Browsing by Subject "Postmenopause"
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Item Open Access A protocol for remote collection of skeletal muscle mass via D3-creatine dilution in community-dwelling postmenopausal women from the Women's Health Initiative.(PloS one, 2024-01) Banack, Hailey R; Wactawski-Wende, Jean; Ochs-Balcom, Heather M; Feliciano, Elizabeth M Cespedes; Caan, Bette; Lee, Catherine; Anderson, Garnet; Shankaran, Mahalakshmi; Evans, William JBackground
There is emerging evidence that cancer and its treatments may accelerate the normal aging process, increasing the magnitude and rate of decline in functional capacity. This accelerated aging process is hypothesized to hasten the occurrence of common adverse age-related outcomes in cancer survivors, including loss of muscle mass and decrease in physical function. However, there is no data describing age-related loss of muscle mass and its relation to physical function in the long-term in cancer survivors.Methods
This study protocol describes the use of a novel method of muscle mass measurement, D3-creatine dilution method (D3Cr), in a large sample (n~6000) of community dwelling postmenopausal women from the Women's Health Initiative (WHI). D3Cr will be used to obtain a direct measure of muscle mass remotely. Participants will be drawn from two sub-cohorts embedded within the WHI that have recently completed an in-home visit. Cancer survivors will be drawn from the Life and Longevity After Cancer (LILAC) cohort, and cancer-free controls will be drawn from the WHI Long Life Study 2. The overall objective of this study is to examine the antecedents and consequences of low muscle mass in cancer survivors. The study aims are to: 1) create age-standardized muscle mass percentile curves and z-scores to characterize the distribution of D3- muscle mass in cancer survivors and non-cancer controls, 2) compare muscle mass, physical function, and functional decline in cancer survivors and non- cancer controls, and 3) use machine learning approaches to generate multivariate risk-prediction algorithms to detect low muscle mass.Discussion
The D3Cr method will transform our ability to measure muscle mass in large-scale epidemiologic research. This study is an opportunity to advance our understanding of a key source of morbidity among older and long-term female cancer survivors. This project will fill knowledge gaps, including the antecedents and consequences of low muscle mass, and use innovative methods to overcome common sources of bias in cancer research. The results of this study will be used to develop interventions to mitigate the harmful effects of low muscle mass in older adults and promote healthy survivorship in cancer survivors in the old (>65) and oldest-old (>85) age groups.Item Open Access Endometriosis of the liver containing mullerian adenosarcoma: case report.(Am J Obstet Gynecol, 2004-11) Jelovsek, John E; Winans, Charles; Brainard, Jennifer; Falcone, TommasoWe present a case of a liver endometrioma in a postmenopausal woman. After failed management with leuprolide acetate, the mass was resected and contained focal areas of mullerian adenosarcoma. This is a rare case of mullerian adenosarcoma that appeared to arise within an endometrioma of the liver.Item Open Access ERα PvuII and XbaI polymorphisms in postmenopausal women with posterior tibial tendon dysfunction: a case control study.(Journal of orthopaedic surgery and research, 2018-12) Pontin, PA; Nogara, PRB; Fonseca, FCP; Cesar Netto, C; Carvalho, KC; Soares Junior, JM; Baracat, EC; Fernandes, TD; Maffulli, N; Santos, MCL; Godoy-Santos, ALBackground
Posterior tibial tendon (PTT) insufficiency is considered as the main cause of adult acquired flat foot and is three times more frequent in females. High estrogen levels exert a positive effect on the overall collagen synthesis in tendons. We have previously demonstrated the association between some genetic single-nucleotide polymorphism (SNP) and tendinopathy. In the present study, we investigated the association of PvuII c454-397T>C (NCBI ID: rs2234693) and XbaI c454-351A>G (NCBI ID: rs9340799) SNPs in estrogen receptor alfa (ER-α) gene with PPT dysfunction.Methods
A total of 92 female subjects with PTT dysfunction, with histopathological examination of the tendon and magnetic resonance image (MRI) evidence of tendinopathy, were compared to 92 asymptomatic females who presented an intact PPT at MRI for PvuII and XbaI SNPs in the ER-α gene. Genomic DNA was extracted from saliva and genotypes were obtained by polymerase chain reaction restriction fragment length polymorphism.Results
The analysis of PvuII SNPs showed no significant differences in the frequency of alleles and genotypes between control and PTT dysfunction groups. The XbaI SNPs in the ER-α gene showed significant differences in the frequency of genotypes between control and test groups (p = 0.01; OR 95% 1.14 (0.55-2.33).Conclusions
The XbaI SNP in the ERα gene may contribute to tendinopathy, and the A/A genotype could be a risk factor for PTT tendinopathy in this population. The PvuII SNP studied was not associated with PTT tendinopathy.Item Open Access Impact of gene variants on sex-specific regulation of human Scavenger receptor class B type 1 (SR-BI) expression in liver and association with lipid levels in a population-based study.