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1.
J Cancer Res Clin Oncol ; 146(7): 1725-1735, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32394054

RESUMO

OBJECTIVE: The plasminogen activator system (PAS) and vascular endothelial growth factor (VEGF) are important in the carcinogenesis and play a key role in cancer invasion and mediating metastasis of carcinomas. The aim of the study was to evaluate the correlation of serum levels of VEGF and components of the PAS with clinicopathological risk factors and outcome in patients with endometrial cancer (EC). METHODS: Preoperative blood was collected from 173 patients treated for EC between 1999 and 2009. Serum concentrations of VEGF, urokinase plasminogen activator (uPA) tissue plasminogen activator (tPA), plasminogen activator inhibitor type-1 (PAI-1) and -2 (PAI-2) were assessed by enzyme-linked immunosorbent assays (ELISA). RESULTS: Serum levels of VEGF and components of the PAS were significantly associated with stage of the disease, tumor histology, tumor grade, myometrial invasion (MI), presence of lymphovascular space invasion (LVSI) and lymph node metastases (LNM). Preoperative serum levels of PAI-1 and -2 and tPA were higher in patients who experienced a recurrence than in patients who remained disease free (p < 0.01). PAI-1 and -2 and tPA were significantly independent prognostic factors for DFS with a HR of 3.85 (95% CI 1.84-8.07), 3.90 (95% CI 1.75-8.66) and 2.53 (95% CI 1.16-5.55), respectively. PAI-1 and tPA turned out to be independent prognostic factors for OS, with a HR of 2.09 (95% CI 1.08-4.05) and 2.16 (95% CI 1.06-4.44), respectively. CONCLUSION: Serum levels of VEGF and components of the PAS at primary diagnosis were associated with well-known clinicopathological risk factors such as; FIGO stage, tumor histology, tumor grade, MI, LVSI and LNM. High concentrations of PAI-1 and-2 and tPA are independent factors for poor prognosis in patients with endometrial cancer.


Assuntos
Neoplasias do Endométrio/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Idoso , Biomarcadores Tumorais , Transformação Celular Neoplásica , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/mortalidade , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Modelos Moleculares , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Ativador de Plasminogênio Tecidual/sangue , Ativador de Plasminogênio Tecidual/metabolismo , Fator A de Crescimento do Endotélio Vascular/sangue
2.
PLoS One ; 15(4): e0232231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32343732

RESUMO

BACKGROUND: To inform treatment decisions in women diagnosed with endometrial hyperplasia, quantification of the potential for concurrent endometrial cancer and the future risk of progression to cancer is required. METHODS: We identified studies up to September 2018 that reported on the prevalence of concurrent cancer (within three months of endometrial hyperplasia diagnosis), or the incidence of cancer, identified at least three months after hyperplasia diagnosis. Random-effects meta-analyses produced pooled estimates and 95% confidence intervals (CIs). RESULTS: A total of 36 articles were identified; 15 investigating concurrent and 21 progression to cancer. In pooled analysis of 11 studies of atypical hyperplasia, the pooled prevalence of concurrent endometrial cancer was 32.6% (95% CI: 24.1%, 42.4%) while no studies evaluated concurrent cancer in non-atypical hyperplasia. The risk of progression to cancer was high in atypical hyperplasia (n = 5 studies, annual incidence rate = 8.2%, 95% CI 3.9%, 17.3%) and only one study reported on non-atypical hyperplasia (annual incidence rate = 2.6%, 95% CI: 0.6%, 10.6%). CONCLUSIONS: Overall, a third of women with atypical hyperplasia had concurrent endometrial cancer, although the number of studies, especially population-based, is small. Progression to cancer in atypical hyperplasia was high, but few studies were identified. Population-based estimates are required, in both atypical and non-atypical hyperplasia patients to better inform treatment strategies.


Assuntos
Hiperplasia Endometrial/complicações , Neoplasias do Endométrio/etiologia , Progressão da Doença , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/epidemiologia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/epidemiologia , Endométrio/patologia , Feminino , Humanos , Incidência , Lesões Pré-Cancerosas/complicações , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/epidemiologia , Prevalência , Fatores de Risco
3.
BMC Cancer ; 20(1): 101, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024485

