Cigarette Smoking and Other Risk Factors in Relation to p53 Expression in Breast Cancer among Young Women

Cigarette Smoking and Other Risk Factors in Relation to p53 Expression in Breast Cancer among Young Women1

Columbia University, The Joseph L. Mailman School of Public Health, Division of Epidemiology, New York, New York 10032 [M. D. G., M. B. T.]; Columbia College of Physicians and Surgeons, Department of Pathology, New York, New York 10032 [H. H., S. B.]; New Jersey State Department of Health and Senior Services, Applied Cancer Epidemiology Program, Trenton, New Jersey 08625 [J. B. S.]; National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, Maryland 20892 [L. A. B.]; Mt. Sinai Medical Center, Department of Community and Preventive Medicine, New York, New York 10029 [J. L. B.]; and University of Southern Maine, Department of Applied Sciences, Portland, Maine 04103 [W. D. T.]

Abstract

p53 mutations may be a fingerprint for cigarette smoking and other environmental carcinogens, including breast carcinogens. This study was undertaken to explore whether p53 mutations are associated with environmental or other suspected or established risk factors for breast cancer. p53 protein detection by immunohistochemistry (which is more easily quantified in large epidemiological studies than are mutations, and are highly correlated with them) was determined for 378 patients from a case-control study of breast cancer. In this population-based sample of women under the age of 45 years, 44.4% (168/378) of the cases had p53 protein detected by immunohistochemistry (p53+). Polytomous logistic regression was used to calculate the odds ratios (ORs) for p53+ and p53− breast cancer, as compared with the controls, in relation to cigarette smoking and other factors. The ratio of the ORs was used as an indicator of heterogeneity in risk for p53+ versus p53− cancer. The ratio of the ORs in a multivariate model was substantially elevated among women with a greater than high school education [2.39; 95% confidence interval (CI), 1.43–4.00], current cigarette smokers (1.96; 95% CI, 1.10–3.52), and users of electric blankets, water beds, or mattresses (1.78; 95% CI, 1.11–2.86). Nonsignificant heterogeneity was noted for family history of breast cancer and ethnicity but not for other known or suspected risk factors. Coupled with the strong biological plausibility of the association, our data support the hypothesis that in breast cancer, as with other tumors, p53 protein immunohistochemical detection may be associated with exposure to environmental carcinogens such as cigarette smoking.

Footnotes

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↵1 This research was supported in part by Grant DAMD-94-j-4250 from the United States Army Medical Research and Material Command and Grant 1R21CA/ ES66224 from the National Cancer Institute and the National Institute of Environmental Health Sciences.
↵2 To whom correspondence should be addressed, at Columbia University, The Joseph L. Mailman School of Public Health, Division of Epidemiology, 622 West 168th Street, PH18, New York, NY 10032. Phone: (212) 305-7992; Fax: (212) 305-3388; E-mail: mdg2{at}columbia.edu
↵3 The abbreviations used are: OR, odds ratio; CI, confidence interval; OC, oral contraceptive; ER, estrogen receptor; PR, progesterone receptor.
- Accepted January 4, 1999.
- Received August 27, 1998.
- Revision received December 7, 1998.