| 1. |
- Collins, Elin, et al.
(författare)
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Menopausal symptoms and surgical complications after opportunistic bilateral salpingectomy, a register-based cohort study
- 2019
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Ingår i: Am J Obstet Gynecol. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 220:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In recent years, the fallopian tubes have been found to play a critical role in the pathogenesis of ovarian cancer. Therefore, bilateral salpingectomy at the time of hysterectomy has been proposed as a preventive procedure, but with scarce scientific evidence to support the efficiency and safety. OBJECTIVE: Our primary objective was to evaluate the risk of surgical complications and menopausal symptoms when performing bilateral salpingectomy in addition to benign hysterectomy. Furthermore, we sought to compare time in surgery, perioperative blood loss/blood transfusion, duration of hospital stay, days to normal activities of daily living, and days out of work for hysterectomy with bilateral salpingectomy compared with hysterectomy only. A secondary objective was to study the uptake of opportunistic salpingectomy in Sweden. STUDY DESIGN: This was a retrospective observational cohort study based on data from the National Quality Register of Gynecological Surgery in Sweden. Women <55 years of age who had a hysterectomy for benign indications with or without bilateral salpingectomy in 1998 through 2016 were included. Possible confounding was adjusted for in multivariable regression models. RESULTS: During the study period, 23,369 women had a hysterectomy for benign indications. The frequency of bilateral salpingectomy at the time of hysterectomy increased mainly from 2013, which is why the period 2013 through mid-2016 was selected for further analysis (n = 6892). There was a low frequency of vaginal hysterectomy with bilateral salpingectomy performed in this period, which is why only abdominal and laparoscopic surgeries were selected for comparative analysis (n = 4906). This study indicates an increased risk of menopausal symptoms (adjusted relative risk, 1.33; 95% confidence interval, 1.04-1.69) 1 year after hysterectomy with bilateral salpingectomy compared with hysterectomy only. Hospital stay was 0.1 days longer in women having salpingectomy (P = .01), and bleeding was slightly reduced in the salpingectomy group (-20 mL, P = .04). Other outcome measures were not significantly associated with salpingectomy, albeit a tendency toward higher risk of minor complications was seen (adjusted relative risk, 1.30; 95% confidence interval, 0.93-1.83). CONCLUSION: Bilateral salpingectomy at the time of hysterectomy was associated with an increased risk of menopausal symptoms 1 year after surgery. Randomized clinical trials reducing the risk of residual and unmeasured confounding and longer follow-up are needed to correctly inform women on the risks and benefits of opportunistic salpingectomy.
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| 2. |
- Collins, Elin, et al.
(författare)
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Physicians' assessment of complications after gynecological surgery in Sweden : The GYNCOM survey
- 2023
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 102:11, s. 1479-1487
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Complications after gynecological surgery in Sweden are registered in the well-established Swedish National Quality Register of Gynecological Surgery, GynOp. The aim of this study was to analyze interrater reliability in assessing complications according to the methods in GynOp, and to explore physicians' perceptions of registering complications.Material and methods: A digital survey was sent to gynecologists and residents in gynecology in Sweden. Participating clinics were recruited through the Swedish network for national clinical studies in Obstetrics and Gynecology, SNAKS. Twenty fictional cases, intended to represent normal postoperative course, failure to cure, and varying degrees of complications, were developed by the research group. The clinical scenarios included abdominal and laparoscopic surgery of the uterus and adnexa, vaginal hysterectomies, as well as hysteroscopy. The respondents graded each case on the presence of a complication (yes/no). Type of complication, severity, and what action the complication required according to Clavien-Dindo was registered if a complication was acknowledged, according to the method in GynOp. Interrater reliability and the opinions of the respondents were presented descriptively. More than 80% of respondents making the same assessment was considered as agreement.Results: The response rate was 41%, with 104 responding physicians from 16 gynecological clinics. Type and severity of complication was considered relevant to register by 88% and 89% of respondents, respectively. Agreement on whether the case described a complication was >80% in 85% (17/20) of cases and agreement using the Clavien-Dindo classification was >90% in 80% (16/20) of cases. There was high agreement in assessments of classically severe complications, such as pulmonary embolism and ureteral damage, in both presence of complication and severity, as well as Clavien-Dindo (>90% for all methods). Cases with agreement <80% on whether the case described a complication were bordering between normal postoperative course and minor complication.Conclusions: This study provides validation for the methods used to register complications after gynecological surgery according to the GynOp register, including the use of Clavien-Dindo in gynecology. However, the results indicate a need to define what should be considered symptoms inherent to each type of surgery.
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| 3. |
- Idahl, Annika, 1965-, et al.
(författare)
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HOPPSA update: changes in the study protocol of Hysterectomy and OPPortunistic SAlpingectomy, a registry-based randomized controlled trial
- 2023
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The HOPPSA trial is a multi-center national registry-based randomized controlled trial to test the safety and effectiveness of performing opportunistic salpingectomy at hysterectomy to reduce the risk of epithelial ovarian cancer (EOC). The study protocol was first published in January 2019 and is available at . Here, we report amendments made to the study protocol since commencement of the trial.Changes in methods and analysis The primary outcomes analyses have been changed. (1) Complications will be analyzed using binomial generalized estimating equation (GEE) with log link function, while the unadjusted analyses according to Miettinen and Nurminen will be performed as a sensitivity analysis. (2) Absolute change in Menopause Rating Scale (MRS) will primarily be analyzed using a mixed effects model, adjusted for baseline MRS and center as a random effect. (3) Time to EOC will be analyzed using the mixed effects Cox regression model with center as random effect, while the unadjusted log-rank test will be performed as a sensitivity analysis.The primary outcome Complications will be based solely on the specific assessment in the GynOp quality registry. The Clavien-Dindo classification will be evaluated as a secondary outcome.Furthermore, MRS is also measured three years postoperatively to better pinpoint the onset of menopausal symptoms.Discussion The changes to the protocol mainly concern the analyses of data. No changes to recruitment, randomization, intervention, or follow-up of primary outcomes have been made. An interim analysis during 2021 concluded that the study should continue until the target sample size is reached.
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| 4. |
- Idahl, Annika, 1965-, et al.
(författare)
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Hysterectomy and opportunistic salpingectomy (HOPPSA): study protocol for a register-based randomized controlled trial
- 2019
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThere is a great need for a prospective randomized trial to evaluate the risks and benefits of opportunistic salpingectomy. Recently, genetic and morphologic studies have indicated that epithelial ovarian cancer predominantly develops in the Fallopian tubes. Consequently, there is reason to believe that salpingectomy would reduce the risk of ovarian cancer. Studies on reducing the risk of ovarian cancer have compared indicated salpingectomy with no salpingectomy, while studies on surgical safety as well as ovarian function after opportunistic salpingectomy have been small with a short follow-up. No study has reported menopausal symptoms.Methods/designIn this national register-based randomized controlled trial, women <55years old, planned for a hysterectomy for a benign cause, will be randomized to concomitant salpingectomy or no salpingectomy. The follow-up will be conducted according to already established routines within the register using on-line questionnaires. Primary outcomes have been defined for three different time points: short-term complications up to 8 weeks postoperatively (n=2800), intermediate-term changes in menopausal symptoms measured by the Menopause Rating Scale at baseline and after 1 year (n=1670), and long-term epithelial ovarian cancer assessed through national registers after 30years (n=5052) (or n=7001 for high-grade serous cancer). In a sub-study of 75 women, ovarian function will be evaluated through change in anti-Mullerian hormone measured before surgery and after 1 year.DiscussionHysterectomy for a benign cause is a common surgical procedure and several national societies recommend salpingectomy while performing a benign hysterectomy, despite a lack of scientific evidence for the safety of the procedure. Sweden has unique conditions for clinical trials because of its national quality registers and health registers with excellent quality and near complete coverage. If no additional risks are associated with concomitant salpingectomy, it can be recommended at the time of benign hysterectomy to reduce the risk of epithelial ovarian cancer. If not, the risks and benefits must be balanced. The results of this study will be important for informing women undergoing a benign hysterectomy.Trial registrationClinicalTrials.gov, NCT03045965. Registered on 8 February 2017.
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| 5. |
- Magarakis, Leonidas, et al.
(författare)
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Efficacy and safety of sterilisation procedures to reduce the risk of epithelial ovarian cancer: a systematic review comparing salpingectomy with tubal ligation
- 2022
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Ingår i: European Journal of Contraception and Reproductive Health Care. - : Informa UK Limited. - 1362-5187 .- 1473-0782. ; 27:3, s. 230-239
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Forskningsöversikt (refereegranskat)abstract
- Purpose: The objective of this systematic review is to evaluate current literature comparing salpingectomy for sterilisation with tubal ligation, regarding the effectiveness and safety, and assess the certainty of evidence. Materials and methods: PubMed, Cochrane, and Embase databases were searched. Randomised (RCT) and observational studies were included. Articles were quality assessed and data extracted by two independent authors. Certainty of evidence was assessed using GRADE. Results: Of 2020 articles, 17 were included. No study investigated the risk of EOC. No difference in anti-Müllerian hormone was reported in one RCT at caesarean section (CS). Two cohort studies evaluated ovarian function with surrogate measures and found no difference at caesarean section. Complications did not differ but were inconsistently reported. Laparoscopic tubal ligation was 7 min faster (95% CI 3.8–10.5). Operative time at caesarean section was dependent on the use of surgical devices. Certainty of evidence was low or very low for all estimates, indicating knowledge gaps. Reliable safety data on salpingectomy for sterilisation is lacking, and there is no effectiveness data. Presently, women cannot be properly counselled regarding salpingectomy for sterilisation.
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| 6. |
- Magarakis, Leonidas, et al.
(författare)
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SALpingectomy for STERilisation (SALSTER): study protocol for a Swedish multicentre register-based randomised controlled trial.
- 2023
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Ingår i: BMJ open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- Salpingectomy is currently suggested as an alternative to tubal ligation for sterilisation. Precursor lesions of ovarian carcinoma can be found in the fallopian tubes; thus, salpingectomy could possibly reduce the incidence. Most of the existing trials on safety are small, on caesarean section and report on surrogate ovarian function measures. Randomised trials in laparoscopy are lacking. Well-designed trials are needed to evaluate safety of laparoscopic opportunistic salpingectomy.In SALSTER, a national register-based randomised controlled non-inferiority trial, 968women <50 years, wishing laparoscopic sterilisation will be randomised to either salpingectomy or tubal ligation. The Swedish National Quality Register of Gynecological Surgery (GynOp) will be used for inclusion, randomisation and follow-up. Primary outcomes are any complication up to 8weeks postoperatively, and age at menopause. Both outcomes are measured with questionnaires, complications are also assessed by a gynaecologist. In a nested trial, ovarian function will be evaluated comparing the mean difference of anti-Müllerian hormone (AMH), assessed preoperatively and 1year after surgery.Performing salpingectomy for sterilisation has become increasingly common, despite the unclear risk-benefit balance. SALSTER studies the safety of salpingectomy compared with tubal ligation. Regardless of the result, SALSTER will provide gynaecologists with high quality evidence to inform women to decide on salpingectomy or not. The central ethical review board of Gothenburg, Sweden (Dnr. 316-18) approved the trial in 2018. Results will be presented at scientific congresses and published in peer-reviewed scientific journals. The results will be communicated through professional organisations and research networks.NCT03860805.
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| 7. |
- Merritt, Melissa A., et al.
(författare)
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Dietary fat intake and risk of epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition
- 2014
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Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 38:5, s. 528-537
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Tidskriftsartikel (refereegranskat)abstract
- There are inconsistent and limited data available to assess the relationship between fat intake and risk of epithelial ovarian cancer (EOC). We examined the consumption of total fat, fat sources and fat subtypes in relation to risk of EOC and its major histologic subtypes in the European Prospective Investigation into Cancer and Nutrition which includes incident invasive (n = 1095) and borderline (n = 96) EOC. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In multivariate models, we observed no association with consumption of total fat, animal or plant fat, saturated fat, cholesterol, monounsaturated fat, or fatty fish and risk of invasive EOC. There was, however, an increased risk of invasive EOC in the highest category of intake (Quartile 4 vs. Quartile 1) of polyunsaturated fat (HR = 1.22, 95% CI = 1.02-1.48, P-trend = 0.02). We did not observe heterogeneity in the risk associations in comparisons of serous and endometrioid histologic subtypes. This study does not support an etiological role for total fat intake in relation to EOC risk; however, based on observations of a positive association between intake of polyunsaturated fat and invasive EOC risk in the current and previous studies, this fat subtype warrants further investigation to determine its potential role in EOC development.
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| 8. |
- Roura, Esther, et al.
(författare)
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The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC).
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| 9. |
- Strandell, Annika, et al.
(författare)
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Evidensbaserad gynekologi
- 2022. - 3
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Ingår i: Gynekologi. - Lund : Studentlitteratur AB. - 9789144144191 ; , s. 109-123
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Besevic, Jelena, et al.
(författare)
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Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study
- 2015
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 113:11, s. 1622-1631
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521 330 total participants (approximately 370 000 women) aged 25-70 years at recruitment from 1992 to 2000. Methods: Information on reproductive characteristics was collected at recruitment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multivariable models were adjusted for age and year of diagnosis, body mass index, tumour stage, smoking status and stratified by study centre. Results: After a mean follow-up of 3.6 years (+/- 3.2 s.d.) following EOC diagnosis, 511 (49.9%) of the 1025 women died from EOC. We observed a suggestive survival advantage in menopausal hormone therapy (MHT) users (ever vs never use, HR = 0.80, 95% CI = 0.62-1.03) and a significant survival benefit in long-term MHT users (>= 5 years use vs never use, HR = 0.70, 95% CI = 0.50-0.99, P-trend = 0.04). We observed similar results for MHT use when restricting to serous cases. Other reproductive factors, including parity, breastfeeding, oral contraceptive use and age at menarche or menopause, were not associated with EOC-specific mortality risk. Conclusions: Further studies are warranted to investigate the possible improvement in EOC survival in MHT users.
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| 11. |
- Braem, Marieke G. M., et al.
(författare)
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Coffee and tea consumption and the risk of ovarian cancer : a prospective cohort study and updated meta-analysis
- 2012
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Ingår i: American Journal of Clinical Nutrition. - Bethesda : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 95:5, s. 1172-1181
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2007 the World Cancer Research Fund Report concluded that there was limited and inconsistent evidence for an effect of coffee and tea consumption on the risk of epithelial ovarian cancer (EOC). Objective: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we aimed to investigate whether coffee intakes, tea intakes, or both are associated with the risk of EOC. Design: All women participating in the EPIC (n = 330,849) were included in this study. Data on coffee and tea consumption were collected through validated food-frequency questionnaires at baseline. HRs and 95% CIs were estimated by using Cox proportional hazards models. Furthermore, we performed an updated meta-analysis of all previous prospective studies until April 2011 by comparing the highest and lowest coffee- and tea-consumption categories as well as by using dose-response random-effects meta-regression analyses. Results: During a median follow-up of 11.7 y, 1244 women developed EOC. No association was observed between the risk of EOC and coffee consumption [HR: 1.05 (95% CI: 0.75, 1.46) for the top quintile compared with no intake] or tea consumption [HR: 1.07 (95% Cl: 0.78, 1.45) for the top quintile compared with no intake]. This lack of association between coffee and tea intake and EOC risk was confirmed by the results of our meta-analysis. Conclusion: Epidemiologic studies do not provide sufficient evidence to support an association between coffee and tea consumption and risk of ovarian cancer. Am J Clin Nutr 2012;95:1172-81.
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| 12. |
- Braem, Marieke G. M., et al.
(författare)
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Multiple Miscarriages Are Associated with the Risk of Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR >= 4vs.0: 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR >= 4vs.0: 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR >= 4vs.0: 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.
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| 13. |
- Broeze, KA, et al.
(författare)
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Chlamydia antibody testing and diagnosing tubal pathology in subfertile women : an individual patient data meta-analysis
- 2011
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Ingår i: Human Reproduction Update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 17:3, s. 301-310
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The Chlamydia IgG antibody test (CAT) shows considerable variations in reported estimates of test accuracy, partly because of the use of different assays and cut-off values. The aim of this study was to reassess the accuracy of CAT in diagnosing tubal pathology by individual patient data (IPD) meta-analysis for three different CAT assays. METHODS We approached authors of primary studies that used micro-immunofluorescence tests (MIF), immunofluorescence tests (IF) or enzyme-linked immunosorbent assay tests (ELISA). Using the obtained IPD, we performed pooled receiver operator characteristics analysis and logistic regression analysis with a random effects model to compare the three assays. Tubal pathology was defined as either any tubal obstruction or bilateral tubal obstruction. RESULTS We acquired data of 14 primary studies containing data of 6191 women, of which data of 3453 women were available for analysis. The areas under the curve for ELISA, IF and MIF were 0.64, 0.65 and 0.75, respectively (P-value < 0.001) for any tubal pathology and 0.66, 0.66 and 0.77, respectively (P-value = 0.01) for bilateral tubal pathology. CONCLUSIONS In Chlamydia antibody testing, MIF is superior in the assessment of tubal pathology. In the initial screen for tubal pathology MIF should therefore be the test of first choice.
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| 14. |
- Chen, Dan, et al.
(författare)
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A variant upstream of HLA-DRB1 and multiple variants in MICA influence susceptibility to cervical cancer in a Swedish population
- 2014
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 3:1, s. 190-198
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Tidskriftsartikel (refereegranskat)abstract
- In a genome-wide association study, we have previously identified and performed the initial replication of three novel susceptibility loci for cervical cancer: rs9272143 upstream of HLA-DRB1, rs2516448 adjacent to MHC class I polypeptide-related sequence A gene (MICA), and rs3117027 at HLA-DPB2. The risk allele T of rs2516448 is in perfect linkage disequilibrium with a frameshift mutation (A5.1) in MICA exon 5, which results in a truncated protein. To validate these associations in an independent study and extend our prior work to MICA exon 5, we genotyped the single-nucleotide polymorphisms at rs9272143, rs2516448, rs3117027 and the MICA exon 5 microsatellite in a nested case–control study of 961 cervical cancer patients (827 carcinoma in situ and 134 invasive carcinoma) and 1725 controls from northern Sweden. The C allele of rs9272143 conferred protection against cervical cancer (odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.65–0.82; P = 1.6 × 10−7), which is associated with higher expression level of HLA-DRB1, whereas the T allele of rs2516448 increased the susceptibility to cervical cancer (OR = 1.33, 95% CI = 1.19–1.49; P = 5.8 × 10−7), with the same association shown with MICA-A5.1. The direction and the magnitude of these associations were consistent with our previous findings. We also identified protective effects of the MICA-A4 (OR = 0.80, 95% CI = 0.68–0.94; P = 6.7 × 10−3) and MICA-A5 (OR = 0.60, 95% CI = 0.50–0.72; P = 3.0 × 10−8) alleles. The associations with these variants are unlikely to be driven by the nearby human leukocyte antigen (HLA) alleles. No association was observed between rs3117027 and risk of cervical cancer. Our results support the role of HLA-DRB1 and MICA in the pathogenesis of cervical cancer.
