Expression of nucleotide excision repair genes and the risk for squamous cell carcinoma of the head and neck.
BACKGROUND
Phenotypic differences in the ability to repair genetic damage induced by tobacco carcinogens may reflect genetic differences in susceptibility to squamous cell carcinoma of the head and neck (SCCHN). The objective of this study was to assess the variation in baseline expression of five nucleotide excision repair genes between individuals with SCCHN and cancer free controls.


METHODS
The authors conducted a hospital-based case-control study of 57 SCCHN patients and 105 cancer free controls. Using peripheral blood lymphocytes, a multiplex reverse transcriptase-polymerase chain reaction assay was used to quantitate in vitro the mRNA levels of five genes (ERCC1, XPB/ERCC3, XPG/ERCC5, CSB/ERCC6, and XPC) involved in the nucleotide excision repair pathway.


RESULTS
The levels of ERCC1, XPB/ERCC3, XPG/ERCC5, and CSB/ERCC6 transcripts were lower in cases than in controls (P =0.0001, 0.096, 0.001, and 0.0001, respectively). In multivariate logistic regression analysis (adjusting for age, gender, race, smoking status, and alcohol use), low expression of ERCC1, XPB/ERCC3, XPG/ERCC5, and CSB/ERCC6 was associated with a statistically significant increased risk for SCCHN (adjusted odds ratios [95% confidence intervals] 6.42 [2.63-15.69], 2.86 [1.39-5.90], 3.69 [1.73-7.90], and 2.46 [1.19-5.09], respectively).


CONCLUSIONS
Reduced expression of ERCC1, XPB/ERCC3, XPG/ERCC5, and CSB/ERCC6 is associated with a more than two-fold increased risk of SCCHN.
Cheng
Lie
L
Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Sturgis
Erich M
EM
Eicher
Susan A
SA
Spitz
Margaret R
MR
Wei
Qingyi
Q
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins; D004720:Endonucleases; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D010865:Pilot Projects; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5
D004265:DNA Helicases; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C078672:hay protein, Drosophila; C071447:ERCC1 protein, human; C078673:ERCC6 protein, human