Publications by authors named "Lesley A Anderson"

87 Publications

Patient's perspectives of living with a precancerous condition: Monoclonal gammopathy of undetermined significance (MGUS).

Eur J Oncol Nurs 2021 Apr 17;51:101901. Epub 2021 Jan 17.

Centre for Public Health, Queen's University Belfast, UK; Aberdeen Centre for Health Data Science, University of Aberdeen, UK. Electronic address:

Purpose: The aim of this study was to investigate patient experiences of living with monoclonal gammopathy of undetermined significance (MGUS). Living with a premalignant condition such as MGUS may elicit negative psychosocial effects including increased anxiety and fear of progression to cancer. To date, no study utilising qualitative methodology has explored the lived experiences of MGUS patients.

Methods: Data was collected via two focus groups and six telephone interviews. MGUS patients (n=14) were recruited via nurse-led haematology telephone-clinics in Northern Ireland. Interviews were transcribed verbatim and the data subjected to thematic analysis.

Outcome: Thematic analysis identified 3 overarching themes; (1) The psychosocial impact of an MGUS diagnosis, (2) Knowledge of MGUS and (3) Experiences of MGUS health services. Patients with MGUS reported experiencing poor psychological adjustment to their condition particularly at the point of diagnosis and approaching follow-up appointments. Feelings of isolation, poor information-provision, increased uncertainty and limited psychosocial support for MGUS patients were also reported. Patients did however reflect positively on their experience of being followed up via nurse-led telephone clinics.

Conclusions: Provision of patient friendly information guides at diagnosis, and additional psychosocial support services such as nurse-led telephone clinics and coordinated patient groups may help MGUS patients adjust better to their diagnosis and in doing so improve quality of life in this patient population.
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http://dx.doi.org/10.1016/j.ejon.2021.101901DOI Listing
April 2021

Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

Carcinogenesis 2021 04;42(3):369-377

Department of Medicine, Institute of Clinical Science, Royal Victoria Hospital, Belfast, UK.

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.
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http://dx.doi.org/10.1093/carcin/bgaa132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052954PMC
April 2021

Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma.

Gastroenterology 2020 12 9;159(6):2065-2076.e1. Epub 2020 Sep 9.

Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Germany.

Background & Aims: Esophageal adenocarcinoma (EA) and its premalignant lesion, Barrett's esophagus (BE), are characterized by a strong and yet unexplained male predominance (with a male-to-female ratio in EA incidence of up to 6:1). Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for these conditions. However, potential sex differences in genetic associations with BE/EA remain largely unexplored.

Methods: Given strong genetic overlap, BE and EA cases were combined into a single case group for analysis. These were compared with population-based controls. We performed sex-specific GWAS of BE/EA in 3 separate studies and then used fixed-effects meta-analysis to provide summary estimates for >9 million variants for male and female individuals. A series of downstream analyses were conducted separately in male and female individuals to identify genes associated with BE/EA and the genetic correlations between BE/EA and other traits.

Results: We included 6758 male BE/EA cases, 7489 male controls, 1670 female BE/EA cases, and 6174 female controls. After Bonferroni correction, our meta-analysis of sex-specific GWAS identified 1 variant at chromosome 6q11.1 (rs112894788, KHDRBS2-MTRNR2L9, P = .039) that was statistically significantly associated with BE/EA risk in male individuals only, and 1 variant at chromosome 8p23.1 (rs13259457, PRSS55-RP1L1, P = 0.057) associated, at borderline significance, with BE/EA risk in female individuals only. We also observed strong genetic correlations of BE/EA with gastroesophageal reflux disease in male individuals and obesity in female individuals.

Conclusions: The identified novel sex-specific variants associated with BE/EA could improve the understanding of the genetic architecture of the disease and the reasons for the male predominance.
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http://dx.doi.org/10.1053/j.gastro.2020.08.052DOI Listing
December 2020

Improving Identification of Cognitive Impairment in Fragility Fracture Patients: Impact of Educational Guidelines on Current Practice.

Geriatr Orthop Surg Rehabil 2020 27;11:2151459320935095. Epub 2020 Jul 27.

Ulster Hospital, South Eastern Health and Social Care Trust, Dundonald, Northern Ireland.

Introduction: Cognitive impairment can hinder a fracture patient's capacity to consent to surgery and negatively impact their postoperative recovery and rehabilitation. National guidelines recommend screening for cognitive impairment upon admission, and the Abbreviated Mental Test Score (AMTS) is a commonly used tool for this. This project aimed to assess current practice regarding documentation of AMTS among frail fracture patients upon admission and to improve AMTS documentation following a simple intervention.

Methods: Baseline data were obtained by inpatient chart review throughout November to December 2018 in a district general hospital with emergency fracture services. All patients admitted with a fragility hip fracture and patients over 65 years with any fracture were included. National guidelines and baseline results were then distributed among junior doctors. Following an intervention, further data were collected throughout January to February 2019.

Results: Preintervention, 40 suitable patients (mean age: 82 years) were identified; 9 (22.0%) of whom had an AMTS recorded upon admission. Among the hip fracture subgroup (n = 25), 7 (26.9%) had an AMTS recorded. Postintervention, 39 patients (mean age: 80 years) were identified; 15 (38.5%) of whom had an AMTS recorded. Among the hip fracture subgroup (n = 30), 11 (36.7%) had an AMTS recorded. Statistical analysis demonstrated a significant improvement in AMTS documentation both among the overall cohort ( = .001) and hip fracture patients ( = .019). No significant association was found between AMTS documentation and patient age ( = .566), grade of admitting doctor ( = .058), or prior cognitive/mental health disorder ( = .256).

Discussion: A small yet significant improvement in AMTS documentation among elderly/hip fracture patients was observed following distribution of educational material. Further work should explore the effect of cognitive impairment on outcomes related to orthopedic injuries beyond hip fractures.
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http://dx.doi.org/10.1177/2151459320935095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388100PMC
July 2020

Does Risk of Progression from Barrett's Esophagus to Esophageal Adenocarcinoma Change Based on the Number of Non-dysplastic Endoscopies?

Dig Dis Sci 2021 Jun 20;66(6):1965-1973. Epub 2020 Jul 20.

Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.

Background: There is a large Barrett's esophagus patient population undergoing endoscopic surveillance. Methods to stratify patients into higher and lower risk groups may enable more varied surveillance intervals for patients with non-dysplastic Barrett's esophagus that could optimize use of endoscopy resources.

Objective: We aimed to assess whether risk of progression to esophageal adenocarcinoma differed in patients with multiple endoscopic biopsies negative for dysplasia.

Methods: We conducted a retrospective cohort study among individuals from the population-based Northern Ireland Barrett's register with a histologically confirmed diagnosis of non-dysplastic Barrett's esophagus (with intestinal metaplasia) between 1993 and 2010, who had at least one endoscopic biopsy conducted at least 12 months after diagnosis. We used Poisson regression to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for the association between number of successive endoscopies showing non-dysplastic Barrett's esophagus and risk of esophageal adenocarcinoma alone, and combined with high-grade dysplasia, at the next endoscopy.

Results: We identified 1761 individuals who met our eligibility criteria. Subsequent risk of progression to esophageal adenocarcinoma was lower at the next endoscopy following two endoscopies showing non-dysplastic Barrett's esophagus (IRR 0.26, 95% CI 0.10-0.66) than following one endoscopy showing non-dysplastic Barrett's esophagus. Similar findings were apparent for risk of progression to esophageal adenocarcinoma or high-grade dysplasia (IRR 0.41, 95% CI 0.22-0.79).

Conclusion: The lower risk of malignant progression in individuals with persistent non-dysplastic Barrett's esophagus over two consecutive endoscopic biopsies but not for longer term persistence does not support hypotheses of persistence being an indicator of less biologically aggressive lesions. Instead, the initial difference may be attributable to post-endoscopy cancers and support the necessity of adhering to robust quality standards for endoscopic procedures.
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http://dx.doi.org/10.1007/s10620-020-06483-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855450PMC
June 2021

Cancer Incidence Projections in Northern Ireland to 2040.

Cancer Epidemiol Biomarkers Prev 2020 07 24;29(7):1398-1405. Epub 2020 Apr 24.

Northern Ireland Cancer Registry, Queen's University Belfast, Belfast, Northern Ireland.

Background: Data on historic trends and estimates of future cancer incidence are essential if cancer services are to be adequately resourced in future years.

Methods: Age-standardized incidence rates (ASIR) for all cancers combined and 19 common cancers diagnosed during 1993-2017 were determined by sex, year of diagnosis, and age. Data were fitted using an age-period-cohort model, which was used to predict rates in future years up to 2040. These were combined with population projections to provide estimates of the future case number.

Results: Compared with the annual average in 2013-2017, for all cancers (excluding nonmelanoma skin) ASIRs are expected by 2040 to fall 9% among males and rise 12% among females, while the number of cases diagnosed is projected to increase by 45% for males and 58% for females. Case volume is projected to rise for all cancer types except for cervical and stomach cancer, with the annual number of cases diagnosed projected to more than double among males for melanoma, liver, and kidney cancers, and among females for liver, pancreatic, and lung cancers.

Conclusions: Increased numbers of cancer cases is projected, due primarily to projected increases in the number of people aged 60 years and over.

Impact: Projected increases will significantly impact the health services which diagnose and treat cancer. However, while population growth is primarily responsible, reduction of exposure to cancer risk factors, especially tobacco use, obesity, alcohol consumption, and UV radiation, could attenuate the predicted increase in cancer cases.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0098DOI Listing
July 2020

Modifiable Lifestyle and Medical Risk Factors Associated With Myeloproliferative Neoplasms.

Hemasphere 2020 Feb 3;4(1):e327. Epub 2020 Jan 3.

Centre for Medical Education, Queen's University Belfast, Belfast, Northern Ireland and Belfast Health and Social Care Trust, Northern Ireland.

Despite the identification of acquired genetic mutations associated with Myeloproliferative Neoplasms (MPNs) there is a paucity of information relating to modifiable risk factors that may lead to these mutations. The MOSAICC Study was an exploratory case-control study of polycythemia vera (PV), essential thrombocythemia (ET), and Myelofibrosis (MF). MPN patients and population controls (identified by General Practitioners) and non-blood relative/friend controls were recruited from 2 large UK centers. Participants completed a telephone-based questionnaire analyzed by unconditional logistic regression analysis adjusting for potential confounders. Risk factors for MPNs identified included increasing childhood household density [odds ratio (OR) 2.55, 95% confidence interval (CI) 1.16-5.62], low childhood socioeconomic status (OR 2.30, 95%CI 1.02-5.18) and high pack years smoking (OR 2.19, 95%CI 1.03-4.66) and current smoking restricted to JAK2 positive PV cases (OR 3.73, 95%CI 1.06-13.15). Obesity was linked with ET (OR 2.59, 95%CI 1.02-6.58) confirming results in previous cohort studies. Receipt of multiple CT scans was associated with a strongly increased risk of MPN although with wide confidence intervals (OR 5.38, 95%CI 1.67-17.3). Alcohol intake was inversely associated with risk of PV (OR 0.41, 95%CI 0.19-0.92) and ET (OR 0.48, 95%CI 0.24-0.98). The associations with childhood household density, high pack years smoking and alcohol were also seen in multivariate analysis. This is the largest case control study in MPNs to date and confirms the previously reported associations with obesity and cigarette smoking from cohort studies in addition to novel associations. In particular, the role of smoking and JAK2 mutation cases merits further evaluation.
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http://dx.doi.org/10.1097/HS9.0000000000000327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000482PMC
February 2020

Association Between Levels of Sex Hormones and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus.

Clin Gastroenterol Hepatol 2020 11 19;18(12):2701-2709.e3. Epub 2019 Nov 19.

Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.

Background & Aims: Esophageal adenocarcinoma (EAC) occurs most frequently in men. We performed a Mendelian randomization analysis to investigate whether genetic factors that regulate levels of sex hormones are associated with risk of EAC or Barrett's esophagus (BE).

