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Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer.

Publication ,  Journal Article
Bell, DA; Taylor, JA; Paulson, DF; Robertson, CN; Mohler, JL; Lucier, GW
Published in: J Natl Cancer Inst
July 21, 1993

BACKGROUND: Numerous studies have associated bladder cancer with exposure to carcinogens present in tobacco smoke and other environmental or occupational exposures. Approximately 50% of all humans inherit two deleted copies of the GSTM1 gene which encodes for the carcinogen-detoxification enzyme glutathione S-transferase M1. Recent findings suggest that the GSTM1 gene may modulate the internal dose of environmental carcinogens and thereby affect the risk of developing bladder cancer. PURPOSE: We investigated whether the absence of the GSTM1 gene affects bladder cancer risk and whether there are racial differences in GSTM1 genotype frequency. METHODS: Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the homozygous deleted genotype (GSTM1 0/0) in 229 patients with transitional cell carcinoma of the bladder and 211 control subjects who were enrolled from the Urology Clinics at Duke University Medical Center and the University of North Carolina Hospitals. Control subjects were urology clinic patients who primarily presented with benign prostatic hypertrophy or impotence, who had no history of any cancer other than nonmelanoma skin cancer, and who were frequency matched to case patients on race, sex, and age (10-year age intervals). In order to explore racial differences in GSTM1 gene frequency, genotype was also determined in a community-based sample of 466 paid, healthy, unrelated volunteers from Durham and Chapel Hill, N.C. The presence or absence of the GSTM1 gene locus was determined by using a differential PCR, a semiquantitative technique in which multiple genes are coamplified. RESULTS: Overall, the GSTM1 0/0 genotype conferred a 70% increased risk of bladder cancer (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.2-2.5; P = .004). Absence of the GSTM1 gene encoding the glutathione S-transferase M1 enzyme significantly increased risk to persons with exposure to the carcinogens in tobacco smoke (OR = 1.8; 95% CI = 1.2-3.0; P = .01) but poses little increased risk to persons without such exposure. Persons with smoking exposure of more than 50 pack-years who had the GSTM1 0/0 genotype had a sixfold greater risk relative to persons in the lowest risk group (i.e., nonsmokers who were GSTM1 +/+ or +/0). In the pooled clinic control and community sample groups (677 individuals), the GSTM1 0/0 genotype occurred less frequently among Blacks (35%) than among Whites (49%, P < .001). CONCLUSIONS: These findings support a protective role for the GSTM1 gene in bladder cancer. From these findings, it is estimated that 25% of all bladder cancer may be attributable to the at-risk GSTM1 0/0 genotype.

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Published In

J Natl Cancer Inst

DOI

ISSN

0027-8874

Publication Date

July 21, 1993

Volume

85

Issue

14

Start / End Page

1159 / 1164

Location

United States

Related Subject Headings

  • Urinary Bladder Neoplasms
  • Smoking
  • Racial Groups
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Molecular Sequence Data
  • Male
  • Isoenzymes
  • Humans
  • Glutathione Transferase
 

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Bell, D. A., Taylor, J. A., Paulson, D. F., Robertson, C. N., Mohler, J. L., & Lucier, G. W. (1993). Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. J Natl Cancer Inst, 85(14), 1159–1164. https://doi.org/10.1093/jnci/85.14.1159
Bell, D. A., J. A. Taylor, D. F. Paulson, C. N. Robertson, J. L. Mohler, and G. W. Lucier. “Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer.J Natl Cancer Inst 85, no. 14 (July 21, 1993): 1159–64. https://doi.org/10.1093/jnci/85.14.1159.
Bell, D. A., et al. “Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer.J Natl Cancer Inst, vol. 85, no. 14, July 1993, pp. 1159–64. Pubmed, doi:10.1093/jnci/85.14.1159.
Journal cover image

Published In

J Natl Cancer Inst

DOI

ISSN

0027-8874

Publication Date

July 21, 1993

Volume

85

Issue

14

Start / End Page

1159 / 1164

Location

United States

Related Subject Headings

  • Urinary Bladder Neoplasms
  • Smoking
  • Racial Groups
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Molecular Sequence Data
  • Male
  • Isoenzymes
  • Humans
  • Glutathione Transferase