The relationship between genetic susceptibility to head and neck cancer with the expression of common fragile sites

Background. Numerous studies have recently been conducted to investigate ge netic mechanisms in cancer causes and pathogenesis. Some of these studies h ave shown that there were certain specific chromosomal defects in normal ce lls of cancer patients and in their first-degree relatives. It was suggeste d that these individuals were susceptible to cancer development when compar ed with people without these defects. Materials and Methods, Chromosomal anomalies, such as gaps, breaks, and ace ntric fragments, and fragile site expression rates were determined in perip heral blood lymphocyte cultures in 14 head and neck cancer patients, 17 fir st-degree relatives of these patients, and 20 healthy individuals as a cont rol group in this study. RPMI 1640 medium, composed of aphidicolin, 5-bromo deoxyuridine, and caffeine were used for the induction of fragile sites. Results. In cytogenetic and statistical evaluation, it was observed that bo th chromosomal aberration rates and fragile site expression frequencies in head and neck cancer patients and in their first-degree relatives were sign ificantly greater than the control group (p < .05). It was found that fragi le site expression was site specific in head and neck cancer patients and i n their first-degree relatives. These specific sites were determined to be 1p21-22, 1q21, 1q25, 2q21, 2q31-33, 3p14, 16q22-23, 18q21, and 22q12 sites. Conclusions. These findings support studies showing that the fragile sites might be unstable factors in human genomes and their expression could be af fected by some genetic factors, such as tumor suppressor genes acid mismatc h repair genes, and by some environmental factors, such as benzo (a) pyrene , dimethylnitrosamine, and dimethylsulfate. In conclusion, fragile sites ma y be playing an important role in the genetic tendency to head and neck can cer. Overexpression of these sites in normal lymphocytes may be used as a r eliable marker to determine the genetic susceptibility in head and neck can cer patients and in their first-degree relatives. (C) 2000 John Wiley & Son s, Inc.