Cancer Research Cell Death Mechanisms and Cancer Therapy Sign up for Cancer Research eTOC's
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xiong, P.
Right arrow Articles by Wei, Q.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xiong, P.
Right arrow Articles by Wei, Q.
[Cancer Research 61, 8465-8469, December 1, 2001]
© 2001 American Association for Cancer Research

Epidemiology and Prevention

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 Study1

Ping Xiong, Melissa L. Bondy, Donghui Li, Hongbing Shen, Li-E Wang, S. Eva Singletary, Margaret R. Spitz and Qingyi Wei2

Departments of Epidemiology [P. X., M. L. B., H. S., L-E. W., M. R. S., Q. W.], Gastrointestinal Medical Oncology [D. L.], and Surgical Oncology [S. E. S.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030


   ABSTRACT
Top
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
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 µM 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.


   INTRODUCTION
Top
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Breast cancer is the most common incident cancer in women in the United States, with an estimated 192,000 new cases and 42,200 deaths in 2001 (1) . Although the role of genetic factors in the etiology of breast cancer is well established in familial breast cancer (2) , the contribution of environmental factors is still largely unknown. However, mounting epidemiological evidence suggests that cigarette smoking increases the risk for breast cancer in high-risk breast cancer families (3) , that smoking during pregnancy increases breast cancer risk in very young women (4) , and that smoking may be associated with risk in subsets of breast cancer patients such as hormone receptor-negative breast cancer (5) .

A number of PAHs3 are widespread environmental contaminants known to cause mammary cancers in experimental animals (6) . Benzo(a)pyrene is one of the PAHs found in tobacco smoke, and its metabolite BPDE is considered a classic DNA-damaging carcinogen (7) . GSTs catalyze the detoxification of carcinogen metabolites including BPDE and ROS and, therefore, modulate the level of in vivo DNA adducts (8) . Several genes that code for these enzymes are polymorphic, and their genetic polymorphisms are likely to be associated with tobacco-induced mutagenesis.

Although evidence is still lacking in supporting a direct link between smoking and risk of breast cancer, tobacco-related DNA adducts have been found in breast tumor and adjacent normal tissues (9, 10, 11) . Tobacco smoke contains various chemicals including PAHs and ROS that induce various types of DNA damage including strand breaks, suggesting that these chemicals could be involved in breast carcinogenesis (6 , 12) . Therefore, genetic polymorphisms in enzymes that are involved in the metabolism of PAHs and ROS may also play a role in individual susceptibility to breast disease (13 , 14) . Chromosomal aberrations, particularly those induced by ionizing radiation and impaired repair of DNA strand breaks have been shown to increase the risk of breast cancer (15, 16, 17, 18) . Recently, some studies demonstrated that polymorphisms of GSTM1 and GSTT1 are associated with a moderately increased risk of breast cancer and act as modifiers of breast cancer risk (19 , 20) , whereas some other studies failed to find them as risk factors for breast cancer (21 , 22) . To examine the role of BPDE-induced mutagen sensitivity in the development of breast cancer and possible modulation by genetic polymorphisms that are involved in metabolism of BPDE, we conducted a pilot case-control study to investigate the role of BPDE-induced chromosomal aberrations in susceptibility to breast cancer and the role of null GSTM1 and GSTT1 genotypes as modifiers of the risk associated with BPDE-induced chromosomal aberrations.


   MATERIALS AND METHODS
Top
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study Subjects.
Incident breast cancer cases (n = 100) were consecutively recruited from female patients who were undergoing breast surgery in the Department of Surgical Oncology at The University of Texas M. D. Anderson Cancer Center between August 1998 and March 2001. All of the cases had histopathologically confirmed breast cancer. To facilitate the study of genetic susceptibility, we limited our case subjects to those <=50 years of age. Cancer-free controls (n = 105) were obtained from patients (n = 22) undergoing breast reduction surgery and spouses of the cancer patients (n = 83) unrelated to the cases. Each participant donated 10 ml of blood collected in heparinized tubes and completed a short questionnaire that elicited information on age, sex, ethnicity, smoking status, and alcohol consumption. Cases and controls were frequency matched for age (±5 years), sex, ethnicity, and smoking status (ever- and never-smokers).

