Single-nucleotide polymorphisms in base excision repair, nucleotide excision repair, and double strand break genes as markers for response to radiotherapy in patients with Stage I to II head-and-neck cancer.
OBJECTIVE
Polymorphisms in DNA repair genes can influence response to radiotherapy. We analyzed single-nucleotide polymorphisms (SNP) in nine DNA repair genes in 108 patients with head-and-neck cancer (HNSCC) who had received radiotherapy only.


METHODS
From May 1993 to December 2004, patients with Stage I and II histopathologically confirmed HNSCC underwent radiotherapy. DNA was obtained from paraffin-embedded tissue, and SNP analysis was performed using a real-time polymerase chain reaction allelic discrimination TaqMan assay with minor modifications.


RESULTS
Patients were 101 men (93.5%) and 7 (6.5%) women, with a median age of 64 years (range, 40 to 89 years). Of the patients, 76 (70.4%) patients were Stage I and 32 (29.6%) were Stage II. The XPF/ERCC1 SNP at codon 259 and XPG/ERCC5 at codon 46 emerged as significant predictors of progression (p = 0.00005 and 0.049, respectively) and survival (p = 0.0089 and 0.0066, respectively). Similarly, when variant alleles of XPF/ERCC1, XPG/ERCC5 and XPA were examined in combination, a greater number of variant alleles was associated with shorter time to progression (p = 0.0003) and survival (p = 0.0002).


CONCLUSIONS
Genetic polymorphisms in XPF/ERCC1, XPG/ERCC5, and XPA may significantly influence response to radiotherapy; large studies are warranted to confirm their role in HNSCC.
Carles
Joan
J
Department of Medical Oncology, Hospital del Mar, University Autonoma of Barcelona, Barcelona, Spain. jcarles@imas.imim.es
Monzo
Mariano
M
Amat
Marta
M
Jansa
Sonia
S
Artells
Rosa
R
Navarro
Alfons
A
Foro
Palmira
P
Alameda
Francesc
F
Gayete
Angel
A
Gel
Bernat
B
Miguel
Maribel
M
Albanell
Joan
J
Fabregat
Xavier
X
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000532:radiotherapy*; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D011379:Prognosis; D011878:Radiotherapy / Q000706:statistics & numerical data*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; D004265:DNA Helicases; C106893:XRCC5 protein, human; D000072200:Ku Autoantigen