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1.
Cancer ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31490550

RESUMO

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; I2  = 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; I2  = 0.0%), and 30% for EA/EGJA combined (OR, 1.30; 95% CI, 1.06-1.58; I2  = 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.

2.
Ann Clin Transl Neurol ; 6(8): 1510-1518, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31402615

RESUMO

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.

3.
BMC Fam Pract ; 20(1): 61, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088396

RESUMO

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.

4.
Br J Cancer ; 120(8): 827-833, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30890775

RESUMO

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.

5.
Clin Gastroenterol Hepatol ; 17(11): 2227-2235.e1, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30716477

RESUMO

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.

7.
Gut ; 2018 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-30448774

RESUMO

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 (ptrend=0.016) and cumulative dose of statins (ptrend=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, pheterogeneity=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.

8.
Gastroenterology ; 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30243622

RESUMO

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.

9.
Am J Gastroenterol ; 113(8): 1148-1155, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29880962

RESUMO

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 (I2 = 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; I2 = 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.

10.
Br J Haematol ; 181(4): 505-514, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29676453

RESUMO

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.

11.
Clin Gastroenterol Hepatol ; 16(10): 1598-1606.e4, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29551738

RESUMO

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 = 2.18×10-7). 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 = 1.70×10-7, P = 1.83×10-7, and P = 3.58×10-7, 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 = 4.44×10-7) and pack-years of smoking history (P = 2.82×10-7), 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.

12.
Clin Gastroenterol Hepatol ; 16(8): 1229-1236.e4, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29559360

RESUMO

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.

13.
PLoS One ; 13(1): e0190325, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29342161

RESUMO

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.


Assuntos
Adenocarcinoma/sangue , Neoplasias Esofágicas/sangue , Hormônios Esteroides Gonadais/sangue , Feminino , Humanos , Masculino
14.
Eur J Haematol ; 100(1): 20-26, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28885714

RESUMO

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.


Assuntos
Pessoal de Saúde , Hematologia , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Médicos , Estudos Transversais , Progressão da Doença , Feminino , Pesquisas sobre Serviços de Saúde , Comunicação em Saúde , Humanos , Masculino , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Pacientes , Medição de Risco , Fatores de Risco
15.
Ann Hum Genet ; 82(2): 114-118, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29076129

RESUMO

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.

16.
Int J Cancer ; 142(6): 1174-1181, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29114849

RESUMO

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.


Assuntos
Carcinoma Basocelular/epidemiologia , Distrofia Miotônica/epidemiologia , Atenção Primária à Saúde/estatística & dados numéricos , Neoplasias Cutâneas/epidemiologia , Adolescente , Adulto , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Miotônica/genética , Miotonina Proteína Quinase/genética , Medição de Risco , Expansão das Repetições de Trinucleotídeos/genética , Reino Unido/epidemiologia , Adulto Jovem
17.
Gastroenterology ; 154(5): 1273-1281.e3, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29247777

RESUMO

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.


Assuntos
Adenocarcinoma/epidemiologia , Adenocarcinoma/genética , Esôfago de Barrett/epidemiologia , Esôfago de Barrett/genética , Técnicas de Apoio para a Decisão , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/genética , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Adenocarcinoma/diagnóstico , Área Sob a Curva , Austrália/epidemiologia , Esôfago de Barrett/diagnóstico , Estudos de Casos e Controles , Bases de Dados Factuais , Neoplasias Esofágicas/diagnóstico , Europa (Continente)/epidemiologia , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Herança Multifatorial , América do Norte/epidemiologia , Razão de Chances , Fenótipo , Valor Preditivo dos Testes , Curva ROC , Medição de Risco , Fatores de Risco
18.
Lancet Oncol ; 18(8): 1022-1039, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28687376

RESUMO

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).


Assuntos
Neoplasias/epidemiologia , Neoplasias/terapia , Doenças Raras/epidemiologia , Doenças Raras/terapia , Institutos de Câncer , Assistência à Saúde , Europa (Continente)/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Neoplasias/mortalidade , Doenças Raras/mortalidade , Sistema de Registros , Taxa de Sobrevida
19.
Br J Nutr ; 117(9): 1323-1331, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28571591

RESUMO

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.


Assuntos
Adenocarcinoma/etiologia , Esôfago de Barrett/etiologia , Dieta/efeitos adversos , Neoplasias Esofágicas/etiologia , Esofagite Péptica/etiologia , Inflamação/induzido quimicamente , Adenocarcinoma/patologia , Idoso , Estudos de Casos e Controles , Neoplasias Esofágicas/patologia , Feminino , Análise de Alimentos , Humanos , Masculino , Pessoa de Meia-Idade
20.
Eur J Gastroenterol Hepatol ; 29(7): 817-825, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28252462

RESUMO

BACKGROUND AND AIMS: Human papilloma virus (HPV), which may reach the esophagus through orogenital transmission, has been postulated to be associated with esophageal adenocarcinoma (EAC). A systematic review of the literature investigating the prevalence of infectious agents in EAC and Barrett's esophagus (BE) was carried out. METHODS: Using terms for viruses and EAC, the Medline, Embase, and Web of Science databases were systematically searched for studies published, in any language, until June 2016 that assessed the prevalence of viral agents in EAC or BE. Random-effects meta-analyses of proportions were carried out to calculate the pooled prevalence and 95% confidence intervals (CIs) of infections in EAC and BE. RESULTS: A total of 30 studies were included. The pooled prevalence of HPV in EAC tumor samples was 13% (n=19 studies, 95% CI: 2-29%) and 26% (n=6 studies, 95% CI: 3-59%) in BE samples. HPV prevalence was higher in EAC tissue than in esophageal tissue from healthy controls (n=5 studies, pooled odds ratio=3.31, 95% CI: 1.15-9.50). The prevalence of Epstein-Barr virus (EBV) in EAC was 6% (n=5, 95% CI: 0-27%). Few studies have assessed other infectious agents. For each of the analyses, considerable between-study variation was observed (I=84-96%); however, sensitivity analyses did not show any major sources of heterogeneity. CONCLUSION: The prevalence of HPV and EBV in EAC is low compared with other viral-associated cancers, but may have been hampered by small sample sizes and detection methods susceptible to fixation processes. Additional research with adequate sample sizes and high-quality detection methods is required.


Assuntos
Adenocarcinoma/virologia , Esôfago de Barrett/virologia , Infecções por Vírus Epstein-Barr/virologia , Neoplasias Esofágicas/virologia , Herpesvirus Humano 4/isolamento & purificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiologia , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/epidemiologia , Distribuição de Qui-Quadrado , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/epidemiologia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Humanos , Razão de Chances , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Prevalência , Fatores de Risco
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