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Ovarian cancer is a lethal gynecologic cancer mostly diagnosed in an advanced stage with an accumulation of ascites. Interleukin-6 (IL-6), a pro-inflammatory cytokine is highly elevated in malignant ascites and plays a pleiotropic role in cancer progression. Mitochondria are dynamic organelles that undergo fission and fusion in response to external stimuli and dysregulation in their dynamics has been implicated in cancer progression and metastasis. Here, we investigate the effect of IL-6 on mitochondrial dynamics in ovarian cancer cells (OVCs) and its impact on metastatic potential. Treatment with IL-6 on ovarian cancer cell lines (SKOV3 and PA-1) led to an elevation in the metastatic potential of OVCs. Interestingly, a positive association was observed between dynamin-related protein 1 (Drp1), a regulator of mitochondrial fission, and IL-6R in metastatic ovarian cancer tissues. Additionally, IL-6 treatment on OVCs was linked to the activation of Drp1, with a notable increase in the ratio of the inhibitory form p-Drp1(S637) to the active form p-Drp1(S616), indicating enhanced mitochondrial fission. Moreover, IL-6 treatment triggered the activation of ERK1/2, and inhibiting ERK1/2 mitigated IL-6-induced mitochondrial fission. Suppressing mitochondrial fission through siRNA transfection and a pharmacological inhibitor reduced the IL-6-induced migration and invasion of OVCs. This was further supported by 3D invasion assays using patient-derived spheroids. Altogether, our study suggests the role of mitochondrial fission in the metastatic potential of OVCs induced by IL-6. The inhibition of mitochondrial fission could be a potential therapeutic approach to suppress the metastasis of ovarian cancer.
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Dinaminas , Interleucina-6 , Sistema de Señalización de MAP Quinasas , Dinámicas Mitocondriales , Neoplasias Ováricas , Humanos , Femenino , Dinámicas Mitocondriales/efectos de los fármacos , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Interleucina-6/metabolismo , Dinaminas/metabolismo , Línea Celular Tumoral , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metástasis de la Neoplasia , Mitocondrias/metabolismo , Receptores de Interleucina-6/metabolismo , Movimiento Celular/efectos de los fármacosRESUMEN
Functionality in biological materials arises from complex hierarchical structures formed through self-assembly processes. Here, we report a kinetically trapped self-assembly of an elastic network of liquid droplets and its utility for tough and fast-acting underwater adhesives. This complex structure was made from a one-pot mixture of scalable small-molecule precursors. Liquid-liquid phase separation accompanied by silanol hydrolysis, condensation, and zwitterionic self-association yields a viscoelastic solid with interconnected liquid droplets. These hierarchical microstructures increase toughness and enable underwater adhesion for a range of substrates, offering a platform for robust adhesives for rapid underwater repair or emergency wound care.
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Dissipative behaviors in biology are fuel-driven processes controlled by living cells, and they shape the structural and functional complexities in biological materials. This concept has inspired the development of various forms of synthetic dissipative materials controlled by time-dependent consumption of chemical or physical fuels, such as reactive chemical species, light, and electricity. To date, synthetic living materials featuring dissipative behaviors directly controlled by the fuel consumption of their constituent cells is unprecedented. In this paper, we report a chemical fuel-driven dissipative behavior of living materials comprising Staphylococcus epidermidis and telechelic block copolymers. The macroscopic phase transition is controlled by d-glucose which serves a dual role of a competitive disassembling agent and a biological fuel source for living cells. Our work is a significant step toward constructing a synthetic dissipative living system and provides a new tool and knowledge to design emergent living materials.
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Glucosa , Azúcares , Polímeros , ElectricidadRESUMEN
Natural biological materials are formed by self-assembly processes and catalyze a myriad of reactions. Here, we report a programmable molecular assembly of designed synthetic polymers with engineered bacterial spores. This self-assembly process is driven by dynamic covalent bond formation on spore surface glycan and yields macroscopic materials that are structurally stable, self-healing, and recyclable. Molecular programming of polymer species shapes the physical properties of these materials while metabolically dormant spores allow for prolonged ambient storage. Incorporation of spores with genetically encoded functionalities enables operationally simple and repeated enzymatic catalysis. Our work combines molecular and genetic engineering to offer scalable and programmable synthesis of robust materials for sustainable biocatalysis.