(BMC Med Genet, 2010-01-19) Chiba-Falek, Ornit; Nichols, Marshall; Suchindran, Sunil; Guyton, John; Ginsburg, Geoffrey S; Barrett-Connor, Elizabeth; McCarthy, Jeanette JBACKGROUND: Several studies have noted that genetic variants of SCARB1, a lipoprotein receptor involved in reverse cholesterol transport, are associated with serum lipid levels in a sex-dependent fashion. However, the mechanism underlying this gene by sex interaction has not been explored. METHODS: We utilized both epidemiological and molecular methods to study how estrogen and gene variants interact to influence SCARB1 expression and lipid levels. Interaction between 35 SCARB1 haplotype-tagged polymorphisms and endogenous estradiol levels was assessed in 498 postmenopausal Caucasian women from the population-based Rancho Bernardo Study. We further examined associated variants with overall and SCARB1 splice variant (SR-BI and SR-BII) expression in 91 human liver tissues using quantitative real-time PCR. RESULTS: Several variants on a haplotype block spanning intron 11 to intron 12 of SCARB1 showed significant gene by estradiol interaction affecting serum lipid levels, the strongest for rs838895 with HDL-cholesterol (p=9.2x10(-4)) and triglycerides (p=1.3x10(-3)) and the triglyceride:HDL cholesterol ratio (p=2.7x10(-4)). These same variants were associated with expression of the SR-BI isoform in a sex-specific fashion, with the strongest association found among liver tissue from 52 young women<45 years old (p=0.002). CONCLUSIONS: Estrogen and SCARB1 genotype may act synergistically to regulate expression of SCARB1 isoforms and impact serum levels of HDL cholesterol and triglycerides. This work highlights the importance of considering sex-dependent effects of gene variants on serum lipid levels.Item Open Access Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis.(BMC cancer, 2006-01) Zhai, Xiangjun; Gao, Jun; Hu, Zhibin; Tang, Jinhai; Qin, Jianwei; Wang, Shui; Wang, Xuechen; Jin, Guangfu; Liu, Jiyong; Chen, Wenshen; Chen, Feng; Wang, Xinru; Wei, Qingyi; Shen, HongbingBACKGROUND: Accumulative evidence suggests that low folate intake is associated with increased risk of breast cancer. Polymorphisms in genes involved in folate metabolism may influence DNA methylation, nucleotide synthesis, and thus individual susceptibility to cancer. Thymidylate synthase (TYMS) is a key enzyme that participates in folate metabolism and catalyzes the conversion of dUMP to dTMP in the process of DNA synthesis. Two potentially functional polymorphisms [a 28-bp tandem repeat in the TYMS 5'-untranslated enhanced region (TSER) and a 6-bp deletion/insertion in the TYMS 3'-untranslated region (TS 3'-UTR)] were suggested to be correlated with alteration of thymidylate synthase expression and associated with cancer risk. METHODS: To test the hypothesis that polymorphisms of the TYMS gene are associated with risk of breast cancer, we genotyped these two polymorphisms in a case-control study of 432 incident cases with invasive breast cancer and 473 cancer-free controls in a Chinese population. RESULTS: We found that the distribution of TS3'-UTR (1494del6) genotype frequencies were significantly different between the cases and controls (P = 0.026). Compared with the TS3'-UTR del6/del6 wild-type genotype, a significantly reduced risk was associated with the ins6/ins6 homozygous variant genotype (adjusted OR = 0.58, 95% CI = 0.35-0.97) but not the del6/ins6 genotype (OR = 1.09, 95% CI = 0.82-1.46). Furthermore, breast cancer risks associated with the TS3'-UTR del6/del6 genotype were more evident in older women, postmenopausal subjects, individuals with a younger age at first-live birth and individuals with an older age at menarche. However, there was no evidence for an association between the TSER polymorphism and breast cancer risks. CONCLUSION: These findings suggest that the TS3'-UTR del6 polymorphism may play a role in the etiology of breast cancer. Further larger population-based studies as well as functional evaluation of the variants are warranted to confirm our findings.Item Restricted Rationale and design of the Exercise Intensity Trial (EXCITE): A randomized trial comparing the effects of moderate versus moderate to high-intensity aerobic training in women with operable breast cancer.(BMC Cancer, 2010-10-06) Jones, Lee W; Douglas, Pamela S; Eves, Neil D; Marcom, P Kelly; Kraus, William E; Herndon, James E; Inman, Brant A; Allen, Jason D; Peppercorn, JeffreyBACKGROUND: The Exercise Intensity Trial (EXcITe) is a randomized trial to compare the efficacy of supervised moderate-intensity aerobic training to moderate to high-intensity aerobic training, relative to attention control, on aerobic capacity, physiologic mechanisms, patient-reported outcomes, and biomarkers in women with operable breast cancer following the completion of definitive adjuvant therapy. METHODS/DESIGN: Using a single-center, randomized design, 174 postmenopausal women (58 patients/study arm) with histologically confirmed, operable breast cancer presenting to Duke University Medical Center (DUMC) will be enrolled in this trial following completion of primary therapy (including surgery, radiation therapy, and chemotherapy). After baseline assessments, eligible participants will be randomized to one of two supervised aerobic training interventions (moderate-intensity or moderate/high-intensity aerobic training) or an attention-control group (progressive stretching). The aerobic training interventions will include 150 mins.wk⁻¹ of supervised treadmill walking per week at an intensity of 60%-70% (moderate-intensity) or 60% to 100% (moderate to high-intensity) of the individually determined peak oxygen consumption (VO₂peak) between 20-45 minutes/session for 16 weeks. The progressive stretching program will be consistent with the exercise interventions in terms of program length (16 weeks), social interaction (participants will receive one-on-one instruction), and duration (20-45 mins/session). The primary study endpoint is VO₂peak, as measured by an incremental cardiopulmonary exercise test. Secondary endpoints include physiologic determinants that govern VO₂peak, patient-reported outcomes, and biomarkers associated with breast cancer recurrence/mortality. All endpoints will be assessed at baseline and after the intervention (16 weeks). DISCUSSION: EXCITE is designed to investigate the intensity of aerobic training required to induce optimal improvements in VO₂peak and other pertinent outcomes in women who have completed definitive adjuvant therapy for operable breast cancer. Overall, this trial will inform and refine exercise guidelines to optimize recovery in breast and other cancer survivors following the completion of primary cytotoxic therapy. TRIAL REGISTRATION: NCT01186367.