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

Although obesity is one of the established risk factors for postmenopausal breast cancer, it is not clear whether this positive association differs across estrogen receptor (ER) and progesterone receptor (PR) status of breast tumors. We evaluated the association between body weight and ER/PR defined breast cancer risk stratified by postmenopausal hormone (PMH) use and a family history of breast cancer in the population-based Swedish Mammography Screening Cohort comprising 51,823 postmenopausal women. Relative body weight was measured by body mass index (kg/m2) based on self-reported weight and height collected in 1987 and 1997. Relative risks (RRs) were estimated by hazard ratios derived from Cox proportional hazards regression models. During an average of 8.3-year follow-up, 1,188 invasive breast cancer cases with known ER and PR status were diagnosed. When comparing to normal weight group, we observed a positive association between obesity and risk for the development of ER+ PR+ tumors (RR = 1.67, 95% CI = 1.34-2.07) and an inverse association for the development of all PR- tumors (RR = 0.68, 95% CI = 0.47-0.98). Statistically significant heterogeneity was observed in the RRs between ER+ PR+ tumors and all PR- tumors (p(heterogeneity) < 0.0001). The positive association of obesity with the development of ER+ PR+ tumors was confined to never-users of PMHs (RR = 1.90 (CI 95%:1.38-2.61)) and to those without a family history of breast cancer (RR = 1.82 (CI 95%:1.45-2.29)). Our results support the hypothesis that excess endogenous estrogen due to obesity contributes to an increased risk of ER+ PR+ postmenopausal breast cancer.
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PMID:Body weight and postmenopausal breast cancer risk defined by estrogen and progesterone receptor status among Swedish women: A prospective cohort study. 1664 51

The soy isoflavone genistein targets adipose tissue and elicits physiological effects that may vary based on dietary intake. We hypothesized that the adipose effects of genistein are dose and gender dependent. Four-week-old C57BL/6 male and female mice received daily oral doses of genistein (50-200,000 microg/kg.d) or 17beta-estradiol (E2) (5 microg/kg.d) for 15 d or a diet containing 800 ppm genistein. Genistein increased epididymal and renal fat pad and adipocyte size at doses up to 50,000 microg/kg.d or at 800 ppm in the diet in males but not in females. The alteration in adipocity correlated with changes in peripheral insulin resistance. These treatments increased genistein serum concentrations from 35+/-6 to 103+/-26 nM 12 h after treatment and lowered plasma triglycerides and cholesterol levels. The 200,000 microg/kg.d genistein dose decreased adipose tissue weight similarly to E2. This genistein dose down-regulated estrogen receptor (beta more than alpha) and progesterone receptor expression and induced estrogen-dependent adipose differentiation factors; it did not change expression of the minimal consensus estrogen-responsive element in ERE-tK-LUC mice, which was positively modulated in other tissues (e.g. the lung). E2 down-regulated almost all examined adipogenic factors. Gene microarray analysis identified factors in fat metabolism and obesity-related phenotypes differentially regulated by low and high doses of genistein, uncovering its adipogenic and antiadipogenic actions. The lower dose induced the phospholipase A2 group 7 and the phospholipid transfer protein genes; the 200,000 microg/kg.d dose inhibited them. The antiadipogenic action of genistein and down-regulation of adipogenic genes required the expression of ERbeta. In conclusion, nutritional doses of genistein are adipogenic in a gender-specific manner, whereas pharmacological doses inhibited adipose deposition.
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PMID:Genistein affects adipose tissue deposition in a dose-dependent and gender-specific manner. 1695 45