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| 15. |
- Clendenen, Tess V, et al.
(författare)
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Circulating inflammation markers and risk of epithelial ovarian cancer.
- 2011
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:5, s. 799-810
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Tidskriftsartikel (refereegranskat)abstract
- Background: Factors contributing to chronic inflammation appear to be associated with increased risk of ovarian cancer. The purpose of this study was to assess the association between circulating levels of inflammation mediators and subsequent risk of ovarian cancer. Methods: We conducted a case-control study of 230 cases and 432 individually matched controls nested within three prospective cohorts to evaluate the association of prediagnostic circulating levels of inflammation-related biomarkers (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFα, IL-1Ra, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1, and sTNF-R2) measured using Luminex xMap technology with risk of ovarian cancer. Results: We observed a trend across quartiles for IL-2 (ORQ4 vs. Q1: 1.57, 95% CI: 0.98–2.52, P = 0.07), IL-4 (ORQ4 vs. Q1: 1.50, 95% CI: 0.95–2.38, P = 0.06), IL-6 (ORQ4 vs. Q1: 1.63, 95% CI: 1.03–2.58, P = 0.03), IL-12p40 (ORQ4 vs. Q1: 1.60, 95% CI: 1.02–2.51, P = 0.06), and IL-13 (ORQ4 vs. Q1: 1.42, 95% CI: 0.90–2.26, P = 0.11). Trends were also observed when cytokines were modeled on the continuous scale for IL-4 (P trend = 0.01), IL-6 (P trend = 0.01), IL-12p40 (P trend = 0.01), and IL-13 (P trend = 0.04). ORs were not materially different after excluding cases diagnosed less than 5 years after blood donation or when limited to serous tumors. Conclusions and Impact: This study provides the first direct evidence that multiple inflammation markers, specifically IL-2, IL-4, IL-6, IL-12, and IL-13, may be associated with risk of epithelial ovarian cancer, and adds to the evidence that inflammation is involved in the development of this disease.
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| 16. |
- Clendenen, Tess V., et al.
(författare)
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Circulating prolactin levels and risk of epithelial ovarian cancer
- 2013
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Ingår i: Cancer Causes and Control. - : Springer Netherlands. - 0957-5243 .- 1573-7225. ; 24:4, s. 741-748
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Tidskriftsartikel (refereegranskat)abstract
- Indirect evidence from experimental and epidemiological studies suggests that prolactin may be involved in ovarian cancer development. However, the relationship between circulating prolactin levels and risk of ovarian cancer is unknown.We conducted a nested case-control study of 230 cases and 432 individually matched controls within three prospective cohorts to evaluate whether pre-diagnostic circulating prolactin is associated with subsequent risk of ovarian cancer. We also assessed whether lifestyle and reproductive factors are associated with circulating prolactin among controls.Prolactin levels were significantly lower among post- versus pre-menopausal women, parous versus nulliparous women, and past versus never users of oral contraceptives in our cross-sectional analysis of controls. In our nested case-control study, we observed a non-significant positive association between circulating prolactin and ovarian cancer risk (ORQ4vsQ1 1.56, 95 % CI 0.94, 2.63, p trend 0.15). Our findings were similar in multivariate-adjusted models and in the subgroup of women who donated blood a parts per thousand yen5 years prior to diagnosis. We observed a significant positive association between prolactin and risk for the subgroup of women with BMI a parts per thousand yen25 kg/m(2) (ORQ4vsQ1 3.10, 95 % CI 1.39, 6.90), but not for women with BMI < 25 kg/m(2) (ORQ4vsQ1 0.81, 95 % CI 0.40, 1.64).Our findings suggest that prolactin may be associated with increased risk of ovarian cancer, particularly in overweight/obese women. Factors associated with reduced risk of ovarian cancer, such as parity and use of oral contraceptives, were associated with lower prolactin levels, which suggests that modulation of prolactin may be a mechanism underlying their association with risk.
