Cancer Research Annual Meeting 2010 Genetics and Biology of Brain Cancer
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 Li, D.
Right arrow Articles by Bondy, M. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, D.
Right arrow Articles by Bondy, M. L.
[Cancer Research 62, 4566-4570, August 15, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Genetic and Environmental Determinants on Tissue Response to in Vitro Carcinogen Exposure and Risk of Breast Cancer1

Donghui Li2, Farzana L. Walcott, Ping Chang, Weiqing Zhang, Jijiang Zhu, Elaine Petrulis, Sonja E. Singletary, Aysegul A. Sahin and Melissa L. Bondy

Departments of Gastrointestinal Medical Oncology [D. L., P. C., W. Z., J. Z.], Epidemiology [F. L. W., E. P., M. L. B.], Surgical Oncology [S. E. S.], and Pathology [A. A. S.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030


   ABSTRACT
Top
 ABSTRACT
Introduction
 Patients and Methods
 Results
 Discussion
 REFERENCES
 
To test the hypothesis that individual susceptibility to carcinogen exposure is a risk factor for breast cancer, we measured DNA adduct formation in normal breast tissues treated in vitro with 4 µM benzo(a)pyrene in 76 cancer cases and 60 noncancer controls. We found a significantly higher level of adducts (134.6 ± 21.2/109) among cases compared with controls (66.9 ± 7.5; P = 0.007). The level of adducts was significantly associated with the risk of breast cancer (odds ratio, 4.38; 95% confidence interval, 1.04 to 18.50; P = 0.044) after adjusting for confounders. Stratified analysis and regression analysis demonstrated that race, pack-years of smoking, family history of breast cancer, and CYP1B1 genotype were significant predictors of the level of benzo(a)pyrene-induced adducts in the breast tissues. These observations suggest that genetic susceptibility to carcinogen exposure may play an important role in breast carcinogenesis.


   Introduction
Top
 ABSTRACT
 Introduction
Patients and Methods
 Results
 Discussion
 REFERENCES
 
Breast cancer is the most frequent malignancy in American women (1) . Epidemiological data from studies of migrants and regional differences in breast cancer suggest that environmental factors play an important role in breast cancer etiology, but the precise effects of these factors have not been well defined (2) . Genetic studies have shown that several breast cancer susceptibility genes, such as BRCA1, ATM, and p53, play important roles in cellular response to DNA damage (3, 4, 5, 6) . Furthermore, the susceptibility of breast tissues to radiation indicates that breast tissues are susceptible to DNA-damaging agents. As demonstrated in other carcinogen-related human cancers, such as cancers of the lung, most human cancers are a consequence of gene-environment interaction (7) . Individuals with deficient detoxification mechanisms or DNA repair capacity are at a greater risk for carcinogen-related human cancer. If carcinogen exposure does play a role in breast cancer, we would expect to see the same association between individual susceptibility to carcinogen exposure and risk of breast cancer. Indeed, results from several studies have suggested that DNA repair proficiency is a potential susceptibility factor for breast cancer (8, 9, 10) . Most studies in cancer susceptibility are limited by lack of access to the target tissues. Therefore, the association between carcinogen metabolism in breast tissues and risk of breast cancer is not fully understood. The study reported here took advantage of the available target tissue and tested the hypothesis that tissue susceptibility to carcinogens is a risk factor for breast cancer using a previously established carcinogen sensitivity assay (11 , 12) . In this small-scale, case-control study, we examined DNA adduct formation in the target tissues exposed in vitro to a tobacco carcinogen, BP.3 Because all tissue samples were exposed to the same dose of carcinogen under the same experimental conditions, the level of DNA adducts detected in this study reflects individual sensitivity to carcinogen challenge in breast tissues. The effects of some environmental factors, such as tobacco and alcohol use, and some genetic factors, such as CYP1A1, CYP1B1, and GSTM1 genotypes, on the level of BP-induced DNA adducts were also examined in this unique study. The data demonstrated that the level of in vitro carcinogen-induced DNA adducts in the breast tissues was a significant risk factor for breast cancer. Furthermore, both environmental and genetic factors may influence individual response to carcinogen exposure and therefore the risk of cancer.


