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Waf-1 (p21) and p53 Polymorphisms in Breast Cancer

Toxicology and Molecular Biology Branch [C. K., B. L. F., A. W.] and Biostatistics Branch [E. C. M.], Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia 26505, and Mount Sinai School of Medicine, New York, New York 10029 [M. S. W.]

p53 is a transcription factor for Waf-1/p21, a cyclin-dependent kinase inhibitor. Certain polymorphic variants of Waf-1 and p53 have been evaluated for their association with cancer risk. Previous studies indicated that certain p53 polymorphisms confer an increased risk of breast cancer [odds ratios (ORs) and 95% confidence intervals (CIs) = 2.9, 1.4–6.3 Carcinogenesis (Lond.), 17: 1313, 1996; 2.5, 1.3–4.8 Cancer Epidemiol. Biomark. Prev., 6: 105, 1997; and 1.5, 1.1–2.0, Anticancer Res., 18: 2095, 1998). The primary objectives of this study were to test the hypotheses that the serine variant (codon 31 polymorphism) of Waf-1 is also involved in this process and that there is an interaction between Waf-1 and p53 polymorphisms. To do this, Waf-1 and p53 genotypes were determined for women enrolled in a breast cancer case-control study (Caucasians, African-Americans and Latinas; 487 Waf-1 and 504 p53 genotypes were obtained). Multivariate logistic regression was used to evaluate possible associations between Waf-1 and p53 polymorphisms, race, and menopause. The primary aim was to determine whether an interaction between Waf-1 and p53^1–2-1 existed. Whereas multivariate analysis suggested associations between breast cancer and inheritance of Waf-1^ser31 in African-Americans (OR, 2.32; 95% CI = 0.66–5.60; n = 37 cases and 65 controls) and Latinas (OR, 2.22; 95% CI = 0.71–6.89; n = 30 cases and 75 controls), and inheritance of p53^1–2-1 in Caucasians (OR, 3.15; 95% CI = 1.14–8.89; n = 93 cases and 187 controls), we did not see an interaction between Waf-1^ser31 and p53^1–2-1. Consistent with the finding that p53^1–2-1 is a risk factor for Caucasian women was the observation of a strong interaction between race and p53 (P < 0.01).

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