Waf-1 (p21) and p53 polymorphisms in breast cancer

Channa Keshava, Bonnie L. Frye, Ainsley Weston, Erin C. McCanlies, Mary S. Wolff

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70 Scopus citations

Abstract

p53 is a transcription factor for Waf-1/p21, a cyclindependent 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 p531-2-1 existed. Whereas multivariate analysis suggested associations between breast cancer and inheritance of Waf-1ser31 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 p531-2-1 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-1ser31 and p531-2-1. Consistent with the finding that p531-2-1 is a risk factor for Caucasian women was the observation of a strong interaction between race and p53 (P < 0.01).

Original languageEnglish
Pages (from-to)127-130
Number of pages4
JournalCancer Epidemiology Biomarkers and Prevention
Volume11
Issue number1
StatePublished - 2002

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