Methods: We conducted a Mendelian randomization analysis using data from patients with EAC (n = 2488) or BE (n = 3247) and control participants (n = 2127), included in international consortia of genome-wide association studies in Australia, Europe, and North America. Genetic risk scores or single-nucleotide variants were used as instrumental variables for 9 specific sex hormones. Logistic regression provided odds ratios (ORs) with 95% CIs.

Results: Higher genetically predicted levels of follicle-stimulating hormones were associated with increased risks of EAC and/or BE in men (OR, 1.14 per allele increase; 95% CI, 1.01-1.27) and in women (OR, 1.28; 95% CI, 1.03-1.59). Higher predicted levels of luteinizing hormone were associated with a decreased risk of EAC in men (OR, 0.92 per SD increase; 95% CI, 0.87-0.99) and in women (OR, 0.93; 95% CI, 0.79-1.09), and decreased risks of BE (OR, 0.88; 95% CI, 0.77-0.99) and EAC and/or BE (OR, 0.89; 95% CI, 0.79-1.00) in women. We found no clear associations for other hormones studied, including sex hormone-binding globulin, dehydroepiandrosterone sulfate, testosterone, dihydrotestosterone, estradiol, progesterone, or free androgen index.

Conclusions: In a Mendelian randomization analysis of data from patients with EAC or BE, we found an association between genetically predicted levels of follicle-stimulating and luteinizing hormones and risk of BE and EAC.
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http://dx.doi.org/10.1016/j.cgh.2019.11.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580878PMC
November 2020

Comparison of Molecular Assays for HPV Testing in Oropharyngeal Squamous Cell Carcinomas: A Population-Based Study in Northern Ireland.

Cancer Epidemiol Biomarkers Prev 2020 01 30;29(1):31-38. Epub 2019 Oct 30.

Northern Ireland Molecular Pathology Laboratory, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.

Background: Determination of human papillomavirus (HPV) status has become clinically relevant for patient stratification under UICC TNM8 staging. Within the United Kingdom, a combination of p16 IHC and HPV DNA-ISH is recommended for classifying HPV status. This study will assess a series of clinically applicable second-line molecular tests to run in combination with p16 IHC to optimally determine HPV status.

Methods: The ability of HPV RNA-ISH, HPV DNA-ISH, and HPV DNA-PCR to identify p16-positive/HPV-positive patients was investigated in a population-based oropharyngeal squamous cell carcinoma (OPSCC) cohort of patients diagnosed in Northern Ireland from 2000 to 2011.

Results: Only 41% of the Northern Irish OPSCC patient population was associated with HPV-driven carcinogenesis. Both ISH assays were more specific than the DNA-PCR assay (100% and 95% vs. 67%) and were less likely to be affected by preanalytic factors such as increasing block age. A pooled HPV genotype probe for RNA-ISH was found to be the most accurate molecular assay assessed (95% accuracy) when compared with p16 positivity.

Conclusions: Our study demonstrates the advantage of tissue-based molecular assays when determining HPV status in retrospective samples. Specifically, we demonstrate the enhanced sensitivity and specificity of ISH techniques compared with PCR-based methodology when working with formalin-fixed paraffin-embedded tissue, and found HPV RNA-ISH to be the most effective assay for determining HPV status.

Impact: As p16 IHC is a relatively inexpensive, accessible, and sensitive test for stratifying patients by HPV status, this study finds that more patients would benefit from first-line p16 IHC followed by specific HPV testing using HPV RNA-ISH to confirm HPV status.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0538DOI Listing
January 2020

Association Between Aspirin Use and Biliary Tract Cancer Survival.

JAMA Oncol 2019 12;5(12):1802-1804

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.

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http://dx.doi.org/10.1001/jamaoncol.2019.4328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802421PMC
December 2019

Diabetes in relation to Barrett's esophagus and adenocarcinomas of the esophagus: A pooled study from the International Barrett's and Esophageal Adenocarcinoma Consortium.

Cancer 2019 12 6;125(23):4210-4223. Epub 2019 Sep 6.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Background: Diabetes is positively associated with various cancers, but its relationship with tumors of the esophagus/esophagogastric junction remains unclear.

Methods: Data were harmonized across 13 studies in the International Barrett's and Esophageal Adenocarcinoma Consortium, comprising 2309 esophageal adenocarcinoma (EA) cases, 1938 esophagogastric junction adenocarcinoma (EGJA) cases, 1728 Barrett's esophagus (BE) cases, and 16,354 controls. Logistic regression was used to estimate study-specific odds ratios (ORs) and 95% CIs for self-reported diabetes in association with EA, EGJA, and BE. Adjusted ORs were then combined using random-effects meta-analysis.

Results: Diabetes was associated with a 34% increased risk of EA (OR, 1.34; 95% CI, 1.00-1.80; I  = 48.8% [where 0% indicates no heterogeneity, and larger values indicate increasing heterogeneity between studies]), 27% for EGJA (OR, 1.27; 95% CI, 1.05-1.55; I  = 0.0%), and 30% for EA/EGJA combined (OR, 1.30; 95% CI, 1.06-1.58; I  = 34.9%). Regurgitation symptoms modified the diabetes-EA/EGJA association (P for interaction = .04) with a 63% increased risk among participants with regurgitation (OR, 1.63; 95% CI, 1.19-2.22), but not among those without regurgitation (OR, 1.03; 95% CI, 0.74-1.43). No consistent association was found between diabetes and BE.

Conclusions: Diabetes was associated with increased EA and EGJA risk, which was confined to individuals with regurgitation symptoms. Lack of an association between diabetes and BE suggests that diabetes may influence progression of BE to cancer.
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http://dx.doi.org/10.1002/cncr.32444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001889PMC
December 2019

Benign tumors in myotonic dystrophy type I target disease-related cancer sites.

Ann Clin Transl Neurol 2019 08 26;6(8):1510-1518. Epub 2019 Jul 26.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Objectives: Recent evidence showed that myotonic dystrophy type I (DM1) patients are at increased risk of certain cancers, but the risk of benign tumors is unknown. We compared the risk of benign tumors in DM1 patients with matched DM1-free individuals and assessed the association between benign tumors and subsequent cancers.

Methods: We identified 927 DM1 patients and 13,085 DM1-free individuals matched on gender, birth-year, clinic, and clinic-registration year from the UK Clinical Practice Research Datalink, a primary care records database. We used Cox regression models for statistical analyses.

