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Sensitivity to benzo(a)pyrene diol-epoxide associated with risk of breast cancer in young women and modulation by glutathione S-transferase polymorphisms: a case-control study.
Cancer Res. 2001 Dec 01; 61(23):8465-9.CR

Abstract

Mounting epidemiological evidence suggests that smoking may play a role in the etiology of breast cancer. Because smoking-related DNA adducts are detectable in both normal and malignant breast tissues, we hypothesized that breast cancer patients may be sensitive to tobacco-induced carcinogenesis, and this sensitivity could be modulated by variants of metabolic genes. To test this hypothesis, we evaluated benzo(a)pyrene diol-epoxide (BPDE)-induced mutagen sensitivity and polymorphisms of GSTM1 and GSTT1 in a pilot case-control study of breast cancer. Short-term cell cultures were established from blood samples of 100 female breast cancer patients and 105 healthy controls. After 5 h of in vitro exposure to 4 microM of BPDE, we harvested the lymphocytes for cytogenetic evaluation and recorded and compared the frequency of BPDE-induced chromatid breaks between cases and controls. We used a multiplex PCR-based assay to simultaneously detect polymorphisms of GSTM1 and GSTT1 from genomic DNA. We performed univariate and multivariate logistic regression analyses and calculated odds ratios (OR) and 95% confidence intervals (CIs). Cases had a significantly higher frequency of chromatid breaks than did controls (P < 0.0001). The level of chromatid breaks greater than the median value of controls was associated with a >3-fold increased risk of breast cancer [adjusted odds ratio (ORadj) = 3.11; 95% CI = 1.72-5.64]. The risk was more pronounced in those who were < 45 years (ORadj = 4.79; 95% CI = 1.87-12.3), ever-smokers (ORadj = 5.55; 95% CI = 1.85-16.6), alcohol drinkers (ORadj = 4.64; 95% CI = 1.70-12.7), and those who had the GSTT1 null variant (ORadj = 8.01; 95% CI = 1.16-55.3). These data suggest that sensitivity to BPDE-induced chromosomal aberrations may contribute to the risk of developing breast cancer, and such sensitivity may be modulated by both genetic and environmental factors. Larger studies are needed to confirm our findings.

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Authors+Show Affiliations

Xiong P
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Bondy ML
No affiliation info available
Li D
No affiliation info available
Shen H
No affiliation info available
Wang LE
No affiliation info available
Singletary SE
No affiliation info available
Spitz MR
No affiliation info available
Wei Q
No affiliation info available

MeSH

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxideAdultBreast NeoplasmsCarcinogensCase-Control StudiesChromosome AberrationsCocarcinogenesisFemaleGenetic Predisposition to DiseaseGlutathione TransferaseHumansMiddle AgedPilot ProjectsPolymorphism, Genetic

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11731429

Citation

Xiong, P, et al. "Sensitivity to Benzo(a)pyrene Diol-epoxide Associated With Risk of Breast Cancer in Young Women and Modulation By Glutathione S-transferase Polymorphisms: a Case-control Study." Cancer Research, vol. 61, no. 23, 2001, pp. 8465-9.
Xiong P, Bondy ML, Li D, et al. Sensitivity to benzo(a)pyrene diol-epoxide associated with risk of breast cancer in young women and modulation by glutathione S-transferase polymorphisms: a case-control study. Cancer Res. 2001;61(23):8465-9.
Xiong, P., Bondy, M. L., Li, D., Shen, H., Wang, L. E., Singletary, S. E., Spitz, M. R., & Wei, Q. (2001). Sensitivity to benzo(a)pyrene diol-epoxide associated with risk of breast cancer in young women and modulation by glutathione S-transferase polymorphisms: a case-control study. Cancer Research, 61(23), 8465-9.
Xiong P, et al. Sensitivity to Benzo(a)pyrene Diol-epoxide Associated With Risk of Breast Cancer in Young Women and Modulation By Glutathione S-transferase Polymorphisms: a Case-control Study. Cancer Res. 2001 Dec 1;61(23):8465-9. PubMed PMID: 11731429.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sensitivity to benzo(a)pyrene diol-epoxide associated with risk of breast cancer in young women and modulation by glutathione S-transferase polymorphisms: a case-control study. AU - Xiong,P, AU - Bondy,M L, AU - Li,D, AU - Shen,H, AU - Wang,L E, AU - Singletary,S E, AU - Spitz,M R, AU - Wei,Q, PY - 2001/12/4/pubmed PY - 2002/1/5/medline PY - 2001/12/4/entrez SP - 8465 EP - 9 JF - Cancer research JO - Cancer Res VL - 61 IS - 23 N2 - Mounting epidemiological evidence suggests that smoking may play a role in the etiology of breast cancer. Because smoking-related DNA adducts are detectable in both normal and malignant breast tissues, we hypothesized that breast cancer patients may be sensitive to tobacco-induced carcinogenesis, and this sensitivity could be modulated by variants of metabolic genes. To test this hypothesis, we evaluated benzo(a)pyrene diol-epoxide (BPDE)-induced mutagen sensitivity and polymorphisms of GSTM1 and GSTT1 in a pilot case-control study of breast cancer. Short-term cell cultures were established from blood samples of 100 female breast cancer patients and 105 healthy controls. After 5 h of in vitro exposure to 4 microM of BPDE, we harvested the lymphocytes for cytogenetic evaluation and recorded and compared the frequency of BPDE-induced chromatid breaks between cases and controls. We used a multiplex PCR-based assay to simultaneously detect polymorphisms of GSTM1 and GSTT1 from genomic DNA. We performed univariate and multivariate logistic regression analyses and calculated odds ratios (OR) and 95% confidence intervals (CIs). Cases had a significantly higher frequency of chromatid breaks than did controls (P < 0.0001). The level of chromatid breaks greater than the median value of controls was associated with a >3-fold increased risk of breast cancer [adjusted odds ratio (ORadj) = 3.11; 95% CI = 1.72-5.64]. The risk was more pronounced in those who were < 45 years (ORadj = 4.79; 95% CI = 1.87-12.3), ever-smokers (ORadj = 5.55; 95% CI = 1.85-16.6), alcohol drinkers (ORadj = 4.64; 95% CI = 1.70-12.7), and those who had the GSTT1 null variant (ORadj = 8.01; 95% CI = 1.16-55.3). These data suggest that sensitivity to BPDE-induced chromosomal aberrations may contribute to the risk of developing breast cancer, and such sensitivity may be modulated by both genetic and environmental factors. Larger studies are needed to confirm our findings. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/11731429/Sensitivity_to_benzo_a_pyrene_diol_epoxide_associated_with_risk_of_breast_cancer_in_young_women_and_modulation_by_glutathione_S_transferase_polymorphisms:_a_case_control_study_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=11731429 DB - PRIME DP - Unbound Medicine ER -