RESUMO
OBJECTIVE: To investigate the association between hysterectomy with conservation of one or both adnexa and ovarian and tubal cancer. DESIGN: Prospective cohort study. SETTING: Thirteen NHS Trusts in England, Wales and Northern Ireland. POPULATION: A total of 202 506 postmenopausal women recruited between 2001 and 2005 to the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and followed up until 31 December 2014. METHODS: Multiple sources (questionnaires, hospital notes, Hospital Episodes Statistics, national cancer/death registries, ultrasound reports) were used to obtain accurate data on hysterectomy (with conservation of one or both adnexa) and outcomes censored at bilateral oophorectomy, death, ovarian/tubal cancer diagnosis, loss to follow up or 31 December 2014. Cox proportional hazards regression models were used to assess the association. MAIN OUTCOME MEASURES: Invasive epithelial ovarian and tubal cancer (WHO 2014) on independent outcome review. RESULTS: Hysterectomy with conservation of one or both adnexa was reported in 41 912 (20.7%; 41 912/202 506) women. Median follow up was 11.1 years (interquartile range 9.96-12.04), totalling >2.17 million woman-years. Among women who had undergone hysterectomy, 0.55% (231/41 912) were diagnosed with ovarian/tubal cancer, compared with 0.59% (945/160 594) of those with intact uterus. Multivariable analysis showed no evidence of an association between hysterectomy and invasive epithelial ovarian/tubal cancer (hazard ratio 0.98, 95% CI 0.85-1.13, P = 0.765). CONCLUSIONS: This large cohort study provides further independent validation that hysterectomy is not associated with alteration of invasive epithelial ovarian and tubal cancer risk. These data are important both for clinical counselling and for refining risk prediction models. TWEETABLE ABSTRACT: Hysterectomy does not alter risk of invasive epithelial ovarian and tubal cancer.
Assuntos
Carcinoma Epitelial do Ovário/mortalidade , Neoplasias das Tubas Uterinas/mortalidade , Histerectomia/estatística & dados numéricos , Neoplasias Ovarianas/mortalidade , Idoso , Carcinoma Epitelial do Ovário/cirurgia , Estudos de Coortes , Inglaterra , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Irlanda do Norte , Neoplasias Ovarianas/cirurgia , Estudos Prospectivos , Fatores de Risco , Medicina Estatal , Inquéritos e Questionários , País de GalesRESUMO
OBJECTIVE: Estrogen is a well-established risk factor for various cancers. It causes endometrial proliferation, which is assessed routinely as endometrial thickness (ET) using transvaginal ultrasound (TVS). Only one previous study, restricted to endometrial and breast cancer, has considered ET and the risk of non-endometrial cancer. The aim of this study was to explore the association between baseline and serial ET measurements and nine non-endometrial hormone-sensitive cancers, in postmenopausal women, using contemporary statistical methodology that attempts to minimize the biases typical of endogenous serial data. METHODS: This was a cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). In the ultrasound arm of UKCTOCS, 50639 postmenopausal women, aged 50-74, underwent annual TVS examination, of whom 38 105 had a valid ET measurement, no prior hysterectomy and complete covariate data, and were included in this study. All women were followed up through linkage to national cancer registries. The effect of ET on the risk of six estrogen-dependent cancers (breast, ovarian, colorectal, bladder, lung and pancreatic) was assessed using joint models for longitudinal biomarker and time-to-event data, and Cox models were used to assess the association between baseline ET measurement and these six cancers in addition to liver cancer, gastric cancer and non-Hodgkin's lymphoma (NHL). All models were adjusted for current hormone-replacement therapy (HRT) use, body mass index, age at last menstrual period, parity and oral contraceptive pill use. RESULTS: The 38 105 included women had a combined total of 267 567 (median, 8; interquartile range, 5-9) valid ET measurements. During a combined total of 407 838 (median, 10.9) years of follow-up, 1398 breast, 351 endometrial, 381 lung, 495 colorectal, 222 ovarian, 94 pancreatic, 79 bladder, 62 gastric, 38 liver cancers and 52 NHLs were registered. Using joint models, a doubling of ET increased significantly the risk of breast (hazard ratio (HR), 1.21; 95% CI, 1.09-1.36; P = 0.001), ovarian (HR, 1.39; 95% CI, 1.06-1.82; P = 0.018) and lung (HR, 1.25; 95% CI, 1.02-1.54; P = 0.036) cancers. There were no statistically significant associations between ET and the remaining six cancers. CONCLUSION: Postmenopausal women with high/increasing ET on TVS are at increased risk of breast, ovarian and lung cancer. It is important that clinicians are aware of these risks, as TVS is a common investigation. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Detecção Precoce de Câncer/métodos , Hiperplasia Endometrial/diagnóstico por imagem , Neoplasias/diagnóstico por imagem , Pós-Menopausa , Ultrassonografia/métodos , Idoso , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Hiperplasia Endometrial/complicações , Endométrio/diagnóstico por imagem , Endométrio/patologia , Estrogênios/metabolismo , Feminino , Humanos , Armazenamento e Recuperação da Informação , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/metabolismo , Pessoa de Meia-Idade , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Fatores de Risco , Reino Unido , Vagina/diagnóstico por imagemRESUMO
BACKGROUND: We investigated the association between self-reported skirt size (SS) and change in SS, and incidence of chronic liver disease (CLD) in a prospective cohort study of women recruited to the UKCTOCS trial. METHODS: Women recruited to UKCTOCS in England without documented CLD self-reported their current UK SS during trial participation and were asked to recall their SS when aged in 20s (via completion of a questionnaire 3-5 years after recruitment). Participants were followed up via electronic health record linkage and hazard ratios (HR) calculated for incident liver-related events (LRE). RESULTS: Three hundred twenty-two (0.3%) of 94,124 women experienced a first LRE. Compared to SS ≤ 16, rates of LRE were higher in the SS ≥ 18 groups (both when aged in 20s and at questionnaire completion). Event rates were higher if there was no change in SS or an increase in SS, compared to a decrease in SS. In the models adjusted for potential confounders, HRs for LRE were higher in the groups of women reporting SS ≥ 18 both when aged in 20s (HR = 1.39 (95% CI; 0.87-2.23)) and at questionnaire completion (HR = 1.37 (95% CI; 1.07-1.75)). Compared to a decrease in SS, HRs were higher in the no change (HR = 1.78 (95% CI; 0.95-3.34)) and increase (HR = 1.80 (95% CI; 1.01-3.21)) groups. CONCLUSION: CLD is associated with high SS and an increase in SS over time. These data suggest SS can be used in simple public health messages about communicating the risk of liver disease. TRIAL REGISTRATION: UKCTOCS is registered as an International Standard Randomised Controlled Trial, number ISRCTN22488978 . Registered 06/04/2000.
Assuntos
Hepatopatias/epidemiologia , Pós-Menopausa , Circunferência da Cintura , Idoso , Doença Crônica , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Estudos Prospectivos , Autorrelato , Reino Unido/epidemiologiaRESUMO
OBJECTIVES: The negative publicity about menopausal hormone therapy (MHT) has led to increased use of complementary and alternative medicines (CAM) and non-pharmacological interventions (NPI) for menopausal symptom relief. We report on the prevalence and predictors of CAM/NPI among UK postmenopausal women. METHOD: Postmenopausal women aged 50-74 years were invited to participate in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). A total of 202 638 women were recruited and completed a baseline questionnaire. Of these, 136 020 were sent a postal follow-up-questionnaire between September 2006 and May 2009 which included ever-use of CAM/NPI for menopausal symptom relief. Both questionnaires included MHT use. RESULTS: A total of 88 430 (65.0%) women returned a completed follow-up-questionnaire; 22 206 (25.1%) reported ever-use of one or more CAM/NPI. Highest use was reported for herbal therapies (43.8%; 9725/22 206), vitamins (42.6%; 9458/22 206), lifestyle approaches (32.1%; 7137/22 206) and phytoestrogens (21.6%; 4802/22 206). Older women reported less ever-use of herbal therapies, vitamins and phytoestrogens. Lifestyle approaches, aromatherapy/reflexology/acupuncture and homeopathy were similar across age groups. Higher education, Black ethnicity, MHT or previous oral contraceptive pill use were associated with higher CAM/NPI use. Women assessed as being less hopeful about their future were less likely to use CAM/NPI. CONCLUSION: One in four postmenopausal women reported ever-use of CAM therapies/NPI for menopausal symptom relief, with lower use reported by older women. Higher levels of education and previous MHT use were positive predictors of CAM/NPI use. UKCTOCS Trial registration: ISRCTN22488978.
