Research Papers:

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

Anna Brzozowska _, Radosław Mlak, Iwona Homa-Mlak, Paweł Gołębiowski, Marcin Mazurek, Marzanna Ciesielka and Teresa Małecka-Massalska

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Oncotarget. 2018; 9:29644-29653. https://doi.org/10.18632/oncotarget.25662

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Anna Brzozowska1, Radosław Mlak2, Iwona Homa-Mlak2, Paweł Gołębiowski1, Marcin Mazurek2, Marzanna Ciesielka3 and Teresa Małecka-Massalska2

1Department of Oncology, Medical University of Lublin, Lublin 20-090, Poland

2Department of Human Physiology, Medical University of Lublin, Lublin 20-080, Poland

3Department of Forensic Medicine, Medical University of Lublin, Lublin 20-090, Poland

Correspondence to:

Anna Brzozowska, email: [email protected]

Keywords: oral mucositis; survival; radiotherapy; head and neck cancer; polymorphism

Received: April 10, 2018     Accepted: June 04, 2018     Published: July 03, 2018


Background: The study purpose was to examine the correlation between SNP in the regulatory region (c.-521G>C, rs4855883) of APEH 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 APEH 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; p = 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; p = 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; p = 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; p = 0.0266).

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

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