Cytogenetic Analysis.
The BPDE-induced mutagen sensitivity assays were performed as described previously (23) . Briefly, two primary lymphocyte cultures were established from each individual by inoculating 1 ml of blood into a T-25 plastic culture flask with 9 ml of RPMI 1640 (Life Technologies, Inc., Grand Island, NY) containing 112.5 µg/ml phytohemagglutinin (Murex Biotech Limited, Dartford, England). A dose-response curve was constructed, and the 4-µM BPDE was found to be adequate for in vitro treatment (24) . After ~67 h of incubation at 37°C, the cultures were treated with BPDE for 5 h. The 5-h exposure period was chosen to avoid possible cytotoxic effects of longer exposure and because BPDE-DNA adduct levels appear to reach a steady-state level ~5 h after exposure to doses of BPDE <=4 µM (24) . Mitotic arrest was induced during the final hour of incubation with Colcemid (Life Technologies, Inc.) at a final concentration of 0.06 µg/ml. For harvesting, the cells were treated with a hypotonic KCl solution (60 mM) for 15 min and subsequently fixed with a freshly prepared methanol:acetic acid mixture (3:1 v:v) for another 15 min. After washing, the cells were allowed to air dry on wet slides. The unbanded chromosomes were first inspected by using a 4% Giemsa staining (for ~7 min). Because we did not use banding techniques, only the frequency of nonspecific chromatid breaks was evaluated. The slides were read by a researcher (P. X.) blinded to case status. By reading 50 well-spread metaphases per sample, the average number of chromatid breaks per cell was determined. It has been shown statistically that the efficiency of reading 50 metaphases is as good as scoring >=100 metaphases (25) . Each simple chromatid break was counted as a single break, whereas each isochromatid break, exchange figure, or interstitial deletion was scored as two breaks (23) .

Genotypying of GSTM1 and GSTT1.
The leukocyte cell pellet obtained from the buffy coat by centrifugation of whole blood samples was used for DNA extraction with a Qiagen DNA extraction kit (Qiagen Inc., Valencia, CA). A multiplex PCR assay was established to simultaneously genotype GSTT1 and GSTM1 plus the DHFR gene as an internal control for amplification failure attributable to DNA degradation. The primers used for these genes were: F5'-TTCCTTACTGGTCCTCACATCTC-3' and R5'-TCACCGGATCATGGCCAGCA-3' for GSTT1, which generate a 480-bp fragment; F5'-GAACTCCCTGAAAAGCTAAAGC-3' and R5'-GTTGGGCTCAAATATACGGTGG-3' for GSTM1, which generate a 215-bp fragment; and F5'-GCATGTCTTTGGGATGTGGA-3' and R5'-GGAATGGAGAACCAGGTCTT-3' for DHFR, which generate a 280-bp fragment and served as an internal assay control. In this PCR assay, the absence of a 480-bp band or a 215-bp band indicates the GSTT1 null or GSTM1 null genotypes, respectively. When none of these fragments were present, either the PCR was not successful or the DNA was degraded, because DHFR is an essential gene and normally should be easily amplified.

GSTM1, GSTT1, and DHFR were coamplified in a 25-µl reaction mixture containing 100 ng of genomic DNA as the template, 3.5 pmol of each GSTM1 primer, 2.9 pmol of each GSTT1 primer, 6.2 pmol of each DHFR primer, 0.1 mM each deoxynucleotide triphosphate, 1 x PCR buffer [500 mM KCl, 100 mM Tris-HCl (pH 9.0), 1% Triton X-100, and 2.5 mM MgCl2], and 1.5 units of Taq polymerase (Promega, Madison, WI). The PCR profile consisted of an initial melting step at 95°C for 5 min followed by 30 cycles of 95°C for 30 s, 56°C for 45 s, and 72°C for 45 s, with a final step of 72°C for 10 min for elongation. The PCR products were separated on 1.2% agarose gels and photographed by using Polaroid films (Fig. 1)Citation .