Results: DM1 patients had elevated risks of thyroid nodules (Hazard Ratio [HR] = 10.4; 95% Confidence Interval [CI] = 3.91-27.52; P < 0.001), benign tumors of the brain or nervous system (HR = 8.4; 95% CI = 2.48-28.47; P < 0.001), colorectal polyps (HR = 4.3; 95% CI = 1.76-10.41; P = 0.001), and possibly uterine fibroids (HR = 2.7; 95% CI = 1.22-5.88; P = 0.01). Pilomatricomas and salivary gland adenomas occurred almost exclusively in DM1 patients (Fisher's exact P < 0.001). The HR for colorectal polyps was elevated in DM1 males but not in females (HR = 8.2 vs. 1.3, respectively; P-heterogeneity < 0.001), whereas endocrine and brain tumors occurred exclusively in females. The data suggested an association between benign tumors and subsequent cancer in classic DM1 patients (HR = 2.7; 95% CI = 0.93-7.59; P = 0.07).

Interpretation: Our study showed a similar site-specific benign tumor profile to that previously reported for DM1-associated cancers. The possible association between benign tumors and subsequent cancer in classic DM1 patients warrants further investigation as it may guide identifying patients at elevated risk of cancer. Our findings underscore the importance of following population-based screening recommendations in DM1 patients, for example, for colorectal cancer.
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http://dx.doi.org/10.1002/acn3.50856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689687PMC
August 2019

Low knowledge and awareness of monoclonal gammopathy of undetermined significance (MGUS) among general practitioners.

BMC Fam Pract 2019 05 14;20(1):61. Epub 2019 May 14.

Cancer Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Grosvenor Road, Belfast, BT12 6BJ, Northern Ireland.

Introduction: While multiple myeloma (MM) is a rare diagnosis within primary care, its precursor MGUS (monoclonal gammopathy of undetermined significance) is more common, particularly among older populations. Upon first detection, the majority of MGUS patients will be under the care of their General Practitioner (GP)/Family Doctor who is also often the first healthcare professional that patients report symptoms of progression to. However, our previous work with MGUS patients and haematology healthcare professionals has suggested that knowledge and awareness of MGUS is low among GPs.

Methods: An online survey was undertaken to investigate knowledge and awareness of MGUS and services needed by GPs/GP trainees to support these patients. The survey was promoted at a large European primary care conference and via social media. Descriptive statistics were utilised to compare participant responses.

Results: In total 58 GPs (n = 35 GPs and n = 23 GP trainees) from 24 countries responded. Overall, self-reported familiarity with the term MGUS was low (mean score: 2.21/5, standard deviation (SD): 1.09), but higher among GPs who reported having at least one MGUS patient (mean score: 2.83/5, SD 0.99). The majority (88.2%) of GPs/GP trainees stated they would feel uncomfortable discussing MGUS with patients. The increased risk of haematological malignancies was identified by 62.1% of GPs/GP trainees with MM, lymphoma and myelodysplastic syndromes the most commonly reported cancers associated with MGUS. The majority (81.6%) of GPs/GP trainees were supportive of patient follow-up via telephone clinics (phlebotomy performed in GP practice with patient management maintained by haematology) but only 27.1% stated they would be happy to solely manage all low/low-intermediate risk MGUS patients. A laboratory report alerting to the possibility of MGUS or a haematological malignancy was reported as the most useful service which could be implemented to help GPs manage MGUS patients. The need for MGUS focused information and education resources for GPs was also highlighted.

Conclusions: The findings of this study highlight a lack of knowledge and awareness of MGUS among GPs/ GP trainees. The majority of GPs/GP trainees are happy to support haematology in managing these patients but require assistance and support in providing these services.
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http://dx.doi.org/10.1186/s12875-019-0944-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518797PMC
May 2019

Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach.

Br J Cancer 2019 04 20;120(8):827-833. Epub 2019 Mar 20.

Centre for Cell Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, UK.

Background: TNM8 staging for oropharyngeal squamous cell carcinomas (OPSCC) surrogates p16 immunohistochemistry for HPV testing. Patients with p16+ OPSCC may lack HPV aetiology. Here, we evaluate the suitability of TNM8 staging for guiding prognosis in such patients.

Methods: HPV status was ascertained using p16 immunohistochemistry and high-risk HPV RNA and DNA in situ hybridisation. Survival by stage in a cohort of OPSCC patients was evaluated using TNM7/TNM8 staging. Survival of p16+/HPV- patients was compared to p16 status.

Results: TNM8 staging was found to improve on TNM7 (log rank p = 0·0190 for TNM8 compared with p = 0·0530 for TNM7) in p16+ patients. Patients who tested p16+ but were HPV- (n = 20) had significantly reduced five-year survival (33%) compared to p16+ patients (77%) but not p16- patients (35%). Cancer stage was reduced in 95% of p16+/HPV- patients despite having a mortality rate twice (HR 2.66 [95% CI: 1.37-5.15]) that of p16+/HPV+ patients under new TNM8 staging criteria.

Conclusion: Given the significantly poorer survival of p16+/HPV- OPSCCs, these data provide compelling evidence for use of an HPV-specific test for staging classification. This has particular relevance in light of potential treatment de-escalation that could expose these patients to inappropriately reduced treatment intensity as treatment algorithms evolve.
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http://dx.doi.org/10.1038/s41416-019-0414-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474272PMC
April 2019

No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study.

Clin Gastroenterol Hepatol 2019 10 1;17(11):2227-2235.e1. Epub 2019 Feb 1.

Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.

Background & Aims: Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett's esophagus (BE).

Methods: We conducted a Mendelian randomization study using a 2-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs; rs3755967, rs10741657, rs12785878, rs10745742, rs8018720, and rs17216707) associated with circulating concentrations of 25(OH)D were used as instrumental variables. We collected data from 6167 patients with BE, 4112 patients with EAC, and 17,159 individuals without BE or EAC (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium, as well as studies from Bonn, Germany, and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC.

