American Journal of Epidemiology Vol. 144, No. 10: 924-933
Copyright © 1996 by The Johns Hopkins University School of Hygiene and Public Health
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p53 Protein Overexpression in Relation to Risk Factors for Breast Cancer
1Department of Epidemiology, The Netherlands Cancer Institute 1066 CX Amsterdam, The Netherlands
2Department of Pathology, The Netherlands Cancer Institute 1066 CX Amsterdam, The Netherlands
Reprint requests to Dr. Flora E. van Leeuwen, The Netherlands Cancer Institute, Department of Epidemiology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
To investigate whether breast tumors developing through a pathway with p53 protein overexpression (p53+) show different risk factor associations compared with breast tumors without p53 overexpression (p53–), the authors determined p53 overexpression in tissue sections of 528 patients with invasive breast cancer by using immunohistochemistry. These patients and 918 healthy controls aged 20–54 years participated in a Netherlands population-based case-control study on oral contraceptives in 1986–1989. A total of 142 tumors (27%) demonstrated clear p53 overexpression (p53+). Most risk factors did not show different associations with p53+ and p53– tumors. However, use of oral contraceptives for 9 or more years was associated with a 2.5-fold increase in the risk of p53+ tumors (95% confidence interval 1.4–4.4; test for trend with months of use, p = 0.01), whereas such use increased the risk of p53– tumors only 1.4-fold (95% confidence interval 0.9–2.1; test for trend, p = 0.06). Prolonged lactation (
25 weeks) was associated with a 40% reduction in risk of p53+ tumors (odds ratio = 0.6; 95% confidence interval 0.3–1.0; test for trend with weeks of lactation, p = 0.09), whereas the risk of p53– tumors was not associated with lactation. The authors conclude that p53+ and p53– breast tumors are not associated with very distinct risk profiles but that the stronger associations of p53+ tumors with oral contraceptive use and lactation suggest differences in risks that deserve further investigation. If these findings can be confirmed and possible molecular mechanisms explored, this may help to elucidate the associations between these risk factors and breast cancer in general. Am J Epidemiol 1996; 144: 924-33.
breast neoplasms; immunohistochemistry; protein p53; risk factors
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