   Patients and Methods
Top
 ABSTRACT
 Introduction
 Patients and Methods
Results
 Discussion
 REFERENCES
 
Study Participants.
The case subjects were women newly diagnosed with breast cancer at The University of Texas M. D. Anderson Cancer Center from 1997 to 2000. The inclusion criteria were ages 25–50 years, no prior chemotherapy or radiotherapy, no recent blood transfusions or immune-suppressing medication within the last 6 months, and undergoing surgical treatment. Noncancer control subjects were recruited from women undergoing reduction mammoplasty at a local plastic surgery clinic. The exclusion criterion was prior cancer (except for nonmelanoma skin cancers). Informed consent was obtained from all study participants. A trained interviewer collected information on demographics, tobacco use, exposure to secondhand tobacco smoke and other environmental contaminants, alcohol use, and other epidemiological risk factors. Each eligible study participant was interviewed by telephone, and a residual surgical normal tissue sample was obtained for the laboratory assays. An individual who smoked >100 cigarettes in their lives was considered an ever-smoker. An individual who consumed alcoholic beverages, at least four drinks/month for 6 months or more, was defined as an alcohol user. All tissue samples were processed within 6 h after surgery. Tissue samples from case and control groups were handled in the same manner. Certified pathologists examined all of the samples treated with BP to ensure that there was no tumor tissue present.

The study protocol was approved by the Institutional Review Boards of M. D. Anderson Cancer Center, St. Luke’s Hospital, and Memorial Hermann Hospital (where the reduction mammoplasties were performed). Information on the pathological features of the tumors was abstracted from the patients’ medical records.

Tissue Culture and Carcinogen Treatment.
Fresh normal breast tissue (about 1–5 g) was cut into small pieces (<0.5 cm3) for in vitro carcinogen treatment. Those tissues were cultured at 37°C in 10 ml of minimal essential medium with 4 µM BP for 24 h. Then, the tissues were frozen at -80°C until DNA was isolated. At the beginning of the study, a series of dose-response experiments with 0.001, 0.01, 1, 2, 4, and 10 µM BP was performed on tissue samples from four individuals (data not shown). The final dose of 4 µM was chosen because it induced a level of DNA adducts frequently detected in human breast tissues (13, 14, 15) .

DNA Isolation and Adduct Analysis.
DNA was extracted using the phenol/chloroform method, and DNA concentration was measured by spectrophotometry. DNA adduct detected used the nuclease P1-enhanced version of the 32P-postlabeling assay (16) . Ten µg of breast tissue DNA were used in each assay. An internal standard DNA from mouse skin treated with dibenzo[a,j]acridine was included in each DNA sample to monitor the quality of enzymatic digestion, radioactive labeling, and chromatography. The levels of DNA adducts are expressed as RAL values. Because samples were coded during laboratory analysis, the laboratory personnel were blind to the case-control status of the subjects. The codes were broken only at the time of data analysis.

Genotyping of CYP1A1, CYP1B1, and GSTM1 Genes.
We examined the MspI polymorphism of CYP1A1 in this study. Polymerase chain reaction amplification of the gene and detection of the polymorphism were performed as described previously (17) . Analysis of the GSTM1 polymorphism was performed essentially as described by Bell et al. (18) . The presence and absence of the 215-bp band revealed the GSTM1-wild-type and GSTM1-null genotypes, respectively. The ß-actin gene was simultaneously amplified as an internal control. The m1 (V432L) and m2 (A453S) polymorphisms of the CYP1B1 gene were detected as reported previously by Bailey et al. (19) with some modifications. The restriction products were separated by electrophoresis with 10% native polyacrylamide gel.

Statistical Analysis.
DNA adduct levels were expressed as mean ± SE of the RAL values and were analyzed as both continuous and categorical variables. Potential differences in demographic variables and levels of DNA adducts between cases and controls and within subgroups were analyzed by ANOVA and Mann-Whitney test for continuous data and {chi}2 test for categorical data. Comparison of the mean level of DNA adducts was performed before and after natural log transformation of the RAL values. RAL data are reported as arithmetic means to be consistent with other studies. Possible determinants of the BP-induced DNA adduct levels in the breast tissues were evaluated by multiple linear regression analyses. The variables included demographic factors (i.e., age and ethnicity), sources of exposure such as smoking and alcohol use, and genetic factors such as family history of cancer and CYP1A1, CYP1B1, and GSTM1 genotypes. The association between the level of adducts and cancer risk was determined by logistic regression and expressed as ORs and 95% CIs.


