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Chromosomal Instability in Peripheral Blood Lymphocytes and Risk of Prostate Cancer

Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Randa El-Zein, Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Box 189, Houston, TX 77030. Phone: 713-792-3020; Fax: 713-792-0807. E-mail: relzein{at}mdanderson.org

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.

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