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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 20% of all deaths in the United States are due to cancer. Cancers of the hormonal tissues such as breast, uterus, ovary in women and prostate in men account for about 8% and 5% of total mortality and 30% and 11% of cancer mortality in women and men, respectively. Diet is considered to be a major and important environmental factor contributing to cancers of hormonal tissues. Breast, uterus, and ovary cancers in women and prostate cancers in men were positively correlated with high fat consumption, high body weight (body mass), body fat, and obesity. A major mechanism for development of these cancers appears to be mediated through increased levels of hormones, especially estrogens. Adipose tissue is considered to be one of the major sources of extraglandular estrogen, produced by aromatization of androgen precursors. Weight reduction decreases the estrogen levels possibly due to a decrease in body fat, thus decreasing the risk for cancers of the hormonal tissues. Dietary fiber may modify the risk for these cancers by influencing estrogen metabolism, recirculation, and excretion. Vitamin A and its precursors may decrease the risk for prostate cancer. Iodine deficiency may increase the risk for thyroid neoplasms in humans and experimental animals. Tumors of the hormonal tissues are the most common tumors in laboratory rodents, especially rats and mice. Incidences of mammary and anterior pituitary tumors had significant and positive correlation with body weight in rats and mice. Lowering the body weight by either decreased caloric intake or other means (e.g., exercise, increased fiber consumption) markedly lowered the incidences of these tumors in laboratory rodents. Laboratory studies indicated that mammary tumor rates in rats may not depend on the amount of fat consumed per day. The mammary tumor-promoting effect of fat may be due to complex interactions involving energy intake and energy retention (body mass) mediated through paracrine, endocrine, and neurohormonal mechanisms. Dietary protein may influence chemically induced tumors by affecting the metabolism of chemicals through enzyme induction. Thus, environmental factors such as diet are considered to be major and important factors for tumors of the hormonal tissues such as breast, uterus, and ovary in women and prostate in men. Diet and associated body weight are considered to be the major factors for tumors of hormonal tissues such as mammary and pituitary glands in rodents, especially rats. Modification of diet and a decrease in caloric intake may markedly decrease the incidence or delay the development of tumors of hormonal tissues in humans and in experimental animals.
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PMID:Influence of diet on tumors of hormonal tissues. 877 7

In the present case-control study several dietary and nutritional factors were investigated to determine if a relationship exists between diet and development of mammary tumors in female dogs. Control female dogs (n = 86) were compared with a case group of dogs (n = 102) with dysplasias or tumors of the mammary gland. A questionnaire providing information on the dog's body conformation and dietary and reproductive histories was answered by the owners. Serum selenium and retinol concentrations and the fatty acid profile in subcutaneous adipose tissue were analyzed as indicators of nutritional status. Obesity at 1 year of age and 1 year before the diagnosis of mammary nodules was found to be significantly related to a higher prevalence of mammary tumors and dysplasias. The intake of homemade meals (compared to that of commercial foods) was also significantly related to a higher incidence of tumors and dysplasias. Other significant risk factors were a high intake of red meat, especially beef and pork, and a low intake of chicken. The subcutaneous fatty acid profile and the serum selenium concentration were not significantly different in the cases and the controls, with the exception of C18:1 fatty acid (oleic acid) content, which was significantly higher in the cases than in healthy controls. Serum retinol concentration was significantly lower in the cases than in the controls. In the multivariate analysis, older age, obesity at 1 year of age, and a high red meat intake were independently and significantly associated with the risk of developing mammary tumor and dysplasias.
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PMID:Relation between habitual diet and canine mammary tumors in a case-control study. 959 73

Obesity is a risk factor for postmenopausal breast cancer and is associated with shortened latency and/or increased mammary tumor (MT) incidence in animals. Elevated body weight is usually associated with hormone-responsive tumors. In agreement with these data we previously showed that latency of hormone-responsive MTs in MMTV-TGF-alpha mice with diet-induced obesity was significantly shortened. Here, we used the same protocol to determine the impact of diet-induced obesity on estrogen receptor-negative MT development in MMTV-neu (strain 202) mice. Mice were fed a low-fat diet (n=20) or a high-fat diet (n=54) from 10 wk of age. Body weight at 19 wk of age was used to assign high-fat mice to obesity-prone, overweight, and obesity-resistant groups. Mice were euthanized due to MT size or at 85 wk of age. Final body weights of obesity-prone mice were heaviest, and those of obesity-resistant and low-fat groups were similar. Fat pad weights were heaviest in obesity-prone mice followed by overweight and obesity-resistant groups, and lightest in low-fat mice. Serum IGF-I levels were similar for low-fat and high-fat mice, whereas leptin was higher in high-fat mice (P <0.0001). MT latency, incidence, metastasis, and burden were similar for all groups. These findings support that obesity is not a risk factor for development of estrogen-negative breast cancer.
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PMID:Diet-induced obesity and mammary tumor development in MMTV-neu female mice. 1562 64