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Polímeros , Esporas Bacterianas , Esporas Bacterianas/genética , Esporas Bacterianas/química , Polímeros/química , Catálisis , Biocatálisis , Ingeniería GenéticaRESUMEN
Fluid accumulation in the abdominal cavity is commonly found in advanced-stage ovarian cancer patients, which creates a specialized tumor microenvironment for cancer progression. Using single-cell RNA sequencing (scRNA-seq) of ascites cells from five patients with ovarian cancer, we identified seven cell types, including heterogeneous macrophages and ovarian cancer cells. We resolved a distinct polarization state of macrophages by MacSpectrum analysis and observed subtype-specific enrichment of pathways associated with their functions. The communication between immune and cancer cells was predicted through a putative ligand-receptor pair analysis using NicheNet. We found that CCL5, a chemotactic ligand, is enriched in immune cells (T cells and NK cells) and mediates ovarian cancer cell survival in the ascites, possibly through SDC4. Moreover, SDC4 expression correlated with poor overall survival in ovarian cancer patients. Our study highlights the potential role of T cells and NK cells in long-term survival patients with ovarian cancer, indicating SDC4 as a potential prognostic marker in ovarian cancer patients.
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Ascitis/patología , Quimiocina CCL5/genética , Quimiocina CCL5/metabolismo , Neoplasias Ováricas/mortalidad , Sindecano-4/genética , Sindecano-4/metabolismo , Ascitis/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Polaridad Celular , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Células Asesinas Naturales/metabolismo , Macrófagos/metabolismo , Persona de Mediana Edad , Modelos Teóricos , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Pronóstico , Análisis de Secuencia de ARN , Análisis de la Célula Individual/métodos , Análisis de Supervivencia , Linfocitos T/metabolismo , Microambiente TumoralRESUMEN
OBJECTIVE: This study aimed to determine the association of serum GGT levels with the risk of developing endometrial cancer. Women's obesity and menopausal status were also taken into account in our analysis. METHODS: We used a nationwide cohort to examine the association between serum GGT levels and endometrial cancer development in Korean women. Data were retrieved from the Korean National Health Insurance Service (NHIS) healthcare system. Women aged over 19 years who participated in the Korea National Health Screening Examination in 2009 and were not diagnosed with endometrial cancer 1-year post-examination were included in our study (n = 2,736,588). RESULTS: Obese (BMI, ≥25 kg/m2) women with increased GGT levels were at high risk of endometrial cancer (HR = 1.415, 95% CI: 1.236-1.621). Interestingly, in pre-menopausal women, high GGT level (Q4) was associated with the increased endometrial cancer risk only for obese women (HR = 1.482, 95% CI: 1.205-1.821). In post-menopausal women, only a high GGT level (Q4) was also associated with the increased cancer risk for obese women (HR = 1.313, 95% CI: 1.096-1.573). We observed a significant association between high GGT levels and increased risk of endometrial cancer in pre-menopausal women with abdominal obesity (WC, ≥85 cm) (HR = 1.647, 95% CI: 1.218-2.227). CONCLUSIONS: Increased GGT level is an independent risk factor of endometrial cancer, especially for post-menopausal women and obese pre-menopausal women. These results may suggest that serum GGT levels might be useful in the risk stratification of endometrial cancer. Adopting a healthy lifestyle for lowering serum GGT level is warranted, especially for women with a higher risk of developing endometrial cancer.
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Neoplasias Endometriales/epidemiología , Obesidad Abdominal , gamma-Glutamiltransferasa/sangre , Biomarcadores de Tumor/sangre , Estudios de Cohortes , Neoplasias Endometriales/sangre , Femenino , Humanos , Incidencia , Persona de Mediana Edad , República de Corea/epidemiologíaRESUMEN
Here we report a bio-adhesive porous organic module (Glue COF) composed of hexagonally packed 1D nanopores based on a covalent organic framework. The nanopores are densely decorated with guanidinium ion (Gu+ ) pendants capable of forming salt bridges with oxyanionic species. Glue COF strongly adheres to biopolymers through multivalent salt-bridging interactions with their ubiquitous oxyanionic species. By taking advantage of its strong bio-adhesive nature, we succeeded in creating a gate that possibly opens the nanopores through a selective interaction with a reporter chemical and releases guest molecules. We chose calmodulin (CaM) as a gating component that can stably entrap a loaded guest, sulforhodamineâ B (SRB), within the nanopores (CaM COFâSRB). CaM is known to change its conformation on binding with Ca2+ ions. We confirmed that mixing CaM COFâSRB with Ca2+ resulted in the release of SRB from the nanopores, whereas the use of weakly binding Mg2+ ions resulted in a much slower release of SRB.
