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DNA repair genes XPC, XPD, XRCC1, and XRCC3 are associated with risk and survival of squamous cell carcinoma of the head and neck
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
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2015 (English)In: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 31, 64-72 p.Article in journal (Refereed) Published
Abstract [en]

Head and neck squamous cell carcinomas (HNSCC) are a heterogenous group of tumors with a high rate of early recurrences, second primary tumors, and mortality. Despite advances in diagnosis and treatment over the past decades, the overall 5-year survival rate remains around 50%. Since the head-and neck-region is continuously exposed to potentially DNA-damaging exogenous and endogenous factors, it is reasonable to expect that the DNA repair genes play a part in the development, progression, and outcome of HNSCC. The aim of this study was to investigate the SNPs XPC A499V, XPD K751Q XRCC1 R399Q and XRCC3 T241M as potential risk factors and indicators of survival among Caucasian patients. One-hundred-sixty-nine patients as well as 344 healthy controls were included and genotyped with PCR-RFLP. We showed that XPC A499V was associated with increased risk of HNSCC, especially laryngeal carcinoma. Among women, XPD K751Q was associated with increased risk of oral SCC. Furthermore, XPD homozygous mutant individuals had the shortest survival time, a survival time that increased however after full dose radiotherapy. Wild-type individuals of XRCC3 T241M demonstrated an earlier age of onset. HPV-positive never smokers had lower frequencies of p53 mutation. Among HNSCC patients, HPV-positivity was significantly associated with XRCC1 R399Q homozygous mutant genotype. Moreover, combinations of putative risk alleles seemed to act synergistically, increasing the risk of HNSCC. In conclusion, our results suggest that SNPs of the DNA repair genes XPC, XPD, XRCC1, and XRCC3 may affect risk and survival of HNSCC. (C) 2015 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
Elsevier , 2015. Vol. 31, 64-72 p.
Keyword [en]
Head and neck squamous cell carcinoma; XPC; XPD; HPV; p53; Overall survival
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-120212DOI: 10.1016/j.dnarep.2015.05.003ISI: 000357138600007PubMedID: 26001739OAI: oai:DiVA.org:liu-120212DiVA: diva2:842695
Note

Funding Agencies|Swedish Cancer Society; Laryngfonden

Available from: 2015-07-21 Created: 2015-07-20 Last updated: 2015-07-21

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Farnebo, LovisaFredrikson, MatsAnsell, AnnaGarvin, StinaThunell, Lena
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Division of Neuro and Inflammation ScienceDepartment of Otorhinolaryngology in LinköpingFaculty of Medicine and Health SciencesDivision of Cell BiologyDepartment of Clinical Pathology and Clinical Genetics
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DNA Repair
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