Short Communication The Interaction between Alcohol Consumption and GSTM1 Genotype on Polycyclic Aromatic Hydrocarbon-DNA Adduct Levels in Breast Tissue 1 Andrew Rundle, Deliang Tang, LaVerne Mooney, Surah Grumet, and Frederica Perera 2 Departments of Epidemiology [A. R.] and Environmental Health Sciences [D. T., L. M., S. G., F. P.], Mailman School of Public Health, Columbia University, New York, New York 10032 Abstract We investigated the association between alcohol consumption, GSTM1 genotype, and polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels in breast tissue. Women referred for breast surgery were enrolled prior to surgery, responded to an interview, and gave a blood sample. Women diagnosed with ductal carcinoma in situ and invasive ductal or lobular cancer were defined as cases, and women with benign conditions without atypia were defined as controls. Paraffin-embedded tumor and nontumor tissue from cases and benign tissue from controls were retrieved from the pathology samples. GSTM1 genotype status was determined by PCR using WBC DNA, and PAH-DNA adduct levels were measured in breast tissue using immunohistochemistry. In tumor and nontumor tissue from cases, the GSTM1-null genotype was associated with increased adduct levels among current alcohol consumers but not among nondrinkers. In nontumor tissue, the interaction between genotype and alcohol consumption was significant (P  0.02), but in tumor tissue, the interaction did not achieve statistical significance (P  0.10). In benign tissue from controls, there was no association between genotype and adducts, regardless of drinking status. Among subjects with the null genotype who drank alcohol, adduct levels were significantly higher in tumor and nontumor tissue from cases than in benign tissue from controls. These results indicate the presence of a novel gene-lifestyle interaction that influences PAH-DNA adduct levels in breast tissue from cases but not controls. This apparent difference in PAH metabolism in response to alcohol may be an important clue as to how alcohol influences breast cancer risk. Introduction We have been investigating the genetic and lifestyle determi- nants of PAH 3 -DNA adduct levels in breast tissue and the association between increased levels and breast cancer case- control status (1–3). When adduct levels in tumor tissue from cases were compared with adduct levels in benign tissue from controls, high adduct levels were associated with breast cancer case-control status (1). The GSTM1-null genotype was associ- ated with increased adduct levels in tumor and nontumor tissue from cases, but it was not associated with adduct levels in benign tissue from controls (2). Case-control differences in adduct levels were stronger among those with the GSTM1-null genotype. As in many other studies of breast cancer (4, 5), we found current alcohol consumption to be associated with breast cancer case-control status (3). The mechanisms through which alcohol may cause breast cancer are unknown, although several have been have proposed (4). We have hypothesized that alcohol consumption may influence breast cancer risk by inducing and suppressing genes responsible for the metabolism of xenobiot- ics (6, 7). Several animal and cell culture studies have demon- strated that ethanol exposure alters PAH metabolism and in- creases adduct formation (7–11). Recent experiments with MCF-10F breast cells have shown that cotreatment of cells with B[a]P and ethanol produced higher adduct levels than treatment with B[a]P alone (7). Ethanol treatment was shown to reduce the expression of GSTP1, and the authors attributed the in- creased adduct levels to ethanol-induced reductions in B[a]P metabolism by GSTP1 (7). GSTP1 and GSTM1 both detoxify PAH, creating water-soluble conjugates that are less reactive than the PAH diol-epoxide metabolites (12, 13). Thus, the GST enzymes are thought to prevent reactive xenobiotics from dam- aging DNA (2, 12). Here we extend our earlier findings on GSTM1 and show that the GSTM1 genotype is a stronger predictor of PAH-DNA adduct levels in subjects who were regular alcohol drinkers. Materials and Methods Study Population. Patient recruitment has been described pre- viously in detail (1) and will only be described briefly here. From 1994 to 1998, women referred for breast surgery at Columbia-Presbyterian Medical Center were enrolled before surgery into a hospital-based case-control study. After informed consent had been obtained, during their preoperative tests, patients took part in a structured interview covering established reproductive breast cancer risk factors, active and passive smoking, dietary practices, other environmental and occupa- Received 10/11/02; revised 5/5/03; accepted 5/22/03. 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 by grants from the Department of the Army, United States Army Medical Research and Materiel Command, DAMD17-94-J-4251, Noreen T. Hol- land Foundation, and National Cancer Institute Grant K07 CA92348. 2 To whom requests for reprints should be addressed, at Department of Environ- mental Health Sciences, Mailman School of Public Health, 60 Haven Avenue B1, New York, NY 10032. Phone: (212) 304-7280; Fax: (212) 544-1943; E-mail: fpp1@columbia.edu. 3 The abbreviations used are: PAH, polycyclic aromatic hydrocarbon; B[a]P, benzo(a)pyrene; GST, glutathione S-transferase; BBD, benign breast disease. 911 Vol. 12, 911–914, September 2003 Cancer Epidemiology, Biomarkers & Prevention on June 29, 2017. © 2003 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from