Sensitivity to radiation-induced chromosome damage may be a marker of genetic predisposition in young head and neck cancer patients.

We previously showed that levels of chromosome damage induced by ionizing radiation were, on average, higher in G(2)and G(0)lymphocytes of breast cancer patients than of normal healthy controls, but that there was no correlation between the results in the two assays. We proposed that enhanced sensitivity to G(2)or G(0)irradiation was a marker of low-penetrance predisposition to breast cancer, and have recently demonstrated heritability of sensitivity in families of breast cancer cases. We have now applied these assays to patients with head and neck cancers, for whom there is epidemiological evidence of inherited predisposition in addition to environmental causes. The mean frequency of radiation-induced G(2)aberrations was higher in the 42 patients than in 27 normal controls, but not significantly so. However, cases less than 45 years old were significantly more sensitive than normals of the same age range (P = 0.046), whereas there was no difference between patients and normals of less than 45 years. Also, there was an inverse correlation between G(2)sensitivity and age for patients but not for normals. Radiation-induced micronuclei in G(0)cells were more frequent in 49 patients than in 31 normals (P = 0.056) but, as with the G(2)assay, the greatest difference was seen between early-onset patients and young normals. Again there was an inverse correlation with age for patients but not for normals. Six patients with enhanced toxicity to radiotherapy were G(2)tested and four other such patients were G(0)tested; levels of chromosome damage were not significantly greater than in patients with normal reactions. Both assays were used on 64 individuals (39 patients, 25 normals) and there was no significant correlation between the results. We suggest that a proportion of early-onset head and neck cancer patients are genetically predisposed and that each of the two assays detects a different subset of these cases. Copyright 2001 Cancer Research Campaign.