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Tumor-suppressive effects of resveratrol have been shown in various types of cancer. However, regulation of tumor microenvironment by resveratrol is still unclear. Recent findings suggest resveratrol can potentiate its tumor-suppressive effect through modulation of the signaling pathways of cellular components (fibroblasts, macrophages and T cells). Also, studies have shown that resveratrol can suppress malignant phenotypes of cancer cells acquired in response to stresses of the tumor microenvironment, such as hypoxia, oxidative stress and inflammation. We discuss the effects of resveratrol on cancer cells in stress environment of tumors as well as interactions between cancer cells and non-cancer cells in this review.
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Antineoplásicos Fitogénicos/uso terapéutico , Suplementos Dietéticos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Resveratrol/uso terapéutico , Microambiente Tumoral/efectos de los fármacos , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Biomarcadores , Humanos , Neoplasias/etiología , Neoplasias/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Resveratrol/química , Resveratrol/farmacología , Transducción de Señal/efectos de los fármacos , Estrés Fisiológico/efectos de los fármacosRESUMEN
With regard to fluorescence quenching commonly observed during metal-ion detection, "turn-on" chemical sensing has been rarely reported, but could be extremely important because it facilitates the selective recognition of target objects of interest against a dark background. A metal-organic framework (MOF) chemosensor has been prepared that serves as an efficient platform for the selective detection of Cu2+ and Cd2+ ions over other metal ions. In particular, this framework shows the highest fluorescence enhancement (≈60-fold relative to Cd-free MOF) for the hazardous metal ion Cd2+ among luminescent MOFs and displays excellent reusability in repeated cycles. The direct diffusion of Cd2+ into the crystal pores has also been visualized for the first time.
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A series of metal-organic frameworks (MOFs) M2 (dobpdc) (M=Mn, Co, Ni, Zn; H4 dobpdc=4,4'-dihydroxy-1,1'-biphenyl-3,3'-dicarboxylic acid), with a highly dense arrangement of open metal sites along hexagonal channels were prepared by microwave-assisted or simple solvothermal reactions. The activated materials were structurally expanded when guest molecules including CO2 were introduced into the pores. The Lewis acidity of the open metal sites varied in the order Mn
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Facile postsynthetic oxidation of the thiol-laced UiO-66-type framework UiO-66(SH)2 enabled the generation of UiO-66(SO3 H)2 with sulfonic acid groups covalently linked to the backbone of the system. The oxidized material exhibited a superprotonic conductivity of 8.4×10(-2) â S cm(-1) at 80 °C and 90 % relative humidity, and long-term stability of the conductivity was observed. This level of conductivity exceeds that of any proton-conducting MOF reported to date and is equivalent to the conductivity of the most effective known electrolyte, Nafion.
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Ovarian cancer is a leading cause of death among gynecologic tumors, often detected at advanced stages. Metabolic reprogramming and increased lipid biosynthesis are key factors driving cancer cell growth. Stearoyl-CoA desaturase 1 (SCD1) is a crucial enzyme involved in de novo lipid synthesis, producing mono-unsaturated fatty acids (MUFAs). Here, we aimed to investigate the expression and significance of SCD1 in epithelial ovarian cancer (EOC). Comparative analysis of normal ovarian surface epithelial (NOSE) tissues and cell lines revealed elevated SCD1 expression in EOC tissues and cells. Inhibition of SCD1 significantly reduced the proliferation of EOC cells and patient-derived organoids and induced apoptotic cell death. Interestingly, SCD1 inhibition did not affect the viability of non-cancer cells, indicating selective cytotoxicity against EOC cells. SCD1 inhibition on EOC cells induced endoplasmic reticulum (ER) stress by activating the unfolded protein response (UPR) sensors and resulted in apoptosis. The addition of exogenous oleic acid, a product of SCD1, rescued EOC cells from ER stress-mediated apoptosis induced by SCD1 inhibition, underscoring the importance of lipid desaturation for cancer cell survival. Taken together, our findings suggest that the inhibition of SCD1 is a promising biomarker as well as a novel therapeutic target for ovarian cancer by regulating ER stress and inducing cancer cell apoptosis.
