| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Hageman, S., et al.
(författare)
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SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 42:25, s. 2439-2454
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Tidskriftsartikel (refereegranskat)abstract
- Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40-69 years in Europe. Methods and results We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65-0.68) to 0.81 (0.76-0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low- risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries. Conclusion SCORE2-a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations-enhances the identification of individuals at higher risk of developing CVD across Europe.
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| 4. |
- Strakova, A., et al.
(författare)
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Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for 'selfish' traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby 'selfish' positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells.
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| 5. |
- Aalbers, J., et al.
(författare)
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A next-generation liquid xenon observatory for dark matter and neutrino physics
- 2023
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 50:1
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Forskningsöversikt (refereegranskat)abstract
- The nature of dark matter and properties of neutrinos are among the most pressing issues in contemporary particle physics. The dual-phase xenon time-projection chamber is the leading technology to cover the available parameter space for weakly interacting massive particles, while featuring extensive sensitivity to many alternative dark matter candidates. These detectors can also study neutrinos through neutrinoless double-beta decay and through a variety of astrophysical sources. A next-generation xenon-based detector will therefore be a true multi-purpose observatory to significantly advance particle physics, nuclear physics, astrophysics, solar physics, and cosmology. This review article presents the science cases for such a detector.
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| 9. |
- Kaptoge, S., et al.
(författare)
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Life expectancy associated with different ages at diagnosis of type 2 diabetes in high-income countries: 23 million person-years of observation
- 2023
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Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 11:10, s. 731-742
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of type 2 diabetes is increasing rapidly, particularly among younger age groups. Estimates suggest that people with diabetes die, on average, 6 years earlier than people without diabetes. We aimed to provide reliable estimates of the associations between age at diagnosis of diabetes and all-cause mortality, cause-specific mortality, and reductions in life expectancy. Methods: For this observational study, we conducted a combined analysis of individual-participant data from 19 high-income countries using two large-scale data sources: the Emerging Risk Factors Collaboration (96 cohorts, median baseline years 1961–2007, median latest follow-up years 1980–2013) and the UK Biobank (median baseline year 2006, median latest follow-up year 2020). We calculated age-adjusted and sex-adjusted hazard ratios (HRs) for all-cause mortality according to age at diagnosis of diabetes using data from 1 515 718 participants, in whom deaths were recorded during 23·1 million person-years of follow-up. We estimated cumulative survival by applying age-specific HRs to age-specific death rates from 2015 for the USA and the EU. Findings: For participants with diabetes, we observed a linear dose–response association between earlier age at diagnosis and higher risk of all-cause mortality compared with participants without diabetes. HRs were 2·69 (95% CI 2·43–2·97) when diagnosed at 30–39 years, 2·26 (2·08–2·45) at 40–49 years, 1·84 (1·72–1·97) at 50–59 years, 1·57 (1·47–1·67) at 60–69 years, and 1·39 (1·29–1·51) at 70 years and older. HRs per decade of earlier diagnosis were similar for men and women. Using death rates from the USA, a 50-year-old individual with diabetes died on average 14 years earlier when diagnosed aged 30 years, 10 years earlier when diagnosed aged 40 years, or 6 years earlier when diagnosed aged 50 years than an individual without diabetes. Using EU death rates, the corresponding estimates were 13, 9, or 5 years earlier. Interpretation: Every decade of earlier diagnosis of diabetes was associated with about 3–4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes. Funding: British Heart Foundation, Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.
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| 10. |
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| 11. |
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| 14. |
- Gaziano, Liam, et al.
(författare)
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Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
- 2022
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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| 15. |
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The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
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Tidskriftsartikel (refereegranskat)abstract
- This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Bolton, Douglas K., et al.
(författare)
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Continental-scale land surface phenology from harmonized Landsat 8 and Sentinel-2 imagery
- 2020
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Ingår i: Remote Sensing of Environment. - : Elsevier BV. - 0034-4257. ; 240
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Tidskriftsartikel (refereegranskat)abstract
- Dense time series of Landsat 8 and Sentinel-2 imagery are creating exciting new opportunities to monitor, map, and characterize temporal dynamics in land surface properties with unprecedented spatial detail and quality. By combining imagery from the Landsat 8 Operational Land Imager and the MultiSpectral Instrument on-board Sentinel-2A and -2B, the remote sensing community now has access to moderate (10–30 m) spatial resolution imagery with repeat periods of ~3 days in the mid-latitudes. At the same time, the large combined data volume from Landsat 8 and Sentinel-2 introduce substantial new challenges for users. Land surface phenology (LSP) algorithms, which estimate the timing of phenophase transitions and quantify the nature and magnitude of seasonality in remotely sensed land surface conditions, provide an intuitive way to reduce data volumes and redundancy, while also furnishing data sets that are useful for a wide range of applications including monitoring ecosystem response to climate variability and extreme events, ecosystem modelling, crop-type discrimination, and land cover, land use, and land cover change mapping, among others. To support the need for operational LSP data sets, here we describe a continental-scale land surface phenology algorithm and data product based on harmonized Landsat 8 and Sentinel-2 (HLS) imagery. The algorithm creates high quality times series of vegetation indices from HLS imagery, which are then used to estimate the timing of vegetation phenophase transitions at 30 m spatial resolution. We present results from assessment efforts evaluating LSP retrievals, and provide examples illustrating the character and quality of information related to land cover and terrestrial ecosystem properties provided by the continental LSP dataset that we have developed. The algorithm is highly successful in ecosystems with strong seasonal variation in leaf area (e.g., deciduous forests). Conversely, results in evergreen systems are less interpretable and conclusive.
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| 20. |
- Brausi, M., et al.
(författare)
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ECCO Essential Requirements for Quality Cancer Care: Prostate cancer
- 2020
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Ingår i: Critical Reviews in Oncology Hematology. - : Elsevier BV. - 1040-8428. ; 148
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Tidskriftsartikel (refereegranskat)abstract
- Background: ECCO Essential Requirements for Quality Cancer Care (ERQCC) are written by experts representing all disciplines involved in cancer care in Europe. They give oncology teams, patients, policymakers and managers an overview of essential care throughout the patient journey. Prostate cancer: Prostate cancer is the second most common male cancer and has a wide variation in outcomes in Europe. It has complex diagnosis and treatment challenges, and is a major healthcare burden. Care must only be a carried out in prostate/urology cancer units or centres that have a core multidisciplinary team (MDT) and an extended team of health professionals. Such units are far from universal in European countries. To meet European aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.
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| 21. |
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| 22. |
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| 23. |
- Kalyanasundaram, M., et al.
(författare)
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Effects of improved information and volunteer support on segregation of solid waste at the household level in urban settings in Madhya Pradesh, India (I-MISS) : protocol of a cluster randomized controlled trial
- 2021
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Ingår i: BMC Public Health. - : Springer Nature. - 1471-2458. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Segregation of household waste at the source is an effective and sustainable strategy for management of municipal waste. However, household segregation levels remain insufficient as waste management approaches are mostly top down and lack local support. The realisation and recognition of effective, improved and adequate waste management may be one of the vital drivers for attaining environmental protection and improved health and well-being. The presence of a local level motivator may promote household waste segregation and ultimately pro-environmental behaviour. The present cluster randomized control trial aims to understand if volunteer based information on waste segregation (I-MISS) can effectively promote increased waste segregation practices at the household level when compared with existing routine waste segregation information in an urban Indian setting.Methods: This paper describes the protocol of an 18 month two-group parallel,cluster randomised controlled trialin the urban setting of Ujjain, Madhya Pradesh, India. Randomization will be conducted at ward level, which is the last administrative unit of the municipality. The study will recruit 425 households in intervention and control groups. Assessments will be performed at baseline (0 months), midline (6 months), end line (12 months) and post intervention (18 months). The primary outcome will be the comparison of change in proportion of households practicing waste segregation and change in proportion of mis-sorted waste across the study period between the intervention and control groups as assessed by pick analysis. Intention to treat analysis will be conducted. Written informed consent will be obtained from all participants.Discussion: The present study is designed to study whether an external motivator, a volunteer selected from the participating community and empowered with adequate training, could disseminate waste segregation information to their community, thus promoting household waste segregation and ultimately pro-environmental behaviour. The study envisages that the volunteers could link waste management service providers and the community, give a local perspective to waste management, and help to change community habits through information, constant communication and feedback.Trial registration: The study is registered prospectively with Indian Council of Medical Research- Clinical Trial Registry of India (CTRI/2020/03/024278).
