BACKGROUND: While radiation has been the only well-established risk factor for salivary and thyroid cancers, the exact mechanisms remain unknown. We hypothesized that individuals with altered apoptotic response to gamma irradiation may be susceptible to salivary and thyroid cancers. METHODS: We tested our hypothesis in a pilot case-control study of 29 patients with neoplasms of the salivary and thyroid glands and 29 cancer-free control subjects. Patients and control subjects were matched on age, sex, and ethnicity. In vitro gamma radiation-induced apoptosis in lymphocytes was quantified utilizing the TUNEL assay and flow cytometry. RESULTS: The mean apoptotic capacity was 13.55 +/- 10.54 for control subjects, 5.75 +/- 4.96 for patients with salivary gland carcinomas (p =.003), and 6.87 +/- 4.45 for patients with thyroid carcinomas (p =.006). These differences were associated with a 10-fold increased risk of salivary gland carcinoma (odds ratio [OR] = 10.71; 95% confidence interval [CI], 1.21-94.86) and a four-fold increased risk of thyroid carcinoma (OR = 3.93; 95% CI, 0.90-17.08). CONCLUSIONS: Our data suggests that gamma radiation-induced apoptosis may serve as a biomarker of genetic susceptibility to salivary and thyroid carcinoma, and further confirmatory studies with larger sample size are warranted.