title: Waf-1 (p21) and p53 polymorphisms in breast cancer.
abstract: 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).
authors.affiliation: Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Road, Morgantown, WV 26505, USA.
authors.forename: Channa
authors.initials: C
authors.lastname: Keshava
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Frye
authors.forename: Mary S
authors.initials: MS
authors.lastname: Wolff
authors.forename: Erin C
authors.initials: EC
authors.lastname: McCanlies
authors.forename: Ainsley
authors.initials: A
authors.lastname: Weston
mesh_terms: D000328:Adult; D044383:Black People / Q000235:genetics; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D016001:Confidence Intervals; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011336:Probability; D012016:Reference Values; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins