A Case-control Study for Assessment of Risk Factors of Breast Cancer by the p53 Mutation

Kim, Heon; Ahn, Se Hyun; Lee, Moo Song

Abstract

p53 is the most frequently mutated gene in female breast cancer tissues and the prognosis of breast cancer could be changed by mutation of the gene. This study was performed to examine risk factors for breast cancer subtypes classified by p53 mutation and to investigate the roles of p53 gene mutation in carcinogenesis of breast cancer. The study subjects were 81 breast cancer patients and 121 controls who were matched to cases 1:1 or 1:2 by age, residence, education level and menopausal status. All the subjects were interviewed by a well-trained nurse with standardized questionnaire on reproductive factors, and were asked to fill the self-administrative food frequency and 24 hour recall questionnaires. p53 gene mutation in the cancer tissue was screened using polymerase chain reaction (PCR)-single strand conformational polymorphism (SSCP) method. Mutation type was identified by direct sequencing of the exon of which mobility shift was observed in SSCP analysis. Mutations were detected in p53 gene of 25 breast cancer tissues. By direct sequencing, base substitutions were found in 20 cancer tissues (10 transition and 10 transversion), and frame shift mutations in 5 (4 insertions and 1 deletion). For the whole cases and controls, risk of breast cancer incidence decreased when the parity increased, and increased when intake amount of total calory, fat, or protein increased. Fat and protein were statistically significant risk factors for breast cancer with p53 mutation. For breast cancer without p53 mutation, protein intake was the only significant dietary factor. These results suggests that causes of p53 positive breast cancer would be different from those of p53 negative cancer, and that dietary factors or related hormonal factors induce mutation of p53, which may be the first step of breast cancer development or a promoter following some unidentified genetic mutations.