Environment and Breast Cancer: Science Review
About
The association between glutathione S-transferase M1 genotype and polycyclic aromatic hydrocarbon-DNA adducts in breast tissue
Rundle, A., Tang, D., Zhou, J., Cho, S., Perera, F. Cancer Epidemiol Biomarkers Prev. 2000. 9:10, 1079-85.
Topic area
Environmental pollutant - PAH
Environmental pollutant - PAH
Study design
case-control study - hospital-based
case-control study - hospital-based
Funding agency
Not reported
Not reported
Study Participants
Menopausal Status
Post menopausal
The menopausal status of women included in this study is listed here.
Pre menopausalPost menopausal
Number of Controls
Controls: 87
Controls: 87
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Women referred for breast surgery: breast cancer compared to benign breast disease
Comment about participation selection
Benign breast disease patients are at slightly increased risk for breast cancer than a general population. In this study, the prevalence of family history was similar between cases (20%) and controls (18%), potentially biasing results to the null.
Benign breast disease patients are at slightly increased risk for breast cancer than a general population. In this study, the prevalence of family history was similar between cases (20%) and controls (18%), potentially biasing results to the null.
Exposures investigated
PAH-DNA adducts in tumor, nontumor, and benign breast tissue; variants of the xenobiotic detoxifying gene, glutathione S-transferase M1 (GSTM1) gene
PAH-DNA adducts in tumor, nontumor, and benign breast tissue; variants of the xenobiotic detoxifying gene, glutathione S-transferase M1 (GSTM1) gene
How exposure was measured
Biological
Biological
Statistical Analysis
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
No
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Breast cancer risk factors, PAH-related diet, tobacco smoke
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Yes
Description of major analysis
Linear regression
Linear regression
Strength of associations reported
GSTM1 genotype was not associated with breast cancer risk
Increasing adduct levels in tumor tissue and tissue from controls were associated with case-control status (P=0.04); adduct levels in tumor and nontumor tissue from cases were significantly correlated (P < 0.001). Adducts in nontumor tissue and tissue from controls were associated with case-control status, but not significantly. (previously reported)
After controlling for confounding, GSTM! null genotype was associated with increased PAH-DNA adduct levels tumor tissue, but not nontumor tissue from cases or benign tissue from controls. A significant interaction was observed In linear regression, controlled for breast cancer risk factors and PAH exposure, of case-control status and GSTM1 genotype on adduct levels. GSTM1 genotype was associated with ER expression.
GSTM1 genotype was not associated with breast cancer risk
Increasing adduct levels in tumor tissue and tissue from controls were associated with case-control status (P=0.04); adduct levels in tumor and nontumor tissue from cases were significantly correlated (P < 0.001). Adducts in nontumor tissue and tissue from controls were associated with case-control status, but not significantly. (previously reported)
After controlling for confounding, GSTM! null genotype was associated with increased PAH-DNA adduct levels tumor tissue, but not nontumor tissue from cases or benign tissue from controls. A significant interaction was observed In linear regression, controlled for breast cancer risk factors and PAH exposure, of case-control status and GSTM1 genotype on adduct levels. GSTM1 genotype was associated with ER expression.
Results Comments
Authors discuss alternative interpretations: inherited susceptibility to breast cancer among women who are GSTM1 deleted or higher adduct levels in tumor tissue are to to acquired changes in metabolic pathways in tumor cells. Finding of an association between adduct levels and GSTM1 in nontumor tissue argues for the first alternative. Results indicative of GSTM1 playing "a role in preventing the accumulation of environmentally induced genetic damage in breast tissue."
Authors discuss alternative interpretations: inherited susceptibility to breast cancer among women who are GSTM1 deleted or higher adduct levels in tumor tissue are to to acquired changes in metabolic pathways in tumor cells. Finding of an association between adduct levels and GSTM1 in nontumor tissue argues for the first alternative. Results indicative of GSTM1 playing "a role in preventing the accumulation of environmentally induced genetic damage in breast tissue."
Author address
Division of Environmental Health Sciences, Joseph L. Mailman School of Public Health, Columbia University, New York, New York 10032, USA.
Division of Environmental Health Sciences, Joseph L. Mailman School of Public Health, Columbia University, New York, New York 10032, USA.
Controls participation rate
Not reported
Not reported