Excess weight gain accelerates 1-methyl-1-nitrosourea-induced mammary carcinogenesis in a rat model of premenopausal breast cancer.
Cancer Prev Res (Phila)
; 7(3): 310-8, 2014 Mar.
Article
em En
| MEDLINE
| ID: mdl-24441676
ABSTRACT
In contrast to the null effects generally reported, high-risk premenopausal women (Gail score ≥1.66) enrolled in the Breast Cancer Prevention P-1 Trial were recently reported to be at increased risk for breast cancer when overweight (HR = 1.59) or obese (HR = 1.70). To investigate this clinical observation in a preclinical setting, ovary-intact female rats were intraperitoneally injected with 50 mg/kg 1-methyl-1-nitrosourea at 21 days of age to simulate premenopausal women with increased risk. Two commercially available strains of Sprague-Dawley rat (Taconic Farms) were used, which are dietary resistant (DR) or dietary susceptible (DS) to excess weight gain when fed a purified diet containing 32% kcal from fat, similar to levels consumed by the typical American woman. DS rats were approximately 15.5% heavier than DR rats at study termination and plasma leptin indicated a marked difference in adiposity. DS rats had higher incidence (26% increase), multiplicity (2.5-fold increase), and burden (5.4-fold increase) of mammary carcinomas with a concomitant reduction in cancer latency (16% earlier detection) compared with DR rats (P < 0.001 for all analyses), and displayed a higher proportion of hormone receptor negative tumors compared with DR rats [OR = 1.78; 95% confidence interval (CI), 0.83-3.81]. Circulating levels of several breast cancer-risk factors, including leptin, adiponectinleptin ratio, insulin, insulin-like growth factor (IGF)-1, IGF-1IGF-1 binding protein-3 ratio, and calculated insulin resistance (HOMA-IR) were negatively impacted in DS rats (P < 0.05 for all analyses). These findings support further investigation of the effects of excess weight in high-risk premenopausal women and demonstrate a useful preclinical model for rapid evaluation of mechanistic hypotheses.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinógenos
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Aumento de Peso
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Neoplasias Mamárias Experimentais
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Metilnitrosoureia
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Prev Res (Phila)
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2014
Tipo de documento:
Article