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).
Keshava
Channa
C
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.
Frye
Bonnie L
BL
Wolff
Mary S
MS
McCanlies
Erin C
EC
Weston
Ainsley
A
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
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins