Title

Clinical implications of mutations in thep53 tumor suppressor gene in female patients with breast cancer

Date of Award

2002

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Epidemiology and Public Health

First Committee Member

Edward Trapido, Committee Chair

Abstract

Breast cancer is the most commonly diagnosed cancer in women in the United States. Mutation in the p53 tumor suppressor gene occurs in about 50% of all human tumors. This study investigated the association between different types and locations of point mutation in the p53 gene and race/ethnicity, the age at diagnosis, tumor status of breast cancer and the survival of patients with breast cancer. A total of 271 female breast cancer patients were included in the investigation. Logistic regression analysis was used to evaluate the association between the mutations and the age at diagnosis or tumor status of breast cancer. Cox regression analysis was used to evaluate the predictive value of mutations in p53 gene for survival of the patients. Hispanic patients were twice less likely to have p53 gene mutation in their tumor cells compared to non-Hispanic patients (OR and 95% CI: 0.48, 0.27--0.85). Early-age breast cancer (defined as age ≤40 years at diagnosis) was associated with nonsense mutations, mutations in exons 7 and 8 (11.91, 2.49--56.99; 3.50, 1.55--7,90 and 5.23, 2.38--11.50, respectively). Mutations in p53 gene predicted higher rates of overall mortality (RR and 95% CI: 2.46, 1.27--4.77) and breast-cancer-specific mortality (2.47, 1.15--5.30) of the patients after adjustment for tumor stage, chemotherapy and number of mutations. Transversional mutations in p53 gene predicted higher rates of overall mortality (RR and 95% CI: 2.46, 1.27--4.77) and breast-cancer-specific mortality (2.47, 1.15--5.30) of the patients after adjustment for tumor stage, chemotherapy and number of mutations. Transversional mutations in p53 gene were associated with higher overall mortality (RR and 95% CI: 4.90, 2.21--10.82) and breast-cancer-specific mortality (5.12, 1.94--12.51). Nonsense mutations were associated with higher breast-cancer-specific mortality (4.53, 1.77--11.631). This study suggests that (1) Hispanic women with breast cancer are less likely to carry mutations in their tumor cells, (2) mutations in the p53 gene, particularly nonsense mutations or mutations in exons 7 and 8, might contribute to an accelerated development of breast cancer. Mutation, particularly transversional/nonsense mutations in the gene might play a role in breast cancer progression. Clinical implications of this study are that (1) the patients whose breast cancer is diagnosed at young age may more likely have carried mutations in the p53 tumor suppressor gene and (2) breast cancer patients who carry p53 gene mutations may be more likely to have a poorer prognosis.

Keywords

Biology, Molecular; Health Sciences, Public Health

Link to Full Text

http://access.library.miami.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3032379