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| 17. |
- Clendenen, Tess V, et al.
(författare)
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Factors associated with inflammation markers, a cross-sectional analysis
- 2011
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Ingår i: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 56:3, s. 769-778
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological studies have reported associations between circulating inflammation markers and risk of chronic diseases. It is of interest to examine whether risk factors for these diseases are associated with inflammation. We conducted a cross-sectional analysis to evaluate whether reproductive and lifestyle factors and circulating vitamin D were associated with inflammation markers, including C-reactive protein, cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFα), and cytokine modulators (IL-1RA, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1/R2), among 616 healthy women. We confirmed associations of several inflammation markers with age and BMI. We also observed significantly higher levels of certain inflammation markers in postmenopausal vs. premenopausal women (TNFα, sIL-1RII, sIL-2Ra), with increasing parity (IL-12p40), and with higher circulating 25(OH) vitamin D (IL-13) and lower levels among current users of non-steroidal anti-inflammatory drugs (NSAIDs) (IL-1β, IL-2, IL-10, IL-12p70, and IL-12p40), current smokers (IL-4, IL-13, IL-12p40), and women with a family history of breast or ovarian cancer (IL-4, IL-10, IL-13). Our findings suggest that risk factors for chronic diseases (age, BMI, menopausal status, parity, NSAID use, family history of breast and ovarian cancer, and smoking) are associated with inflammation markers in healthy women.
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| 18. |
- Clendenen, Tess V., et al.
(författare)
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Premenopausal Circulating Androgens and Risk of Endometrial Cancer : results of a Prospective Study
- 2016
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Ingår i: Hormones & cancer. - : Springer Science and Business Media LLC. - 1868-8500 .- 1868-8500 .- 1868-8497. ; 7:3, s. 178-187
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Tidskriftsartikel (refereegranskat)abstract
- Endometrial cancer risk is increased by estrogens unopposed by progesterone. In premenopausal women, androgen excess is often associated with progesterone insufficiency, suggesting that premenopausal androgen concentrations may be associated with risk. In a case-control study nested within three cohorts, we assessed the relationship between premenopausal androgens and risk of endometrial cancer (161 cases and 303 controls matched on age and date of blood donation). Testosterone, DHEAS, androstenedione, and SHBG were measured in serum or plasma. Free testosterone was calculated from testosterone and SHBG. We observed trends of increasing risk across tertiles of testosterone (ORT3-T1 = 1.59, 95 % CI = 0.96, 2.64, p = 0.08) and free testosterone (ORT3-T1 = 1.76, 95 % CI = 1.01, 3.07, p = 0.047), which were not statistically significant after adjustment for body mass index (BMI). There was no association for DHEAS, androstenedione, or SHBG. There were significant interactions by age at diagnosis (<55 years, n = 51 cases; ≥55 years, n = 110 cases). Among women who were ≥55 years of age (predominantly postmenopausal) at diagnosis, the BMI-adjusted OR was 2.08 (95 % CI = 1.25, 3.44, p = 0.005) for a doubling in testosterone and 1.55 (95 % CI = 1.04, 2.31, p = 0.049) for a doubling in free testosterone. There was no association among women aged <55 years at diagnosis, consistent with the only other prospective study to date. If pre- and post-menopausal concentrations of androgens are correlated, our observation of an association of premenopausal androgens with risk among women aged ≥55 years at diagnosis could be due to the effect on the endometrium of postmenopausal androgen-derived estrogens in the absence of progesterone, which is no longer secreted.
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| 19. |
- Clendenen, Tess V, et al.
(författare)
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Temporal reliability of cytokines and growth factors in EDTA plasma
- 2010
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Ingår i: BMC research notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 3:1, s. 302-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cytokines are involved in the development of chronic diseases, including cancer. It is important to evaluate the temporal reproducibility of cytokines in plasma prior to conducting epidemiologic studies utilizing these markers. FINDINGS: We assessed the temporal reliability of CRP, 22 cytokines and their soluble receptors (IL-1alpha, IL-1beta, IL-1Ra, IL-2, sIL-2R, IL-4, IL-5, IL-6, sIL-6R, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, IL-17, TNFalpha, sTNF-R1, sTNF-R2, IFNalpha, IFNgamma) and eight growth factors (GM-CSF, EGF, bFGF, G-CSF, HGF, VEGF, EGFR, ErbB2) in repeated EDTA plasma samples collected an average of two years apart from 18 healthy women (age range: 42-62) enrolled in a prospective cohort study. We also estimated the correlation between serum and plasma biomarker levels using 18 paired clinical samples from postmenopausal women (age range: 75-86). Twenty-six assays were able to detect their analytes in at least 70% of samples. Of those 26 assays, we observed moderate to high intra-class correlation coefficients (ICCs)(ranging from 0.53-0.89) for 22 assays, and low ICCs (0-0.47) for four assays. Serum and plasma levels were highly correlated (r > 0.6) for most markers, except for seven assays (r < 0.5). CONCLUSIONS: For 22 of the 31 biomarkers, a single plasma measurement is a reliable estimate of a woman's average level over a two-year period.