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| 24. |
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| 26. |
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| 27. |
- Heinze, Karolin, et al.
(författare)
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Validated biomarker assays confirm ARID1A loss is confounded with MMR deficiency, CD8 TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas.
- 2021
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Ingår i: The Journal of pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 256:4, s. 388-401
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Tidskriftsartikel (refereegranskat)abstract
- ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1,623 endometriosis-associated ovarian carcinomas, including 1,078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8+ tumour-infiltrating lymphocytes (CD8+ TIL), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOC and 25% of ENOC. We found no associations between ARID1A loss and outcomes, stage, age, or CD8+ TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p=0.012), and associated with MMRd (p<0.001), and presence of CD8+ TIL (p=0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOC we also observed an association between ARID1A loss-of-function mutation as a result of small indels (p=0.035, versus single nucleotide variants). In ENOC, the association between ARID1A loss, CD8+ TIL, and age, appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8+ TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss-of-function mutations in endometriosis-associated ovarian cancers and brings clarity to the prognostic significance. This article is protected by copyright. All rights reserved.
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| 33. |
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| 34. |
- Leong, C, et al.
(författare)
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Psychotropic Medication Use Before and During COVID-19: A Population-Wide Study
- 2022
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Ingår i: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13, s. 886652-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The coronavirus disease 2019 (COVID-19) pandemic and public health measures that took place have led to concerns regarding mental health and receipt of psychotropic medications. We aimed to study the changes in psychotropic medication dispensation rates before and during the COVID-19 pandemic in the general population.Methods: Administrative health data from the Canadian province of Manitoba was used to describe the quarterly incidence and prevalence of antipsychotics, antidepressants, and anxiolytic/sedative-hypnotics from January 1, 2015 to December 31, 2020. Individuals who received at least one prescription within each quarter were considered exposed to the medication. The denominator was the total population within each quarter. Incidence was defined as no receipt of medication in the 3 years prior to the quarter of interest. Autoregression models for time series data plus indicator variables were used to compare each quarter of 2020 after public health measures were implemented in March 2020 in relation to the expected trend. Analyses were stratified by age and sex.Results: There were 1,394,885 individuals in the first quarter of 2020, with a mean (SD) age of 38.9 (23.4) years, 50.3% were female, and 36.1% had a psychiatric diagnosis in the previous 5 years. A significant decrease was observed for incident antidepressant use (p < 0.05 for both sexes and all age groups except for those 65 years and older) and anxiolytic use (p < 0.05 for both sexes and all age groups except 80 years and older) in the second quarter (April-June) of 2020 compared to the expected trend. Females and those aged 40 years and older had a significantly higher incidence of antidepressant and antipsychotic use in the final quarter of 2020 compared to the expected trend (p < 0.05).Conclusion: Our findings indicate a decrease in new prescriptions for antidepressants and anxiolytics in the 3 months after COVID-19 in-person restrictions were first implemented. We then observed an increase in the new use of antidepressants and antipsychotics at the end of 2020, in females and people aged 40 years and older, with the highest rates of use in the population 80 years and older.
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| 35. |
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| 36. |
- Mitchell, James W., et al.
(författare)
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Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Adults with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations
- 2024
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Ingår i: EPILEPSIA. - 0013-9580 .- 1528-1167.