RESUMO

BACKGROUND: Epidemiological studies on the association between coffee intake and cancer risk have yielded inconsistent results. To summarize and appraise the quality of the current evidence, we conducted an umbrella review of existing findings from meta-analyses of observational studies. METHODS: We searched PubMed, Embase, Web of Science and the Cochrane database to obtain systematic reviews and meta-analyses of associations between coffee intake and cancer incidence. For each association, we estimated the summary effect size using the fixed- and random-effects model, the 95% confidence interval, and the 95% prediction interval. We also assessed heterogeneity, evidence of small-study effects, and excess significance bias. RESULTS: Twenty-eight individual meta-analyses including 36 summary associations for 26 cancer sites were retrieved for this umbrella review. A total of 17 meta-analyses were significant at P ≤ 0.05 in the random-effects model. For the highest versus lowest categories, 4 of 26 associations had a more stringent P value (P ≤ 10- 6). Associations for five cancers were significant in dose-response analyses. Most studies (69%) showed low heterogeneity (I2 ≤ 50%). Three and six associations had evidence of excessive significance bias and publication bias, respectively. Coffee intake was inversely related to the risk of liver cancer and endometrial cancer and was characterized by dose-response relationships. There were no substantial changes when we restricted analyses to meta-analysis of cohort studies. CONCLUSIONS: There is highly suggestive evidence for an inverse association between coffee intake and risk of liver and endometrial cancer. Further research is needed to provide more robust evidence for cancer at other sites.


Assuntos
Café/efeitos adversos , Neoplasias do Endométrio/epidemiologia , Neoplasias Hepáticas/epidemiologia , Bebidas/efeitos adversos , Viés , Neoplasias do Endométrio/etiologia , Feminino , Humanos , Incidência , Neoplasias Hepáticas/etiologia , Masculino , Metanálise como Assunto , Tamanho da Amostra
4.
Breast Cancer Res Treat ; 180(1): 1-19, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31897901

RESUMO

PURPOSE: Epidemiological evidence on the risk factors for uterine/endometrial cancer in breast cancer (BCa) survivors is limited and inconsistent. Therefore, we critically reviewed and summarized available evidence related to the risk factors for uterine/endometrial cancer in BCa survivors. METHODS: We conducted a literature search through PubMed, Web of Science Core Collection/Cited Reference Search, as well as through manual searches of the bibliographies of the articles identified in electronic searches. We included in this review studies that were published up to November 30, 2018 that were accessible in full-text format and were published in English. RESULTS: Of the 27 eligible studies, 96% had > 700 participants, 74% were prospective cohorts, 70% originated outside of the US, 44% reported as having pre-/postmenopausal women, and 26% reported having racially heterogeneous populations. Risk factors positively associated with uterine/endometrial cancer risk among BCa survivors included age at BCa diagnosis > 50 years, African American race, greater BMI/weight gain, and Tamoxifen treatment. For other lifestyle, reproductive and clinical factors, associations were either not significant (parity) or inconsistent (HRT use, menopausal status, smoking status) or had limited evidence (alcohol intake, family history of cancer, age at first birth, oral contraceptive use, age at menopause, comorbidities). CONCLUSION: We identified several methodological concerns and limitations across epidemiological studies on potential risk factors for uterine/endometrial cancer in BCa survivors, including lack of details on uterine/endometrial cancer case ascertainment, varying and imprecise definitions of important covariates, insufficient adjustment for potential confounders, and small numbers of uterine/endometrial cancer cases in the overall as well as stratified analyses. Based on the available evidence, older age and higher body weight measures appear to be a shared risk factor for uterine/endometrial cancer in the general population as well as in BCa survivors. In addition, there is suggestive evidence that African American BCa survivors have a higher risk of uterine/endometrial cancer as compared to their White counterparts. There is also evidence that Tamoxifen contributes to uterine/endometrial cancer in BCa survivors. Given limitations of existing studies, more thorough investigation of these associations is warranted to identify additional preventive strategies needed for BCa survivors to reduce uterine/endometrial cancer risk and improve overall survival.


Assuntos
Neoplasias da Mama/epidemiologia , Sobreviventes de Câncer , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Neoplasias Uterinas/epidemiologia , Neoplasias Uterinas/etiologia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Feminino , Humanos , Vigilância em Saúde Pública , Medição de Risco , Fatores de Risco
5.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31614364

RESUMO

CONTEXT: Polycystic ovary syndrome (PCOS) is a prevalent disorder in reproductive aged women associated with a number of endocrine and metabolic complications, including increased risk of endometrial cancer. OBJECTIVE: To study the effect of the characteristic increased androgen levels in PCOS on the endometrium, a novel scaffold-free multicellular endometrial organoid was established. DESIGN: Human endometrial organoids were constructed using primary endometrial epithelial and stromal cells from endometrial tissues. Organoids were treated for 14 days with physiologic levels of estradiol and testosterone to mimic a normal follicular phase or PCOS hormone profiles. Organoids were harvested for immunostaining and ribonucleic acid sequencing. SETTING: Academic institution. PATIENTS: Endometrial tissues from 10 premenopausal women undergoing hysterectomy for benign pathologies were obtained following written consent. MAIN OUTCOME MEASURES: Organoid architecture, cell specific markers, functional markers, proliferation, and gene expression were measured. RESULTS: A method to generate scaffold-free endometrial organoids containing epithelial and stromal cells was established. These organoids exhibited distinct organization with epithelial cells lining the outer surface and stromal cells in the center of the organoids. Epithelial cells were polarized, organoids expressed cell type specific and functional markers, as well as androgen, estrogen, and progesterone receptors. Treatment with PCOS hormones increased cell proliferation and dysregulated genes in endometrial organoids. CONCLUSIONS: A new multicellular, scaffold-free endometrial organoid system was established that resembled physiology of the native endometrium. Excess androgens in PCOS promoted cell proliferation in endometrial organoids, revealing new mechanisms of PCOS-associated with risk of endometrial neoplasia.


Assuntos
Androgênios/efeitos adversos , Neoplasias do Endométrio/patologia , Endométrio/patologia , Hiperandrogenismo/complicações , Organoides/patologia , Síndrome do Ovário Policístico/patologia , Células Estromais/patologia , Adulto , Estudos de Casos e Controles , Proliferação de Células , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/metabolismo , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Organoides/efeitos dos fármacos , Organoides/metabolismo , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Prognóstico , Estudos Prospectivos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo
6.
J Infect Public Health ; 13(4): 613-618, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31519382

RESUMO

BACKGROUND: Endometrial and cervical carcinomas are the most common gynecologic malignancies in Western world and many countries. The human papillomavirus (HPV) high-risk genotypes are associated with cervical carcinoma (CC). Chlamydia trachomatis (C. trachomatis), the most common sexually transmitted bacterial infection worldwide, considered a cofactor for HPV infection and CC. Information on HPV infection rate and type distribution among Jordanian women having CC is currently limited and unavailable among those with endometrial carcinoma. Therefore, the present study aimed to provide an updated estimate on HPV infection rate and its high-risk genotypes' distribution among Jordanian women by comparing data from invasive cervical carcinoma (ICC) to normal cervical tissues. Similarly, assessment of HPV infection rate was extended to the endometrial tissues. C. trachomatis infection was investigated as well to explore its possibility as HPV cofactor for induction of such carcinomas. METHODS: Total DNA was extracted from 144 formaldehyde-fixed paraffin-embedded cervical and endometrial tissue, equally divided between age-matched control and carcinoma cases. Polymerase chain reaction (PCR) was used for general detection of HPV-DNA, high risk HPV-16 and 18 genotypes and C. trachomatis DNA using specific primers. RESULTS: HPV infection was detected in 91.7% and 61.1% of cervical cancer patients and controls, respectively. Likewise, it was higher among cases (47.2%) than controls (13.8%) in endometrial biopsies. Significantly higher HPV infection rates were found among ICC and endometrial control biopsies of women >50 years. Out of 33 HPV positive ICC cases, single HPV-16 infections were detected in 69.7% compared to HPV-18 (15.2%), while HPV-16/18 co-infections were only found in three (9%) samples. C. trachomatis was not detected in all studied groups. CONCLUSION: The present study has successfully provided an updated estimate on HPV infection rate among Jordanian women with and without ICC and endometrial carcinoma. In addition, a lack of co-infection was observed between HPV and C. trachomatis in both cancer types.


Assuntos
Neoplasias do Endométrio/virologia , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/virologia , Fatores Etários , Infecções por Chlamydia/complicações , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis , Neoplasias do Endométrio/etiologia , Feminino , Humanos , Jordânia/epidemiologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Reação em Cadeia da Polimerase , Fatores de Risco , Neoplasias do Colo do Útero/etiologia
7.
Gynecol Endocrinol ; 36(1): 30-32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31429335

RESUMO

Hyperparathyroidism-jaw tumor (HPT-JT) is an autosomal dominant disorder responsible for benign and/or malignant tumors. Affected women often present life-threatening menorrhagia that leads to the identification of uterine tumors, and experience miscarriages and infertility. Overall though, fewer data concerning gynecological pathologies related to HPT-JT syndrome are available. We report the case of a 32-year-old woman with HPT-JT syndrome, referred for recurrent vaginal bleeding, with a history of repeated endometrial polyps and infertility. We also review the literature that explores medical options for these women.