View larger version (51K):
[in this window]
[in a new window]
[Download PPT slide]
  		Fig. 1. Multiplex PCR assay of genotyping for GSTM1 and GSTT1. M, molecular marker; 1, GSTT1 null/GSTM1 null; 2, GSTT1 wild type/GSTM1 null; 3, GSTT1 null/GSTM1 wild type; 4, GSTT1 wild type/GSTM1 wild type; 5, water control.

 
Statistical Analysis.
The chromatid b/c were analyzed as a continuous variable. Student’s t test was used to compare the mean b/c values between groups. We have reported previously that 92.7% of the observed aberrations induced by BPDE were chromatid breaks, and the rest were isochromatid breaks (7.1%) and exchange figures (0.2%; Ref. 23 ). Consequently, we did not analyze these kinds of BPDE-induced chromosomal aberrations in this study. Those who had smoked <100 cigarettes in their lifetimes were defined as "never users of tobacco," and the rest were "ever-smokers." We performed univariate analysis to determine the association between BPDE-induced b/c, the GSTM1 and GSTT1 genotypes, and risk of breast cancer. To calculate crude ORs, the median b/c value of the controls was used as the cutoff value; subjects with values greater than this median were considered to be mutagen sensitive. The GST genotypes were analyzed as dichotomous variables. All of the statistical analyses were performed using Statistical Analysis System software (Version 6; SAS Institute Inc., Cary, NC).


   RESULTS
Top
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
The characteristics of these 100 cases and 105 controls are summarized in Table 1Citation . The frequency matching on age and ethnicity resulted in a mean age of 43.2 (range = 23–50 years; SD = 6) and 42.2 (range = 28–55 years; SD = 7.9) years for both cases and controls with a median of 45 and 44 years, respectively (data not shown). Although there were more cases than controls >=45 years of age, this difference was not statistically significant (P = 0.186). There was also no significant difference in the distribution of ethnic groups (P = 0.388); ~80% of the subjects were Caucasians in both cases and controls. These results suggest that frequency matching on age and ethnicity was adequate. There were more ever-smokers among the controls than the cases, but the difference was not statistically significant (P = 0.386). The proportion of ever-drinkers in the cases (43%) was nearly identical to that in the controls (43.8%).


View this table:
[in this window]
[in a new window]

  		Table 1 Distribution of selected variables for breast cancer patients and healthy controls

 
There were no differences in the distribution of the GSTM1 and GSTT1 null genotypes between cases and controls (P = 0.743 and P = 0.690, respectively), and these null genotypes were not associated with risk of breast cancer (Table 2)Citation . However, 74% of the cases exhibited a mutagen sensitivity value >0.38 (the median of the control values) b/c (P < 0.0001). This elevated sensitivity to BPDE was associated with >3-fold increased risk of breast cancer (OR = 3.01; 95% CI = 1.67–5.43), which did not change after adjustment for age, ethnicity, smoking, and alcohol use (adjusted OR = 3.11; 95% CI = 1.72–5.64; Table 2Citation ).


View this table:
[in this window]
[in a new window]

  		Table 2 Logistic regression analysis for GST genotypes and the BPDE mutagen sensitivity associated risk of breast cancer

 
The mean b/c value was also significantly higher in the 100 cases (0.52; median = 0.48) than in the 105 controls (0.40; median = 0.38; P < 0.001; Table 3Citation ). To evaluate whether the elevated sensitivity to BPDE is modulated by genetic and environmental factors listed in Table 1Citation , we performed stratified analysis. In general, the mean mutagen sensitivity value of the cases in each subgroup was significantly higher than that of the controls, except among small subgroups of 8 African Americans and 13 Mexican Americans (Table 3)Citation .


