烟草烟雾和酒精的使用在头颈部鳞状细胞癌(SCCHN)的病因中起重要作用。吸烟会导致DNA损伤,包括双链DNA断裂(DSB),导致致癌作用.为了检验DSB修复能力次优与SCCHN风险相关的假设,我们应用基于流式细胞术的方法,首先在4种EBV永生化人淋巴母细胞系,然后在人外周血T淋巴细胞(PBTLs)中检测DSB修复表型.通过这种基于血液的实验室检测,我们对100例新诊断的患者进行了一项试点病例对照研究,以前未经治疗的SCCHN和124例非西班牙裔白人的无癌对照。我们发现,病例的平均DSB修复能力水平(42.1%)显着低于对照组(54.4%)(P<0.001)。当我们使用对照中的中位数DSB修复能力水平作为计算赔率比(ORs)的截止值,并根据年龄进行调整时,性别,吸烟和饮酒状况,病例比对照组更有可能具有降低的DSB修复能力(调整后的OR=1.93;95%置信区间,CI=1.04-3.56,P=0.037),尤其是那些曾经饮酒的受试者(校正后OR=2.73;95%CI=1.17~6.35,P=0.020)和有口咽肿瘤的受试者(校正后OR=2.17;95%CI=1.06~4.45,P=0.035).总之,这些研究结果表明,DSB修复能力降低的个体发生SCCHN的风险可能增加.需要更大规模的研究来证实这些初步发现。
Tobacco smoke and alcohol use play important roles in the etiology of squamous cell carcinoma of the head and neck (SCCHN). Smoking causes DNA damage, including double-strand DNA breaks (DSBs), that leads to carcinogenesis. To test the hypothesis that suboptimal DSB repair capacity is associated with risk of SCCHN, we applied a flow cytometry-based method to detect the DSB repair phenotype first in four EBV-immortalized human lymphoblastoid cell lines and then in human peripheral blood T-lymphocytes (PBTLs). With this blood-based laboratory assay, we conducted a pilot
case-control study of 100 patients with newly diagnosed, previously untreated SCCHN and 124 cancer-free controls of non-Hispanic whites. We found that the mean DSB repair capacity level was significantly lower in cases (42.1%) than that in controls (54.4%) (P<0.001). When we used the median DSB repair capacity level in the controls as the cutoff value for calculating the odds ratios (ORs) with adjustment for age, sex, smoking and drinking status, the cases were more likely than the controls to have a reduced DSB repair capacity (adjusted OR=1.93; 95% confidence interval, CI=1.04-3.56, P=0.037), especially for those subjects who were ever drinkers (adjusted OR=2.73; 95% CI=1.17-6.35, P=0.020) and had oropharyngeal tumors (adjusted OR=2.17; 95% CI=1.06-4.45, P=0.035). In conclusion, these findings suggest that individuals with a reduced DSB repair capacity may be at an increased risk of developing SCCHN. Larger studies are warranted to confirm these preliminary findings.