Assuntos
Adenoma/complicações , Adenomioma/diagnóstico por imagem , Neoplasias do Endométrio/diagnóstico por imagem , Fibroma/complicações , Hiperparatireoidismo/complicações , Neoplasias Maxilomandibulares/complicações , Pólipos/diagnóstico por imagem , Adenomioma/etiologia , Adenomioma/cirurgia , Adulto , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histeroscopia , Infertilidade Feminina/etiologia , Imagem por Ressonância Magnética , Pólipos/cirurgia
8.
Nutr Rev ; 78(1): 1-18, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31393566

RESUMO

CONTEXT: Excess weight has been linked to increased risks of 13 types of cancers. Physical activity is a non-nutritional modifiable lifestyle factor that is not only crucial for weight control but is also known to regulate hormones and metabolic pathways that may contribute to carcinogenesis. There is solid evidence that being physically active during middle and late adulthood lowers the risks of 3 obesity-related cancers, namely breast cancer, colon cancer, and endometrial cancer. However, the associations between physical activity at a young age (childhood, adolescence, and young adulthood; age 5 to ≤30 yr) and lifetime physical activity and the risks of breast cancer, colon cancer, and endometrial cancer are less defined. OBJECTIVE: The present systematic review and meta-analysis of observational studies was performed in accordance with the MOOSE guidelines to determine whether physical activity at a young age and lifetime physical activity may lower the risks of breast cancer, colon cancer, and endometrial cancer. DATA SOURCES: The PubMed and Web of Science databases were searched for relevant observational studies published from inception to July 2018. STUDY SELECTION: Observational studies (prospective cohort, case-cohort, nested case-control, historical cohort, and case-control) were considered relevant if they investigated the association between physical activity at a young age or lifetime physical activity and the risks of developing selected cancers. DATA EXTRACTION: A random-effects meta-analysis was performed to generate the summary relative risk (RR) with 95%CI for the highest vs the lowest category of physical activity of any type. RESULTS: Eighty publications were included in the present meta-analysis. Higher physical activity at a young age was associated with lower risks of breast cancer (RR 0.81, 95%CI 0.76, 0.87) and colon cancer (RR 0.67, 95%CI 0.50, 0.88). Similarly, lifetime physical activity was inversely associated with the risks of breast cancer (RR 0.79, 95%CI 0.72, 0.86) and colon cancer (RR 0.75, 95%CI 0.69, 0.82). For breast cancer, menopausal status did not appear to modify the observed inverse association. The benefit with respect to endometrial cancer risk reduction was only observed with higher lifetime physical activity (RR 0.77, 95%CI 0.67, 0.88), not with higher physical activity at a young age (RR 0.89, 95%CI 0.73, 1.07). CONCLUSIONS: Being physically active over a lifetime, starting from early childhood, may lower the risks of developing breast cancer, colon cancer, and endometrial cancer.


Assuntos
Neoplasias da Mama/etiologia , Neoplasias do Colo/etiologia , Neoplasias do Endométrio/etiologia , Exercício Físico , Obesidade/complicações , Fatores Etários , Neoplasias da Mama/epidemiologia , Neoplasias do Colo/epidemiologia , Neoplasias do Endométrio/epidemiologia , Feminino , Humanos , Estudos Observacionais como Assunto , Fatores de Risco
9.
Medicine (Baltimore) ; 98(51): e18279, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860975

RESUMO

RATIONALE: Lynch syndrome (LS) is an autosomal dominant cancer predisposition condition caused by germline heterozygous mutations in mismatch repair (MMR) genes. However, as one of the MMR genes, PMS2 mutation-induced LS-associated endometrial cancer (LSAEC) was rarely reported. PATIENT CONCERNS: A 26-year-old female patient suffered from prolonged menstrual period and increased menstrual flow for 2 months. DIAGNOSES: The patient was diagnosed with cervix CIN III, endometrial cancer (EC), anemia, and LS. INTERVENTIONS: Total hysterectomy, bilateral salpingectomy, pelvic lymphadenectomy were performed for treating EC, while ovariectomy was refused by the patient. The patient underwent postoperative chemotherapy with paclitaxel combined with carboplatin for 6 courses of treatment. Laparoscopic partial enterectomy was applied for treating colon cancer 5 years later after the surgery treatment for EC. Besides, Sanger sequencing and high-throughput genome sequencing were employed to detect the genetic status of the family that included two generations with four members. Immunohistochemistry (IHC) staining was used to identify the function of PMS2 mutation. OUTCOMES: The 26-year-old Chinese patient suffered from LSAEC and recovered well after surgery. A PMS2 germline heterozygous mutation (c.1577delA) was confirmed by gene sequencing 5 years later. In addition, PMS2 mutation was verified by IHC. The patient was followed up for 7 years. LESSONS: Carrying PMS2 germline mutation (c.1577delA) confers an extremely high susceptibility of suffering from LS-associated cancers. Thus, close clinical monitoring and prophylactic surgery are highly recommended to reduce the morbidity and mortality of LS-associated cancers.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias do Endométrio/genética , Mutação em Linhagem Germinativa/genética , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Adulto , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA/genética , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/patologia , Endométrio/patologia , Feminino , Humanos
10.
Tex Med ; 115(12): e1, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31800088