We report a rare case of sertoliform endometrioid carcinoma of the endometrium in a 71-year-old African American woman who presented with postmenopausal bleeding. Her medical condition was remarkable for hypertension, diabetes, and obesity. She underwent total hysterectomy, right salpingo-oophorectomy and lymph node sampling. The endometrium was occupied by a 4.5-cm solid polypoid tumor, which grossly invaded into the myometrium. Microscopically, the tumor consisted of small hollow tubules, anastomosing cords and trabeculae, and tightly packed nests. Microglandular areas mimicking adult granulosa cell tumors were also present. But true Call-Exner bodies were absent. Component of typical endometrioid carcinoma was noted only focally. The uninvolved endometrium demonstrated atypical complex hyperplasia. The tumor cells were diffusely immunoreactive for epithelial membrane antigen, estrogen receptor, and progesterone receptor (PR), and focally for vimentin. The tumor cells were also diffusely positive for inhibin alpha and CD99. Immunostains for other sex cord markers (calretinin, WT-1, and Melan-A) were also positive in approximately 30% to 40% of the tumor cells. Immunostains for CD10, smooth muscle actin, desmin, or HHF35 were negative. Two ovarian sertoliform endometrioid carcinomas from our archived tissue were, however, immunoreactive for epithelial membrane antigen but negative for inhibin alpha. Despite the prominent sertoliform features, both histologically and immunohistochemically, the tumor was of a high-grade endometrial carcinoma and will likely behave as such. As of today, dual differentiation of epithelium and sex cord by immunohistochemical staining has not been demonstrated in sertoliform endometrioid carcinomas of either endometrial or ovarian origin. Our case is the first documentation of such example and suggests that endometrial carcinoma can undergo true sex cord differentiation.
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PMID:Sertoliform endometrioid carcinoma of the endometrium with dual immunophenotypes for epithelial membrane antigen and inhibin alpha: case report and literature review. 1758 14

Body mass index (BMI) is associated with breast cancer risk, but its relationship with stage at diagnosis is unclear. BMI was calculated for patients in the North American Fareston and Tamoxifen Adjuvant trial, and was correlated with clinicopathologic factors, including stage at diagnosis. One thousand eight hundred fourteen patients were enrolled in the North American Fareston and Tamoxifen Adjuvant study; height and weight were recorded in 1451 (80%) of them. The median BMI was 27.1 kg/m2 (range, 14.7-60.7). The median patient age was 68 years (range, 42-100); median tumor size was 1.3 cm (range, 0.1-14 cm). One thousand seven hundred ninety-three (99.0%) patients were estrogen receptor positive, and 1519 (84.7%) were progesterone receptor positive. There was no significant relationship between BMI (as a continuous variable) and nodal status (P = 0.469), tumor size (P = 0.497), American Joint Committee on Cancer stage (P = 0.167), grade (P = 0.675), histologic subtype (P = 0.179), or estrogen receptor status (P = 0.962). Patients with palpable tumors, however, had a lower BMI than those with nonpalpable tumors (median 26.4 kg/m2 vs 27.5 kg/m2, P < 0.001). Similar results were found when BMI was classified as a categorical variable (<25 vs 25-29.9 vs > or =30). Increased BMI does not lead to a worse stage at presentation. Obese patients, however, tend to have nonpalpable tumors. Mammography in this population is especially important.
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PMID:Body mass index influences palpability but not stage of breast cancer at diagnosis. 1765 91

The relation of body mass index (BMI) and weight gain to breast cancer risk is complex, and little information is available on Black women, among whom the prevalence of obesity is high. We assessed BMI and weight gain in relation to breast cancer risk in prospective data from the Black Women's Health Study. In 1995, 59,000 African American women enrolled in the Black Women's Health Study by completing mailed questionnaires. Data on anthropometric factors were obtained at baseline and every 2 years afterwards. In 10 years of follow-up, 1,062 incident cases of breast cancer occurred. Incidence rate ratios (IRR) were computed in multivariable Cox proportional hazards regression. BMI at age 18 years of >/=25 relative to <20 was associated with a reduced risk of breast cancer among both premenopausal women (IRR, 0.68; 95% confidence interval, 0.46-0.98) and postmenopausal women (IRR, 0.53; 95% confidence interval, 0.35-0.81). There was an inverse association of current BMI with premenopausal breast cancer but no association with postmenopausal breast cancer, either overall or among never-users of hormone therapy. Weight gain was not associated with postmenopausal breast cancer risk. In analyses restricted to breast cancers that were estrogen and progesterone receptor positive, IRRs for current BMI and weight gain were elevated but not statistically significant. The findings indicate that being overweight at age 18 years is associated with a reduced risk of both premenopausal and postmenopausal breast cancer in African American women. Understanding the reasons for the association may help elucidate the pathways through which adolescent exposures influence breast cancer risk. The lack of association of obesity with receptor-negative tumors in postmenopausal African American women may partially explain why breast cancer incidence in older Black women is not high relative to other ethnic groups in spite of the high prevalence of obesity in Black women.
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PMID:A prospective study of body size and breast cancer in black women. 1785 97

