Polymorphisms of the XRCC3 C722T and the RAD51 G135C genes and the risk of head and neck cancer in a Polish population.
Genetic variations in DNA repair genes may affect an individual's susceptibility to head and neck cancer. We performed a case-control study to test the association between head and neck cancer risk and two polymorphisms: the C722T of the XRCC3 and the G135C of the RAD51-genes of DNA double strand break (DSB) repair by homologous recombination (HRR). Genotypes were determined by PCR-restriction fragment length polymorphism (PCR-RFLP). DNA was isolated from peripheral blood lymphocytes of a group of 288 patients consisting of 97 subjects with precancerous hyperplastic laryngeal lesions (PHLL) and 191 subjects with head and neck squamous cell carcinoma (HNSCC) as well as 353 healthy control donors. We found an association between PHLL and the 722CT (OR 6.67; 95% CI 3.02-14.74) as well as 722TT (OR 4.65; 95% CI 2.30-9.43) variants of the XRCC3 gene. Similar relation was observed between these genotypes and HNSCC (OR 2.59; 95% CI 1.61-4.16 and OR 5.54; 95% CI 3.22-9.52, respectively). Moreover, we also observed an association between PHLL (OR 6.04; 95% CI 3.69-9.90) and HNSCC (OR 6.04; 95% CI 3.69-9.90) and the 135GC variant of the RAD51 gene. The gene-gene interaction between XRCC3 and RAD51 polymorphic variants may contribute to higher prevalence of PHLL. The increased risk of this disease was observed in case of the combination of the 722CT/135GC (OR 3.81; 95% CI 1.55-9.75) as well as the 722TT/135GC genotypes (OR 5.33; 95% CI 1.96-14.47). The presence of the same genes combinations plays a part in higher probability of HNSCC occurrence (OR 2.42; 95% CI 1.22-4.79 for 722CT/135GC and OR 3.63; 95% CI 1.69-7.76 for 722TT/135GC). We also found an association between these XRCC3 or RAD51 polymorphic variants and smoking status in PHLL (ORs 2.85-10.28 and 1.82-7.35, respectively) and HNSCC patients (ORs 2.94-13.93 and 1.36-3.94, respectively) as well as alcohol intake among PHLL (ORs 3.44-6.12 and 3.52-8.43, respectively) and HNSCC subjects (ORs 2.71-7.01 and 2.33-4.62, respectively). In conclusion our data showed that the C722T and the G135C polymorphisms of the XRCC3 and the RAD51 genes might be associated with HNSCC. Finally we suggested that these polymorphisms might be used as predictive factor of precancerous lesion for head and neck cancer in a Polish population.
Sliwinski
Tomasz
T
Department of Molecular Genetics, University of Lodz, Lodz, Poland.
Walczak
Anna
A
Przybylowska
Karolina
K
Rusin
Pawel
P
Pietruszewska
Wioletta
W
Zielinska-Blizniewska
Hanna
H
Olszewski
Jurek
J
Morawiec-Sztandera
Alina
A
Jendrzejczyk
Slawomir
S
Mlynarski
Wojciech
W
Majsterek
Ireneusz
I
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011044:Poland; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000235:genetics; D051135:Rad51 Recombinase / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D044465:White People / Q000235:genetics
D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; C495153:RAD51 protein, human; D051135:Rad51 Recombinase