RESUMO

In 2016, the UT Southwestern Medical Center's Cancer Genetics Program was awarded a grant (PP160103) by the Cancer Prevention and Research Institute of Texas (CPRIT) to increase awareness of hereditary cancer syndromes, particularly Lynch syndrome (LS), and implement a population-based genetic screening program to identify those at high genetic risk for cancer.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Detecção Precoce de Câncer , Família , Testes Genéticos , Programas de Rastreamento , Anamnese , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/genética , Feminino , Humanos , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/genética , Fatores de Risco , Texas
12.
Stem Cell Reports ; 13(4): 730-746, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31564647

RESUMO

Uterine endometrial cancer is associated with poor survival outcomes in patients with advanced-stage disease. Here, we developed a three-dimensional cell cultivation method of endometrioid cancer stem-like cells with high aldehyde dehydrogenase (ALDH) activity from clinical specimens. ALDH inhibition synergized with paclitaxel to block cancer proliferation. In the clinical setting, high ALDH1A1 expression was associated with poor survival. A high level of ALDH correlated with an increase of glucose uptake, activation of the glycolytic pathway, and elevation of glucose transporter 1 (GLUT1). Blockade of GLUT1 inhibited characteristics of cancer stem cells. Similarly to ALDH inhibition, GLUT1 inhibition synergized with paclitaxel to block endometrial cancer proliferation. Our data indicated that ALDH-dependent GLUT1 activation and the resulting glycolytic activation are of clinical importance for both prognostic evaluation and therapeutic decision-making in endometrial cancer patients. In addition, the synergistic effects of taxane compounds and ALDH or GLUT1 inhibitors may serve as a new clinical treatment option for endometrial cancer.


Assuntos
Aldeído Desidrogenase/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/metabolismo , Células-Tronco Neoplásicas/metabolismo , Paclitaxel/farmacologia , Aldeído Desidrogenase/metabolismo , Biomarcadores , Linhagem Celular Tumoral , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Ativação Enzimática , Feminino , Expressão Gênica , Glicólise , Humanos , Esferoides Celulares , Células Tumorais Cultivadas
13.
Rev Med Liege ; 74(9): 479-483, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31486319

RESUMO

Lynch syndrome is a hereditary predisposition to several cancers. The goals of our study were to know the different mutations in our Lynch population, to evaluate the prevalence of cancers in this population and to determine the mean age of onset of those cancers. This retrospective study includes proven carriers of a MMR mutation diagnosed either by the CHU of Liège or either by the CHC Saint-Joseph in Liège, Belgium. We noted a clear majority of MSH2 mutations (50 %) in the Lynch families recorded in Liège, which is different from the main literature. In our study population (106 subjects), 65 % of subjects were affected by at least one cancer. Prevalences for colorectal and endometrial cancers are, respectively, 50 % and 27.5 %. We found no difference in the mean age of onset of cancers compared to literature. We discuss the follow-up of Lynch patients and the interest of additional exams such as hysteroscopy and cystoscopy.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Neoplasias do Endométrio , Predisposição Genética para Doença , Bélgica , Neoplasias Colorretais/etiologia , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias do Endométrio/etiologia , Feminino , Humanos , Mutação , Estudos Retrospectivos
14.
Klin Onkol ; 32(4): 281-287, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31426644

