© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 19, 1492,
October 3, 2001
© 2001 Oxford University Press
CORRESPONDENCE |
Re: Biomarker Risk Assessment and Bladder Cancer Detection in a Cohort Exposed to Benzidine
Correspondence to: Armen K. Nersesyan, Ph.D., D.Sc., Laboratory of Carcinogenesis, Cancer Research Center, 76 Fanardjian St., Yerevan 375052 Armenia (e-mail: genetik{at}ysu.am).
I studied with great interest the paper by Hemstreet et al. (1). However, I disagree with the authors on several points. First, I disagree that " . . . approximately 20%–25% (of bladder cancers) are related to occupational exposure to chemicals, such as benzo[a]pyrene, benzidine, and 
-naphthyamine . . . " (1), because benzo[a]pyrene is not a recognized human bladder carcinogen (2,3).
Second, the authors cited articles [references 43–45 in (1)] that stated that genetic changes in chromosomes 9 and 17 may play a role in bladder cancer development. However, there are several other chromosomes that have been implicated in bladder cancer development, including chromosome 11, which was originally mentioned in one of the references cited by Hemstreet et al. [reference 43 in (1)]. Moreover, cytogenetic studies of transitional cell carcinomas, the most common bladder tumor, have not identified any single specific aberration (4) but have identified changes in chromosomes 1 (a wide variety of changes), 3, 5, and 10; trisomy of chromosome 7; and loss of one copy of chromosome 9 (4). The most likely candidates for a primary pathogenetic role in transitional cell carcinomas are trisomy of chromosome 7, monosomy of chromosome 9, and deletion of chromosome 10 (4). DNA-level studies [reviewed in (4)] have shown that bladder cancer is also associated with losses of genetic material in chromosomes 9, 11, 17, 8, 4, and 13 (listed in order of decreasing frequency). Thus, the article by Hemstreet et al. (1) provided only limited information regarding cytogenetic changes associated with bladder cancer.
Third, if atypical and suspicious results in Table 2 (1) were considered to be positive, then the sensitivity of the Pap test in exposed workers would be much higher at the time of tumor diagnosis (70.8%).
It is my opinion that the authors minimized the role of genetic or cytogenetic testing as a biomarker for risk assessment in bladder cancer. Chromosomal aberration frequency in surrogate cells, such as lymphocytes, is a good predictor for cancer risk—subjects with high frequency of cytogenetic disorders are generally cancer prone (5). The predictive value of cytogenetic testing would increase if the genetic anomalies were studied in target bladder cells (4). For example, testing for the presence of micronuclei in exfoliated bladder cells obtained from urine is a very sensitive assay to identify subjects at high risk for bladder cancer (6) because micronuclei, which are bodies formed from whole or fragmented chromosomes, reflect either structural or numeric (or both) chromosomal aberrations. In addition, application of the fluorescent in situ hybridization (FISH) technique with probes for chromosomes 1, 5, 7, 9, 10, and Y [although in my opinion, probes for chromosomes 7, 9, and 10 are enough because other chromosomal abnormalities seem secondary and nonspecific (4)], which often contain genetic changes associated with bladder cancer, could possibly increase the specificity and sensitivity of micronucleus test for human bladder cancer risk assessment (7).
In conclusion, I suggest that the application of the micronucleus test and FISH technique for individual screening, monitoring, and diagnosis of occupationally exposed workers at risk for bladder cancer might be a more efficient approach than the molecular biomarkers proposed by Hemstreet et al. (1). Future investigations in this area are certainly warranted.
REFERENCES
1
Hemstreet GP 3rd, Yin S, Ma Z, Bonner RB, Bi W, Rao JY, et al. Biomarker risk assessment and bladder cancer detection in a cohort exposed to benzidine. J Natl Cancer Inst 2001;93:427–36.
2 IARC monographs on the evaluation of carcinogenic risks to humans. Overall evaluations of carcinogenicity: an updating of IARC monographs. Vols. 1–42. Suppl 7. Lyon (France); 1987.
3 Weisburger JH, Williams GM. Causes of cancer. In: Murphy GP, Laurence W, Luhard RE, editors. Clinical oncology. Washington (DC): American Cancer Society Publication; 1995. p. 1–39.
4 Heim S, Mitelman F. Cancer Cytogenetics. Chromosomal and molecular genetic aberrations of tumor cells. New York (NY): Wiley-Liss; 1995.
5 Hagmar L, Bonassi S, Stromberg U, Mikoczy Z, Lando C, Hansteen IL, et al. Cancer predictive value of cytogenetic markers used in occupational health surveillance programs: a report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health. Mutat Res 1998;405:171–8.[Web of Science][Medline]
6 Rosin MP. The use of the micronucleus test on exfoliated cells to identify anti-clastogenic action in humans: a biological marker for the efficacy of chemopreventive agents. Mutat Res 1992;267:265–76.[Medline]
7 Sandberg AA. Chromosome changes in early bladder neoplasms. J Cell Biochem Suppl 1992;161:76–9.
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