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 r adiation were, on average, higher in G(2) and G(0) lymphocytes of breast ca ncer patients than of normal healthy controls, but that there was no correl ation between the results in the two assays. We proposed that enhanced sens itivity to G(2) or G(0) irradiation was a marker of low-penetrance predispo sition to breast cancer, and have recently demonstrated heritability of sen sitivity in families of breast cancer cases, We have now applied these assa ys to patients with head and neck cancers, for whom there is epidemiologica l 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 normal s of the same age range (P = 0.046), whereas there was no difference betwee n patients and normals of less than 45 years. Also, there was an inverse co rrelation between G(2) sensitivity and age for patients but not for normals . Radiation-induced micronuclei in G(0) cells were more frequent in 49 pati ents than in 31 normals (P = 0.056) but, as with the G(2) assay, the greate st difference was seen between early-onset patients and young normals. Agai n there was an inverse correlation with age for patients but not for normal s. Six patients with enhanced toxicity to radiotherapy were G(2) tested and four other such patients were G(0) tested; levels of chromosome damage wer e not significantly greater than in patients with normal reactions. Both as says 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 an d that each of the two assays detects a different subset of these cases. (C ) 2001 Cancer Research Campaign http://www.bjcancer.com.