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Tidskriftsartikel (refereegranskat)abstract
- At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. Therefore, the International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy and their representatives to develop minimum sets of standardized outcomes and outcomes measurement methods for clinical practice that support patient-clinician decision-making and quality improvement. Consensus methods identified 20 core outcomes. Measurement tools were recommended based on their evidence of strong clinical measurement properties, feasibility, and cross-cultural applicability. The essential outcomes included many non-seizure outcomes: anxiety, depression, suicidality, memory and attention, sleep quality, functional status, and the social impact of epilepsy. The proposed set will facilitate the implementation of the use of patient-centered outcomes in daily practice, ensuring holistic care. They also encourage harmonization of outcome measurement, and if widely implemented should reduce the heterogeneity of outcome measurement, accelerate comparative research, and facilitate quality improvement efforts.
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| 37. |
- Patterson, Allison, et al.
(författare)
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Foraging range scales with colony size in high-latitude seabirds
- 2022
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:17, s. 3800-3807
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Tidskriftsartikel (refereegranskat)abstract
- Density-dependent prey depletion around breeding colonies has long been considered an important factor controlling the population dynamics of colonial animals.1, 2, 3, 4 Ashmole proposed that as seabird colony size increases, intraspecific competition leads to declines in reproductive success, as breeding adults must spend more time and energy to find prey farther from the colony.1 Seabird colony size often varies over several orders of magnitude within the same species and can include millions of individuals per colony.5,6 As such, colony size likely plays an important role in determining the individual behavior of its members and how the colony interacts with the surrounding environment.6 Using tracking data from murres (Uria spp.), the world’s most densely breeding seabirds, we show that the distribution of foraging-trip distances scales to colony size0.33 during the chick-rearing stage, consistent with Ashmole’s halo theory.1,2 This pattern occurred across colonies varying in size over three orders of magnitude and distributed throughout the North Atlantic region. The strong relationship between colony size and foraging range means that the foraging areas of some colonial species can be estimated from colony sizes, which is more practical to measure over a large geographic scale. Two-thirds of the North Atlantic murre population breed at the 16 largest colonies; by extrapolating the predicted foraging ranges to sites without tracking data, we show that only two of these large colonies have significant coverage as marine protected areas. Our results are an important example of how theoretical models, in this case, Ashmole’s version of central-place-foraging theory, can be applied to inform conservation and management in colonial breeding species.
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| 38. |
- Saur, Joachim, et al.
(författare)
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Alternating North-South Brightness Ratio of Ganymede's Auroral Ovals : Hubble Space Telescope Observations Around the Juno PJ34 Flyby
- 2022
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 49:23
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Tidskriftsartikel (refereegranskat)abstract
- We report results of Hubble Space Telescope observations from Ganymede's orbitally trailing side which were taken around the flyby of the Juno spacecraft on 7 June 2021. We find that Ganymede's northern and southern auroral ovals alternate in brightness such that the oval facing Jupiter's magnetospheric plasma sheet is brighter than the other one. This suggests that the generator that powers Ganymede's aurora is the momentum of the Jovian plasma sheet north and south of Ganymede's magnetosphere. Magnetic coupling of Ganymede to the plasma sheet above and below the moon causes asymmetric magnetic stresses and electromagnetic energy fluxes ultimately powering the auroral acceleration process. No clear statistically significant timevariability of the auroral emission on short time scales of 100s could be resolved. We show that electron energy fluxes of several tens of mW m(-2) are required for its OI 1,356 angstrom emission making Ganymede a very poor auroral emitter.
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| 39. |
- Trabert, Britton, et al.
(författare)
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The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles : An Analysis from the Ovarian Cancer Cohort Consortium (OC3)
- 2020
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 80:5, s. 1210-1218
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Tidskriftsartikel (refereegranskat)abstract
- Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60-2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10-1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04-1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09-1.17)], endometrioid [1.20 (1.10-1.32)], and clear cell [1.37 (1.18-1.58)], but not mucinous [0.99 (0.88-1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies.
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