Obesity is associated with an increased risk of breast cancer. Leptin, a hormone synthesised essentially by adipose tissue, may be involved in cancer development. We examined the expression of leptin and leptin receptor (Ob-R) in human primary breast cancer and adjacent non-cancerous tissue. We also analysed their relationships with histological variables such as the oestrogen and progesterone receptors, Ki67 proliferation factor and tumour size. The expressions of leptin and Ob-R were investigated by immunohistochemical staining in 35 primary breast cancers and 17 adjacent non-cancerous tissues. Samples and histological features were obtained from the Anti-Cancer Centre. Expressions of leptin and Ob-R were detected in, respectively, 85 and 75% of the primary breast cancer cases studied. The expression of leptin was significantly correlated with Ob-R detection (p=0.008). In addition, Ob-R expression in primary breast carcinoma was positively correlated with oestrogen receptor expression (p=0.028) and tumour size (p=0.045) but not with Ki67 or progesterone receptor expressions. However, the expression of leptin showed no statistical correlation with these variables. First, the co-expression of leptin and Ob-R in primary breast cancer shows that leptin acts on mammary tumour cells via an autocrine pathway. Second, the co-expression of Ob-R and oestrogen receptors suggests a possible interaction between leptin and oestrogen systems to promote breast carcinogenesis. Finally, the fact that Ob-R expression was positively correlated with tumour size may point to a potential role of leptin as a growth factor and of Ob-R as a new prognostic factor.
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PMID:Leptin and leptin receptor involvement in cancer development: a study on human primary breast carcinoma. 1835 74

Endometrial carcinoma is the most common malignancy of the female genital tract in industrialized countries, and occurs predominantly after the menopause. Although most endometrial carcinomas are detected at low stage, there is still a significant mortality from the disease. In postmenopausal women, prolonged life expectancy, changes in reproductive behavior and prevalence of overweight and obesity, as well as hormone replacement therapy use, may partially account for the observed increases of incidence rates in some countries. In order to improve treatment and follow-up of endometrial carcinoma patients, the importance of various prognostic factors has been extensively studied. The identification of high-risk groups would make it possible to avoid unnecessary adjuvant treatment among patients with a good prognosis. Over the past few decades, several studies have demonstrated the prognostic importance of different parameters including lymph node status, histological type of carcinoma (serous carcinoma and clear cell carcinomas are poor prognostic types), histological grade, stage of disease, depth of myometrial invasion, lymphovascular space involvement and cervical involvement. Other factors currently being investigated are estrogen and progesterone receptor status, p53 status, flow cytometric analysis for ploidy and S-phase fraction, and oncogenes such as HER-2/neu (c-erbB-2).
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PMID:Prognostic factors in endometrial carcinoma. 1895 27

Appropriate feed intake level would enhance embryo survival. This study investigated the relationship among feed intake level, embryo survival, hormone secretion and mRNA expression. Fifty-four Landrace x Yorkshire crossbred gilts were allotted to three treatment groups of high (H, 2 x maintenance), medium (M, 1.2 x maintenance) and low (L, 0.6 x maintenance) after mating, to study the effect of feed intake levels on embryo survival, hormone secretion and mRNA expression of leptin, obesity receptor (ob-R), signal transducer and activator of transcription-3 (STAT3), DNA methyltransferase 1 (DNMT1), retinol-binding protein 4 (RBP4), fibroblast growth factor receptor 2 (FGFR2) and progesterone receptor (PGR) in embryos. Blood samples and embryos were collected for hormone concentrations determination and gene expression analysis. Slaughter weight, total weight gain and net weight gain were affected (p < 0.05) by dietary treatment. Embryonic survival was 80.23% and 78.45% in M group on days 25 and 35 of pregnancy, respectively, and was greater (p < 0.05) in M than H and L groups. Serum insulin-like growth factor-I and leptin concentrations enhanced (p < 0.05) with the increased feed intake, but progesterone concentrations were lower (p < 0.05) in H than M and L groups and no difference (p > 0.05) between M and L on days 25 and 35 of pregnancy. Real-Time PCR indicated that gene expression pattern of leptin, ob-R, STAT3 and DNMT1 were the highest (p < 0.05) in H group on days 25 and 35 of pregnancy. Transcript expression level of RBP4 and FGFR2 were the highest (p < 0.05) in M group on days 25 and 35 of pregnancy. Significantly higher (p < 0.05) expression of PGR was observed in L group on day 25 and in M group on day 35 of pregnancy. Our data suggest that 1.2 x maintenance feed intake level promoted the appropriate hormone secretion and enhanced genes expression in RBP4, FGFR2 and PGR, and thus resulted in better embryo survival compared with the high and low groups.
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PMID:The level of feed intake affects embryo survival and gene expression during early pregnancy in gilts. 1921 Jun 67