   Results
Top
 ABSTRACT
 Introduction
 Patients and Methods
 Results
Discussion
 REFERENCES
 
Because of the difficulties in obtaining breast tissue samples from noncancer controls, our sample size was limited to 76 cases and 60 controls for this study. The demographic characteristics of the study subjects are described in Table 1Citation . Young minorities were overrepresented in the control group (P < 0.001 for age and P = 0.002 for ethnicity; Table 1Citation ). Most of the cancers were invasive ductal carcinomas (60%) or ductal carcinomas in situ (26%). The tumors were predominantly diagnosed at early stages (23% carcinoma in situ, 51% stage I, 25% stage II, and 1% stage III).


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

  		Table 1 Distribution of select variables and level of in vitro BP-induced DNA adducts in breast tissues between cases and controlsa (RAL x 109)

 
There were no significant differences between cases and controls in the frequency of ever-smokers (Table 1)Citation and exposure to secondhand tobacco smoke, age started smoking, and exposure to solvents, oils, metals, pesticides, automobile exhaust, and wood dust (data not shown). There was no significant difference in the frequencies of first-degree relatives with a history of other cancers, alcohol use, CYP1A1, CYP1B1, and GSTM1 genotypes. Significantly more cases than controls had first-degree relatives with a history of breast cancer (P = 0.004; Table 1Citation ).

The level of in vitro BP-induced DNA adducts in breast tissue of the cases was twice of that of controls; the mean adduct levels (RAL x 109) were 134.6 ± 21.2 for the case subjects and 66.9 ± 7.5 for the controls (P = 0.007; Fig. 1Citation ). Stratified analyses showed that the differences between cases and controls were statistically significant among nonwhites, individuals <34 years of age (median age of the controls), never-smokers, alcohol users, women with a family history of cancer, CYP1A1 *1/*1 allele (common allele), CYP1B1 m2 Asn/Asn (common allele), and GSTM1 wild-type carriers (Table 1)Citation . These significant differences between cases and controls were also confirmed by the nonparametric Mann-Whitney test (Table 1)Citation and ANOVA of the geometric means (data not shown).



View larger version (14K):
[in this window]
[in a new window]
[Download PPT slide]
  		Fig. 1. Level of in vitro BP-induced DNA adducts in normal breast tissues of cancer cases and noncancer controls. Solid line, median; dotted line, mean; boxes, 25th and 75th percentile of the observed values; bars, 10th and 90th percentiles.

 
Comparisons of DNA adduct level within each subgroup showed that non-Hispanic whites had a significantly higher adduct level than did other ethnic groups among women without breast cancer (P = 0.01; Table 1Citation ). When case-control status and race were considered in a general linear model ANOVA, both factors were found to have significant effects on the level of BP-induced adducts (P = 0.03 and 0.042, respectively). Among cases, those with first-degree relatives having a history of breast cancer displayed a higher level of adducts than those without such a history (P = 0.046; Table 1Citation ). Heavy smokers (>=20 pack-years) tended to have a higher level of adducts than light smokers (P = 0.1; Table 1Citation ). Other factors, such as age, family history of other cancers, alcohol use, and CYP1A1, CYP1B1, and GSTM1 genotypes did not display any significant effect on the level of BP-induced adducts in breast tissues in subgroup analysis.

When multiple factors were considered in a linear regression model, pack-years of smoking was found to be a significant predictor of the level of in vitro BP-induced DNA adducts in breast tissues of cases (P = 0.025; Table 2Citation ). Age and family history of breast cancer also showed a borderline significant association with the level of adducts (P = 0.063 and 0.069, respectively; Table 2Citation ). Younger women and women with a family history of breast cancer seemed to be more sensitive to BP-induced DNA damage than their counterparts. Of those factors examined among noncancer controls, however, CYP1B1 m1 polymorphism was the sole significant predictor for the level of adducts (P = 0.048; Table 2Citation ). To rule out the possibility that the higher level of in vitro BP-induced adducts among smokers was attributable to a higher level of in vivo smoking-induced adducts, we subtracted the in vivo adduct from the total level of in vitro BP-induced adduct. However, the main observations were not affected by the subtraction. As shown in Table 2Citation , pack-years of smoking and CYP1B1 m1 polymorphism remained the significant predictors of the level of adducts for cases and controls, respectively.


