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Article ; Online: An epigenetic hypothesis for ovarian cancer prevention by oral contraceptive pill use.

Avramenko, Anna S / Flanagan, James M

2023 Volume 15, Issue 1, Page(s) 165

Abstract: Background: Ovarian cancer is the second most common gynecological cancer type after uterine cancers. In 2020, according to worldwide statistics, there were more than 313,000 new cases of ovarian cancer. Most concerning with ovarian cancer is the poor ... ...

Abstract	Background: Ovarian cancer is the second most common gynecological cancer type after uterine cancers. In 2020, according to worldwide statistics, there were more than 313,000 new cases of ovarian cancer. Most concerning with ovarian cancer is the poor overall survival, with only 30% of patients surviving for longer than 5 years after diagnosis. The reason for this poor outcome includes late diagnosis due to non-specific symptoms and a lack of any highly effective biomarkers of the early stages of ovarian carcinogenesis. However, it is important to note that some modifiable lifestyle factors can be preventative [pregnancy, breastfeeding and combined oral contraceptives pill (COCP) use]. Results: There is now increasing data reporting the role of epigenetic changes, which are detectable in ovarian cancer tumors, suggesting the possibility that epigenetics may also play a key role in the mechanism of long-term effective prevention of ovarian cancer. To our knowledge, there is a lack of high-quality data on the molecular mechanisms of ovarian cancer prevention, although several hypotheses have been proposed. Conclusions: This review focusses on the evidence for a proposed novel hypothesis-that COCPs act as a chemoprevention through the impact on the epigenome of the cells of origin of ovarian cancer-fallopian tubes epithelium.
MeSH term(s)	Pregnancy ; Humans ; Female ; Contraceptives, Oral ; DNA Methylation ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/prevention & control
Chemical Substances	Contraceptives, Oral
Language	English
Publishing date	2023-10-18
Publishing country	Germany
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-023-01584-9
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Article ; Online: Unraveling noncoding DNA variants and epimutations: a paradigm shift in hereditary cancer research.

Ibrahim, Maria Baz / Flanagan, James / Ibrahim, Tony / Rouleau, Etienne

Future oncology (London, England)

2024

Abstract: Exhaustive efforts have been dedicated to uncovering genomic aberrations linked to cancer susceptibility. Noncoding sequence variants and epigenetic alterations significantly influence gene regulation and could contribute to cancer development. However, ... ...

Abstract	Exhaustive efforts have been dedicated to uncovering genomic aberrations linked to cancer susceptibility. Noncoding sequence variants and epigenetic alterations significantly influence gene regulation and could contribute to cancer development. However, exploring noncoding regions in hereditary cancer susceptibility demands cutting-edge methodologies for functionally characterizing genomic discoveries. Additionally, comprehending the impact on cancer development of variants in noncoding DNA and the epigenome necessitates integrating diverse data through bioinformatic analyses. As novel technologies and analytical methods continue to advance, this realm of research is rapidly gaining traction. Within this mini-review, we delve into future research domains concerning aberrations in noncoding DNA regions, such as pseudoexons, promoter variants and
Language	English
Publishing date	2024-05-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2274956-1
ISSN	1744-8301 ; 1479-6694
ISSN (online)	1744-8301
ISSN	1479-6694
DOI	10.2217/fon-2023-0665
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Article ; Online: Testing Behavioral Messages to Increase Recruitment to Health Research When Embedded Within Social Media Campaigns on Twitter: Web-Based Experimental Study.

Stoffel, Sandro T / Law, Jing Hui / Kerrison, Robert / Brewer, Hannah R / Flanagan, James M / Hirst, Yasemin

JMIR formative research

2024 Volume 8, Page(s) e48538

Abstract: Background: Social media is rapidly becoming the primary source to disseminate invitations to the public to consider taking part in research studies. There is, however, little information on how the contents of the advertisement can be communicated to ... ...

Abstract	Background: Social media is rapidly becoming the primary source to disseminate invitations to the public to consider taking part in research studies. There is, however, little information on how the contents of the advertisement can be communicated to facilitate engagement and subsequently promote intentions to participate in research. Objective: This paper describes an experimental study that tested different behavioral messages for recruiting study participants for a real-life observational case-control study. Methods: We included 1060 women in a web-based experiment and randomized them to 1 of 3 experimental conditions: standard advertisement (n=360), patient endorsement advertisement (n=345), and social norms advertisement (n=355). After seeing 1 of the 3 advertisements, participants were asked to state (1) their intention to take part in the advertised case-control study, (2) the ease of understanding the message and study aims, and (3) their willingness to be redirected to the website of the case-control study after completing the survey. Individuals were further asked to suggest ways to improve the messages. Intentions were compared between groups using ordinal logistic regression, reported in percentages, adjusted odds ratio (aOR), and 95% CIs. Results: Those who were in the patient endorsement and social norms-based advertisement groups had significantly lower intentions to take part in the advertised study compared with those in the standard advertisement group (aOR 0.73, 95% CI 0.55-0.97; P=.03 and aOR 0.69, 95% CI 0.52-0.92; P=.009, respectively). The patient endorsement advertisement was perceived to be more difficult to understand (aOR 0.65, 95% CI 0.48-0.87; P=.004) and to communicate the study aims less clearly (aOR 0.72, 95% CI 0.55-0.95; P=.01). While the patient endorsement advertisement had no impact on intention to visit the main study website, the social norms advertisement decreased willingness compared with the standard advertisement group (157/355, 44.2% vs 191/360, 53.1%; aOR 0.74, 95% CI 0.54-0.99; P=.02). The majority of participants (395/609, 64.8%) stated that the messages did not require changes, but some preferred clearer (75/609, 12.3%) and shorter (59/609, 9.7%) messages. Conclusions: The results of this study indicate that adding normative behavioral messages to simulated tweets decreased participant intention to take part in our web-based case-control study, as this made the tweet harder to understand. This suggests that simple messages should be used for participant recruitment through Twitter (subsequently rebranded X).
Language	English
Publishing date	2024-02-05
Publishing country	Canada
Document type	Journal Article
ISSN	2561-326X
ISSN (online)	2561-326X
DOI	10.2196/48538
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Article ; Online: Association Between Purchase of Over-the-Counter Medications and Ovarian Cancer Diagnosis in the Cancer Loyalty Card Study (CLOCS): Observational Case-Control Study.

Brewer, Hannah R / Hirst, Yasemin / Chadeau-Hyam, Marc / Johnson, Eric / Sundar, Sudha / Flanagan, James M

JMIR public health and surveillance

2023 Volume 9, Page(s) e41762

Abstract: Background: Over-the-counter (OTC) medications are frequently used to self-care for nonspecific ovarian cancer symptoms prior to diagnosis. Monitoring such purchases may provide an opportunity for earlier diagnosis.: Objective: The aim of the Cancer ... ...

Abstract	Background: Over-the-counter (OTC) medications are frequently used to self-care for nonspecific ovarian cancer symptoms prior to diagnosis. Monitoring such purchases may provide an opportunity for earlier diagnosis. Objective: The aim of the Cancer Loyalty Card Study (CLOCS) was to investigate purchases of OTC pain and indigestion medications prior to ovarian cancer diagnosis in women with and without ovarian cancer in the United Kingdom using loyalty card data. Methods: An observational case-control study was performed comparing purchases of OTC pain and indigestion medications prior to diagnosis in women with (n=153) and without (n=120) ovarian cancer using loyalty card data from two UK-based high street retailers. Monthly purchases of pain and indigestion medications for cases and controls were compared using the Fisher exact test, conditional logistic regression, and receiver operating characteristic (ROC) curve analysis. Results: Pain and indigestion medication purchases were increased among cases 8 months before diagnosis, with maximum discrimination between cases and controls 8 months before diagnosis (Fisher exact odds ratio [OR] 2.9, 95% CI 2.1-4.1). An increase in indigestion medication purchases was detected up to 9 months before diagnosis (adjusted conditional logistic regression OR 1.38, 95% CI 1.04-1.83). The ROC analysis for indigestion medication purchases showed a maximum area under the curve (AUC) at 13 months before diagnosis (AUC=0.65, 95% CI 0.57-0.73), which further improved when stratified to late-stage ovarian cancer (AUC=0.68, 95% CI 0.59-0.78). Conclusions: There is a difference in purchases of pain and indigestion medications among women with and without ovarian cancer up to 8 months before diagnosis. Facilitating earlier presentation among those who self-care for symptoms using this novel data source could improve ovarian cancer patients' options for treatment and improve survival. Trial registration: ClinicalTrials.gov NCT03994653; https://clinicaltrials.gov/ct2/show/NCT03994653.
MeSH term(s)	Humans ; Female ; Case-Control Studies ; Dyspepsia ; Early Detection of Cancer ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/drug therapy ; Pain
Language	English
Publishing date	2023-01-26
Publishing country	Canada
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2369-2960
ISSN (online)	2369-2960
DOI	10.2196/41762
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Article ; Online: Understanding Public Attitudes and Willingness to Share Commercial Data for Health Research: Survey Study in the United Kingdom.