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Neoplasias Ováricas , Estearoil-CoA Desaturasa , Femenino , Humanos , Estearoil-CoA Desaturasa/metabolismo , Apoptosis , Estrés del Retículo Endoplásmico , Carcinoma Epitelial de Ovario , LípidosRESUMEN
Herein, we report the first example of programmable living materials constructed with a dynamic covalent interface between designed synthetic polymers and engineered B. subtilis cells. We identified a molecular motif that forms reversible dynamic covalent bonds on the B. subtilis cell surface. Combining block copolymers bearing this motif with genetically engineered B. subtilis yields programmable living materials that can be equipped with functionalities such as biosensing and on-demand elution of recombinant proteins. Encapsulated cells in these living materials could be reversibly retrieved and subjected to biological analyses. Further, the block copolymer in these living materials could be recycled to produce a new batch of living materials. This work advances the current capabilities in engineered living materials, establishes the groundwork for building a myriad of synthetic polymeric materials integrating engineered living cells, and provides a platform for understanding the biology of cells confined within materials.
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Bacillus subtilis , Polímeros , Bacillus subtilis/metabolismo , Membrana Celular , Ingeniería Genética , Polímeros/metabolismoRESUMEN
Ovarian cancer is mostly diagnosed at advantaged stages due to the lack of early diagnostic biomarkers. The common metastasis pattern is characterized by peritoneal dissemination with a formation of malignant ascites. Extracellular vesicles (EVs) are emerging as promising clinical biomarkers in liquid biopsy. Here, we aimed to investigate robust liquid biopsy-based EV miRNA biomarkers for ovarian cancer diagnosis and metastasis regulation. EVs were isolated from malignant ascites and plasma of ovarian cancer patients as well as the benign control counterparts of patients with benign gynecologic diseases. EV small RNA sequencing identified a panel of eight miRNAs (miR-1246, miR-1290, miR-483, miR-429, miR-34b-3p, miR-34c-5p, miR-145-5p, miR-449a) based on dysregulated miRNAs overlapped in the ascites and plasma subset. The ovarian cancer EV miRNA (OCEM) signature developed based on these eight miRNAs demonstrated high diagnostic accuracy in our in-house dataset and multiple public datasets across diverse clinical samples (blood, tissue and urine). In addition, malignant ascites-derived EVs could significantly facilitate the aggressive property of ovarian cancer cells and boost the growth of ascites-derived organoids. Notably, miR-1246 and miR-1290 shuttled in malignant ascites-derived EVs were identified to promote the invasion and migration of ovarian cancer cells through regulating a common target RORα.
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Vesículas Extracelulares , MicroARNs , Neoplasias Ováricas , Ascitis/diagnóstico , Ascitis/genética , Biomarcadores de Tumor/genética , Carcinoma Epitelial de Ovario/diagnóstico , Carcinoma Epitelial de Ovario/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/patología , Femenino , Humanos , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patologíaRESUMEN
Background: A positive relationship was reported between metabolic syndrome and the risk of endometrial cancer. Studies on the relationship between metabolic syndrome and endometrial cancer have been mainly conducted in post-menopausal women. We aimed to investigate the risk of endometrial cancer according to metabolic syndrome and menopausal status using the Korean nationwide population-based cohort. Methods: We enrolled 2,824,107 adults (endometrial cancer group; N = 5,604 and control group; N= 2,818,503) from the Korean National Health Insurance Service checkup database from January 1 to December 31, 2009. The median follow-up duration was 8.37 years. Metabolic syndrome was diagnosed as having at least three of the following five components: abdominal obesity, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, raised blood pressure, and hyperglycemia. Multivariate Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate endometrial cancer risk. Results: The endometrial cancer risk was higher in the metabolic syndrome group than that in the non-metabolic syndrome group (HR, 1.362; 95% CI, 1.281-1.449). The association between metabolic syndrome and endometrial cancer risk was significant in the premenopausal subgroup (HR, 1.543; 95% CI, 1.39-1.713) and postmenopausal subgroup (HR, 1.306; 95% CI, 1.213-1.407). The incidence of endometrial cancer was more closely related to metabolic syndrome components in the pre-menopausal subgroup than those in the post-menopausal subgroup (for waist circumference, blood pressure, triglycerides and high-density lipoprotein cholesterol, all p for interaction <0.0001 respectively, and for fasting blood glucose, p for interaction 0.0188). The incidence of endometrial cancer positively correlated with the number of metabolic syndrome components (log-rank p <0.0001). Conclusion: Our large population-based cohort study in Korean women suggests that metabolic syndrome and its accumulated components may be risk factors for endometrial cancer, particularly in the pre-menopausal women.