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

  		Table 2 Multiple linear regression analysis of possible predictors of in vitro BP-induced DNA adduct levels in breast tissues

 
When the mean adduct level of the control group was used as a cutoff point, 50% of case subjects, but only 17% of controls, were in the higher level (P = 0.01; Table 3Citation ). Multiple logistic regression analysis revealed that the in vitro BP-induced DNA adducts in breast tissue were significantly associated with cancer risk after adjustment for age, ethnicity, smoking, alcohol use, family history of breast cancer, and CYP1A1, CYP1B1, and GSTM1 genotypes (OR, 4.38; 95% CI, 1.04–18.50; P = 0.044).


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

  		Table 3 Logistic regression analysis of adjusted ORs and CIs for in vitro induced DNA adducts in breast tissues and associated risk of cancer

 

   Discussion
Top
 ABSTRACT
 Introduction
 Patients and Methods
 Results
 Discussion
REFERENCES
 
To test the hypothesis that genetic susceptibility to carcinogen exposure is a risk factor for breast cancer, we conducted a small-scale, case-control study to demonstrate individual variability in tissue response to carcinogen insult. We further explored the genetic and environmental factors that affect such variability. When breast tissues were exposed in vitro to a classic tobacco carcinogen, BP, women with breast cancer displayed a significantly higher level of BP-DNA adducts than did healthy controls. After adjusting for several confounding factors, the level of BP-induced DNA adducts was found to be a significant risk factor for breast cancer. Because all tissue samples were exposed to the same level of BP under the same experimental conditions, the level of DNA adducts detected in this study reflects intrinsic factors that determine the tissue response to such damage, i.e., carcinogen metabolism and DNA repair capacities. The higher level of DNA damage among cases thus suggests that cases had an elevated activation, deficient detoxification, and reduced DNA repair capacity compared with controls.

Limited by accessibility to breast tissues, our study was restrained in premenopausal women, and our controls were overrepresented with young minorities. This unbalanced design raises the question of whether the higher level of adducts detected in cases than in controls was a consequence of the differences in age and ethnic distributions between the two groups. In both stratified analysis and multiple regression analysis, age was found to have a negative effect on the level of BP-induced DNA adducts. Younger women seemed more sensitive to the carcinogen challenge. Because controls were significantly younger than cases, the higher level of adducts among cases compared with controls was obviously not related to age. On the other hand, non-Hispanic whites displayed a significantly higher level of BP-induced DNA adducts than other races, whereas controls were overrepresented by non-white races. ANOVA found that the difference in BP-induced DNA adducts between cases and controls remained statistically significant after being controlled for ethnicity. Therefore, the higher level of BP-induced DNA adducts in breast tissues of cases compared with that of controls could not be explained by the differences in ethnicity alone; other factors might be involved as well.

When we further explored the genetic and environmental factors that affect the level of BP-induced DNA adducts in breast tissues, we found that family history of breast cancer and pack-years of smoking were significantly associated with the level of BP-induced DNA adducts in breast tissues among cases. The association between family history of breast cancer and higher level of BP-induced DNA adducts supports the notion that hereditary factors in carcinogen metabolism and DNA repair play a role in breast cancer etiology. This notion is consistent with the fact that several breast cancer susceptibility genes, including BRCA1, ATM, and p53, are involved in the cellular response to DNA damage. The significant association between pack-years smoked and the level of BP-induced DNA adducts among cases is intriguing. During the quantitative analysis of the in vitro BP-induced DNA adducts, only BP-specific DNA adducts were included in the assay; therefore, the higher level of in vitro BP-induced adducts among smokers was not attributable to a higher level of in vivo smoking-induced adducts in the same samples. In fact, the association between pack-years of smoking and the level of in vitro BP-induced adducts remained significant even after the in vivo adducts were subtracted from the total in vitro adducts. Although this effect was not observed among noncancer controls, it could be partially explained by the fact that there were no heavy smokers in this group. These results suggest that smoking not only directly induces DNA damage in breast tissues but also alters the tissue defense mechanism against carcinogen-induced DNA damage. We speculate that heavy smoking may modulate breast tissue response to carcinogen challenges by either reducing DNA repair and detoxification capacities or increasing carcinogen activation capacity, which would result in a higher level of DNA adduct formation. Further investigation on the gene expression profiles of these BP-treated tissues is warranted to test this hypothesis.

Among control subjects, ethnicity and CYP1B1 m1 polymorphism were significantly associated with the level of BP-induced DNA adducts in breast tissues. Non-Hispanic whites were more sensitive to the BP-induced DNA damage compared with other races. This ethnic difference could be related to genetic variations in carcinogen metabolism and DNA repair, but the sample size in this study was too small to examine this issue.