Hirst, Yasemin / Stoffel, Sandro T / Brewer, Hannah R / Timotijevic, Lada / Raats, Monique M / Flanagan, James M

JMIR public health and surveillance

2023 Volume 9, Page(s) e40814

Abstract: Background: Health research using commercial data is increasing. The evidence on public acceptability and sociodemographic characteristics of individuals willing to share commercial data for health research is scarce.: Objective: This survey study ... ...

Abstract	Background: Health research using commercial data is increasing. The evidence on public acceptability and sociodemographic characteristics of individuals willing to share commercial data for health research is scarce. Objective: This survey study investigates the willingness to share commercial data for health research in the United Kingdom with 3 different organizations (government, private, and academic institutions), 5 different data types (internet, shopping, wearable devices, smartphones, and social media), and 10 different invitation methods to recruit participants for research studies with a focus on sociodemographic characteristics and psychological predictors. Methods: We conducted a web-based survey using quota sampling based on age distribution in the United Kingdom in July 2020 (N=1534). Chi-squared tests tested differences by sociodemographic characteristics, and adjusted ordered logistic regressions tested associations with trust, perceived importance of privacy, worry about data misuse and perceived risks, and perceived benefits of data sharing. The results are shown as percentages, adjusted odds ratios, and 95% CIs. Results: Overall, 61.1% (937/1534) of participants were willing to share their data with the government and 61% (936/1534) of participants were willing to share their data with academic research institutions compared with 43.1% (661/1534) who were willing to share their data with private organizations. The willingness to share varied between specific types of data-51.8% (794/1534) for loyalty cards, 35.2% (540/1534) for internet search history, 32% (491/1534) for smartphone data, 31.8% (488/1534) for wearable device data, and 30.4% (467/1534) for social media data. Increasing age was consistently and negatively associated with all the outcomes. Trust was positively associated with willingness to share commercial data, whereas worry about data misuse and the perceived importance of privacy were negatively associated with willingness to share commercial data. The perceived risk of sharing data was positively associated with willingness to share when the participants considered all the specific data types but not with the organizations. The participants favored postal research invitations over digital research invitations. Conclusions: This UK-based survey study shows that willingness to share commercial data for health research varies; however, researchers should focus on effectively communicating their data practices to minimize concerns about data misuse and improve public trust in data science. The results of this study can be further used as a guide to consider methods to improve recruitment strategies in health-related research and to improve response rates and participant retention.
MeSH term(s)	Humans ; Public Opinion ; Privacy/psychology ; Information Dissemination/methods ; Smartphone ; Surveys and Questionnaires
Language	English
Publishing date	2023-03-23
Publishing country	Canada
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2369-2960
ISSN (online)	2369-2960
DOI	10.2196/40814
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Article ; Online: Cancer Loyalty Card Study (CLOCS): feasibility outcomes for an observational case-control study focusing on the patient interval in ovarian cancer.

Brewer, Hannah R / Chadeau-Hyam, Marc / Johnson, Eric / Sundar, Sudha / Flanagan, James / Hirst, Yasemin

BMJ open

2023 Volume 13, Issue 6, Page(s) e066022

Abstract: Objectives: Ovarian cancer symptoms are often non-specific and can be normalised before patients seek medical help. The Cancer Loyalty Card Study investigated self-management behaviours of patients with ovarian cancer prior to their diagnosis using ... ...

Abstract	Objectives: Ovarian cancer symptoms are often non-specific and can be normalised before patients seek medical help. The Cancer Loyalty Card Study investigated self-management behaviours of patients with ovarian cancer prior to their diagnosis using loyalty card data collected by two UK-based high street retailers. Here, we discuss the feasibility outcomes for this novel research. Design: Observational case-control study. Setting: Control participants were invited to the study using social media and other sources from the general public. Once consented, control participants were required to submit proof of identification (ID) for their loyalty card data to be shared. Cases were identified using unique National Health Service (NHS) numbers (a proxy for ID) and were recruited through 12 NHS tertiary care clinics. Participants: Women in the UK, 18 years or older, with at least one of the participating high street retailers' loyalty cards. Those with an ovarian cancer diagnosis within 2 years of recruitment were considered cases, and those without an ovarian cancer diagnosis were considered controls. Primary outcome measures: Recruitment rates, demographics of participants and identification of any barriers to recruitment. Results: In total, 182 cases and 427 controls were recruited with significant differences by age, number of people in participants' households and the geographical region in the UK. However, only 37% (n=160/427) of control participants provided sufficient ID details and 81% (n=130/160) matched retailers' records. The majority of the participants provided complete responses to the 24-Item Ovarian Risk Questionnaire. Conclusions: Our findings show that recruitment to a study aiming to understand self-care behaviours using loyalty card data is challenging but feasible. The general public were willing to share their data for health research. Barriers in data sharing mechanisms need to be addressed to maximise participant retention. Trial registration number: ISRCTN14897082, CPMS 43323, NCT03994653.
MeSH term(s)	Humans ; Female ; Case-Control Studies ; Feasibility Studies ; State Medicine ; Ovarian Neoplasms/therapy ; Publications
Language	English
Publishing date	2023-06-14
Publishing country	England
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-066022
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Article ; Online: Anti-factor Xa vs aPTT for heparin monitoring in extracorporeal membrane oxygenation.