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The poor prognosis of ovarian cancer patients mainly results from a lack of early diagnosis approaches and a high rate of relapse. Only a very modest improvement has been made in ovarian cancer patient survival with traditional treatments. More targeted therapies precisely matching each patient are strongly needed. The aberrant activation of Wnt/ß-catenin signaling pathway plays a fundamental role in cancer development and progression in various types of cancer including ovarian cancer. Recent insight into this pathway has revealed the potential of targeting Wnt/ß-catenin in ovarian cancer treatment. This study aims to investigate the effect of CWP232291, a small molecular Wnt/ß-catenin inhibitor on ovarian cancer progression. Various in vitro, in vivo and ex vivo models are established for CWP232291 testing. Results show that CWP232291 could significantly attenuate ovarian cancer growth through inhibition of ß-catenin. Noticeably, CWP232291 could also s suppress the growth of cisplatin-resistant cell lines and ovarian cancer patient-derived organoids. Overall, this study has firstly demonstrated the anti-tumor effect of CWP232291 in ovarian cancer and proposed Wnt/ß-catenin pathway inhibition as a novel therapeutic strategy against ovarian cancer.
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Resveratrol (3,4',5-trans-trihydroxystilbene) and piceatannol (3,3',4',5-trans-tetraphydroxystilbene) are major stilbene compounds that are predominantly present in various natural foods, such as berries and fruits. Both phytochemical compounds are consumed as dietary supplements to prevent various metabolic diseases and for their anti-aging properties. Adipose-derived stem cells from human visceral adipose tissue (vASCs) are a useful in vitro model for evaluating their adipogenic effect. Treatment with resveratrol and piceatannol significantly inhibited lipid accumulation in vASCs. Their effective concentrations were 5, 10, and 20 µM for inhibiting adipogenesis of vASCs. Interestingly, despite the similar chemical structures of the two compounds, piceatannol showed a higher anti-adipogenic effect at 20 µM than resveratrol in vASCs. Moreover, the inhibitory capacity of lipid droplet generation was higher for piceatannol at 20 µM than that of resveratrol. Piceatannol significantly attenuated the expression level of adipogenic markers (e.g., CCAAT/enhanced binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), and adipocyte fatty acid binding protein (aP2)) compared to resveratrol at the mRNA and protein levels. These results suggest that piceatannol is a superior anti-adipogenic compound compared to resveratrol in the vASC model of visceral obesity.
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BACKGROUND: The incidence of breast cancer has been gradually increasing in Korea. Recently, the elevated level of serum gamma-glutamyltransferase (GGT) has emerged to be associated with the development and progression of some malignancies. This study aimed to determine the effect of serum GGT levels on the risk of developing breast cancer in Korean women. METHODS: We used National Health Insurance Service Health Checkup data to examine the association between serum GGT levels and breast cancer development in Korean women. Women aged 40 years or older who participated in the Korean National Health Screening Examination between January 2009 and December 2009 and who did not develop any cancer within 1-year post examination were included in this analysis (n = 3,109,506). Cox proportional hazard regression analysis was conducted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Overall, an elevated serum GGT level was associated with the increased risk of developing breast cancer; compared to the Q1 group, the Q4 group showed a significantly increased breast cancer risk (HR: 1.120,95% CI: 1.08-1.162). Such a relationship was stronger in post-menopausal women than pre-menopausal women (HR: 1.173, 95% CI: 1.107-1.243; HR: 1.070, 95% CI:1.019-1.124). Women with a high GGT level (Q4) were also at an increased risk of developing carcinoma in situ (CIS) (HR: 1.114, 95% CI: 1.04-1.192). In post-menopausal women, the Q4 group also exhibited higher CIS risk (HR: 1.266, 95% CI: 1.132-1.416). However, no significant difference in the risk of developing CIS was observed between the Q1 and Q4 groups in pre-menopausal women. Further analysis revealed that obese, post-menopausal women with a high GGT level (Q4) were associated with an increased risk of developing breast cancer (HR: 1.214, 95% CI: 1.125-1.31) and CIS (HR: 1.348, 95% CI: 1.159-1.569). CONCLUSIONS: Our study results demonstrate that increased serum GGT level is a risk factor for developing breast cancer. The post-menopausal women group with obesity and elevated serum GGT level showed the highest incidence of breast cancer. Thus, serum GGT concentration could be a novel and potential risk factor for breast cancer. Further validation in different ethnic groups would be warranted.
