Chromosomal Instability in Peripheral Blood Lymphocytes and Risk of Prostate Cancer

Abstract

Prostate cancer is an extremely complex disease, and it is likely that chromosomal instability is involved in the genetic mechanism of tumorigenesis. Several chromosomes have been labeled as “players” in the development of prostate cancer, among them chromosome 1 and X chromosome have been reported to harbor prostate cancer susceptibility loci. However, there is little information regarding the background levels of chromosome instability in these patients. In this pilot study, we examined spontaneous chromosome instability in short-term lymphocyte cultures from 126 study subjects, 61 prostate cancer patients, and 65 healthy controls. We evaluated chromosomal instability using a fluorescence in situ hybridization assay using two probes targeting specific regions on X chromosome and chromosome 1. Our results showed a significantly higher mean level of spontaneous breaks involving the X chromosome in patients compared with controls (mean ± SE, 2.41 ± 0.26 and 0.62 ± 0.08, respectively; P < 0.001). Similarly, chromosome 1 spontaneous breaks were significantly higher among cases compared with controls (mean ± SE, 1.95 ± 0.24 and 1.09 ± 0.16, respectively; P < 0.001). Using the median number of breaks in the controls as the cutoff value, we observed an odds ratio (95% confidence interval) of 15.53 (5.74 - 42.03; P < 0.001) for spontaneous X chromosome breaks and 3.71 (1.60 - 8.63; P < 0.001) for chromosome 1 breaks and risk of development of prostate cancer. In conclusion, our preliminary results show that spontaneous chromosome instability could be a risk factor for prostate cancer.

Spontaneous and radiation-induced chromosomal instability and persistence of chromosome aberrations after radiotherapy in lymphocytes from prostate cancer patients

“…Their spontaneous rates were significantly increased in ten patients, as well. These results are similar to data published by El-Zein et al (2005), who also examined spontaneous chromosome instability in prostate cancer patients and healthy controls. They used short-term lymphocyte cultures and evaluated chromosomal instability using fluorescence in situ hybridization assay with two probes targeting specific regions on chromosome X and chromosome 1.…”

“…Although there are numerous reports in literature on prostate cancer, there is little information regarding the spontaneous background levels of chromosomal alterations in these patients (De Ruyck et al 2008; Dotan et al 2004; El-Zein et al 2005; Ozen et al 2000; Steiner et al 2002; Varga et al 2005; Verhagen et al 2002; Wolter et al 2002). Varga et al reported that spontaneous, as well as radiation-induced, micronuclei were not increased in sporadic prostate cancer patients compared to healthy male controls.…”

“…On the other hand, an increased frequency of chromosome aberrations in circulating lymphocytes is often considered indicative of increased cancer risk after exposure to DNA-damaging agents, such as irradiation (Barrios et al 1991; Bonassi et al 2000; El-Zein et al 2005; Hagmar et al 1998; Heng et al 2006; Hsu 1983; Kolusayin Ozar and Orta 2005; Lockett et al 2006; Scott et al 1999; Tzancheva and Komitowski 1997). …”

The Role of Chromosomal Instability in Cancer and Therapeutic Responses

“…These studies found that the X-chromosome had a significantly higher mean level of spontaneous breaks in patients compared to those observed in controls. These results showed that spontaneous CIN in PBLs might be a potential biomarker for PC susceptibility [ 59 ]. In fact, an increased frequency of CIN in PBLs reflects the early biological effects of genotoxic carcinogens and individual cancer susceptibilities [ 60 ].…”

Why it is crucial to analyze non clonal chromosome aberrations or NCCAs?

“…Cancer Genet Cytogenet 137(1): 59-63 [ 105 ] El-Zein R et al (2005). Cancer Epidemiol Biomarkers Prev 14: 748-52 [ 30 ] Kolusayin Ozar MO et al (2005). J Exp Clin Cancer Res 24: 217-22 [ 34 ] Petersen I et al (2009).…”