Results: Overall, we found no evidence for an association between genetically estimated 25(OH)D concentration and risk of BE or EAC. The odds ratio per 20 nmol/L increase in genetically estimated 25(OH)D concentration for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% CI, 0.77-1.92; P = .41). The odds ratio for EAC risk, estimated by combining the individual SNP association using inverse variance weighting, was 0.68 (95% CI, 0.39-1.19; P = .18).

Conclusions: In a Mendelian randomization study, we found that low genetically estimated 25(OH)D concentrations were not associated with risk of BE or EAC.
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http://dx.doi.org/10.1016/j.cgh.2019.01.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675666PMC
October 2019

Changing incidence of myeloproliferative neoplasms in Australia, 2003-2014.

Am J Hematol 2019 04 12;94(4):E107-E109. Epub 2019 Feb 12.

School of Public Health, Curtin University, Perth, Western Australia, Australia.

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http://dx.doi.org/10.1002/ajh.25407DOI Listing
April 2019

Statin use and reduced risk of biliary tract cancers in the UK Clinical Practice Research Datalink.

Gut 2019 08 17;68(8):1458-1464. Epub 2018 Nov 17.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

Objective: To evaluate the association between statin use and risk of biliary tract cancers (BTC).

Design: This is a nested case-control study conducted in the UK Clinical Practice Research Datalink. We included cases diagnosed with incident primary BTCs, including cancers of the gall bladder, bile duct (ie, both intrahepatic and extrahepatic cholangiocarcinoma), ampulla of Vater and mixed type, between 1990 and 2017. For each case, we selected five controls who did not develop BTCs at the time of case diagnosis, matched by sex, year of birth, calendar time and years of enrolment in the general practice using incidence density sampling. Exposures were defined as two or more prescription records of statins 1 year prior to BTC diagnosis or control selection. ORs and 95% CIs for associations between statins and BTC overall and by subtypes were estimated using conditional logistic regression, adjusted for relevant confounders.

Results: We included 3118 BTC cases and 15 519 cancer-free controls. Current statin use versus non-use was associated with a reduced risk of all BTCs combined (adjusted OR=0.88, 95% CI 0.79 to 0.98). The reduced risks were most pronounced among long-term users, as indicated by increasing number of prescriptions (p=0.016) and cumulative dose of statins (p=0.008). The magnitude of association was similar for statin use and risk of individual types of BTCs. The reduced risk of BTCs associated with a record of current statin use versus non-use was more pronounced among persons with diabetes (adjusted OR=0.72, 95% CI 0.57 to 0.91). Among non-diabetics, the adjusted OR for current statin use versus non-use was 0.91 (95% CI 0.81 to 1.03, p=0.007).

Conclusion: Compared with non-use of statins, current statin use is associated with 12% lower risk of BTCs; no association found with former statin use. If replicated, particularly in countries with a high incidence of BTCs, our findings could pave the way for evaluating the value of statins for BTC chemoprevention.
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http://dx.doi.org/10.1136/gutjnl-2018-317504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525087PMC
August 2019

Information on Genetic Variants Does Not Increase Identification of Individuals at Risk of Esophageal Adenocarcinoma Compared to Clinical Risk Factors.

Gastroenterology 2019 01 19;156(1):43-45. Epub 2018 Sep 19.

Cancer Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom; Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.

We previously developed a tool that identified individuals who later developed esophageal adenocarcinoma (based on age, sex, body mass index, smoking status, and prior esophageal conditions) with an area under the curve of 0.80. In this study, we collected data from 329,463 individuals in the UK Biobank cohort who were tested for genetic susceptibility to esophageal adenocarcinoma (a polygenic risk score based on 18 recognized genetic variants). We found that after inclusion of this genetic information, the area under the curve for identification of individuals who developed esophageal adenocarcinoma remained at 0.80. Testing for genetic variants associated with esophageal adenocarcinoma therefore seems unlikely to improve identification of individuals at risk of esophageal adenocarcinoma.
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http://dx.doi.org/10.1053/j.gastro.2018.09.038DOI Listing
January 2019

Helicobacter pylori Infection Is Associated With Reduced Risk of Barrett's Esophagus: An Analysis of the Barrett's and Esophageal Adenocarcinoma Consortium.

Am J Gastroenterol 2018 08 8;113(8):1148-1155. Epub 2018 Jun 8.

Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland. Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA. San Francisco Medical Center, Kaiser Permanente Northern California, San Francisco, CA, USA. Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA. Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, USA. Center for Clinical Management Research, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, MI, USA. Barrett's Esophagus Program, Division of Gastroenterology Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA. Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.

Objectives: Epidemiological studies of Helicobacter pylori infection and risk of Barrett's esophagus (BE) have reported conflicting results. We examined the association between H. pylori infection and BE and sought to determine whether the association is mediated by gastroesophageal reflux disease (GERD) and to identify potential effect modifiers.

Methods: We used individual level data from 1308 patients with BE (cases), 1388 population-based controls, and 1775 GERD controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). We estimated study-specific odds ratios (ORs) and 95% CIs using multivariable logistic regression models and obtained summary risk estimates using a random-effects meta-analytic approach. We examined potential effect modification by waist-to-hip ratio (WHR), body mass index (BMI), and smoking status by conducting stratified analyses.

Results: For comparisons with population-based controls, H. pylori infection was inversely associated with the risk of BE (adjusted OR = 0.44, 95% CI = 0.36-0.55), with no evidence of between-study heterogeneity (I = 0%). A stronger inverse association between H. pylori and BE was observed among individuals with the CagA-positive strain (P for interaction = 0.017). We found no evidence of interaction between WHR, BMI, smoking status, and H. pylori infection on the risk of BE. There was no association between H. pylori infection and BE for comparisons with GERD controls (OR = 0.96, 95% CI = 0.67-1.37; I = 48%).

Conclusions: This study provides the strongest evidence yet that H. pylori infection is strongly inversely associated with BE. This effect is probably mediated by a decrease in GERD in infected patients, since the protective effect disappears in patients with GERD symptoms.
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http://dx.doi.org/10.1038/s41395-018-0070-3DOI Listing
August 2018

Risk factors for Burkitt lymphoma: a nested case-control study in the UK Clinical Practice Research Datalink.

Br J Haematol 2018 05 20;181(4):505-514. Epub 2018 Apr 20.

Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Burkitt lymphoma (BL) occurs as three subtypes: endemic BL, immunosuppression-related BL and sporadic BL. Descriptive studies of BL age-specific incidence patterns have suggested multimodal peaks near 10, 40 and 70 years of age, but the risk factors for BL at different ages are unknown. We investigated risk factors for BL in the United Kingdom among 156 BL cases and 608 matched BL-free controls identified in the Clinical Practice Research Datalink (CPRD) between 1992 and 2016. Associations with pre-diagnostic body mass index, cigarette smoking, alcohol consumption, hepatitis, Epstein-Barr virus (EBV), human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS), malaria, allergic and autoimmune conditions, and prednisone use were evaluated. Overall, we identified inverse associations between smoking and BL risk, and positive associations between prior EBV infection, HIV/AIDS and prescription or use of prednisone with BL risk. In age-group stratified analyses, BL was associated with malaria exposure (vs. no exposure, odds ratio [OR] 8·00, 95% confidence interval [CI] 1·46-43·7) among those aged 20-59 years old and with hepatitis infection (vs. no infection, OR 3·41, 95% CI 1·01-11·5) among those aged 60+ years old. The effects of EBV, malaria, HIV/AIDS, prednisone and hepatitis on BL remained significant in mutually-adjusted age-group-specific analyses. No risk factors were associated with childhood BL. We report novel associations for BL in non-endemic settings.
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http://dx.doi.org/10.1111/bjh.15229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980720PMC
May 2018

Model for Identifying Individuals at Risk for Esophageal Adenocarcinoma.

Clin Gastroenterol Hepatol 2018 08 17;16(8):1229-1236.e4. Epub 2018 Mar 17.

Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom; Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.

Background & Aims: The prognosis for most patients with esophageal adenocarcinoma (EAC) is poor because they present with advanced disease. Models developed to identify patients at risk for EAC and increase early detection have been developed based on data from case-control studies. We analyzed data from a prospective study to identify factors available to clinicians that identify individuals with a high absolute risk of EAC.

Methods: We collected data from 355,034 individuals (all older than 50 years) without a prior history of cancer enrolled in the UK Biobank prospective cohort study from 2006 through 2010; clinical data were collected through September 2014. We identified demographic, lifestyle, and medical factors, measured at baseline, that associated with development of EAC within 5 years using logistic regression analysis. We used these data to create a model to identify individuals at risk for EAC. Model performance was assessed using area under the receiver operating characteristics curve (AUROC), sensitivity, and specificity analyses.

Results: Within up to 5 years of follow up, 220 individuals developed EAC. Age, sex, smoking, body mass index, and history of esophageal conditions or treatments identified individuals who developed EAC (AUROC, 0.80; 95% CI, 0.77-0.82). We used these factors to develop a scoring system and identified a point cut off that 104,723 individuals (29.5%), including 170 of the 220 cases with EAC, were above. The scoring system identified individuals who developed EAC with 77.4% sensitivity and 70.5% specificity. The 5-year risk of EAC was 0.16% for individuals with scores above the threshold and 0.02% for individuals with scores below the threshold.

Conclusion: We combined data on several well-established risk factors that are available to clinicians to develop a system to identify individuals with a higher absolute risk of EAC within 5 years. Studies are needed to evaluate the utility of these factors in a multi-stage, triaged, screening program.
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http://dx.doi.org/10.1016/j.cgh.2018.03.014DOI Listing
August 2018

Interactions Between Genetic Variants and Environmental Factors Affect Risk of Esophageal Adenocarcinoma and Barrett's Esophagus.

Clin Gastroenterol Hepatol 2018 10 15;16(10):1598-1606.e4. Epub 2018 Mar 15.

Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas. Electronic address:

Background & Aims: Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for esophageal adenocarcinoma (EA) and Barrett's esophagus (BE). However, variants in these loci account for a small fraction of cases of EA and BE. Genetic factors might interact with environmental factors to affect risk of EA and BE. We aimed to identify single nucleotide polymorphisms (SNPs) that may modify the associations of body mass index (BMI), smoking, and gastroesophageal reflux disease (GERD), with risks of EA and BE.

Methods: We collected data on single BMI measurements, smoking status, and symptoms of GERD from 2284 patients with EA, 3104 patients with BE, and 2182 healthy individuals (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium GWAS, the UK Barrett's Esophagus Gene Study, and the UK Stomach and Oesophageal Cancer Study. We analyzed 993,501 SNPs in DNA samples of all study subjects. We used standard case-control logistic regression to test for gene-environment interactions.

Results: For EA, rs13429103 at chromosome 2p25.1, near the RNF144A-LOC339788 gene, showed a borderline significant interaction with smoking status (P = 2.18×10). Ever smoking was associated with an almost 12-fold increase in risk of EA among individuals with rs13429103-AA genotype (odds ratio=11.82; 95% CI, 4.03-34.67). Three SNPs (rs12465911, rs2341926, rs13396805) at chromosome 2q23.3, near the RND3-RBM43 gene, interacted with GERD symptoms (P = 1.70×10, P = 1.83×10, and P = 3.58×10, respectively) to affect risk of EA. For BE, rs491603 at chromosome 1p34.3, near the EIF2C3 gene, and rs11631094 at chromosome 15q14, at the SLC12A6 gene, interacted with BMI (P = 4.44×10) and pack-years of smoking history (P = 2.82×10), respectively.

Conclusion: The associations of BMI, smoking, and GERD symptoms with risks of EA and BE appear to vary with SNPs at chromosomes 1, 2, and 15. Validation of these suggestive interactions is warranted.
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http://dx.doi.org/10.1016/j.cgh.2018.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162842PMC
October 2018

Association between circulating levels of sex steroid hormones and esophageal adenocarcinoma in the FINBAR Study.

PLoS One 2018 17;13(1):e0190325. Epub 2018 Jan 17.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, United States of America.

Background: Esophageal adenocarcinoma (EA) is characterized by a strong male predominance. Sex steroid hormones have been hypothesized to underlie this sex disparity, but no population-based study to date has examined this potential association.

Methods: Using mass spectrometry and ELISA, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in plasma from males- 172 EA cases and 185 controls-within the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation conducted in Northern Ireland and Ireland. Multivariable adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA.

