyngeal carcinoma patients treated with radiotherapy: association with genetic polymorphism in DNA DSB repair genes. Int J Radiat Biol. 2013; 90(3):256-61. DOI: 10.3109/09553002.2014.873558. View