RESUMO

INTRODUCTION: The incidence of malignant tumors of the uterine body is increasing in the Czech Republic. Endometrial adenocarcinoma is one of the most frequent morphological types. Obesity or even overweight is a risk factor for the development of this disease. More accurate stratification of risk relative to body mass index (BMI) has not yet been determined in the Czech Republic, although the risk of overweight (BMI 25-29.9) has been reported in one study as comparable to that of first or second degree obesity (BMI 30-30.9). PATIENTS AND METHODS: The study population included 376 women of Caucasian race diagnosed with endometrial adenocarcinoma, with BMI measured simultaneously, in 2005-2017. A control group consisted of an equal number of age-matched women not diagnosed with any oncological or gynecological disease. These two files were statistically processed. RESULTS: Odds (OR, 95% CI) relative to normal weight women, overweight women were at 2.26-times higher odds of endometrial adenocarcinoma, and women with obesity were at 5.18-8.67-, and 24.70-times higher odds, depending on the severity of obesity. CONCLUSION: The hypothesis that overweight represents same risk for the development of endometrial adenocarcinoma, as lower degrees of obesity was not verified. However overweight is serious risk for endometrial adenocarcinoma development. The odds of endometrial adenocarcinoma is correlated with increasing BMI and in the population studied is higher than reported previously for all endometrial carcinoma subtypes. This work was carried out with the support of an internal grant of Krajská zdravotní, a.s., for the years 2017-2019: IGA217129002. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 29. 4. 2019 Accepted: 22. 7. 2019.


Assuntos
Adenocarcinoma/etiologia , Índice de Massa Corporal , Neoplasias do Endométrio/etiologia , Sobrepeso/complicações , Estudos de Casos e Controles , República Tcheca , Feminino , Humanos , Obesidade/complicações , Razão de Chances
15.
Biomed Res Int ; 2019: 8584130, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275987

RESUMO

Object: The association of age at menopause with endometrial cancer remains controversial. Therefore, we quantitatively summarized the evidence from observational studies with a meta-analysis. Methods: We searched PubMed, Web of Science, Embase, Medline, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang Med online up to March 2019, and all eligible case-control and cohort studies were included in the study. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using the random-effects model. The dose-response relationship was assessed by restricted cubic spline model. The heterogeneity among studies was evaluated by I2. Metaregression was used to explore the potential sources of between-study heterogeneity. Egger's test was used to estimate publication bias. Results: Eighteen articles including 957242 subjects with 4781 cases were included in the meta-analysis. The pooled RR (95%CI) of endometrial cancer for the highest versus the lowest age at menopause was 1.89 (95%CI: 1.58-2.26). For dose-response analysis, a nonlinear relationship was found between age at menopause and endometrial cancer, and the positive association became statistically significant when age at menopause was greater than 46.5 years old. Conclusions: This meta-analysis suggested that age at menopause was positively associated with endometrial cancer. For women whose menopausal age over 46.5 years old, the risk of endometrial cancer increased with the age at menopause.


Assuntos
Neoplasias do Endométrio/etiologia , Menopausa/fisiologia , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Viés de Publicação , Análise de Regressão , Risco , Fatores de Risco
16.
Cancer Commun (Lond) ; 39(1): 42, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307542

RESUMO

BACKGROUND: The prevalence of Lynch syndrome and screening strategies for this disorder in Chinese patients with endometrial cancer have seldom been investigated. Such data would be essential for the screening, prevention, genetic counseling, and treatment of Lynch syndrome. The purpose of this prospective study was to determine the accuracy of the mismatch repair (MMR) protein immunohistochemistry (IHC), microsatellite instability (MSI) test, and clinical diagnostic criteria in screening for Lynch syndrome-associated endometrial cancer (LS-EC) in a prospective Chinese cohort. METHODS: All patients with newly diagnosed endometrial cancer (EC) were evaluated using clinical diagnostic criteria (Amsterdam II criteria and the revised Bethesda guidelines), MSI test, and IHC of MMR proteins in tumor tissues. For all patients, the screening results were compared with results of germline sequencing for pathogenic variants of MMR genes. RESULTS: Between December 2017 and August 2018, a total of 111 unselected patients with newly diagnosed EC were enrolled. Six patients (5.4%) harbored a pathogenic germline mutation of MMR genes: 1 had a mutation in MutL homolog 1 (MLH1), 2 in MutS homolog 2 (MSH2), and 3 in MutS homolog 6 (MSH6). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying LS-EC were 33.3%, 88.6%, 14.3%, and 95.9%, for the clinical criteria, 66.7%, 75.0%, 14.3%, and 97.3% for IHC of MMR proteins, 100%, 89.9%, 33.3%, and 100% for MSI test, and 100%, 72.4%, 20.0% and 100% for combined IHC and MSI test, respectively. The combination of IHC and MSI test had higher sensitivity and PPV than the clinical criteria (p = 0.030). MSI test and IHC were highly concordant for LS-EC screening (73/77, 94.8%). CONCLUSION: The accuracy of the combination of IHC of MMR proteins and MSI test for screening LS among Chinese patients with EC was superior to that of the clinical criteria. Trial registration NCT03291106. Registered on September 25, 2017.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Detecção Precoce de Câncer/métodos , Neoplasias do Endométrio/diagnóstico , Programas de Rastreamento/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/metabolismo , Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA/metabolismo , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Feminino , Mutação em Linhagem Germinativa , Humanos , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/metabolismo , Proteína 1 Homóloga a MutL/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Estudos Prospectivos
17.
BMC Cancer ; 19(1): 547, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31174495