View this table:
[in this window]
[in a new window]

  		Table 3 BPDE-induced mutagen sensitivity in breast cancer patients and controls

 
To evaluate the modulation of the sensitivity by other factors, we additionally stratified the mutagen sensitivity values by the median of the control b/c values to calculate crude and adjusted ORs and 95% CI in logistic regression analyses (Table 4)Citation . Again, consistent with the results in Table 3Citation , significantly increased ORs were observed in all but nonwhites for each stratum. These risk estimates were unchanged after adjustment for age, ethnicity, smoking, and alcohol use in multivariate logistic regression models (Table 4)Citation . However, the elevated risk associated with the sensitivity to BPDE was more pronounced in subgroups of <45 years (adjusted OR = 4.79; 95% CI = 1.87–12.3); ever-smokers (OR = 5.55; 95% CI = 1.85–16.6); alcohol ever-drinkers (OR = 4.64; 95% CI = 1.70–12.7), and the GSTT1 null genotype (OR = 8.01; 95% CI = 1.16–55.3). These data suggest that the risk for breast cancer associated with in vitro sensitivity to BPDE may be modulated by genetic and environmental factors. However, there were few observations in some of the cells for additionally testing possible interactions.


View this table:
[in this window]
[in a new window]

  		Table 4 Logistic regression analysis of the BPDE mutagen sensitivity associated risk of breast cancer stratified by selected variables

 

   DISCUSSION
Top
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
BPDE mutagen sensitivity has consistently been shown to be a susceptibility marker for tobacco-induced cancers including those of the lung and head and neck (26, 27, 28) . In this pilot study, we demonstrated that the BPDE-induced mutagen sensitivity is also a risk factor for breast cancer. This risk appears to be modulated by young age, smoking status, alcohol use, and the GSTT1 null genotype, additionally suggesting a possible role of gene-environment interaction. These findings are consistent with previous reports on detectable tobacco-induced DNA adducts in breast tissues and the possible role of GSTM1 and GSTT1 null genotypes in the etiology of breast cancer (19 , 20) . Our findings suggest that combining genotypic and phenotypic biomarkers for studies of genetic susceptibility may be a more powerful approach than using either phenotypic or genotypic biomarkers alone for future studies of breast cancer etiology.

The exact mechanism of how BPDE induces chromosomal aberrations remains to be determined. Our early data suggested that with the BPDE dose (4 µM) used in this study, we could induce DNA adducts in vitro 15 min after treatment and that the level of adducts increased 100-fold over the background adduct levels as measured by the 32P-postlabeling method (24) . BPDE-induced bulky DNA adducts are repaired by the NER pathway (29 , 30) . During the repair process, it is likely that delayed completion of initial nicking of DNA strands by NER may induce DNA strand breaks that eventually lead to chromatid breaks. However, no studies have shown that sensitivity to chemical carcinogen-induced adducts and chromosome aberrations in lymphocytes are directly correlated with those in breast tissue, although such a correlation has been established between lymphocytes and lung tissue (31) .

It has been shown that the risk of developing breast cancer in women is associated with the frequencies of chromosomal aberrations induced by X-ray (9) or {gamma} radiation (32 , 33) in peripheral blood lymphocytes. Elevated risk has been reported in association with a polymorphism (Lys751Gln) in the XPD, a NER gene (34) . These findings suggest that sensitivity to radiation-induced chromosomal aberrations in lymphocytes may contribute to genetic susceptibility to breast cancer. In breast tumors and normal tissues, DNA adducts induced by carcinogens characteristic of complex mixtures of aromatic compounds (such as PAHs) and tobacco smoke are found in some studies (9 , 10 , 35) but not in others (11 , 36) . The GST null genotypes may modulate PAH-DNA adduct levels in both malignant and nonmalignant breast tissue (37) and are associated with increased risk of breast cancer (38) , particularly in those women who had more than one null genotype and heavy alcohol consumption (19) . These results suggest a role of GST polymorphisms in the formation of PAH-DNA adducts that contribute to genetic susceptibility to breast cancer and a possible gene-environment interaction in the etiology of breast cancer.

However, results from several other studies do not support an association between any specific polymorphism of GSTM1, GSTT1, and GSTP1 in susceptibility to sporadic breast cancer (21 , 22) , either independently or in combination. Indeed, we did not observe any increased risk associated with the GSTM1 and GSTT1 null genotypes alone, but these null genotypes modulated the risk associated with sensitivity to BPDE in our study population. Therefore, our results emphasize the importance of studying phenotypic and genotypic biomarkers simultaneously.