We used BP instead of the ultimate carcinogen BP diol epoxide in the in vitro assay because we wanted to explore the role of in situ carcinogen activation in breast tissues during chemical carcinogenesis. Our result showed that CYP1A1 genotype did not have a significant effect on the level of BP-induced adducts. In fact, subjects with the variant CYP1A1 *1/*2 and *2/*2 genotypes tended to have fewer adducts than did the subjects with the common CYP1A1 *1/*1 genotype. On the other hand, women with homozygous V432L (m1) or A453S m2 CYP1B1 genotypes showed lower levels of the BP-induced DNA adducts compared with their counterparts. A previous in vitro study has observed that the combined V432L and A453 alleles are associated with a higher activity for carcinogen activation (20) . Our observations suggest that the rare V432L and A453S alleles are associated with a lower activation activity of BP in the breast tissues. The precise role of the functional CYP1B1 polymorphisms in the metabolic activation of carcinogens in breast tissues needs further investigation.

It is unlikely that the higher level of adducts in cases than in controls is a consequence of disease status. Most patients had very early breast cancer, and none had received chemotherapy or radiotherapy before obtaining the sample. Our finding that the level of in vitro BP-induced DNA adducts in breast tissue is a significant risk factor for breast cancer supports the hypothesis that individuals with unfavorable genetic makeup in carcinogen metabolism and DNA repair, especially those who have been exposed to carcinogens, may have an increased risk for breast cancer.

In summary, we conducted a small-scale, case-control study of breast cancer. Although the controls were not well matched to cases by age and ethnic group, we made several interesting and important observations: (a) a high level of in vitro BP-induced DNA adducts was a significant risk factor for breast cancer; (b) non-Hispanic white women and women with a family history of breast cancer were more susceptible to carcinogen insult than their counterparts; and (c) pack year of smoking and CYP1B1 genotype were significant factors determining the level of BP-induced DNA adducts in breast tissues. These observations underscore the significance of individual susceptibility to carcinogen exposure in breast carcinogenesis. Most importantly, our data show that environmental carcinogen exposure may modify individual susceptibility to carcinogen exposure and in turn the risk of breast cancer.


   ACKNOWLEDGMENTS
 
We thank Dr. Regine Goth-Goldstein and Yingqiu Du for technical assistance on the CYP1B1 genotype assays. We also thank Drs. Manal Hassan and Xuemei Wang for assistance with the statistical analyses and Dr. Maureen E. Goode for editing the manuscript.


   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 This work was supported by NIH Grant CA 70264, National Institute of Environmental Health Sciences Center Grant P30 ES 07784, and NIH Cancer Center Core Grant CA 16672. Back

2 To whom requests for reprints should be addressed, at Department of Gastrointestinal Medical Oncology, Box 426, The University of Texas M. D. Anderson Cancer Center, 1400 Holcombe Boulevard, Box 426, Houston, TX 77030. Phone: (713) 792-2012; Fax: (713) 745-1163; E-mail: dli{at}mdanderson.org Back

3 The abbreviations used are: BP, benzo(a)pyrene; RAL, relative adduct labeling; OR, odds ratio; CI, confidence interval. Back

Received 5/22/02. Accepted 7/ 8/02.


   REFERENCES
Top
 ABSTRACT
 Introduction
 Patients and Methods
 Results
 Discussion
 REFERENCES
 

