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

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).