Polymorphisms of the XRCC3 C722T and the RAD51 G135C genes and the risk of head and neck cancer in a Polish population |
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| Authors: | Tomasz Sliwinski Anna Walczak Karolina Przybylowska Pawel Rusin Wioletta Pietruszewska Hanna Zielinska-Blizniewska Jurek Olszewski Alina Morawiec-Sztandera Slawomir Jendrzejczyk Wojciech Mlynarski Ireneusz Majsterek |
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| Affiliation: | 1. Thoracic Oncology Unit, Department of Medical Oncology;2. Evaluative Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan;3. Department of Medical Oncology, Universita Politecnica delle Marche, Ancona;4. Department of Molecular and Clinical Endocrinology and Oncology, ‘Federico II’, University, Naples;5. Department of Oncology and Hematology, Humanitas Cancer Center, Rozzano;6. Laboratory of Molecular Pharmacology, IRCCS ‘Mario Negri’, Milan;7. Departments of Thoracic Surgery;8. Pathology;9. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;1. New York University Cancer Institute, New York, NY, USA;2. Department of Oncology, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;3. Instituto Oncologico Veneto – IRCCS, Padova, Italy;4. Department of Pathology, School of Medicine, University of Melbourne, Parkville, Victoria, Australia;5. Faculty of Medicine in the Galilee, Bar Ilan University, Safid, Israel;1. The Cancer Therapy Center, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China;2. Genetics and Molecular Biology Laboratory, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China;3. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China;1. Department of Biochemistry, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan;2. RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo-cho, Sayo-Gun, Hyogo 679-5148, Japan;3. Japan Synchrotron Radiation Research Institute (JASRI), SPring-8, Kouto, Sayo, Hyogo 679-5198, Japan;4. Department of Biological Sciences, Osaka University, 1-1 Machikaneyamacho, Toyonaka, Osaka 560-0043, Japan |
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| Abstract: | ![]()
Genetic variations in DNA repair genes may affect an individual's susceptibility to head and neck cancer. We performed a case–control study to test the association between head and neck cancer risk and two polymorphisms: the C722 T of the XRCC3 and the G135C of the RAD51 —genes of DNA double strand break (DSB) repair by homologous recombination (HRR). Genotypes were determined by PCR-restriction fragment lenght polymorphism (PCR-RFLP). DNA was isolated from peripheral blood lymphocytes of a group of 288 patients consisting of 97 subjects with precancerous hyperplastic laryngeal lesions (PHLL) and 191 subjects with head and neck squamous cell carcinoma (HNSCC) as well as 353 healthy control donors. We found an association between PHLL and the 722CT (OR 6.67; 95% CI 3.02–14.74) as well as 722 TT (OR 4.65; 95% CI 2.30–9.43) variants of the XRCC3 gene. Similar relation was observed between these genotypes and HNSCC (OR 2.59; 95% CI 1.61–4.16 and OR 5.54; 95% CI 3.22–9.52, respectively). Moreover, we also observed an association between PHLL (OR 6.04; 95% CI 3.69–9.90) and HNSCC (OR 6.04; 95% CI 3.69–9.90) and the135GC variant of the RAD51 gene. The gene–gene interaction between XRCC3 and RAD51 polymorphic variants may contribute to higher prevalence of PHLL. The increased risk of this disease was observed in case of the combination of the 722CT/135GC (OR 3.81; 95% CI 1.55–9.75) as well as the 722 TT/135GC genotypes (OR 5.33; 95% CI 1.96–14.47). The presence of the same genes combinations plays a part in higher probability of HNSCC occurrence (OR 2.42; 95% CI 1.22–4.79 for 722CT/135GC and OR 3.63; 95% CI 1.69–7.76 for 722 TT/135GC). We also found an association between these XRCC3 or RAD51 polymorphic variants and smoking status in PHLL (ORs 2.85–10.28 and 1.82–7.35, respectively) and HNSCC patients (ORs 2.94–13.93 and 1.36–3.94, respectively) as well as alcohol intake among PHLL (ORs 3.44–6.12 and 3.52–8.43, respectively) and HNSCC subjects (ORs 2.71–7.01 and 2.33–4.62, respectively). In conclusion our data showed that the C722 T and the G135C polymorphisms of the XRCC3 and the RAD51 genes might be associated with HNSCC. Finally we suggested that these polymorphisms might be used as predictive factor of precancerous lesion for head and neck cancer in a Polish population. |
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