In summary, our results from this pilot study suggest that the BPDE mutagen sensitivity phenotype may be a risk factor for genetic susceptibility to breast cancer, and the risk is modulated by the GSTM1 and GSTT1 null genotype. Although we did not have detailed information on alcohol consumption in our study population, we also observed a remarkable risk associated with the BPDE mutagen sensitivity in smokers. The high risk associated with such sensitivity in subgroups of young age and smoking additionally suggest a possible gene-environment interaction in the etiology of breast cancer. Although this pilot case-control study was hospital-based and may not provide generalizable findings to the general population, the difference in phenotype by genotypes suggests that the findings are biologically plausible and important for future studies. In addition, because this study had a relatively small sample and used multiple comparisons, some of the findings could have been attributable to chance. However, the consistently significant findings of a main effect and risk modulation existing in most subgroups examined exclude the possibility of the findings occurring by chance. Larger studies with more rigorous designs are warranted to confirm these findings as well as to investigate the possible risk modulation by genetic polymorphisms of DNA repair genes that are relevant to the phenotype.


   ACKNOWLEDGMENTS
 
We thank Dr. Maureen Goode for her scientific editing; Min Fu, Ping Chang, and Weiqing Zhang for their technical support; Margaret Lung, Farzana Lukmanji, and Elaine Petrulis for their recruitment of the subjects; and Joanne Sider and Joyce Brown for manuscript preparation.


   FOOTNOTES
 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Supported in part by NIH Grants CA 70334, CA 74851, and ES 11740 (to Q. W.), CA 70264 (to D. L.), CA55769 and CA 60374 (to M. R. S.), and CA 16672 (to M.D. Anderson Cancer Center); by National Institute of Environmental Health Sciences Grant ES 07784; and by funds collected pursuant to the Comprehensive Tobacco Settlement of 1998 and appropriated by the 76th Legislature to The University of Texas M. D. Anderson Cancer Center. Back

2 To whom requests for reprints should be addressed, at Department of Epidemiology, Box 189, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: (713) 792-3020; Fax: (713) 792-0807; E-mail: qwei{at}mdanderson.org Back

3 The abbreviations used are: PAH, polycyclic aromatic hydrocarbons; GST, glutathione S-transferase; ROS, reactive oxygen species; DHFR, dihydrofolate reductase; BPDE, benzo(a)pyrene diol-epoxide; OR, odds ratio; b/c, breaks/cell; NER, nucleotide excision repair; CI, confidence interval. Back

Received 6/ 4/01. Accepted 10/ 1/01.


