Glutathione S-transferases M1, T1, and P1 and Breast Cancer: A Pooled Analysis

The glutathione S -transferase ( GST ) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1 and a base transition polymorphism at codon 105 (Ile→Val) in GSTP1 were investigated in relation to breast cancer risk. Tobacco smoking and reproduc...

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Published in:Cancer epidemiology, biomarkers & prevention Vol. 13; no. 9; pp. 1473 - 1479
Main Authors: Vogl, Florian D, Taioli, Emanuela, Maugard, Christine, Zheng, Wei, Pinto, Luis F Ribeiro, Ambrosone, Christine, Parl, Fritz F, Nedelcheva-Kristensen, Vessela, Rebbeck, Timothy R, Brennan, Paul, Boffetta, Paolo
Format: Journal Article
Language:English
Published: Philadelphia, PA American Association for Cancer Research 01-09-2004
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Abstract The glutathione S -transferase ( GST ) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1 and a base transition polymorphism at codon 105 (Ile→Val) in GSTP1 were investigated in relation to breast cancer risk. Tobacco smoking and reproductive factors were examined as potential effect modifiers. Individual data from seven case-control studies were pooled within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. To measure the effect of GSTs on breast cancer risk, odds ratios and 95% confidence intervals were computed adjusting for study center and age. The modifying effect was investigated by stratification on variables of smoking habits and reproductive history. A total of 2,048 cases with breast cancer and 1,969 controls were analyzed. The relative odds ratio (95% confidence interval) of breast cancer was 0.98 (0.86–1.12) with the GSTM1 null, 1.11 (0.87–1.41) with the GSTT1 null, 1.01 (0.79–1.28) with GSTP1 heterozygous mutants, and 0.93 (0.62–1.38) with GSTP1 homozygous mutants. Stratification by smoking or reproductive factors did not reveal a modifying effect of these variables, nor was there any association between GSTM1 and age at diagnosis of breast cancer. This is the largest study investigating susceptibility to breast cancer due to polymorphisms in the GST genes. The results conclusively show that single gene GST polymorphisms do not confer a substantial risk of breast cancer to its carriers. Furthermore, GSTs did not interact with smoking or reproductive history to modify cancer risk.
AbstractList The glutathione S-transferase (GST) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1 and a base transition polymorphism at codon 105 (Ileright arrowVal) in GSTP1 were investigated in relation to breast cancer risk. Tobacco smoking and reproductive factors were examined as potential effect modifiers. Individual data from seven case-control studies were pooled within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. To measure the effect of GSTs on breast cancer risk, odds ratios and 95% confidence intervals were computed adjusting for study center and age. The modifying effect was investigated by stratification on variables of smoking habits and reproductive history. A total of 2,048 cases with breast cancer and 1,969 controls were analyzed. The relative odds ratio (95% confidence interval) of breast cancer was 0.98 (0.86-1.12) with the GSTM1 null, 1.11 (0.87-1.41) with the GSTT1 null, 1.01 (0.79-1.28) with GSTP1 heterozygous mutants, and 0.93 (0.62-1.38) with GSTP1 homozygous mutants. Stratification by smoking or reproductive factors did not reveal a modifying effect of these variables, nor was there any association between GSTM1 and age at diagnosis of breast cancer. This is the largest study investigating susceptibility to breast cancer due to polymorphisms in the GST genes. The results conclusively show that single gene GST polymorphisms do not confer a substantial risk of breast cancer to its carriers. Furthermore, GSTs did not interact with smoking or reproductive history to modify cancer risk.
The glutathione S -transferase ( GST ) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1 and a base transition polymorphism at codon 105 (Ile→Val) in GSTP1 were investigated in relation to breast cancer risk. Tobacco smoking and reproductive factors were examined as potential effect modifiers. Individual data from seven case-control studies were pooled within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. To measure the effect of GSTs on breast cancer risk, odds ratios and 95% confidence intervals were computed adjusting for study center and age. The modifying effect was investigated by stratification on variables of smoking habits and reproductive history. A total of 2,048 cases with breast cancer and 1,969 controls were analyzed. The relative odds ratio (95% confidence interval) of breast cancer was 0.98 (0.86–1.12) with the GSTM1 null, 1.11 (0.87–1.41) with the GSTT1 null, 1.01 (0.79–1.28) with GSTP1 heterozygous mutants, and 0.93 (0.62–1.38) with GSTP1 homozygous mutants. Stratification by smoking or reproductive factors did not reveal a modifying effect of these variables, nor was there any association between GSTM1 and age at diagnosis of breast cancer. This is the largest study investigating susceptibility to breast cancer due to polymorphisms in the GST genes. The results conclusively show that single gene GST polymorphisms do not confer a substantial risk of breast cancer to its carriers. Furthermore, GSTs did not interact with smoking or reproductive history to modify cancer risk.
