title: DNA repair genes XPC, XPD, XRCC1, and XRCC3 are associated with risk and survival of squamous cell carcinoma of the head and neck.
abstract: 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.
authors.affiliation: Department of Otorhinolaryngology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Lovisa
authors.initials: L
authors.lastname: Farnebo
authors.affiliation: Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Stjernström
authors.affiliation: Division of Environmental and Occupational Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Fredrikson
authors.affiliation: Division of Otorhinolaryngology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Ansell
authors.affiliation: Department of Clinical Pathology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Stina
authors.initials: S
authors.lastname: Garvin
authors.affiliation: Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. Electronic address: lena.thunell@liu.se.
authors.forename: Lena K
authors.initials: LK
authors.lastname: Thunell
mesh_terms: D000368:Aged; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000077195:Squamous Cell Carcinoma of Head and Neck; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; C086984:XPC protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
keywords: HPV; Head and neck squamous cell carcinoma; Overall survival; XPC; XPD; p53