Department of Molecular Genetics, University of Lodz, Lodz, Poland.
Exp Mol Pathol. 2010 Dec;89(3):358-66. doi: 10.1016/j.yexmp.2010.08.005. Epub 2010 Sep 8.
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.
DNA 修复基因中的遗传变异可能会影响个体患头颈部癌症的易感性。我们进行了一项病例对照研究，以测试头颈部癌症风险与两个多态性之间的关联：X 射线修复交叉互补基因 3（XRCC3）的 C722T 和 DNA 双链断裂（DSB）修复同源重组（HRR）的 RAD51 基因的 G135C。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）确定基因型。从一组 288 名患者的外周血淋巴细胞中分离出 DNA，其中包括 97 名具有癌前增生性喉病变（PHLL）的受试者和 191 名患有头颈部鳞状细胞癌（HNSCC）的受试者以及 353 名健康对照供体。我们发现 PHLL 与 XRCC3 基因的 722CT（OR 6.67；95%CI 3.02-14.74）和 722TT（OR 4.65；95%CI 2.30-9.43）变体之间存在关联。在这些基因型和 HNSCC 之间也观察到类似的关系（OR 2.59；95%CI 1.61-4.16 和 OR 5.54；95%CI 3.22-9.52）。此外，我们还观察到 PHLL（OR 6.04；95%CI 3.69-9.90）和 HNSCC（OR 6.04；95%CI 3.69-9.90）与 RAD51 基因的 135GC 变体之间存在关联。XRCC3 和 RAD51 多态性变体之间的基因-基因相互作用可能导致 PHLL 的患病率更高。观察到这种疾病的风险增加，在 XRCC3 722CT/135GC （OR 3.81；95%CI 1.55-9.75）和 722TT/135GC 基因型（OR 5.33；95%CI 1.96-14.47）的组合中。相同基因组合的存在在 HNSCC 发生的可能性更高（722CT/135GC 的 OR 2.42；95%CI 1.22-4.79 和 722TT/135GC 的 OR 3.63；95%CI 1.69-7.76）。我们还发现 XRCC3 或 RAD51 多态性变体与 PHLL （ORs 2.85-10.28 和 1.82-7.35）和 HNSCC 患者（ORs 2.94-13.93 和 1.36-3.94）以及 PHLL （ORs 3.44-6.12 和 3.52-8.43）以及 HNSCC 受试者（ORs 2.71-7.01 和 2.33-4.62）之间的吸烟状况有关。总之，我们的数据表明，XRCC3 和 RAD51 基因的 C722T 和 G135C 多态性可能与 HNSCC 有关。最后，我们建议这些多态性可以作为波兰人群头颈部癌症癌前病变的预测因子。