The glutathione S-transferase (GST) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1 and a base transition polymorphism at codon 105 (Ile-->Val) in GSTP1 were investigated in relation to breast cancer risk. Tobacco smoking and reproductive factors were examined as potential effect modifiers. Individual data from seven case-control studies were pooled within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. To measure the effect of GSTs on breast cancer risk, odds ratios and 95% confidence intervals were computed adjusting for study center and age. The modifying effect was investigated by stratification on variables of smoking habits and reproductive history. A total of 2,048 cases with breast cancer and 1,969 controls were analyzed. The relative odds ratio (95% confidence interval) of breast cancer was 0.98 (0.86-1.12) with the GSTM1 null, 1.11 (0.87-1.41) with the GSTT1 null, 1.01 (0.79-1.28) with GSTP1 heterozygous mutants, and 0.93 (0.62-1.38) with GSTP1 homozygous mutants. Stratification by smoking or reproductive factors did not reveal a modifying effect of these variables, nor was there any association between GSTM1 and age at diagnosis of breast cancer. This is the largest study investigating susceptibility to breast cancer due to polymorphisms in the GST genes. The results conclusively show that single gene GST polymorphisms do not confer a substantial risk of breast cancer to its carriers. Furthermore, GSTs did not interact with smoking or reproductive history to modify cancer risk.
Abstract The glutathione S-transferase (GST) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1 and a base transition polymorphism at codon 105 (Ile→Val) in GSTP1 were investigated in relation to breast cancer risk. Tobacco smoking and reproductive factors were examined as potential effect modifiers. Individual data from seven case-control studies were pooled within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. To measure the effect of GSTs on breast cancer risk, odds ratios and 95% confidence intervals were computed adjusting for study center and age. The modifying effect was investigated by stratification on variables of smoking habits and reproductive history. A total of 2,048 cases with breast cancer and 1,969 controls were analyzed. The relative odds ratio (95% confidence interval) of breast cancer was 0.98 (0.86–1.12) with the GSTM1 null, 1.11 (0.87–1.41) with the GSTT1 null, 1.01 (0.79–1.28) with GSTP1 heterozygous mutants, and 0.93 (0.62–1.38) with GSTP1 homozygous mutants. Stratification by smoking or reproductive factors did not reveal a modifying effect of these variables, nor was there any association between GSTM1 and age at diagnosis of breast cancer. This is the largest study investigating susceptibility to breast cancer due to polymorphisms in the GST genes. The results conclusively show that single gene GST polymorphisms do not confer a substantial risk of breast cancer to its carriers. Furthermore, GSTs did not interact with smoking or reproductive history to modify cancer risk.
Author Paolo Boffetta
Christine Ambrosone
Fritz F. Parl
Emanuela Taioli
Christine Maugard
Luis F. Ribeiro Pinto
Timothy R. Rebbeck
Florian D. Vogl
Wei Zheng
Vessela Nedelcheva-Kristensen
Paul Brennan
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  givenname: Florian D
  surname: Vogl
  fullname: Vogl, Florian D
  email: florian.vogl@eurac.edu
  organization: IARC, Lyon, France. florian.vogl@eurac.edu
– sequence: 2
  givenname: Emanuela
  surname: Taioli
  fullname: Taioli, Emanuela
– sequence: 3
  givenname: Christine
  surname: Maugard
  fullname: Maugard, Christine
– sequence: 4
  givenname: Wei
  surname: Zheng
  fullname: Zheng, Wei
– sequence: 5
  givenname: Luis F Ribeiro
  surname: Pinto
  fullname: Pinto, Luis F Ribeiro
– sequence: 6
  givenname: Christine
  surname: Ambrosone
  fullname: Ambrosone, Christine
– sequence: 7
  givenname: Fritz F
  surname: Parl
  fullname: Parl, Fritz F
– sequence: 8
  givenname: Vessela
  surname: Nedelcheva-Kristensen
  fullname: Nedelcheva-Kristensen, Vessela
– sequence: 9
  givenname: Timothy R
  surname: Rebbeck
  fullname: Rebbeck, Timothy R
– sequence: 10
  givenname: Paul
  surname: Brennan
  fullname: Brennan, Paul
– sequence: 11
  givenname: Paolo
  surname: Boffetta
  fullname: Boffetta, Paolo
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Issue 9
Keywords Human
Genetic variability
Enzyme
Isozyme
Transferases
Tobacco smoking
Genotype
Breast cancer
Malignant tumor
Epidemiology
Mammary gland diseases
Reproduction
Cancerology
Glutathione transferase
Risk factor
Genetics
Public health
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Snippet The glutathione S -transferase ( GST ) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1 and a...
The glutathione S-transferase (GST) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1 and a base...
Abstract The glutathione S-transferase (GST) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1...
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StartPage 1473
SubjectTerms Acyltransferases - genetics
Base Sequence
Biological and medical sciences
Breast Neoplasms - epidemiology
Breast Neoplasms - genetics
Carcinogens, Environmental - pharmacokinetics
Carcinogens, Environmental - toxicity
Case-Control Studies
Chromosome Deletion
Codon
DNA Mutational Analysis
Female
Genetic Carrier Screening
Genetic Predisposition to Disease - genetics
Genotype
Glutathione Transferase - genetics
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Meta-Analysis as Topic
Polymorphism, Genetic - genetics
Risk Factors
Tumors
Title Glutathione S-transferases M1, T1, and P1 and Breast Cancer: A Pooled Analysis
URI http://cebp.aacrjournals.org/content/13/9/1473.abstract
https://www.ncbi.nlm.nih.gov/pubmed/15342448
https://search.proquest.com/docview/18045924
Volume 13
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