Prospective data on ethnic differences in hormone receptor-defined subtypes of breast cancer and their risk factor profiles are scarce. The authors examined the joint distributions of estrogen receptor (ER) and progesterone receptor (PR) status across 5 ethnic groups and the associations of established risk factors with ER/PR status in the Multiethnic Cohort Study (Hawaii and Los Angeles, California). During an average of 10.4 years of follow-up of 84,427 women between 1993-1996 and 2004/2005, 2,543 breast cancer cases with data on ER/PR status were identified: 1,672 estrogen receptor-positive (ER+)/progesterone receptor-positive (PR+); 303 ER+/progesterone receptor-negative (PR-); 77 estrogen receptor-negative (ER-)/PR+; and 491 ER-/PR-. ER/PR status varied significantly across racial/ethnic groups even within the same tumor stage (for localized tumors, P < 0.0001; for advanced tumors, P = 0.01). The highest fraction of ER-/PR- tumors was observed in African Americans (31%), followed by Latinas (25%), Whites (18%), Japanese (14%), and Native Hawaiians (14%). Associations differed between ER+/PR+ and ER-/PR- cases for postmenopausal obesity (P = 0.02), age at menarche (P = 0.05), age at first birth (P = 0.04), and postmenopausal hormone use (P < 0.0001). African Americans are more likely to be diagnosed with ER-/PR- tumors independently of stage at diagnosis, and there are disparate risk factor profiles across the ER/PR subtypes of breast cancer.
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PMID:Breast cancer risk factors defined by estrogen and progesterone receptor status: the multiethnic cohort study. 1931 16

Obesity is a risk factor for breast cancer development. A recent hypothesis suggests that the adipokines, adiponectin and leptin, are involved in breast cancer development. This prompted us to investigate the role of adiponectin and leptin in mammary carcinogenesis. Adiponectin receptors (AdipoR1 and AdipoR2) and leptin receptor (Ob-Rt, representing all the isoforms of Ob-R) proteins were detected by immunohistochemistry in in situ ductal carcinoma, invasive ductal malignancy, and healthy adjacent tissue. In addition, mRNA expression of adiponectin, AdipoR1, AdipoR2, leptin, Ob-Rt, and Ob-Rl (the long isoform of Ob-R) was observed in MCF-7 breast cancer cells. Interestingly, leptin mRNA expression was 34.7-fold higher than adiponectin mRNA expression in the MCF-7 cell line. Moreover, adiponectin (10 microg/ml) tended to decrease the mRNA expression of leptin (-36%) and Ob-Rl (-28%) and significantly decreased Ob-Rt mRNA level (-26%). In contrast, leptin treatment (1 microg/ml) significantly decreased AdipoR1 mRNA (-23%). Adiponectin treatment (10 microg/ml) inhibited the proliferation of MCF-7 cells, whereas leptin (1 microg/ml) stimulated the growth of cancer cells. In addition, adiponectin inhibited leptin-induced cell proliferation (both 1 microg/ml). Using microarray analysis, we found that adiponectin reduced the mRNA levels of genes involved in cell cycle regulation (mitogen-activated protein kinase 3 and ATM), apoptosis (BAG1, BAG3, and TP53), and potential diagnosis/prognosis markers (ACADS, CYP19A1, DEGS1, and EVL), whereas leptin induced progesterone receptor mRNA expression. In conclusion, the current study indicates an interaction of leptin- and adiponectin-signaling pathways in MCF-7 cancer cells whose proliferation is stimulated by leptin and suppressed by adiponectin.
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PMID:Involvement of adiponectin and leptin in breast cancer: clinical and in vitro studies. 1966 Nov 31


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