scholarly journals Practical early cancer detection: distinguishing stable from unstable genomes in pre-cancerous tissues

2020 ◽  
Author(s):  
Sarah Killcoyne ◽  
Rebecca C. Fitzgerald
Keyword(s):  
Cancer Detection ◽  
Early Cancer ◽  
Gene Mutations ◽  
Malignant Progression ◽  
Early Cancer Detection ◽  
Barrett’S Oesophagus ◽  
Oesophageal Adenocarcinoma ◽  
Barrett's Oesophagus ◽  
Individual Gene ◽  
Future Risk

Summary Barrett’s oesophagus has been known for many years to display early changes to the genome consistent with the risk for oesophageal adenocarcinoma. Recently we have shown that this information can be used without knowledge of individual gene mutations to accurately predict a patient’s future risk of malignant progression.

scholarly journals Genomic copy number predicts oesophageal cancer years before transformation

2020 ◽  
Author(s):  
Sarah Killcoyne ◽  
Eleanor Gregson ◽  
David C. Wedge ◽  
Dan J. Woodcock ◽  
Matthew Eldridge ◽  
...  
Keyword(s):  
Copy Number ◽  
Gene Mutations ◽  
Barrett’S Oesophagus ◽  
Oesophageal Adenocarcinoma ◽  
Driver Gene ◽  
Barrett's Oesophagus ◽  
Genomic Copy Number ◽  
Somatic Evolution ◽  
Genomic Copy ◽  
Genomic Signals

SummaryCancer arises through a process of somatic evolution and recent studies have shown that aneuploidies and driver gene mutations precede cancer diagnosis by several years to decades1–4 Here, we address the question whether such genomic signals can be used for early detection and pre-emptive cancer treatment. To this end we study Barrett’s oesophagus, a genomic copy number driven neoplastic precursor lesion to oesophageal adenocarcinoma5. We use shallow whole genome sequencing of 777 biopsies sampled from 88 patients in surveillance for Barrett’s oesophagus over a period of up to 15 years. These data show that genomic signals exist that distinguish progressive from stable disease with an AUC of 0.87 and a sensitivity of 50% even ten years prior to histopathological disease transformation. These finding are validated on two independent cohorts of 75 and 248 patients. Compared against current patient management guidelines genomic risk classification enables earlier treatment for high risk patients as well as reduction of unnecessary treatment and monitoring for patients who are unlikely to develop cancer.

scholarly journals Multitrait genetic association analysis identifies 50 new risk loci for gastro-oesophageal reflux, seven new loci for Barrett’s oesophagus and provides insights into clinical heterogeneity in reflux diagnosis

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323906
Author(s):  
Jue-Sheng Ong ◽  
Jiyuan An ◽  
Xikun Han ◽  
Matthew H Law ◽  
Priyanka Nandakumar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Testing ◽  
Association Studies ◽  
Barrett’S Oesophagus ◽  
Oesophageal Reflux ◽  
Oesophageal Adenocarcinoma ◽  
Specific Gene ◽  
Genome Wide Association Studies ◽  
Disease Heterogeneity ◽  
Barrett's Oesophagus

ObjectiveGastro-oesophageal reflux disease (GERD) has heterogeneous aetiology primarily attributable to its symptom-based definitions. GERD genome-wide association studies (GWASs) have shown strong genetic overlaps with established risk factors such as obesity and depression. We hypothesised that the shared genetic architecture between GERD and these risk factors can be leveraged to (1) identify new GERD and Barrett’s oesophagus (BE) risk loci and (2) explore potentially heterogeneous pathways leading to GERD and oesophageal complications.DesignWe applied multitrait GWAS models combining GERD (78 707 cases; 288 734 controls) and genetically correlated traits including education attainment, depression and body mass index. We also used multitrait analysis to identify BE risk loci. Top hits were replicated in 23andMe (462 753 GERD cases, 24 099 BE cases, 1 484 025 controls). We additionally dissected the GERD loci into obesity-driven and depression-driven subgroups. These subgroups were investigated to determine how they relate to tissue-specific gene expression and to risk of serious oesophageal disease (BE and/or oesophageal adenocarcinoma, EA).ResultsWe identified 88 loci associated with GERD, with 59 replicating in 23andMe after multiple testing corrections. Our BE analysis identified seven novel loci. Additionally we showed that only the obesity-driven GERD loci (but not the depression-driven loci) were associated with genes enriched in oesophageal tissues and successfully predicted BE/EA.ConclusionOur multitrait model identified many novel risk loci for GERD and BE. We present strong evidence for a genetic underpinning of disease heterogeneity in GERD and show that GERD loci associated with depressive symptoms are not strong predictors of BE/EA relative to obesity-driven GERD loci.

