Reduced DNA double-strand break repair capacity and risk of squamous cell carcinoma of the head and neck—A case-control study

• We used a method to detect the DNA double strand break repair capacity.
• We examined the DSBRC in 100 head and neck cancer patients and 124 controls.
• DNA double strand break repair capacity was significantly lower in cases than in controls.
• Decreased DSBRC may be associated with increased risk of head and neck cancer.

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.