Assuntos
Terapias Complementares/estatística & dados numéricos , Terapia de Reposição de Estrogênios/estatística & dados numéricos , Fogachos/terapia , Menopausa/psicologia , Neoplasias Ovarianas/epidemiologia , Idoso , Feminino , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Neoplasias Ovarianas/prevenção & controle , Valor Preditivo dos Testes , Prevalência , Medicina Estatal , Inquéritos e Questionários , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Blood-borne biomarkers for early detection of colorectal cancer (CRC) could markedly increase screening uptake. The aim of this study was to evaluate serum carcinoembryonic antigen (CEA), CYFRA21-1 and CA125 for the early detection of CRC in an asymptomatic cohort. METHODS: This nested case-control study within UKCTOCS used 381 serial serum samples from 40 women subsequently diagnosed with CRC, 20 women subsequently diagnosed with benign disease and 40 matched non-cancer controls with three to four samples per subject taken annually up to 4 years before diagnosis. CEA, CYFRA21-1 and CA125 were measured using validated assays and performance of markers evaluated for different pre-diagnosis time groups. RESULTS: CEA levels increased towards diagnosis in a third of all cases (half of late-stage cases), whereas longitudinal profiles were static in both benign and non-cancer controls. At a threshold of >5 ng ml(-1) the sensitivities for detecting CRC up to 1 and 4 years before clinical presentation were 25% and 13%, respectively, at 95% specificity. At a threshold of >2.5 ng ml(-1), sensitivities were 57.5% and 38.4%, respectively, with specificities of 81% and 83.5%. CYFRA21-1 and CA125 had no utility as screening markers and did not enhance CEA performance when used in combination. CEA gave average lead times of 17-24 months for test-positive cases. CONCLUSIONS: CEA is elevated in a significant proportion of individuals with preclinical CRC, but would not be useful alone as a screening tool. This work sets a baseline from which to develop panels of biomarkers which combine CEA for improved early detection of CRC.