scholarly journals Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma

Gut ◽  
2016 ◽  
Vol 66 (10) ◽  
pp. 1739-1747 ◽  
Author(s):  
Matthew F Buas ◽  
Qianchuan He ◽  
Lisa G Johnson ◽  
Lynn Onstad ◽  
David M Levine ◽  
...  
Keyword(s):  
Barrett’S Oesophagus ◽  
Oesophageal Adenocarcinoma ◽  
Barrett's Oesophagus ◽  
Germline Variation

scholarly journals Small-area data on socioeconomic status and immigrant groups for evaluating equity of early cancer detection and care

2021 ◽  
pp. 1-6
Author(s):  
Ulf Strömberg ◽  
Brandon L. Parkes ◽  
Amir Baigi ◽  
Carl Bonander ◽  
Anders Holmén ◽  
...  
Keyword(s):  
Socioeconomic Status ◽  
Cancer Detection ◽  
Small Area ◽  
Early Cancer ◽  
Early Cancer Detection ◽  
Area Data

Dying To Be Men: Masculinity and Early Cancer Detection Among Nigerian Men

2021 ◽  
pp. 0272684X2110049
Author(s):  
Darlingtina Esiaka ◽  
Candidus Nwakasi ◽  
Kelsey Brodie ◽  
Aaron Philip ◽  
Kalu Ogba
Keyword(s):  
Public Health ◽  
Cancer Detection ◽  
Attachment Styles ◽  
Early Cancer ◽  
Sub Saharan Africa ◽  
Early Cancer Detection ◽  
Anxious Attachment ◽  
Incidence And Mortality ◽  
Nigerian Men ◽  
Sub Saharan

Cancer incidence and mortality in Nigeria are increasing at an alarming rate, especially among Nigerian men. Despite the numerous public health campaigns and education on the importance of early cancer detection in Nigeria, there exist high rate of fatal/advanced stage cancer diagnoses among Nigerian men, even among affluent Nigerian men. However, there is limited information on patterns of cancer screening and psychosocial predictors of early cancer detection behaviors among Nigerian men. In this cross-sectional study, we examined demographic and psychosocial factors influencing early cancer detection behaviors among Nigerian men. Participants (N = 143; Mage = 44.73) responded to survey assessing: masculinity, attachment styles, current and future cancer detection behaviors, and sociodemographic characteristics. We found that among the participants studied, education, masculinity and anxious attachment were significantly associated with current cancer detection behaviors. Additionally, education and anxious attachment were significantly associated with future cancer detection behaviors. Our finding is best served for clinicians and public health professionals, especially those in the field of oncology in Sub-Saharan Africa. Also, the study may be used as a groundwork for future research and health intervention programs targeting men in Sub-Saharan Africa.

scholarly journals MIC-1/GDF15 in Barrett’s oesophagus and oesophageal adenocarcinoma

2015 ◽  
Vol 112 (8) ◽  
pp. 1384-1391 ◽  
Author(s):  
O M Fisher ◽  
A J Levert-Mignon ◽  
S J Lord ◽  
K K M Lee-Ng ◽  
N K Botelho ◽  
...  
Keyword(s):  
Barrett’S Oesophagus ◽  
Oesophageal Adenocarcinoma ◽  
Barrett's Oesophagus
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