   REFERENCES
Top
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. American Cancer Society. Cancer Facts and Figures, 200110-11, American Cancer Society Atlanta 2000.
  2. Thompson P. A., Ambrosone C. Molecular epidemiology of genetic polymorphisms in estrogen metabolizing enzymes in human breast cancer. J. Natl. Cancer Inst. Monogr., 27: 125-134, 2000.
  3. Couch F. J., Cerhan J. R., Vierkant R. A., Grabrick D. M., Therneau T. M., Pankratz V. S., Hartmann L. C., Olson J. E., Vachon C. M., Sellers T. A. Cigarette smoking increases risk for breast cancer in high-risk breast cancer families. Cancer Epidemiol. Biomark. Prev., 10: 327-332, 2001.[Abstract/Free Full Text]
  4. Innes K. E., Byers T. E. Smoking during pregnancy and breast cancer risk in very young women (United States). Cancer Causes Control, 12: 179-185, 2001.[Medline]
  5. Manjer J., Malina J., Berglund G., Bondeson L., Garne J. P., Janzon L. Increased incidence of small and well-differentiated breast tumours in post-menopausal women following hormone-replacement therapy. Int. J. Cancer, 92: 919-922, 2001.[Medline]
  6. Cavalieri E. L., Higginbotham S., RamaKrishna N. V., Devanesan P. D., Todorovic R., Rogan E. G., Salmasi S. Comparative dose-response tumorigenicity studies of dibenzo[{alpha}, l]pyrene versus 7,12-dimethylbenz[{alpha}]anthracene, benzo[{alpha}]pyrene and two dibenzo[{alpha}, l]pyrene dihydrodiols in mouse skin and rat mammary gland. Carcinogenesis (Lond.), 12: 1939-1944, 1991.[Abstract/Free Full Text]
  7. Phillips D. H. Polycyclic aromatic hydrocarbons in the diet. Mutat. Res., 443: 139-147, 1999.[Medline]
  8. Rojas M., Cascorbi I., Alexandrov K., Kriek E., Auburtin G., Mayer L., Kopp-Schneider A., Roots I., Bartsch H. Modulation of benzo(a)pyrene diolepoxide-DNA adduct levels in human white blood cells by CYP1A1, GSTM1 and GSTT1 polymorphism. Carcinogenesis (Lond.), 21: 35-41, 2000.[Abstract/Free Full Text]
  9. Perera F. P., Estabrook A., Hewer A., Channing K., Rundle A., Mooney L. A., Whyatt R., Phillips D. H. Carcinogen-DNA adducts in human breast tissue. Cancer Epidemiol. Biomark. Prev., 4: 233-238, 1995.[Abstract]
  10. Li D., Zhang W., Sahin A. A., Hittelman W. N. DNA adducts in normal tissue adjacent to breast cancer: a review. Cancer Detect. Prev., 23: 454-462, 1999.[Medline]
  11. Santella R. M., Gammon M. D., Zhang Y. J., Motykiewicz G., Young T. L., Hayes S. C., Terry M. B., Schoenberg J. B., Brinton L. A., Bose S., Teitelbaum S. L., Hibshoosh H. Immunohistochemical analysis of polycyclic aromatic hydrocarbon-DNA adducts in breast tumor tissue. Cancer Lett., 154: 143-149, 2000.[Medline]
  12. Matsui A., Ikeda T., Enomoto K., Hosoda K., Nakashima H., Omae K., Watanabe M., Hibi T., Kitajima M. Increased formation of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, in human breast cancer tissue and its relationship to GSTP1 and COMT genotypes. Cancer Lett., 151: 87-95, 2000.[Medline]
  13. Bartsch H., Nair U., Risch A., Rojas M., Wikman H., Alexandrov K. Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. Cancer Epidemiol. Biomark. Prev., 9: 3-28, 2000.[Abstract/Free Full Text]
  14. Goldman R., Shields P. G. Molecular epidemiology of breast cancer. In Vivo (Athens), 12: 43-48, 1998.
  15. Helzlsouer K. J., Harris E. L., Parshad R., Perry H. R., Price F. M., Sanford K. K. DNA repair proficiency: potential susceptibility factor for breast cancer. J. Natl. Cancer Inst., 88: 754-755, 1996.[Free Full Text]
  16. Parshad R., Price F. M., Bohr V. A., Cowans K. H., Zujewski J. A., Sanford K. K. Deficient DNA repair capacity, a predisposing factor in breast cancer. Br. J. Cancer, 74: 1-5, 1996.[Medline]
  17. Burrill W., Barber J. B., Roberts S. A., Bulman B., Scott D. Heritability of chromosomal radiosensitivity in breast cancer patients: a pilot study with the lymphocyte micronucleus assay. Int. J. Radiat. Biol., 76: 1617-1619, 2000.[Medline]