Assuntos
Antígenos de Neoplasias/sangue , Antígeno Ca-125/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Detecção Precoce de Câncer , Queratina-19/sangue , Adulto , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/diagnóstico , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-IdadeRESUMO
Circulating intercellular adhesion molecule-1 (ICAM-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) have been widely proposed as potential diagnostic biomarkers for pancreatic ductal adenocarcinoma (PDAC). We report on serum protein levels prior to clinical presentation of pancreatic cancer. Serum ICAM-1 and TIMP-1 were measured by ELISA in two casecontrol sets: 1) samples from patients diagnosed with pancreatic cancer (n = 40), chronic pancreatitis (n = 20), benign jaundice due to gall stones (n = 20) and healthy subjects (n = 20); 2) a preclinical set from the UK Collaborative Trial of Ovarian Cancer Screening biobank of samples collected from 27 post-menopausal women 012 months prior to diagnosis of pancreatic cancer and controls matched for date of donation and centre. Levels of ICAM-1 and TIMP-1 were significantly elevated in set 1 in PDAC patients with jaundice compared to PDAC patients without jaundice and both proteins were elevated in patients with jaundice due to gall stones. Neither protein was elevated in samples taken 012 months prior to PDAC diagnosis compared to non-cancer control samples. In conclusion, evaluation in pre-diagnosis samples discounts ICAM-1 and TIMP-1 as biomarkers for earlier diagnosis of pancreatic cancer. Failure to account for obstructive jaundice may have contributed to the previous promise of these candidate biomarkers. BIOLOGICAL SIGNIFICANCE: Pancreatic cancer is usually diagnosed when at an advanced stage which greatly limits therapeutic options. Biomarkers that could facilitate earlier diagnosis are urgently sought.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático , Molécula 1 de Adesão Intercelular/sangue , Neoplasias Pancreáticas , Inibidor Tecidual de Metaloproteinase-1/sangue , Adulto , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/diagnóstico , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnósticoRESUMO
BACKGROUND: It has been suggested that lower UK cancer survival may be due to incomplete case ascertainment by cancer registries. METHODS: We assessed concordance between self-reported breast, bowel and lung cancer and cancer registration (CR) for 1995-2007 in England and Wales in the UK Collaborative Trial of Ovarian Cancer Screening. RESULTS: Concordance of breast cancer CR was higher (94.7%:95% CI: 94.1-95.3%) than for bowel (85.1%:95% CI: 82.1-87.8%) and lung (85.4%:95% CI: 76.3-92.0%). CR concordance was lower in breast cancer (94.5% vs 98.8%) survivors compared with deceased but the difference was small. No difference was found for bowel (85.3% vs 94.6%) or lung (87.1% vs 90.5%) cancer. CONCLUSION: Concordance of CR and self-reported cancer is high. Incomplete registration is unlikely to be a major cause of lower UK survival rates.
Assuntos
Neoplasias da Mama/epidemiologia , Detecção Precoce de Câncer/estatística & dados numéricos , Neoplasias Intestinais/epidemiologia , Neoplasias Pulmonares/epidemiologia , Sistema de Registros/normas , Autorrelato , Idoso , Estudos de Coortes , Inglaterra/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , País de Gales/epidemiologiaRESUMO
OBJECTIVE: To estimate the risk of primary epithelial ovarian cancer (EOC) and slow growing borderline or Type I and aggressive Type II EOC in postmenopausal women with adnexal abnormalities on ultrasound. METHODS: This was a prospective cohort study in the ultrasound group of the UK Collaborative Trial of Ovarian Cancer Screening of postmenopausal women with ultrasound-detected abnormal adnexal (unilocular, multilocular, unilocular solid and multilocular solid, solid) morphology on their first scan. Women were followed up through the national cancer registries and by postal questionnaires. Absolute risks of EOC and borderline, Type I and Type II EOC within 3 years of initial scan were calculated. RESULTS: Of 48 053 women who underwent ultrasound examination and had complete scan data, 4367 (9.1% (95% CI, 8.8-9.3%)) had abnormal adnexal morphology. Median follow-up was 7.09 (25(th) -75(th) centiles, 6.03-7.92) years. Forty-seven (32 borderline or Type I, 15 Type II) were diagnosed with EOC. The overall absolute risk of EOC associated with abnormal adnexal morphology was 1.08% (95% CI, 0.79-1.43%); for borderline and Type I it was 0.73% (95% CI, 0.5-1.03%); and for Type II it was 0.34% (95% CI, 0.33-0.79%). In the subgroup (n = 741) with solid elements (unilocular solid, multilocular solid and solid) overall absolute risk was 4.45% (95% CI, 3.08-6.20%), for borderline and Type I it was 3.1% (95% CI, 1.9-4.6%) and for Type II it was 1.3% (95% CI, 0.6-2.4%). 11 982 women had both ovaries visualized and normal annual scans throughout the 3-year follow-up period. In this group, no borderline or Type I and eight Type II cancers were diagnosed. CONCLUSION: Asymptomatic postmenopausal women with ultrasound-detected adnexal abnormalities with solid elements have a 1 in 22 risk for EOC. Despite the higher prevalence of Type II EOC, the risk of borderline or Type I cancer in women with ultrasound abnormalities seems to be higher than does the risk of Type II cancer. This has important immediate implications for patients with incidental adnexal findings as well as for any future ultrasound-based screening.