Results: Higher androgen:estrogen ratio metrics were associated with increased odds of EA (e.g., testosterone:estradiol ratio ORQ4 v. Q1 = 2.58, 95%CI = 1.23-5.43; Ptrend = 0.009). All estrogens and androgens were associated with significant decreased odds of EA. When restricted to individuals with minimal to no decrease in body mass index, the size of association for the androgen:estrogen ratio was not greatly altered.

Conclusions: This first study of sex steroid hormones and EA provides tentative evidence that androgen:estrogen balance may be a factor related to EA. Replication of these findings in prospective studies is needed to enhance confidence in the causality of this effect.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190325PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771564PMC
February 2018

Determining Risk of Barrett's Esophagus and Esophageal Adenocarcinoma Based on Epidemiologic Factors and Genetic Variants.

Gastroenterology 2018 04 13;154(5):1273-1281.e3. Epub 2017 Dec 13.

Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas; Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas. Electronic address:

Background & Aims: We developed comprehensive models to determine risk of Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC) based on genetic and non-genetic factors.

Methods: We used pooled data from 3288 patients with BE, 2511 patients with EAC, and 2177 individuals without either (controls) from participants in the international Barrett's and EAC consortium as well as the United Kingdom's BE gene study and stomach and esophageal cancer study. We collected data on 23 genetic variants associated with risk for BE or EAC, and constructed a polygenic risk score (PRS) for cases and controls by summing the risk allele counts for the variants weighted by their natural log-transformed effect estimates (odds ratios) extracted from genome-wide association studies. We also collected data on demographic and lifestyle factors (age, sex, smoking, body mass index, use of nonsteroidal anti-inflammatory drugs) and symptoms of gastroesophageal reflux disease (GERD). Risk models with various combinations of non-genetic factors and the PRS were compared for their accuracy in identifying patients with BE or EAC using the area under the receiver operating characteristic curve (AUC) analysis.

Results: Individuals in the highest quartile of risk, based on genetic factors (PRS), had a 2-fold higher risk of BE (odds ratio, 2.22; 95% confidence interval, 1.89-2.60) or EAC (odds ratio, 2.46; 95% confidence interval, 2.07-2.92) than individual in the lowest quartile of risk based on PRS. Risk models developed based on only demographic or lifestyle factors or GERD symptoms identified patients with BE or EAC with AUC values ranging from 0.637 to 0.667. Combining data on demographic or lifestyle factors with data on GERD symptoms identified patients with BE with an AUC of 0.793 and patients with EAC with an AUC of 0.745. Including PRSs with these data only minimally increased the AUC values for BE (to 0.799) and EAC (to 0.754). Including the PRSs in the model developed based on non-genetic factors resulted in a net reclassification improvement for BE of 3.0% and for EAC of 5.6%.

Conclusions: We used data from 3 large databases of patients from studies of BE or EAC to develop a risk prediction model based on genetic, clinical, and demographic/lifestyle factors. We identified a PRS that increases discrimination and net reclassification of individuals with vs without BE and EAC. However, the absolute magnitude of improvement is not sufficient to justify its clinical use.
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http://dx.doi.org/10.1053/j.gastro.2017.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880715PMC
April 2018

Risk of skin cancer among patients with myotonic dystrophy type 1 based on primary care physician data from the U.K. Clinical Practice Research Datalink.

Int J Cancer 2018 03 20;142(6):1174-1181. Epub 2017 Nov 20.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.

Myotonic dystrophy type 1 (DM1) is an inherited multisystem neuromuscular disorder caused by a CTG trinucleotide repeat expansion in the DMPK gene. Recent evidence documents that DM1 patients have an increased risk of certain cancers, but whether skin cancer risks are elevated is unclear. Using the U.K. Clinical Practice Research Datalink (CPRD), we identified 1,061 DM1 patients and 15,119 DM1-free individuals matched on gender, birth year (±2 years), attending practice and registration year (±1 year). We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of DM1 diagnosis with skin cancer risk using Cox proportional hazards models, for all skin cancers combined and by histological subtype. Follow-up started at the latest of the age at practice registration, DM1 diagnosis/control selection or January 1st 1988, and ended at the earliest of the age at first skin cancer diagnosis, death, transfer out of the practice, last date of data collection or the end of the CPRD record (October 31, 2016). During a median follow-up of 3.6 years, 35 DM1 patients and 108 matched DM1-free individuals developed a skin cancer. DM1 patients had an increased risk of skin cancer overall (HR = 5.44, 95% CI = 3.33-8.89, p < 0.0001), and basal cell carcinoma (BCC) (HR = 5.78, 95% CI = 3.36-9.92, p < 0.0001). Risks did not differ by gender, or age at DM1 diagnosis (p-heterogeneity > 0.5). Our data confirm suggested associations between DM1 and skin neoplasms with the highest risk seen for BCC. Patients are advised to minimize ultraviolet light exposure and seek medical advice for suspicious lesions.
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http://dx.doi.org/10.1002/ijc.31143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773358PMC
March 2018

The MOSAICC study: Assessing feasibility for biological sample collection in epidemiology studies and comparison of DNA yields from saliva and whole blood samples.

Ann Hum Genet 2018 03 27;82(2):114-118. Epub 2017 Oct 27.

Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland.

Biological sample collection is becoming more common in epidemiology research to obtain DNA for genetic analysis. There are many different DNA collection methods but little evidence on their relative effectiveness. Therefore, we took the opportunity of a prospective case-control study in myeloproliferative neoplasms (MPNs) to compare DNA yield from 8.5 mL PAXgene tubes for whole blood collection versus 2 mL Oragene OG-500 saliva collection kits. MPNs include polycythaemia vera, essential thrombocythaemia, and primary myelofibrosis. These are rare diseases and our exploratory case-control study (MOSAICC) sought to improve knowledge regarding their aetiology and to determine optimal methodology for a larger UK-wide study. Overall, 233 participants were recruited to the MOSIACC study, and we collected 187 blood and 214 saliva samples. The mean DNA yield from blood was 659.18 ng/μL, significantly higher than the mean DNA yield from saliva samples (275.79 ng/μL). The higher provision of saliva samples might reflect its non-invasive and more convenient nature, compared to blood sample provision. The differences in mean DNA yields might reflect differences in clinical assistance, adherence to instructions, and health status of individuals. In conclusion, both sample collection techniques are simple, effective, and suitable for DNA collection for genetic analysis in future epidemiological research studies but OG-500 kits offer a less invasive alternative for those who refuse to provide blood.
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http://dx.doi.org/10.1111/ahg.12227DOI Listing
March 2018

Monoclonal gammopathy of undetermined significance as viewed by haematology healthcare professionals.