Epidemiologic studies show a positive association between obesity and cancer risk. In addition to increased body adiposity and secretion of fat-derived hormones, obesity is also linked to insulin resistance, type 2 diabetes, and chronic inflammation. We used the fatless A-ZIP/F-1 transgenic mouse to dissociate the relative role of each of these underlying factors in the development of cancer. These mice are unique in that they do not have white fat but do develop type 2 diabetes. In two cancer models, the classic two-stage skin carcinogenesis protocol and the C3(1)/T-Ag transgenic mouse mammary tumor model, A-ZIP/F-1 mice displayed higher tumor incidence, tumor multiplicity, and decreased tumor latency than wild-type mice. We examined circulating levels of adipokines, growth factors, and cytokines. As expected, adipokines (i.e., leptin, adiponectin, and resistin) were undetectable or found at very low levels in the blood of fatless mice. However, insulin, insulin-like growth factor-I, growth hormone, vascular endothelial growth factor, and proinflammatory Th2 cytokines, such as interleukin (IL)-1beta, IL-4, and IL-6, were elevated in A-ZIP/F-1 mice. Additionally, we examined multiple phosphorylated proteins (i.e., protein kinase B/Akt and ErbB2/HER-2 kinase) associated with cancer development. Results show that many of these phosphorylated proteins were activated specifically in the A-ZIP/F-1 skin but not in the wild-type skin. These findings suggest that adipokines are not required for the promotion of tumor development and thus contradict the epidemiologic data linking obesity to carcinogenesis. We postulate that insulin resistance and inflammation are responsible for the positive correlation with cancer observed in A-ZIP/F-1 mice.
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PMID:Accelerated tumor formation in a fatless mouse with type 2 diabetes and inflammation. 1670 76

Obesity is associated with increased risk for postmenopausal, but not premenopausal breast cancer. Recently, we reported that intact obese Zucker rats had increased susceptibility to DMBA-induced mammary tumors compared to lean Zucker rats. In the present study, we investigated whether excessive adipose tissue would promote mammary tumor induction in the absence of ovarian estrogen. Lean and obese rats were sham-operated or ovariectomized at 40 days old and were gavaged at 50 days old with 65 mg/kg DMBA. Rats were weighed and palpated twice weekly for detection of mammary tumors and sacrificed 135 days post-DMBA treatment. Obese sham-operated (O/S) rats had a shorter latency period (102 days) compared to lean sham-operated (L/S) (134 days) and obese ovariectomized (O/O) rats (123 days). At the end of the experiment, 36% of the O/O rats developed mammary tumors while lean ovariectomized (L/O) rats developed no mammary tumors (P<0.001), and 59% of the O/S rats developed mammary tumors compared to 30% of the L/S rats (P<0.05). In summary, obesity increases the susceptibility of ovariectomized Zucker rats to DMBA-induced mammary tumors, suggesting that adipose tissue-derived estrogen in obese animals may be sufficient to promote DMBA-induced tumors in this model. These results suggest that obesity in postmenopausal women may increase breast cancer risk due to increased breast tissue exposure to adipose tissue-derived estrogen. In conclusion, we have developed an animal model to further investigate the role of obesity in breast cancer development in postmenopausal women.
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PMID:Obesity increases the incidence of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in an ovariectomized Zucker rat model. 1727 56

Obesity is an established risk factor for breast cancer incidence and mortality. However, the mechanism that links obesity to tumorigenesis is not well understood. Here we combined nonlinear optical imaging technologies with an early-onset diet-induced obesity breast cancer animal model to evaluate the impact of obesity on the composition of mammary gland and tumor stroma. Using coherent anti-Stokes Raman scattering and second harmonic generation on the same platform, we simultaneously imaged mammary adipocytes, blood capillaries, collagen fibrils, and tumor cells without any labeling. We observed that obesity increases the size of lipid droplets of adipocytes in mammary gland and collagen content in mammary tumor stroma, respectively. Such impacts of obesity on mammary gland and tumor stroma could not be analyzed using standard two-dimensional histologic evaluation. Given the importance of mammary stroma to the growth and migration of tumor cells, our observation provides the first imaging evidence that supports the relationship between obesity and breast cancer risk.
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PMID:Nonlinear optical imaging to evaluate the impact of obesity on mammary gland and tumor stroma. 1753 86