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The interaction of immune checkpoint molecules in the tumor microenvironment reduces the anti-tumor immune response by suppressing the recognition of T cells to tumor cells. Immune checkpoint inhibitor (ICI) therapy is emerging as a promising therapeutic option for cancer treatment. However, modulating the immune system with ICIs still faces obstacles with severe immunogenic side effects and a lack of response against many cancer types. Plant-derived natural compounds offer regulation on various signaling cascades and have been applied for the treatment of multiple diseases, including cancer. Accumulated evidence provides the possibility of efficacy of phytochemicals in combinational with other therapeutic agents of ICIs, effectively modulating immune checkpoint-related signaling molecules. Recently, several phytochemicals have been reported to show the modulatory effects of immune checkpoints in various cancers in in vivo or in vitro models. This review summarizes druggable immune checkpoints and their regulatory factors. In addition, phytochemicals that are capable of suppressing PD-1/PD-L1 binding, the best-studied target of ICI therapy, were comprehensively summarized and classified according to chemical structure subgroups. It may help extend further research on phytochemicals as candidates of combinational adjuvants. Future clinical trials may validate the synergetic effects of preclinically investigated phytochemicals with ICI therapy.
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Inhibidores de Puntos de Control Inmunológico/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Fitoquímicos/química , Receptor de Muerte Celular Programada 1/metabolismo , Animales , Antígenos CD/metabolismo , Antineoplásicos/farmacología , Antígenos B7/metabolismo , Antígeno B7-H1/metabolismo , Antígeno CTLA-4/metabolismo , Camptotecina/química , Diterpenos/química , Compuestos Epoxi/química , Flavonoides/química , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Humanos , Inmunoterapia , Isotiocianatos/química , Ratones , Fenantrenos/química , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Receptores Inmunológicos/metabolismo , Saponinas/química , Sulfóxidos/química , Terpenos/química , Microambiente Tumoral/efectos de los fármacos , Proteína del Gen 3 de Activación de LinfocitosRESUMEN
BACKGROUND: Studies examining the relationship between obesity and female-specific cancers have been mainly conducted in Western populations. We aimed to investigate the risk of female-specific cancers according to obesity and menopausal status using a nationwide cohort in Korea. METHODS: We identified 2,708,938 women from the National Health Insurance Service cohort, and obtained baseline body mass index (BMI), waist circumference (WC), and other healthcare data, measured and collected during a health examinations and cancer-screening survey. By setting a normal weight/WC group (BMI, 18â¢5-22â¢9 kg/m2 or WC, 80â¢0-84â¢9 cm) as the reference, we conducted multivariate analyses using the Cox proportional hazard model to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) for each cancer. FINDINGS: The total follow-up duration was 22389854â¢63 person-years. In post-menopausal women, the risk of breast, endometrial, and ovarian cancers significantly increased as the BMI classification level increased from normal to class II obesity (aHRs [95% CIs], 1â¢49 [1â¢38-1.61], 2â¢11 [1â¢81-2â¢46], and 1â¢38 [1â¢20-1â¢58], respectively). The risk of breast and endometrial cancers also increased as the WC classification increased from < 75â¢0 to ≥ 95â¢0 cm. With a WC of 80â¢0-84â¢9 cm as the reference, the lowest risk of breast and endometrial cancers was observed in WC < 75â¢0 cm (aHRs [95% CIs], 0â¢85 [0â¢81-0â¢89] and 0â¢75 [0â¢67-0â¢84], respectively) while the highest risk was observed in WC ≥ 95â¢0 cm (aHRs [95% CIs], 1â¢19 [1â¢10-1â¢29] and 1â¢56 [1â¢33-1â¢82], respectively). In pre-menopausal women, the risk of breast cancer significantly decreased in those with class I and II obesity compared to those with normal BMI (aHRs [95% CIs], 0â¢96 [0â¢92-0â¢999] and 0â¢89 [0â¢81-0â¢97], respectively), whereas the trends of endometrial and ovarian cancer incidence in pre-menopausal women were similar to those observed in post-menopausal women. For cervical cancer, only class II obesity was significantly associated with increased risks in both post-menopausal and pre-menopausal women (aHRs [95% CIs], 1â¢18 [1â¢01-1â¢39] and 1â¢27 [1â¢02-1â¢57], respectively). INTERPRETATION: In this large population-based cohort study in Korean women, we observed that the impact of obesity on the development of female-specific cancers differs according to the malignancy type and menopausal status. Similar trends were observed between Korean and Western women. FUNDING: The Korea Health Industry Development Institute (no. HI16C2037).