  18. Baria K., Warren C., Roberts S. A., West C. M., Scott D. Chromosomal radiosensitivity as a marker of predisposition to common cancers? Br. J. Cancer, 84: 892-896, 2001.
  19. Park S. K., Yoo K. Y., Lee S. J., Kim S. U., Ahn S. H., Noh D. Y., Choe K. J., Strickland P. T., Hirvonen A., Kang D. Alcohol consumption, glutathione S-transferase M1 and T1 genetic polymorphisms and breast cancer risk. Pharmacogenetics, 10: 301-309, 2000.[Medline]
  20. Maugard C. M., Charrier J., Pitard A., Campion L., Akande O., Pleasants L., Ali-Osman F. Genetic polymorphism at the glutathione S-transferase (GST) P1 locus is a breast cancer risk modifier. Int. J. Cancer, 91: 334-339, 2001.[Medline]
  21. Ambrosone C. B., Coles B. F., Freudenheim J. L., Shields P. G. Glutathione-S-transferase (GSTM1) genetic polymorphisms do not affect human breast cancer risk, regardless of dietary antioxidants. J. Nutr., 129: 565S-568S, 1999.
  22. Curran J. E., Weinstein S. R., Griffiths L. R. Polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and breast cancer susceptibility. Cancer Lett., 153: 113-120, 2000.[Medline]
  23. Wei Q., Gu J., Cheng L., Bondy M. L., Jiang H., Hong W. K., Spitz M. R. Benzo(a)pyrene diol epoxide-induced chromosomal aberrations and risk of lung cancer. Cancer Res., 56: 3975-3979, 1996.[Abstract/Free Full Text]
  24. Li D., Firozi P. F., Wang L. E., Bosken C. H., Spitz M. R., Hong W. K., Wei Q. Sensitivity to DNA damage induced by benzo(a)pyrene diol epoxide and risk of lung cancer: a case-control analysis. Cancer Res., 61: 1445-1450, 2001.[Abstract/Free Full Text]
  25. Lee J. J., Trizna Z., Hsu T. C., Spitz M. R., Hong W. K. A statistical analysis of the reliability and classification error in application of the mutagen sensitivity assay. Cancer Epidemiol. Biomark. Prev., 5: 191-197, 1996.[Abstract/Free Full Text]
  26. Wang L. E., Sturgis E. M., Eicher S. A., Spitz M. R., Hong W. K., Wei Q. Mutagen sensitivity to benzo(a)pyrene diol epoxide and the risk of squamous cell carcinoma of the head and neck. Clin. Cancer Res., 4: 1773-1778, 1998.[Abstract]
  27. Wu X., Gu J., Hong W. K., Lee J. J., Amos C. I., Jiang H., Winn R. J., Fu K. K., Cooper J., Spitz M. R. Benzo[a]pyrene diol epoxide and bleomycin sensitivity and susceptibility to cancer of upper aerodigestive tract. J. Natl. Cancer Inst., 90: 1393-1399, 1998.[Abstract/Free Full Text]
  28. Wu X., Yu H., Amos C. I., Hong W. K., Spitz M. R. Joint effect of insulin-like growth factors and mutagen sensitivity in lung cancer risk. J. Natl. Cancer Inst., 92: 737-743, 2000.[Abstract/Free Full Text]
  29. Sancer A. DNA repair in humans. Annu. Rev. Genet., 29: 69-105, 1995.[Medline]
  30. Wei Q., Cheng L., Amos C. I., Wang L. E., Guo Z., Hong W. K., Spitz M. R. Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study. J. Natl. Cancer Inst., 92: 1764-1772, 2000.[Abstract/Free Full Text]
  31. Wiencke J. K., Kelsey K. T., Varkonyi A., Semey K., Wain J. C., Mark E., Christiani D. C. Correlation of DNA adducts in blood mononuclear cells with tobacco carcinogen-induced damage in human lung. Cancer Res., 55: 4910-4914, 1995.[Abstract/Free Full Text]
  32. Buchholz T. A., Wu X. Radiation-induced chromatid breaks as a predictor of breast cancer risk. Int. J. Radiat. Oncol. Biol. Phys., 49: 533-553, 2001.[Medline]
  33. Rothfuss A., Schutz P., Bochum S., Volm T., Eberhardt E., Kreienberg R., Vogel W., Speit G. Induced micronucleus frequencies in peripheral lymphocytes as a screening test for carriers of a BRCA1 mutation in breast cancer families. Cancer Res., 60: 390-394, 2000.[Abstract/Free Full Text]
  34. Lunn R. M., Helzlsouer K. J., Parshad R., Umbach D. M., Harris E. L., Sanford K. K., Bell D. A. XPD polymorphisms: effects on DNA repair proficiency. Carcinogenesis (Lond.), 21: 551-555, 2000.[Abstract/Free Full Text]
