title: Reduced mRNA expression of nucleotide excision repair genes in lymphocytes and risk of squamous cell carcinoma of the head and neck.
abstract: Nucleotide excision repair (NER) plays a critical role in the development of smoking-related cancers. We hypothesize that mRNA expression levels of NER genes are associated with risk of the squamous cell carcinoma of head and neck (SCCHN). To test this hypothesis, we conducted a case-control study of 260 SCCHN patients and 246 cancer-free controls by measuring the mRNA expression levels of eight core NER genes in cultured peripheral lymphocytes. Compared with the controls, cases had statistically significantly lower expression levels of DDB1 and ERCC3 (P = 0.015 and 0.041, respectively). Because DDB1 and ERCC3 expression levels were highly correlated, we used DDB1 for further multivariate analyses and modeling. After dividing the subjects by controls' quartiles of expression levels, we found an association between an increased risk of SCCHN and low DDB1 expression levels [adjusted ORs and 95% CIs: 1.92 and 1.11-3.32, 1.48 and 0.85-2.59, 2.00 and 1.15-3.45 for the 2nd-4th quartiles, respectively, compared with the 1st quartile; Ptrend = 0.026]. We also identified a multiplicative interaction between sex and DDB1 expression levels (P = 0.007). Finally, the expanded model with gene expression levels, in addition to demographic and clinical variables, on SCCHN risk was significantly improved, especially among men. In conclusion, reduced DDB1 expression levels were associated with an increased risk of SCCHN. However, these results need to be validated in larger studies.
authors.affiliation: Duke Cancer Institute, Duke University Medical Center and.|Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.|Department of Otorhinolaryngology-Head and Neck Surgery, Second Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi, 710004, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Han
authors.affiliation: Duke Cancer Institute, Duke University Medical Center and.|Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
authors.forename: Fengqin
authors.initials: F
authors.lastname: Gao
authors.affiliation: Duke Cancer Institute, Duke University Medical Center and.|Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Duke Cancer Institute, Duke University Medical Center and.|Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Duke Cancer Institute, Duke University Medical Center and.|Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Duke Cancer Institute, Duke University Medical Center and.|Division of Blood and Marrow Transplantation and.
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Troy
authors.affiliation: Duke Cancer Institute, Duke University Medical Center and.|Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, 27710, USA.
authors.forename: Kouros
authors.initials: K
authors.lastname: Owzar
authors.affiliation: Duke Cancer Institute, Duke University Medical Center and.|Division of Head and Neck Surgery Communications Science, Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA.
authors.forename: Walter
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery and.|Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA and.
authors.forename: Jose P
authors.initials: JP
authors.lastname: Zevallos
authors.affiliation: Departments of Head and Neck Surgery and.|Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.affiliation: Duke Cancer Institute, Duke University Medical Center and.|Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D004265:DNA Helicases / Q000235:genetics; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D004843:Epistasis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger; D012372:ROC Curve; D012306:Risk; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D055815:Young Adult
chemical_list: C091435:DDB1 protein, human; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C072022:XPBC-ERCC-3 protein; D004265:DNA Helicases