  1. American Cancer Society. . Cancer facts and figures: 2001, American Cancer Society Atlanta 2001.
  2. Kelsey J. L., Berkowitz G. S. Breast cancer epidemiology. Cancer Res., 48: 5615-5623, 1988.[Abstract/Free Full Text]
  3. Che Y., Lee W. H., Chew H. K. Emerging roles of BRCA1 in transcriptional regulation and DNA repair. J. Cell Physiol., 181: 385-392, 1999.[Medline]
  4. Welsch P. L., Owens K. N., King M. C. Insights into the functions of BRCA1 and BRCA2. Trends Genet., 16: 69-74, 2000.[Medline]
  5. Li S., Ting N. S., Zheng L., Chen P. L., Ziv Y., Shiloh Y., Lee E. Y., Lee W. H. Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. Nature (Lond.), 406: 210-215, 2000.[Medline]
  6. Cortez D., Wang Y., Qin J., Elledge S. J. Requirement of ATM-dependent phosphorylation of BRCA1 in the DNA damage response to double-strand breaks. Science (Wash. DC), 286: 1162-1166, 1999.[Abstract/Free Full Text]
  7. Lichtenstein P., Holm N. V., Verkasalo P. K., Iliadou A., Kaprio J., Koskenvuo M., Pukkala E., Skytthe A., Hemminki K. Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N. Engl. J. Med., 343: 78-85, 2000.[Abstract/Free Full Text]
  8. 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]
  9. 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]
  10. Xiong P., Bondy M. L., Li D., Shen H., Wang L. E., Singletary S. E., Spitz M. R., Wei Q. 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., 61: 8465-8469, 2001.[Abstract/Free Full Text]
  11. 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]
  12. Li D., Firozi P. F., Chang P., Wang L. E., Xiong P., Sturgis E. M., Eicher S. A., Spitz M. R., Hong W. K., Wei Q. In vitro BPDE-induced DNA adducts in peripheral lymphocytes as a risk factor for squamous cell carcinoma of the head and neck. Int. J. Cancer, 93: 436-440, 2001.[Medline]
  13. Perera F., Estabrook A., Hewer A., Channing K. M., Mooney L. A., Whyatt R., Phillips D. H. Carcinogen-DNA adducts in human breast tissue. Cancer Epidemiol. Biomark. Prev., 4: 233-238, 1995.[Abstract]
  14. Li D., Wang M. Y., 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]
  15. Pfau W., Stone E. M., Brockstedt U., Carmichael P. L., Marquardt H., Phillips D. H. DNA adducts in human breast tissues: association with N-acetyltransferase 2 (NAT2) and NAT1 genotypes. Cancer Epidemiol. Biomark. Prev., 7: 1019-1025, 1998.[Abstract]
  16. Reddy M. V., Randerath K. Nuclease P1-mediated enhancement of sensitivity of 32P-postlabeling test for structurally diverse DNA adducts. Carcinogenesis (Lond.), 7: 1543-1551, 1986.[Abstract/Free Full Text]
  17. Houlston R. S. CYP1A1 polymorphisms and lung cancer risk: a meta-analysis. Pharmacogenetics, 10: 105-114, 2000.[Medline]
  18. Bell D. A., Taylor J. A., Paulson D. F., Robertson C. N., Mohler J. L., Lucier G. W. 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: 1159-1164, 1993.[Abstract/Free Full Text]
  19. Bailey L. R., Roodi N., Dupont W. D., Parl F. F. Association of cytochrome P450 1B1 (CYP1B1) polymorphism with steroid receptor status in breast cancer[erratum appears in Cancer Res., 59: 1388, 1999]. Cancer Res., 58: 5038-5041, 1998.[Abstract/Free Full Text]
  20. Shimada T., Watanabe J., Kawajiri K., Sutter T. R., Guengerich F. P., Gillam E. M. J., Inoue K. Catalytic properties of polymorphic human cytochrome P450 1B1 variants. Carcinogenesis (Lond.), 20: 1607-1614, 1999.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Am J EpidemiolHome page
V. Paracchini, S. Raimondi, I. T. Gram, D. Kang, N. A. Kocabas, V. N. Kristensen, D. Li, F. F. Parl, T. Rylander-Rudqvist, P. Soucek, et al.
Meta- and Pooled Analyses of the Cytochrome P-450 1B1 Val432Leu Polymorphism and Breast Cancer: A HuGE-GSEC Review
Am. J. Epidemiol., January 15, 2007; 165(2): 115 - 125.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. Colilla, P. W. Kantoff, S. L. Neuhausen, A. K. Godwin, M. B. Daly, S. A. Narod, J. E. Garber, H. T. Lynch, M. Brown, B. L. Weber, et al.
The joint effect of smoking and AIB1 on breast cancer risk in BRCA1 mutation carriers
Carcinogenesis, March 1, 2006; 27(3): 599 - 605.
[Abstract] [Full Text] [PDF]

Home page
 Am J EpidemiolHome page
L. F. Masson, L. Sharp, S. C. Cotton, and J. Little
Cytochrome P-450 1A1 Gene Polymorphisms and Risk of Breast Cancer: A HuGE Review
Am. J. Epidemiol., May 15, 2005; 161(10): 901 - 915.
[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 Li, D.
Right arrow Articles by Bondy, M. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, D.
Right arrow Articles by Bondy, M. L.

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