RGD Reference Report - Uterine Carcinomas in Tetrabromobisphenol A-exposed Wistar Han Rats Harbor Increased Tp53 Mutations and Mimic High-grade Type I Endometrial Carcinomas in Women.

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Uterine Carcinomas in Tetrabromobisphenol A-exposed Wistar Han Rats Harbor Increased Tp53 Mutations and Mimic High-grade Type I Endometrial Carcinomas in Women.
Authors:	Harvey, JB Osborne, TS Hong, HH Bhusari, S Ton, TV Pandiri, AR Masinde, T Dunnick, J Peddada, S Elmore, S Hoenerhoff, MJ
Citation:	Harvey JB, etal., Toxicol Pathol. 2015 Dec;43(8):1103-13. doi: 10.1177/0192623315599256. Epub 2015 Sep 8.
RGD ID:	11075084
Pubmed:	PMID:26353976 (View Abstract at PubMed)
PMCID:	PMC4670270 (View Article at PubMed Central)
DOI:	DOI:10.1177/0192623315599256 (Journal Full-text)
Endometrial carcinoma is the most common gynecologic malignancy is the United States and accounts for 6% of all cancers in women. The disease is classified as type I or type II based on clinicopathologic and molecular features. It is a multifactorial disease with a number of risk factors, including environmental exposures. How environmental exposures, such as flame retardants, may affect the incidence of endometrial cancer is a topic of current and ongoing interest. Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant found in a variety of household products. A recent 2-year National Toxicology Program carcinogenicity study found that exposure to TBBPA was associated with a marked increase in the development of uterine tumors, specifically uterine carcinomas, in Wistar Han rats. Molecularly, TBBPA-induced uterine carcinomas in Wistar Han rats were characterized by a marked increase in tumor protein 53 mutation compared to spontaneous uterine carcinomas, as well as overexpression of human epidermal growth factor receptor 2. Similar to spontaneous carcinomas, tumors in TBBPA-exposed rats were estrogen receptor-alpha positive and progesterone receptor negative by immunohistochemistry. The morphologic and molecular features of uterine carcinomas in TBBPA-exposed rats resemble those of high-grade type I tumors in women, and these data suggest that exposure to TBBPA may pose an increased cancer risk.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
endometrial carcinoma		ISO	Tp53 (Rattus norvegicus)	11075084; 11075084	DNA:mutations: :	RGD
endometrial carcinoma		IMP		11075084	DNA:mutations: :	RGD

Objects Annotated

Genes (Rattus norvegicus)

Tp53 (tumor protein p53)

Genes (Mus musculus)

Trp53 (transformation related protein 53)

Genes (Homo sapiens)

TP53 (tumor protein p53)

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Uterine Carcinomas in Tetrabromobisphenol A-exposed Wistar Han Rats Harbor Increased Tp53 Mutations and Mimic High-grade Type I Endometrial Carcinomas in Women.