RESUMO

BACKGROUND: Obesity is an important cause of multiple cancer types, amongst which endometrial cancer (EC). The relation between obesity and cancer is complicated and involves alterations in insulin metabolism, response to inflammation and alterations in estradiol metabolism. Visceral obesity is assumed to play the most important role in the first two mechanisms, but its role in estradiol metabolism is unclear. Therefore, this retrospective study explores the relationship of body mass index (BMI), visceral fat volume (VAV) and subcutaneous fat volume (SAV) and serum levels of sex steroids and lipids in patients with endometrial cancer. METHODS: Thirty-nine postmenopausal EC patients with available BMI, blood serum and Computed Tomography (CT) scans were included. Serum was analyzed for estradiol, dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, cholesterol, triglycerides and high (HDL), low (LDL) and non-high density (NHDL) lipoprotein. VAV and SAV were quantified on abdominal CT scan images. Findings were interpreted using pearson correlation coefficient and linear regression with commonality analysis. RESULTS: Serum estradiol is moderately correlated with BMI (r = 0.62) and VAV (r = 0.58) and strongly correlated with SAV (r = 0.74) (p < 0.001 for all). SAV contributes more to estradiol levels than VAV (10.3% for SAV, 1.4% for VAV, 35.9% for SAV and VAV, p = 0.01). Other sex steroids and lipids have weak and moderate correlations with VAV or SAV. CONCLUSIONS: This study shows that serum estradiol is correlated with BMI and other fat-distribution measures in postmenopausal endometrial cancer patients. Subcutaneous fat tissue contributes more to the estradiol levels indicating that subcutaneous fat might be relevant in endometrial cancer carcinogenesis.


Assuntos
Tecido Adiposo/patologia , Adiposidade , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/patologia , Hormônios Esteroides Gonadais/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Índice de Massa Corporal , Comorbidade , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/etiologia , Feminino , Humanos , Lipídeos/sangue , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Obesidade/complicações , Obesidade/metabolismo , Tamanho do Órgão , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
18.
Cancer ; 125(18): 3172-3183, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31150123

RESUMO

BACKGROUND: Universal tumor testing for defective DNA mismatch repair (MMR) is recommended for all women diagnosed with endometrial cancer to identify those with underlying Lynch syndrome. However, the effectiveness of these screening methods in identifying individuals with Lynch syndrome across the population has not been well studied. The aim of this study was to evaluate outcomes of MMR immunohistochemistry (IHC), mutL homolog 1 (MLH1) methylation, and microsatellite instability (MSI) analysis among patients with endometrial cancer. METHODS: A complete systematic search of online databases (PubMed, EMBASE, MEDLINE, and the Cochrane Library) for 1990-2018 was performed. A DerSimonian-Laird random effects model meta-analysis was used to estimate the weighted prevalence of Lynch syndrome diagnoses. RESULTS: The comprehensive search produced 4400 publications. Twenty-nine peer-reviewed studies met the inclusion criteria. Patients with endometrial cancer (n = 6649) were identified, and 206 (3%) were confirmed to have Lynch syndrome through germline genetic testing after positive universal tumor molecular screening. Among 5917 patients who underwent tumor IHC, 28% had abnormal staining. Among 3140 patients who underwent MSI analysis, 31% had MSI. Among patients with endometrial cancer, the weighted prevalence of Lynch syndrome germline mutations was 15% (95% confidence interval [CI], 11%-18%) with deficient IHC staining and 19% (95% CI, 13%-26%) with a positive MSI analysis. Among 1159 patients who exhibited a loss of MLH1 staining, 143 (13.7%) were found to be MLH1 methylation-negative among those who underwent methylation testing, and 32 demonstrated a germline MLH1 mutation (2.8% of all absent MLH1 staining cases and 22.4% of all MLH1 methylation-negative cases). Forty-three percent of patients with endometrial cancer who were diagnosed with Lynch syndrome via tumor typing would have been missed by family history-based screening alone. CONCLUSIONS: Despite the widespread implementation of universal tumor testing in endometrial cancer, data regarding testing results remain limited. This study provides predictive values that will help practitioners to evaluate abnormal results in the context of Lynch syndrome and aid them in patient counseling.