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| 20. |
- Collins, Elin, et al.
(författare)
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Bridging different realities-a qualitative study on patients' experiences of preoperative care for benign hysterectomy and opportunistic salpingectomy in Sweden
- 2020
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Ingår i: BMC Women's Health. - : BMC. - 1472-6874. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hysterectomy is a common procedure worldwide and removing healthy fallopian tubes at the time of hysterectomy (opportunistic salpingectomy) to possibly prevent ovarian cancer is increasing in frequency, but still controversial. The experiences and perceptions of women, eligible for the procedure, have not been previously investigated. This study aims to, among women waiting to undergo hysterectomy, explore i) experiences and perceptions of self and healthcare in relation to their elective surgery, ii) perceptions of risks and benefits of hysterectomy, including opportunistic salpingectomy.Methods: A qualitative study, with focus group discussions including women < 55 years, planned for hysterectomy with ovarian preservation, was performed. Participants were recruited through purposive sampling from six gynecological departments in different parts of Sweden, including both country and university hospitals. Focus group discussions were conducted using a semi-structured interview guide, digitally recorded, transcribed verbatim and analysed by qualitative manifest and latent content analysis.Results: Twenty-one Swedish-speaking women participated. They were 40-53 years of age, reported varying educational levels, countries of birth and indications for hysterectomy. Analysis rendered a theme "Bridging different realities" over four categories: "Being a woman today", "Experiencing and managing body failure", "Navigating the healthcare system" and "Processing continuously until surgery", including 17 subcategories. The participants displayed varying attitudes towards the significance of their uterus in being a woman. A vague understanding of their body was described, leading to fear related to the reasons for surgery as well as surgery itself. Participants described difficulties understanding and recalling information but also stated that insufficient information was provided. Perceptions of the risks and benefits of opportunistic salpingectomy varied. Involvement in decisions regarding the hysterectomy and potential opportunistic salpingectomy was perceived to be dependent on the counselling gynecologist.Conclusions: The theme Bridging different realities captures the complexity of women deciding on removal of their uterus, and possibly fallopian tubes. It also describes the women's interactions with healthcare and perceived difference between the health professionals and the women's perception of the situation, as viewed by the women. Bridging the different realities faced by patients is required to enable shared decision-making, through sufficient support from healthcare.
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| 21. |
- Cramer, Daniel W., et al.
(författare)
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Anti-CA15.3 and Anti-CA125 Antibodies and ovarian cancer risk : Results from the EPIC cohort
- 2018
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Ingår i: Cancer Epidemiology Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 27:7, s. 790-804
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neoplastic and non-neoplastic events may raise levels of mucins, CA15.3, and CA125, and generate antibodies against them, but their impact on epithelial ovarian cancer (EOC) risk has not been fully defined. Methods: CA15.3, CA125, and IgG1 antibodies against them were measured in 806 women who developed EOC and 1,927 matched controls from the European Prospective Investigation of Nutrition and Cancer. Associations between epidemiologic factors and anti-mucin antibodies were evaluated using generalized linear models; EOC risks associated with anti-mucin antibodies, by themselves or in combination with respective antigens, were evaluated using conditional logistic regression. Results: In controls, lower antibodies against both mucins were associated with current smoking; and, in postmenopausal women, higher levels with longer oral contraceptive use and later-age-at and shorter-interval-since last birth. Lower anti-CA15.3 antibodies were associated with higher body mass and, in premenopausal women, more ovulatory cycles. Higher anti-CA15.3 and anti-CA125 antibodies were associated with higher risk for mucinous EOC occurring ≥ 3 years from enrollment. Long-term risk for serous EOC was reduced in women with low CA125 and high anti-CA125 antibodies relative to women with low concentrations of both. Conclusions: We found general support for the hypothesis that anti-mucin antibody levels correlate with risk factors for EOC. Antibodies alone or in combinations with their antigen may predict longer term risk of specific EOC types. Impact: Anti-CA125 and anti-CA15.3 antibodies alone or in perspective of antigens may be informative in the pathogenesis of EOC subtypes, but less useful for informing risk for all EOC.
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| 22. |
- Dimou, Niki, et al.