Vo, Tai / Bello, Abdel / Ragan, Monika / Flanagan, James / Johnson, Darriel

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists

2022 Volume 80, Issue Suppl 2, Page(s) S77–S83

Abstract: Purpose: The goal of this study was to evaluate the correlation of anti-factor Xa (anti-Xa) and activated partial thromboplastin time (aPTT) measures with heparin dosing in adult patients on extracorporeal membrane oxygenation (ECMO) support.: Methods! ...

Abstract	Purpose: The goal of this study was to evaluate the correlation of anti-factor Xa (anti-Xa) and activated partial thromboplastin time (aPTT) measures with heparin dosing in adult patients on extracorporeal membrane oxygenation (ECMO) support. Methods: This was a retrospective cohort study evaluating adult patients managed on ECMO for at least 24 hours who received unfractionated heparin for systemic anticoagulation and were monitored per protocol using anti-Xa and/or aPTT coagulation assays. The primary outcome was the correlation between aPTT and anti-Xa measures. The secondary outcomes included, but were not limited to, the number of hemorrhagic and thrombotic events. Results: Twenty-seven patients were included in this study. In the 227 events where both laboratory values were collected, a weak correlation was found between anti-Xa and aPTT (Spearman's correlation coefficient = 0.4, P = 0). In the 12 hemorrhagic events that occurred, aPTT was collected for only 10 events. Fifty percent of those events were associated with supratherapeutic aPTT, while none of the hemorrhagic events were associated with a supratherapeutic anti-Xa level. Two thrombotic events occurred, one of which had subtherapeutic anti-Xa and aPTT and the other of which had neither an anti-Xa nor aPTT measure on the day the event occurred. Conclusion: In a population of patients on ECMO, many of whom had coronavirus disease 2019 (COVID-19), there was a weak association between aPTT and anti-Xa measures. Hemorrhagic evens were more common than thrombotic events; however, a relationship between these events and aPTT or anti-Xa levels was not determined. The applicability of these findings to an ECMO population without COVID-19 is unknown and will require further study.
MeSH term(s)	Adult ; Humans ; Heparin/adverse effects ; Partial Thromboplastin Time ; Extracorporeal Membrane Oxygenation/adverse effects ; Retrospective Studies ; COVID-19 ; Heparin, Low-Molecular-Weight
Chemical Substances	Heparin (9005-49-6) ; Heparin, Low-Molecular-Weight
Language	English
Publishing date	2022-12-07
Publishing country	England
Document type	Journal Article
ZDB-ID	1224627-x
ISSN	1535-2900 ; 1079-2082
ISSN (online)	1535-2900
ISSN	1079-2082
DOI	10.1093/ajhp/zxac351
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Article ; Online: Epigenome-wide association studies (EWAS): past, present, and future.

Flanagan, James M

Methods in molecular biology (Clifton, N.J.)

2015 Volume 1238, Page(s) 51–63

Abstract: Just as genome-wide association studies (GWAS) grew from the field of genetic epidemiology, so too do epigenome-wide association studies (EWAS) derive from the burgeoning field of epigenetic epidemiology, with both aiming to understand the molecular ... ...