There are well-established risk factors for breast cancer, most of which relate to estrogens and growth hormones in females. These include early-age menarche, late-age menopause, postmenopausal obesity and use of hormone therapy. However, these factors do not account for the sixfold difference in breast cancer incidence and mortality between countries and the fact that these differences dramatically lessen after migration; nor do they account for male breast cancer. Accordingly, hormone-responsive viruses have become major suspects as etiological agents for human breast cancer. Human papillomaviruses, mouse mammary tumor virus and Epstein-Barr virus are the prime candidate viruses as causes of human breast cancer. Human papillomaviruses and the mouse mammary tumor virus have hormone responsive elements that appear to be associated with enhanced replication of these viruses in the presence of corticosteroid and other hormones. This biological phenomenon is particularly relevant because of the hormone dependence of breast cancer. Viral genetic material for each of these candidate viruses has been identified by polymerase chain reaction in breast tumors but rarely in normal breast tissue controls. Pooled data from controlled studies show substantial odds ratios for the presence of viral genetic material in breast tumors compared with normal controls. These and additional data provide substantial, but not conclusive, evidence that human papillomavirus, the mouse mammary tumor virus and Epstein-Barr virus may have a role in the etiology of human breast cancer. If conclusive evidence for a role of these viruses in breast carcinogenesis can be developed, there is a practical possibility of primary prevention.
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PMID:Viruses and human breast cancer. 1766 84

Obesity increases mammary tumor development in Zucker rats following a single administration of the procarcinogen 7,12-dimenthylbenz(a)anthracene (DMBA). Fifty-day-old obese and lean female Zucker rats were orally gavaged with 65 mg/kg DMBA and sacrificed 139 days post DMBA treatment. At the end of the experiment, mammary tumors were detected in 68% of the obese rats compared to 32% of the lean group (P<0.001). 1H nuclear magnetic resonance (1H-NMR) spectra obtained for hydrophilic and lipophilic extracts from excised tumors illustrated fundamental differences in metabolic profiles between the two groups. Differences were observed for key choline compounds, namely phosphocholine and glycerophosphocholine, both markers of malignancy and apoptosis. In addition, levels of lactate, creatine, myo-inositol, alpha-glucose, alanine, leucine, glutamate, glutamine, tyrosine, phenylalanine, and NADH varied between the lean and obese groups. Principal component analysis indicated class separation between tumors from lean and obese rats based on their metabolic profiles, illustrating the potential for using 1H-NMR metabolomic methods for identifying altered metabolic pathways. Our results suggest that obesity enhances the risk for DMBA-induced mammary tumor development in rats. However, the mechanism for this increase in risk is currently unknown and will require further studies for elucidation.
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PMID:(1)H nuclear magnetic resonance metabolomic analysis of mammary tumors from lean and obese Zucker rats exposed to 7,12-dimethylbenz[a]anthracene. 1778 90

High dietary fat intake and obesity may increase susceptibility to certain forms of cancer. To study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of F(2) mice cosegregating obesity QTL and the MMTV-PyMT transgene. We fed the F(2) mice either a very-high-fat or a matched-control-fat diet and measured growth, body composition, age at mammary tumor onset, tumor number and severity, and formation of pulmonary metastases. SNP genotyping across the genome facilitated analyses of QTL and QTL x diet interaction effects. Here we describe development of the F(2) population (n = 615) which resulted from a cross between the polygenic obesity model M16i and FVB/NJ-TgN (MMTV-PyMT)(634Mul), effects of diet on growth and body composition, and QTL and QTL x diet and/or gender interaction effects for growth and obesity-related phenotypes. We identified 38 QTL for body composition traits that were significant at the genome-wide 0.05 level, likely representing nine distinct loci after accounting for pleiotropic effects. QTL x diet and/or gender interactions were present at 15 of these QTL, indicating that such interactions play a significant role in defining the genetic architecture of complex traits such as body weight and obesity.
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PMID:Genotype X diet interactions in mice predisposed to mammary cancer. I. Body weight and fat. 1828 34

High dietary fat intake and obesity may increase the risk of susceptibility to certain forms of cancer. To study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of F(2) mice cosegregating obesity QTL and the MMTV-PyMT transgene. We fed the F(2) mice either a very high-fat or a matched-control-fat diet, and we measured growth, body composition, age at mammary tumor onset, tumor number and severity, and formation of pulmonary metastases. SNP genotyping across the genome facilitated analyses of QTL and QTL x diet interaction effects. Here we describe effects of diet on mammary tumor and metastases phenotypes, mapping of tumor/metastasis modifier genes, and the interaction between dietary fat levels and effects of cancer modifiers. Results demonstrate that animals fed a high-fat diet are not only more likely to experience decreased mammary cancer latency but increased tumor growth and pulmonary metastases occurrence over an equivalent time. We identified 25 modifier loci for mammary cancer and pulmonary metastasis, likely representing 13 unique loci after accounting for pleiotropy, and novel QTL x diet interactions at a majority of these loci. These findings highlight the importance of accurately modeling not only the human cancer characteristics in mice but also the environmental exposures of human populations.
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PMID:Genotype X diet interactions in mice predisposed to mammary cancer: II. Tumors and metastasis. 1828 25


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