Mutagen sensitivity as a biomarker for second primary tumors after head and neck squamous cell carcinoma

The occurrence of second primary tumors after curative treatment of early s tage head and neck squamous cell carcinoma negatively influences the overal l survival. Our aim was to prospectively evaluate whether mutagen sensitivi ty (mean number of chromatid breaks per cell in cultured lymphocytes expose d to bleomycin) could be used as a biomarker to predict which patients will develop second malignancies in the respiratory or upper digestive tract. P atients treated for head and neck squamous cell carcinoma (n = 218) were fo llowed for approximately 6 Sears. Nineteen patients developed a second prim ary tumor, and each of these patients was matched on age, gender, cumulativ e smoking, tumor site, and tumor stage to two patients who did not develop any second malignancy, No difference between the groups was found with resp ect to mutagen sensitivity. Smoking at the time of the index tumor had a si gnificant influence on the occurrence of second primary tumors (log-rank, P 0.019). There was a significantly (P = 0.005) higher mean breaks-per-cell value in those patients who had developed their second primary tumor greate r than or equal to 3 years after the first tumor (0.97 +/- 0.24; n = 10) co mpared with early second primary tumor patients (0.69 +/- 0.09; n = 9). Con ditional on a more than 3-year second primary tumor-free survival (n = 38), there is a significantly (log-rank, P 0.036) higher probability of a secon d primary tumor for mutagen-sensitive patients [relative risk, 7.8 (95% con fidence interval, 0.99- 61.74; P = 0.05)]. Mutagen sensitivity is a potenti onal biomarker for the occurrence of 'late' second malignancies (>3 years b etween tumors), and additional studies on the inclusion of this biomarker i n chemoprevention trials is commendable because it would greatly improve th eir efficiency.