Abstract	Just as genome-wide association studies (GWAS) grew from the field of genetic epidemiology, so too do epigenome-wide association studies (EWAS) derive from the burgeoning field of epigenetic epidemiology, with both aiming to understand the molecular basis for disease risk. While genetic risk of disease is currently unmodifiable, there is hope that epigenetic risk may be reversible and or modifiable. This review will take a look back at the origins of this field and revisit the past early efforts to conduct EWAS using the 27k Illumina methylation beadarrays, to the present where most investigators are using the 450k Illumina beadarrays and finally to the future where next generation sequencing based methods beckon. There have been numerous diseases, exposures and lifestyle factors investigated with EWAS, with several significant associations now identified. However, much like the GWAS studies, EWAS are likely to require large international consortium-based approaches to reach the numbers of subjects, and statistical and scientific rigor, required for robust findings.
MeSH term(s)	Epigenomics/methods ; Genome-Wide Association Study/methods ; Humans ; Sequence Analysis
Language	English
Publishing date	2015-01-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-1804-1_3
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Article ; Online: Testing the Effectiveness of an Animated Decision Aid to Improve Recruitment of Control Participants in a Case-Control Study: Web-Based Experiment.

Stoffel, Sandro T / Law, Jing Hui / Kerrison, Robert / Brewer, Hannah R / Flanagan, James M / Hirst, Yasemin

Journal of medical Internet research

2022 Volume 24, Issue 8, Page(s) e40015

Abstract: Background: Participation in case-control studies is crucial in epidemiological research. The self-sampling bias, low response rate, and poor recruitment of population representative controls are often reported as limitations of case-control studies ... ...

Abstract	Background: Participation in case-control studies is crucial in epidemiological research. The self-sampling bias, low response rate, and poor recruitment of population representative controls are often reported as limitations of case-control studies with limited strategies to improve participation. With greater use of web-based methods in health research, there is a further need to understand the effectiveness of different tools to enhance informed decision-making and willingness to take part in research. Objective: This study tests whether the inclusion of an animated decision aid in the recruitment page of a study website can increase participants' intentions to volunteer as controls. Methods: A total of 1425 women were included in a web-based experiment and randomized to one of two experimental conditions: one in which they were exposed to a simulated website that included the animation (animation; n=693, 48.6%), and one in which they were exposed to the simulated website without the animation (control; n=732, 51.4%). The simulated website was adapted from a real website for a case-control study, which invites people to consider taking part in a study that investigates differences in purchasing behaviors between women with and without ovarian cancer and share their loyalty card data collected through 2 high street retailers with the researchers. After exposure to the experimental manipulation, participants were asked to state (1) their intention to take part in the case-control study, (2) whether they would be willing to share their loyalty card for research, and (3) their willingness to be redirected to the real website after completing the survey. Data were assessed using ordinal and binary logistic regression, reported in percentages (%), adjusted odds ratio (AOR), and 95% confidence intervals. Results: Including the animation in the simulated website did not increase intentions to participate in the study (AOR 1.09; 95% CI 0.88-1.35) or willingness to visit the real study website after the survey (control 50.5% vs animation 52.6%, AOR 1.08; 95% CI 0.85-1.37). The animation, however, increased the participants' intentions to share the data from their loyalty cards for research in general (control 17.9% vs animation 26%; AOR 1.64; 95% CI 1.23-2.18). Conclusions: While the results of this study indicate that the animated decision aid did not lead to greater intention to take part in our web-based case-control study, they show that they can be effective in increasing people's willingness to share sensitive data for health research.
MeSH term(s)	Case-Control Studies ; Decision Support Techniques ; Female ; Humans ; Intention ; Internet ; Surveys and Questionnaires
Language	English
Publishing date	2022-08-26
Publishing country	Canada
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2028830-X
ISSN	1438-8871 ; 1438-8871
ISSN (online)	1438-8871
ISSN	1438-8871
DOI	10.2196/40015
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Article: Epigenome-wide association studies for breast cancer risk and risk factors.

Johansson, Annelie / Flanagan, James M

Trends in cancer research

2017 Volume 12, Page(s) 19–28

Abstract: There have been six epigenome-wide association studies (EWAS) for breast cancer risk using blood DNA from prospective cohorts published thus far, and the only consistent finding is a global loss of methylation observed in breast cancer cases compared ... ...

Abstract	There have been six epigenome-wide association studies (EWAS) for breast cancer risk using blood DNA from prospective cohorts published thus far, and the only consistent finding is a global loss of methylation observed in breast cancer cases compared with controls, with no individual CpG sites passing validation across studies. In contrast, a more successful approach has been the identification of EWAS signatures of cancer risk factors such as smoking, body mass index, age and alcohol use with numerous validated CpG sites. These signatures may be used as a molecular test to quantify cancer risk associated with these factors. It is clear from the larger EWAS of risk exposures that similar-sized large collaborative studies may be needed to robustly identify DNA methylation signatures of breast cancer risk.
Language	English
Publishing date	2017-09-27
Publishing country	India
Document type	Journal Article
ZDB-ID	2475013-X
ISSN	0973-1040
ISSN	0973-1040
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