Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice.

NZB/NZW F1 mice of both sexes were castrated at 2 wk of age and implanted subcutaneously with silastic tubes containing either 5-alpha-dihydrotestosterone or estradiol-17-beta. Mice receiving androgen showed improved survival, reduced anti-nucleic acid antibodies, or less evidence of glomerulonephritis as determined by light, immunofluorescent, and electron microscopy. By contrast, opposite effects were observed in castrated mice receiving estrogen. Intact male NZB/NZW F1 mice received androgen implants at 8 mo, an age when they develop an accelerated autoimmune disease associated with a decline in serum testosterone concentration. Such treated mice had improved survival and reduced concentrations of antibodies to DNA and to polyadenylic acid (Poly A). Prepubertal castration of male NZB/NZW F1 mice results in an earlier appearance of IgG antibodies to Poly A. This effect of castration was prevented if neonatal thymectomy was also performed

The Obesity-Associated Polymorphisms FTO rs9939609 and MC4R rs17782313 and Endometrial Cancer Risk in Non-Hispanic White Women

Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR)  = 1.17; 95% confidence interval (CI): 1.03–1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91–1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis

Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients

Abstract Background Postmenopausal obesity is associated with increased circulating levels of androgens and estrogens and elevated breast cancer risk. Crown-like structures (CLS; microscopic foci of dying adipocytes surrounded by macrophages) are proposed to represent sites of increased aromatization of androgens to estrogens. Accordingly, we examined relationships between CLS and sex-steroid hormones in breast adipose tissue and serum from postmenopausal breast cancer patients. Methods Formalin-fixed paraffin embedded benign breast tissues collected for research from postmenopausal women ( n \u2009=\u200983) diagnosed with invasive breast cancer in the Polish Breast Cancer Study (PBCS) were evaluated. Tissues were immunohistochemically stained for CD68 to determine the presence of CLS per unit area of adipose tissue. Relationships were assessed between CD68 density and CLS and previously reported sex-steroid hormones quantified using radioimmunoassays in serum taken at the time of diagnosis and in fresh frozen adipose tissue taken at the time of surgery. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relationships between hormones (in tertiles) and CLS. Results CLS were observed in 36% of benign breast tissues, with a higher frequency among obese versus lean women (54% versus 17%, p \u2009=\u20090.03). Detection of CLS was not related to individual hormone levels or breast tumor pathology characteristics. However, detection of CLS was associated with hormone ratios. Compared with women in the highest tertile of estrone:androstenedione ratio in fat, those in the lowest tertile were less likely to have CLS (OR 0.12, 95% CI 0.03\u20130.59). A similar pattern was observed with estradiol:testosterone ratio in serum and CLS (lowest versus highest tertile, OR 0.18, 95% CI 0.04\u20130.72). Conclusions CLS were more frequently identified in the breast fat of obese women and were associated with increased ..