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Chronic Medical Conditions and CA125 Levels among Women without Ovarian Cancer.

ABSTRACT: BACKGROUND:Randomized trials using the biomarker cancer antigen (CA) 125, with or without pelvic ultrasound, have failed to show a clear benefit of general population screening for ovarian cancer. In part, this may be due to a lack of information about conditions, besides ovarian cancer, that can alter CA125 levels and affect specificity or sensitivity. We evaluated the association between common medical conditions and CA125 levels among women without ovarian cancer. METHODS:We used data and specimens from 2,004 women without ovarian cancer who participated in the New England Case Control study between 1992 and 2008. Participants completed in-person interviews and donated blood samples at enrollment. We measured CA125 using the CA125II assay and calculated the association between medical conditions and log-transformed CA125 using linear regression. RESULTS:The median age of participants was 53 years and 1,119 (56%) were postmenopausal. The average CA125 level was 14.5 units/mL for premenopausal and 11.7 for postmenopausal women. Among premenopausal women, CA125 was significantly lower for women with colon polyps (P = 0.06) and hysterectomy (P = 0.01) and significantly higher with endometriosis (P = 0.05). CA125 was also significantly higher in premenopausal women with coronary artery disease (CVD) (P < 0.01, n = 2 cases) but not among postmenopausal with CVD (n = 79). Furthermore, among postmenopausal women, CA125 was significantly lower for women with osteoporosis, hypercholesterolemia, and osteoarthritis (P = 0.03, 0.02, and 0.01 respectively) and higher for women with a history of inflammatory bowel disease (P = 0.04). CONCLUSIONS:Several chronic diseases are associated with CA125, which could influence the interpretation of CA125 in the context of ovarian cancer screening. IMPACT:Consideration of chronic medical conditions may be necessary to interpret CA125 values.

SUBMITTER: Akinwunmi BO

PROVIDER: S-EPMC6279537 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Chronic Medical Conditions and CA125 Levels among Women without Ovarian Cancer.

Akinwunmi Babatunde O BO Babic Ana A Vitonis Allison F AF Cramer Daniel W DW Titus Linda L Tworoger Shelley S SS Terry Kathryn L KL

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20180920 12

<h4>Background</h4>Randomized trials using the biomarker cancer antigen (CA) 125, with or without pelvic ultrasound, have failed to show a clear benefit of general population screening for ovarian cancer. In part, this may be due to a lack of information about conditions, besides ovarian cancer, that can alter CA125 levels and affect specificity or sensitivity. We evaluated the association between common medical conditions and CA125 levels among women without ovarian cancer.<h4>Methods</h4>We us ...[more]

PMID: 30237250

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Project description:BackgroundCancer antigen 125 (CA125) is clinically used to monitor response to therapy in ovarian cancer and has been proposed for use in detecting ovarian cancer. This population-based study examines how demographic characteristics, gynecologic/reproductive history, chronic non-malignant medical conditions, history of non-ovarian cancer, lifestyle practices, and biomarkers of inflammation correlate with serum CA125 in both premenopausal and postmenopausal women without ovarian cancer across the United States.MethodsParticipants were identified from the National Health and Nutrition Examination Survey 2001-2002. Linear and logistic regression models were applied.ResultsHigher CA125 levels were found to correlate with younger age, Non-Hispanic White race/ethnicity, and lower body mass index. In premenopausal women (N = 1157), current smoking was associated with lower CA125 (- 24.95%, p = 0.008), and history of non-ovarian cancer was associated with higher CA125 (40.64%, p = 0.045) by multivariable linear regression; both current smoking (odds ratio (OR) = 0.42, p = 0.043) and oral contraceptive pill (OCP) use of 5-10 years (OR = 0.31, p = 0.032) were less likely to be associated with having CA125 level ≥ 35 U/ml by multivariable logistic regression. In postmenopausal women (N = 1116), coronary artery disease (CAD) history was associated with higher CA125 (28.27%, p = 0.047) by multivariable linear regression; history of CAD (OR = 5.00, p = 0.011), history of breastfeeding (OR = 2.46, p = 0.026), and increased CRP level (OR = 1.41, p = 0.042) were more likely to be associated with having CA125 level ≥ 35 U/ml by multivariable logistic regression.ConclusionsResults suggest CA125 is lower in premenopausal women who are current smokers and OCP users of moderately longer duration but higher in those with non-ovarian cancer. CA125 is higher in those postmenopausal women with CAD, history of breastfeeding and elevated CRP level. These associations can inform clinical interpretation of individual patients' CA125 levels.

Project description:BackgroundOvarian cancer (OC) is a highly aggressive gynecological malignancy prevalent worldwide. Most OC cases are typically diagnosed at advanced stages, which has led to a 5-year overall survival rate of less than 35% following conventional treatment. Furthermore, immune checkpoint inhibitor therapy has shown limited efficacy in the treatment of patients with OC, and CAR-T therapy has also demonstrated modest results owing to inadequate T cell infiltration. Therefore, novel strategies must be developed to enhance T cell persistence and trafficking within the OC tumor microenvironment.MethodsIn this study, we developed a novel adoptive T-cell therapy for ovarian cancer based on a chimeric antigen receptor structure. We used a ligand-receptor binding motif to enhance the therapeutic effect of targeting CA125. Since mesothelin can naturally bind to CA125 with high affinity, we concatenated the core-binding fragment of mesothelin with the 4-1BB and CD3ζ signal fragments to assemble a novel CA125-targeting chimeric receptor (CR). The CAR structure targeting CA125 derived from the 4H11 antibody was also constructed. CR- and CAR-encoding RNA were electroporated into T cells to evaluate their antitumor activity both in vitro and in vivo.ResultsWhile CR-T or CAR-T cells exhibited moderate activity against two ovarian cancer cell lines, T cells co-expressing CR and CAR exhibited a superior killing effect compared to T cells expressing either CR or CAR alone. Furthermore, upon interaction with ovarian tumors, the ability of CR and CAR T cells to release activation markers and functional cytokines increased significantly. Similarly, CR and CAR co-expressing T cells persistently controlled the growth of transplanted ovarian cancer tumors in NSG mice and significantly prolonged the overall survival of tumor-challenged mice. Transcriptome sequencing revealed that the survival and cytotoxicity of T cells co-expressing CR and CAR were significantly altered compared with those of T cells expressing either CR or CAR.ConclusionOur findings demonstrate that CA125 targeting CR and CAR can synergistically kill ovarian cancer cells, indicating that CA125 targeting by the two binding motifs simultaneously in tumors may improve the therapeutic outcomes of ovarian cancer treatment.

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Chronic Medical Conditions and CA125 Levels among Women without Ovarian Cancer.

Publications

Chronic Medical Conditions and CA125 Levels among Women without Ovarian Cancer.

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