  35. Li D., Wang M., Dhingra K., Hittelman W. N. Aromatic DNA adducts in adjacent tissues of breast cancer patients: clues to breast cancer etiology. Cancer Res., 56: 287-293, 1996.[Abstract/Free Full Text]
  36. Rundle A., Tang D., Zhou J., Cho S., Perera F. The association between glutathione S-transferase M1 genotype and polycyclic aromatic hydrocarbon-DNA adducts in breast tissue. Cancer Epidemiol. Biomark. Prev., 9: 1079-1085, 2000.[Abstract/Free Full Text]
  37. Helzlsouer K. J., Selmin O., Huang H. Y., Strickland P. T., Hoffman S., Alberg A. J., Watson M., Comstock G. W., Bell D. Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer. J. Natl. Cancer Inst., 90: 512-518, 1998.[Abstract/Free Full Text]
  38. Rundle A., Tang D., Hibshoosh H., Estabrook A., Schnabel F., Cao W., Grumet S., Perera F. P. The relationship between genetic damage from polycyclic aromatic hydrocarbons in breast tissue and breast cancer. Carcinogenesis (Lond.), 21: 1281-1289, 2000.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 FASEB J.Home page
K.-D. Yu, G.-H. Di, L. Fan, J. Wu, Z. Hu, Z.-Z. Shen, W. Huang, and Z.-M. Shao
A functional polymorphism in the promoter region of GSTM1 implies a complex role for GSTM1 in breast cancer
FASEB J, July 1, 2009; 23(7): 2274 - 2287.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J. Lu, Q. Wei, M. L. Bondy, D. Li, A. Brewster, S. Shete, T.-K. Yu, A. Sahin, F. Meric-Bernstam, K. K. Hunt, et al.
Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women <=55 years
Carcinogenesis, November 1, 2006; 27(11): 2209 - 2216.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
T. G. Natarajan, N. Ganesan, P. Carter-Nolan, C. A. Tucker, P. G. Shields, and L. L. Adams-Campbell
{gamma}-Radiation-Induced Chromosomal Mutagen Sensitivity Is Associated with Breast Cancer Risk in African-American Women: Caffeine Modulates the Outcome of Mutagen Sensitivity Assay.
Cancer Epidemiol. Biomarkers Prev., March 1, 2006; 15(3): 437 - 442.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
L.-E Wang, P. Xiong, S. S. Strom, L. H. Goldberg, J. E. Lee, M. I. Ross, P. F. Mansfield, J. E. Gershenwald, V. G. Prieto, J. N. Cormier, et al.
In Vitro Sensitivity to Ultraviolet B Light and Skin Cancer Risk: A Case-Control Analysis
J Natl Cancer Inst, December 21, 2005; 97(24): 1822 - 1831.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
D. O. Kennedy, M. Agrawal, J. Shen, M. B. Terry, F. F. Zhang, R. T. Senie, G. Motykiewicz, and R. M. Santella
DNA Repair Capacity of Lymphoblastoid Cell Lines From Sisters Discordant for Breast Cancer
J Natl Cancer Inst, January 19, 2005; 97(2): 127 - 132.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
Q. Shi, L.-E. Wang, M. L. Bondy, A. Brewster, S. E. Singletary, and Q. Wei
Reduced DNA repair of benzo[a]pyrene diol epoxide-induced adducts and common XPD polymorphisms in breast cancer patients
Carcinogenesis, September 1, 2004; 25(9): 1695 - 1700.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
K. M. Egan, Q. Cai, X.-O. Shu, F. Jin, T.-L. Zhu, Q. Dai, Y.-T. Gao, and W. Zheng
Genetic Polymorphisms in GSTM1, GSTP1, and GSTT1 and the Risk for Breast Cancer: Results from the Shanghai Breast Cancer Study and Meta-Analysis
Cancer Epidemiol. Biomarkers Prev., February 1, 2004; 13(2): 197 - 204.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Li, F. L. Walcott, P. Chang, W. Zhang, J. Zhu, E. Petrulis, S. E. Singletary, A. A. Sahin, and M. L. Bondy
Genetic and Environmental Determinants on Tissue Response to in Vitro Carcinogen Exposure and Risk of Breast Cancer
Cancer Res., August 15, 2002; 62(16): 4566 - 4570.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xiong, P.
Right arrow Articles by Wei, Q.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xiong, P.
Right arrow Articles by Wei, Q.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online