Assuntos
Anexos Uterinos/anormalidades , Anexos Uterinos/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Neoplasias Epiteliais e Glandulares/epidemiologia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/epidemiologia , Ovário/diagnóstico por imagem , Idoso , Carcinoma Epitelial do Ovário , Estudos de Coortes , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Prevalência , Estudos Prospectivos , Fatores de Risco , Ultrassonografia , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Oestrogens play a crucial role in breast carcinogenesis. Earlier studies have analysed the serum levels of endogenous hormones measured by conventional assays. In this study, we analysed the capacity of serum from breast cancer cases and controls to transactivate the oestrogen receptor alpha (ER-alpha) and beta (ER-beta). METHODS: We used a receptor oestrogen-responsive element (ERE) -- the green fluorescent protein (GFP)-reporter test system in Saccharomyces cerevisiae. Oestrogen receptor-alpha or ER-beta bioactivity was determined in serum from 182 randomly chosen postmenopausal women with breast cancer and from 188 age-matched controls. RESULTS: High serum ER-alpha and ER-beta bioactivity were independently associated with the presence of breast cancer. Women whose levels of serum ER-alpha and ER-beta bioactivity were in the highest quintile among controls had a 7.57-(95% confidence interval (CI): 2.46-23.32; P=0.0004) and a 10.14 (95% CI: 3.19-32.23; P<0.0001)-fold risk for general and oestrogen receptor-positive breast cancer, respectively. CONCLUSION: The use of serum ER-alpha and ER-beta bioactivity assays as clinical tools in the management of breast cancer warrants further research. Future studies will dictate whether surrogate markers of ER-alpha and ER-beta bioactivity will provide a means to monitor the efficacy of anti-endocrine, adjuvant and chemopreventive strategies.
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Neoplasias da Mama/sangue , Receptor alfa de Estrogênio/sangue , Receptor beta de Estrogênio/sangue , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Estudos de Casos e Controles , Estradiol/sangue , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Valor Preditivo dos Testes , Elementos de Resposta , Fatores de Risco , Ativação TranscricionalRESUMO
Genomic imprinting is limited to a subset of genes that play critical roles in fetal growth, development and behaviour. One of the most studied imprinted genes encodes insulin-like growth factor 2, and aberrant imprinting and DNA methylation of this gene is associated with the growth disorders Beckwith-Wiedemann and Silver-Russell syndromes and many human cancers. Specific isoforms of this gene have been shown to be essential for normal placental function, as mice carrying paternal null alleles for the Igf2-P0 transcript are growth restricted at birth. We report here the identification of three novel human transcripts from the IGF2 locus. One is equivalent to the mouse Igf2-P0 transcript, whereas the two others (INSIGF long and short) originate from the upstream INS gene that alternatively splices to downstream IGF2 exons. In order to elucidate the molecular mechanisms involved in the complex imprinting of these novel IGF2 transcripts, both the allele-specific expression and methylation for all the IGF2 promoters including P0 and the INSIGF transcripts were analysed in human tissues. Similar to the mouse, the human IGF2-P0 transcript is paternally expressed; however, its expression is not limited to placenta. This expression correlates with tissue-specific promoter methylation on the maternal allele. The two novel INSIGF transcripts reported here use the INS promoter and show highly restricted tissue expression profiles including the pancreas. As previously reported for INS in the yolk sac, we demonstrate complex, tissue-specific imprinting of these transcripts. The finding of additional transcripts within this locus will have important implications for IGF2 regulation in both cancer and metabolism.