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

Abstract

Background Numerous studies have recently been conducted to investigate genetic mechanisms in cancer causes and pathogenesis. Some of these studies have shown that there were certain specific chromosomal defects in normal cells of cancer patients and in their first‐degree relatives. It was suggested that these individuals were susceptible to cancer development when compared with people without these defects. Materials and Methods Chromosomal anomalies, such as gaps, breaks, and acentric fragments, and fragile site expression rates were determined in peripheral blood lymphocyte cultures in 14 head and neck cancer patients, 17 first‐degree relatives of these patients, and 20 healthy individuals as a control group in this study. RPMI 1640 medium, composed of aphidicolin, 5‐bromodeoxyuridine, and caffeine were used for the induction of fragile sites. Results In cytogenetic and statistical evaluation, it was observed that both chromosomal aberration rates and fragile site expression frequencies in head and neck cancer patients and in their first‐degree relatives were significantly greater than the control group (p < .05). It was found that fragile site expression was site specific in head and neck cancer patients and in 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 affected by some genetic factors, such as tumor suppressor genes and mismatch repair genes, and by some environmental factors, such as benzo (a) pyrene, dimethylnitrosamine, and dimethylsulfate. In conclusion, fragile sites may be playing an important role in the genetic tendency to head and neck cancer. Overexpression of these sites in normal lymphocytes may be used as a reliable marker to determine the genetic susceptibility in head and neck cancer patients and in their first‐degree relatives. © 2000 John Wiley & Sons, Inc. Head Neck 22: 591–598, 2000.

Common Fragile Sites and Cancer: Targeted Cloning by Insertional Mutagenesis

“…In addition to this correlation, breast and cervical cancer patients showed a significantly higher expression of fragile sites when treated with aphidicolin than did control groups 49. Similar results were obtained by many others 35,50–53…”

“…49 Similar results were obtained by many others. 35,[50][51][52][53] In many cases, fragile sites have been suspected as regions harboring tumor suppressor genes (TABLE 2). The most popular example is FHIT (fragile histidine triad), a gene in the telomeric region of FRA3B.…”

A variant of the DNA repair gene XRCC3 and risk of squamous cell carcinoma of the head and neck: A case‐control analysis

“…3,4 However, genetic susceptibility may also modulate the risk of SCCHN because only a fraction of individuals who smoke or drink develop this disease. 5,6 Recent molecular epidemiological studies have demonstrated that polymorphisms in DNA repair genes contribute to genetic susceptibility to SCCHN. 7,8 Therefore, studies of biological relevance of newly identified genetic polymorphisms 9 should ultimately help identify those at high risk for carcinogenesis and eventually improve cancer prevention and chemoprevention programs.…”

Cloning and characterization of the common fragile site FRA6F harboring a replicative senescence gene and frequently deleted in human tumors

“…Activation of common fragile sites by aphidicolin was detected in lymphocytes from colon, rectum, head and neck cancer patients and in their first-degree relatives, with a significant difference compared to lymphocytes of normal controls (Egeli et al, 2000;Tunca et al, 2000a,b). Moreover, several tumor suppressor genes have been cloned from regions containing fragile sites: FHIT from FRA3B (Huebner et al, 1998), TESTIN from FRA7G (Tatarelli et al, 2000) and FOR from FRA16D .…”