(författare)
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Cigarette Smoking and Endometrial Cancer Risk : observational and Mendelian Randomization Analyses
- 2022
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 31:9, s. 1839-1848
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Current epidemiologic evidence indicates that smoking is associated with a lower endometrial cancer risk. However, it is unknown if this association is causal or confounded. To further elucidate the role of smoking in endometrial cancer risk, we conducted complementary observational and Mendelian randomization (MR) analyses.METHODS: The observational analyses included 286,415 participants enrolled in the European Prospective Investigation into Cancer and Nutrition and 179,271 participants in the UK Biobank, and multivariable Cox proportional hazards models were used. In two-sample MR analyses, genetic variants robustly associated with lifetime amount of smoking (n = 126 variants) and ever having smoked regularly (n = 112 variants) were selected and their association with endometrial cancer risk (12,906 cancer/108,979 controls from the Endometrial Cancer Association Consortium) was examined.RESULTS: In the observational analysis, lifetime amount of smoking and ever having smoked regularly were associated with a lower endometrial cancer risk. In the MR analysis accounting for body mass index, a genetic predisposition to a higher lifetime amount of smoking was not associated with endometrial cancer risk (OR per 1-SD increment: 1.15; 95% confidence interval: 0.91-1.44). Genetic predisposition to ever having smoked regularly was not associated with risk of endometrial cancer.CONCLUSIONS: Smoking was inversely associated with endometrial cancer in the observational analyses, although unsupported by the MR. Additional studies are required to better understand the possible confounders and mechanisms underlying the observed associations between smoking and endometrial cancer. IMPACT: The results from this analysis indicate that smoking is unlikely to be causally linked with endometrial cancer risk.
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| 23. |
- Dossus, Laure, et al.
(författare)
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Tumor necrosis factor (TNF)-α, soluble TNF receptors and endometrial cancer risk : the EPIC study
- 2011
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Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 129:8, s. 2032-2037
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-α (TNF-α), one of the major pro-inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case-control study nested within the European prospective investigation into cancer and nutrition (EPIC) to examine the association of TNF-α and its two soluble receptors (sTNFR1 and sTNFR2) with endometrial cancer risk. Two-hundred-seventy cases and 518 matched controls were analyzed using conditional logistic regression. All statistical tests were two-sided. We observed an increased risk of endometrial cancer among women in the highest versus lowest quartile of TNF-α (odds ratio [OR]: 1.73, 95% CI: 1.09-2.73, Ptrend = 0.01), sTNFR1 (OR: 1.68, 95% CI: 0.99-2.86, Ptrend = 0.07) and sTNFR2 (OR: 1.53, 95%CI: 0.92-2.55, Ptrend = 0.03) after adjustment for body-mass-index, parity, age at menopause and previous postmenopausal hormone therapy use. Further adjustments for estrogens and C-peptide had minor effect on risk estimates. Our data show that elevated prediagnostic concentrations of TNF-α and its soluble receptors are related to a higher risk of endometrial cancer, particularly strong in women diagnosed within 2 years of blood donation. This is the first study of its kind and therefore deserves replication in further prospective studies.
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| 24. |
- Fedirko, Veronika, et al.
(författare)
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Alcohol drinking and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
- 2013
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Ingår i: Annals of Epidemiology. - : Elsevier BV. - 1047-2797 .- 1873-2585. ; 23:2, s. 93-98
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Alcohol intake may adversely affect the concentrations of endogenous sex hormones, and thus increase the risk of endometrial cancer. However, epidemiologic studies have provided conflicting results. Therefore, we investigated the association between alcohol intake and endometrial cancer risk a large, multicenter, prospective study. Methods: From 1992 through 2010, 301,051 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were followed for incident endometrial cancer (n = 1382). Baseline alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. Results: The multivariable HRs (and 95% CIs) compared with light drinkers (0.1-6 g/d) were 1.03(0.88-1.20) for 0 g of alcohol per day at baseline, 1.01 (0.86-1.17) for 6.1-12 g/d, 1.03 (0.87-1.22) for 12.1-24 g/d, 1.07(0.87-1.38) for 241-36 g/d, and 0.85(0.61-1.18) for more than 36 g/d (p(trend) = 0.77). No association was observed among former drinkers (OR, 1.28; 95% CI, 0.98-1.68 compared with light drinkers). Null associations were also found between alcohol consumption at age 20 years, lifetime pattern of alcohol drinking, and baseline alcohol intake from specific alcoholic beverages and endometrial cancer risk. Conclusions: Our findings suggest no association between alcohol intake and endometrial cancer risk.
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| 25. |
- Fortner, Renée T., et al.
(författare)
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Anti-Mullerian hormone and endometrial cancer : a multi-cohort study
- 2017
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 117:9, s. 1412-1418
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk. Methods: We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. AntiMullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (ORlog2). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics. Results: Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (ORlog(2): 1.07 (0.99-1.17)), or with any of the examined subgroups. Conclusions: Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.
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