Eur J Haematol 2018 Jan 14;100(1):20-26. Epub 2017 Nov 14.

Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK.

Objectives: To investigate the words and descriptions used by haematology healthcare professionals (HCPs) to describe monoclonal gammopathy of undetermined significance (MGUS) to their patients.

Methods: A cross-sectional survey of haematology HCPs attending an annual haematology conference was undertaken. Content analysis was applied to the returned qualitative responses.

Results: In total, 55 people, many of whom were doctors (n = 32; 58.2%), responded. The majority of respondents reported using simple terminology such as "abnormal protein" to describe MGUS to their patients. Some reported using analogies that the patient was more likely to be familiar with, such as comparing a paraprotein to the finding of a mole or lump. Education level, age and cognitive ability were cited as important factors in deciding how and whether information was relayed to patients. Many respondents supported frequent follow-up and the transfer of low-risk MGUS patients to primary care. However, several highlighted a lack of awareness and understanding of MGUS outside of haematology, particularly within primary care. Only 41.8% of respondents reported providing all of their patients with an information leaflet.

Conclusions: With an ageing population, it is important to consider management strategies for MGUS patients. Our findings will assist those in making these arrangements.
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http://dx.doi.org/10.1111/ejh.12962DOI Listing
January 2018

Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study.

Lancet Oncol 2017 08 4;18(8):1022-1039. Epub 2017 Jul 4.

Evaluative Epidemiology Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.

Background: Rare cancers pose challenges for diagnosis, treatments, and clinical decision making. Information about rare cancers is scant. The RARECARE project defined rare cancers as those with an annual incidence of less than six per 100 000 people in European Union (EU). We updated the estimates of the burden of rare cancers in Europe, their time trends in incidence and survival, and provide information about centralisation of treatments in seven European countries.

Methods: We analysed data from 94 cancer registries for more than 2 million rare cancer diagnoses, to estimate European incidence and survival in 2000-07 and the corresponding time trends during 1995-2007. Incidence was calculated as the number of new cases divided by the corresponding total person-years in the population. 5-year relative survival was calculated by the Ederer-2 method. Seven registries (Belgium, Bulgaria, Finland, Ireland, the Netherlands, Slovenia, and the Navarra region in Spain) provided additional data for hospitals treating about 220 000 cases diagnosed in 2000-07. We also calculated hospital volume admission as the number of treatments provided by each hospital rare cancer group sharing the same referral pattern.

Findings: Rare cancers accounted for 24% of all cancers diagnosed in the EU during 2000-07. The overall incidence rose annually by 0.5% (99·8% CI 0·3-0·8). 5-year relative survival for all rare cancers was 48·5% (95% CI 48·4 to 48·6), compared with 63·4% (95% CI 63·3 to 63·4) for all common cancers. 5-year relative survival increased (overall 2·9%, 95% CI 2·7 to 3·2), from 1999-2001 to 2007-09, and for most rare cancers, with the largest increases for haematological tumours and sarcomas. The amount of centralisation of rare cancer treatment varied widely between cancers and between countries. The Netherlands and Slovenia had the highest treatment volumes.

Interpretation: Our study benefits from the largest pool of population-based registries to estimate incidence and survival of about 200 rare cancers. Incidence trends can be explained by changes in known risk factors, improved diagnosis, and registration problems. Survival could be improved by early diagnosis, new treatments, and improved case management. The centralisation of treatment could be improved in the seven European countries we studied.

Funding: The European Commission (Chafea).
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http://dx.doi.org/10.1016/S1470-2045(17)30445-XDOI Listing
August 2017

Dietary inflammatory index and risk of reflux oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma: a population-based case-control study.

Br J Nutr 2017 May 2;117(9):1323-1331. Epub 2017 Jun 2.

3Centre for Public Health,Queen's University Belfast,BT12 6BJ,Northern Ireland.

The dietary inflammatory index (DIITM) is a novel composite score based on a range of nutrients and foods known to be associated with inflammation. DII scores have been linked to the risk of a number of cancers, including oesophageal squamous cell cancer and oesophageal adenocarcinoma (OAC). Given that OAC stems from acid reflux and that the oesophageal epithelium undergoes a metaplasia-dysplasia transition from the resulting inflammation, it is plausible that a high DII score (indicating a pro-inflammatory diet) may exacerbate risk of OAC and its precursor conditions. The aim of this analytical study was to explore the association between energy-adjusted dietary inflammatory index (E-DIITM) in relation to risk of reflux oesophagitis, Barrett's oesophagus and OAC. Between 2002 and 2005, reflux oesophagitis (n 219), Barrett's oesophagus (n 220) and OAC (n 224) patients, and population-based controls (n 256), were recruited to the Factors influencing the Barrett's Adenocarcinoma Relationship study in Northern Ireland and the Republic of Ireland. E-DII scores were derived from a 101-item FFQ. Unconditional logistic regression analysis was applied to determine odds of oesophageal lesions according to E-DII intakes, adjusting for potential confounders. High E-DII scores were associated with borderline increase in odds of reflux oesophagitis (OR 1·87; 95 % CI 0·93, 3·73), and significantly increased odds of Barrett's oesophagus (OR 2·05; 95 % CI 1·22, 3·47), and OAC (OR 2·29; 95 % CI 1·32, 3·96), when comparing the highest with the lowest tertiles of E-DII scores. In conclusion, a pro-inflammatory diet may exacerbate the risk of the inflammation-metaplasia-adenocarcinoma pathway in oesophageal carcinogenesis.
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http://dx.doi.org/10.1017/S0007114517001131DOI Listing
May 2017
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