Morbidly obese women with and without endometrial cancer: are there differences in measured physical fitness, body composition, or hormones?

OBJECTIVE: Exercise is potentially protective against cancer for obese women. The objectives were to examine differences in activity, body composition, and hormones in overweight/obese women with and without endometrial cancer. METHODS: Women ≥ 50 years old with a body mass index (BMI) ≥ 25 kg/m(2) scheduled for abdominal hysterectomy were enrolled. Demographics, physical activity, and quality of life (QOL) data were collected. Body composition/fitness was evaluated using Air Displacement Plethysmography (BodPod) and a standardized treadmill. Adiponectin, androstenedione, leptin, estradiol, estrone, progesterone, sex hormone binding globulin, insulin and glucose were measured. RESULTS: Thirty-eight women enrolled in this pilot study; 22 had endometrial cancer. Mean age was 58.3 years, mean BMI, fat weight and percent body fat were 41.3 kg/m(2), 55 kg and 51% respectively. Fitness levels were poor; 90% of women had peak oxygen uptakes below the 10th percentile of population normals yet 80% still rated their fitness level as equivalent to other women. Women with and without cancer did not differ in age, BMI, co-morbidities, energy expenditures, body composition, hormones or QOL although glucose levels were higher in women with cancer (119.5 vs. 90.7 mg/dl; p=0.049). Cancer subjects scored worse on every fitness measurement, reaching statistical significance for VO(2 peak) (15.0 vs. 17.9 ml/kg/min; p=0.033). Current exercisers had a lower BMI (p=0.039), decreased fat weight (p=0.024), decreased waist circumference (p=0.05) and improved vitality compared to non-exercisers. CONCLUSION: Physical fitness levels were abysmal in these morbidly obese subjects and worse for cancer patients. Exercise correlated with improved body composition and vitality.

TDP-43 mediates degeneration in a novel Drosophila model of disease caused by mutations in VCP/p97.

Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD) is a dominantly inherited degenerative disorder caused by mutations in the valosin-containing protein (VCP7) gene. VCP (p97 in mouse, TER94 in Drosophila melanogaster, and CDC48 in Saccharomyces cerevisiae) is a highly conserved AAA(+) (ATPases associated with multiple cellular activities) ATPase that regulates a wide array of cellular processes. The mechanism of IBMPFD pathogenesis is unknown. To elucidate the pathogenic mechanism, we developed and characterized a Drosophila model of IBMPFD (mutant-VCP-related degeneration). Based on genetic screening of this model, we identified three RNA-binding proteins that dominantly suppressed degeneration; one of these was TBPH, the Drosophila homolog of TAR (trans-activating response region) DNA-binding protein 43 (TDP-43). Here we demonstrate that VCP and TDP-43 interact genetically and that disease-causing mutations in VCP lead to redistribution of TDP-43 to the cytoplasm in vitro and in vivo, replicating the major pathology observed in IBMPFD and other TDP-43 proteinopathies. We also demonstrate that TDP-43 redistribution from the nucleus to the cytoplasm is sufficient to induce cytotoxicity. Furthermore, we determined that a pathogenic mutation in TDP-43 promotes redistribution to the cytoplasm and enhances the genetic interaction with VCP. Together, our results show that degeneration associated with VCP mutations is mediated in part by toxic gain of function of TDP-43 in the cytoplasm. We suggest that these findings are likely relevant to the pathogenic mechanism of a broad array of TDP-43 proteinopathies, including frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Cancer in obese women: potential protective impact of bariatric surgery.

BACKGROUND: The use of bariatric surgery has been increasing over the last several years in response to the obesity epidemic, and the objective of this study was to report on the types of cancer in morbidly obese women undergoing bariatric surgery and compare these with types of cancer in obese women without surgery. STUDY DESIGN: A retrospective, observational study was conducted. The bariatric surgery database identified women who underwent operations between 1990 and 2006 at the University of Virginia. Medical records and the institution's and state's cancer registries were searched for demographics and cancer data. Morbidly obese patients not undergoing bariatric surgery were used for comparison. RESULTS: There were 1,482 women who had bariatric surgery, and 53 of these (3.6%) were diagnosed with cancer. The most common cancer site was the breast (n = 15, 28.3%) followed by the endometrium (n = 9, 17%) and the cervix (n = 6, 11.3%). The mean age at cancer diagnosis was 39.4 years. Most cancers (n = 34, 64.1%) were diagnosed before the bariatric surgery. Bariatric surgery patients with cancer were older than noncancer patients at time of surgery (mean age 44.7 versus 41.6 years; p=0.019), but otherwise did not differ significantly with regard to race, body mass index, or comorbid conditions. Compared with a control group of 3,495 morbidly obese women who had not undergone bariatric surgery, the surgery patients had fewer cancers (3.6% versus 5.8%, p=0.002), were younger (41.7 versus 46.9 years, p < 0.001), and were younger at cancer diagnosis (45.0 versus 56.8 years, p < 0.001). The most frequent cancers in the control obese women were endometrial, ovarian, and breast cancer. Both groups of obese women with endometrial, breast, ovarian, and colorectal cancers were younger at diagnosis compared with Virginia Cancer Registry means. CONCLUSIONS: Breast and endometrial cancers remain the most common types in obese women and may occur at young ages; bariatric surgery may decrease cancer development in obese women.