Werbrouck Joke, De Ruyck Kim, Duprez Fréderic, Van Eijkeren Marc, Rietzschel Ernst, Bekaert Sofie, Vral Anne, De Neve Wilfried, Thierens Hubert
Department of Anatomy, Embryology, Histology and Medical Physics, Ghent University, and Department of Radiation Oncology, Ghent University Hospital, Proeftuinstraat 86, B-9000 Gent, Belgium.
Mutat Res. 2008 Oct 30;656(1-2):74-81. doi: 10.1016/j.mrgentox.2008.07.013. Epub 2008 Aug 13.
We investigated the effect of different levels of smoking and drinking on the development of squamous cell carcinoma of head and neck (HNSCC) and performed analyses to evaluate possible differences in cancer susceptibility among the anatomical subregions of head and neck. Moreover, we investigated the association between 5 single nucleotide polymorphisms (SNPs) in the homologous recombination DNA repair pathway (XRCC3 c.-1843 A>G, XRCC3 c.562-14 A>G, XRCC3 c.722 C>T, Rad51 c.-3429 G>C, Rad51 c.-3392 G>T) and 4 SNPs in the non- homologous end joining DNA repair pathway (Lig4 c.26 C>T, Lig4 c.1704 T>C, Ku70 c.-1310 C>G and Ku80 c.2110-2408 G>A) on one hand and the risk of the development of HNSCC on the other hand in a case- control setting in a Caucasian population. The study population consisted out of 152 HNSCC patients and 157 healthy controls, matched for age and gender. Polymorphic regions were analysed using the PCR-RFLP and PCR-single base extension assays. Stratification of the populations according to smoking habits and alcohol consumption highlighted the importance of tobacco and alcohol as two risk factors for the development of HNSCC (OR=11.81, p<0.01 and OR=4.66, p<0.01 for high exposure to tobacco and alcohol respectively). A stratification according to the anatomical region of the tumour showed site specific differences in sensitivity to tobacco smoke, with an increase in cancer susceptibility from the oral cavity down to the pharynx and larynx (OR=6.86, p<0.01; OR=9.83, p<0.01 and 36.57, p<0.01 for >25PY). A significant positive association between the XRCC3 c.722 polymorphism and HNSCC was found, with an adjusted odds ratio (OR) of 1.96 (p=0.02). Both the Lig4 c.26 and the Rad51 c.-3429 polymorphisms were associated with a significant reduced risk for HNSCC (OR=0.43, p=0.01; OR=0.43, p=0.05 respectively). Analysis of the gene- smoking interaction revealed no differences in OR for XRCC3 c.722 among the smoking groups. The protective effect seen for the Rad51 c.-3429 and polymorphism was most prominent among the group of heavy smokers (>25 PY). No associations with risk for HNSCC were found for the other SNPs in genes of the DNA DSB repair pathways.
我们研究了不同吸烟和饮酒水平对头颈部鳞状细胞癌（HNSCC）发生发展的影响，并进行了分析以评估头颈部各解剖亚区域之间癌症易感性的可能差异。此外，我们在白种人群的病例对照研究中，一方面研究了同源重组DNA修复途径中的5个单核苷酸多态性（SNP）（XRCC3 c.-1843 A>G、XRCC3 c.562-14 A>G、XRCC3 c.722 C>T、Rad51 c.-3429 G>C、Rad51 c.-3392 G>T）和非同源末端连接DNA修复途径中的4个SNP（Lig4 c.26 C>T、Lig4 c.1704 T>C、Ku70 c.-1310 C>G和Ku80 c.2110-2408 G>A），另一方面研究了其与HNSCC发生风险的关联。研究人群包括152例HNSCC患者和157名健康对照，年龄和性别相匹配。使用PCR-RFLP和PCR单碱基延伸分析方法对多态性区域进行分析。根据吸烟习惯和饮酒量对人群进行分层，突出了烟草和酒精作为HNSCC发生的两个风险因素的重要性（高烟草和酒精暴露的OR分别为11.81，p<0.01和4.66，p<0.01）。根据肿瘤的解剖区域进行分层显示，对烟草烟雾的敏感性存在部位特异性差异，从口腔到咽部和喉部癌症易感性增加（>25包年时的OR分别为6.86，p<0.01；9.83，p<0.01和36.57，p<0.01）。发现XRCC3 c.722多态性与HNSCC之间存在显著正相关，调整后的优势比（OR）为1.96（p=0.02）。Lig4 c.26和Rad51 c.-3429多态性均与HNSCC风险显著降低相关（OR分别为0.43，p=0.01；0.43，p=0.05）。基因-吸烟相互作用分析显示，吸烟组中XRCC3 c.722的OR无差异。Rad51 c.-3429多态性的保护作用在重度吸烟者（>25包年）组中最为显著。DNA双链断裂修复途径基因中的其他SNP与HNSCC风险无关联。