Assuntos
Carcinoma Endometrioide/genética , Neoplasias do Endométrio/genética , Síndrome de Lynch II/diagnóstico , Neoplasias Císticas, Mucinosas e Serosas/genética , Carcinoma Endometrioide/etiologia , Carcinoma Endometrioide/metabolismo , Metilação de DNA/genética , Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA/genética , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Síndrome de Lynch II/complicações , Síndrome de Lynch II/genética , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Técnicas de Diagnóstico Molecular , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Proteína 2 Homóloga a MutS/genética , Neoplasias Císticas, Mucinosas e Serosas/etiologia , Neoplasias Císticas, Mucinosas e Serosas/metabolismo
19.
J Pediatr Adolesc Gynecol ; 32(5): 546-549, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31226466

RESUMO

STUDY OBJECTIVE: To evaluate characteristics of young women with endometrial hyperplasia or cancer. DESIGN: Retrospective chart review. SETTING: Tertiary care referral center. PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We included 10- to 25-year-old young women seen at a single institution between 2006 and 2017 with International Classification of Diseases 9th and 10th revision codes for endometrial cancer or hyperplasia (cases), or who underwent an endometrial biopsy with other benign pathologic diagnoses (controls). Exclusions included a diagnosis of Lynch syndrome. Comparisons were made using χ2, Fisher exact, and nonparametric Wilcoxon rank tests. RESULTS: Sixty-nine patients were identified: 13 cases, 54 controls, and 2 exclusions. Of the 13 cases, 3 had endometrial cancer, 5 had complex atypical hyperplasia (now called endometrioid intraepithelial neoplasia), and 5 had hyperplasia without atypia. A higher proportion of cases had a body mass index (BMI) greater than 30, compared with controls (76.9% vs 40.4%; P < .03). The proportion of patients who had a BMI greater than 30 and were smokers was significantly higher among cases (38.5% vs 9.3%; P < .02). The proportion of patients with a history of polycystic ovary syndrome (PCOS) and smoking was also significantly different between groups (30.8% vs 3.7%; P < .01). CONCLUSION: In women aged 25 years and younger with endometrial sampling, a BMI greater than 30 was statistically more common in patients with endometrioid intraepithelial neoplasia or cancer. Although smoking or PCOS alone was not related to endometrial hyperplasia or cancer in this small cohort study, there might be a relationship between endometrial abnormalities and multiple exposures, including smoking and BMI greater than 30 or smoking and a history of PCOS.


Assuntos
Hiperplasia Endometrial/etiologia , Neoplasias do Endométrio/etiologia , Obesidade/complicações , Síndrome do Ovário Policístico/complicações , Adolescente , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Hiperplasia Endometrial/diagnóstico , Neoplasias do Endométrio/diagnóstico , Feminino , Humanos , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
20.
Fam Cancer ; 18(4): 399-420, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31236808

RESUMO

Lifestyle factors related to energy balance, such as excess body weight, poor diet, and physical inactivity, are associated with risk of sporadic endometrial cancer (EC) and colorectal cancer (CRC). There are limited data on energy balance-related lifestyle factors and EC or CRC risk among individuals with lynch syndrome, who are at extraordinarily higher risk of developing EC or CRC. We conducted a systematic review of evidence related to weight status, weight change, dietary habits, and physical activity on EC and CRC risk among individuals with lynch syndrome. Findings are reported narratively. We searched Medline, EMBASE, CENTRAL, PubMed, and clinicaltrials.gov up to June 14th, 2018. In total, 1060 studies were identified and 16 were included. Three studies were related to EC and 13 to CRC. Overall, evidence suggests that weight status/weight change may not be associated with EC risk and multivitamin and folic-acid supplementation may be associated with decreased EC risk. Early-adulthood overweight/obese weight-status and adulthood weight-gain may be associated with increased CRC risk, whereas multivitamin supplementation, tea and high fruit intake, and physical activity may be associated with decreased CRC risk. Current evidence proposes that recommendations related to weight, some dietary habits, and physical activity recommended for the general public are also relevant to individuals with lynch syndrome. More research is needed, specifically prospective cohorts and randomized controlled trials, to determine if tailored recommendations are needed among individuals with lynch syndrome.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais/etiologia , Neoplasias do Endométrio/etiologia , Ingestão de Energia , Estilo de Vida , Peso Corporal , Neoplasias do Endométrio/prevenção & controle , Metabolismo Energético , Exercício Físico , Comportamento Alimentar , Feminino , Ácido Fólico/farmacologia , Humanos , Masculino , Vitaminas/farmacologia
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