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BRCA1 mislocalization associated with breast carcinogenesis and poor prognosis in Taiwanese women
- Source :
- European Journal of Cancer Prevention. 24:407-415
- Publication Year :
- 2015
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2015.
-
Abstract
- We aimed to elucidate whether and how BRCA1 mislocalization [including membranous nuclear (MN) forms and negative patterns] is associated with the occurrence and the prognosis of breast cancer in young Taiwanese women. A case-control study was carried out to enroll 84 patients with breast cancer and 81 patients with benign breast disease. The subcellular localization of BRCA1 was examined using immunofluorescent assays on fresh tissue touch-imprinting slides to classify staining results into diffuse nuclear (DN), MN, and negative staining. Genetic variations of BRCA1 nuclear localization/transportation-related sequences were analyzed by cDNA sequencing of both nuclear localization signals (NLS) and nuclear export signals (NES). The BRCA1 antibody was verified by two other published ones. Comparisons of immunofluorescent assay with immunohistochemical and H&E staining methods were also performed. BRCA1 mislocalization conferred a 3.13-fold [95% confidence interval (CI): 1.31-7.50] risk of developing breast cancer for the MN form and a 5.79-fold (95% CI:1.58-21.23) risk for BRCA1-negative cases compared with DN staining. However, no genetic variant was found in the NES or the NLS region of the BRCA1 gene. In terms of prognosis, BRCA1 mislocalization showed a 3.5-fold (95% CI: 1.20-10.09) increased risk of breast cancer death compared with DN staining after adjusting for tumor node metastasis stage. BRCA1 MN forms and BRCA1-negative patterns led to a higher risk of carcinogenesis and a poor prognosis of breast cancer. Such BRCA1 mislocalization may not be directly caused by the genetic effects of the NLS and NES domains, but stem from nongenetic modifications (such as epigenetic silencing).
- Subjects :
- Adult
Oncology
Cancer Research
medicine.medical_specialty
Epidemiology
Blotting, Western
Nuclear Localization Signals
Taiwan
Breast Neoplasms
Real-Time Polymerase Chain Reaction
medicine.disease_cause
Breast cancer
Internal medicine
medicine
Humans
RNA, Messenger
skin and connective tissue diseases
Nuclear export signal
Survival rate
Neoplasm Staging
BRCA1 Protein
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Public Health, Environmental and Occupational Health
Case-control study
Middle Aged
Prognosis
medicine.disease
Survival Rate
Protein Transport
Cell Transformation, Neoplastic
Case-Control Studies
Immunohistochemistry
Female
Breast disease
business
Carcinogenesis
Nuclear localization sequence
Follow-Up Studies
Subjects
Details
- ISSN :
- 09598278
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- European Journal of Cancer Prevention
- Accession number :
- edsair.doi.dedup.....ce7ec9c5e195b15f98fd3871b568a4c8