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1.
JCO Clin Cancer Inform ; 4: 711-723, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32755460

RESUMO

PURPOSE: Keratinocyte cancers are exceedingly common in high-risk populations, but accurate measures of incidence are seldom derived because the burden of manually reviewing pathology reports to extract relevant diagnostic information is excessive. Thus, we sought to develop supervised learning algorithms for classifying basal and squamous cell carcinomas and other diagnoses, as well as disease site, and incorporate these into a Web application capable of processing large numbers of pathology reports. METHODS: Participants in the QSkin study were recruited in 2011 and comprised men and women age 40-69 years at baseline (N = 43,794) who were randomly selected from a population register in Queensland, Australia. Histologic data were manually extracted from free-text pathology reports for participants with histologically confirmed keratinocyte cancers for whom a pathology report was available (n = 25,786 reports). This provided a training data set for the development of algorithms capable of deriving diagnosis and site from free-text pathology reports. We calculated agreement statistics between algorithm-derived classifications and 3 independent validation data sets of manually abstracted pathology reports. RESULTS: The agreement for classifications of basal cell carcinoma (κ = 0.97 and κ = 0.96) and squamous cell carcinoma (κ = 0.93 for both) was almost perfect in 2 validation data sets but was slightly lower for a third (κ = 0.82 and κ = 0.90, respectively). Agreement for total counts of specific diagnoses was also high (κ > 0.8). Similar levels of agreement between algorithm-derived and manually extracted data were observed for classifications of keratoacanthoma and intraepidermal carcinoma. CONCLUSION: Supervised learning methods were used to develop a Web application capable of accurately and rapidly classifying large numbers of pathology reports for keratinocyte cancers and related diagnoses. Such tools may provide the means to accurately measure subtype-specific skin cancer incidence.

2.
J Invest Dermatol ; 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32615124

RESUMO

Organ transplant recipients (OTRs) have an elevated risk for keratinocyte cancers (KC); basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). We assessed whether polygenic risk scores (PRSs) generated in non-transplantees from the UK Biobank and 23andMe (13,981 SCC, 33,736 BCC, and >560,000 controls), can predict KC risk in an independent OTR cohort. After adjusting for traditional risk factors, compared to the bottom 20%, OTRs in the top 20% PRS had an increased risk of BCC (OR = 3.25, 95% CI = 1.44-7.31, P = 4.4 × 10-3) and SCC (OR = 2.11, 95% CI = 0.98-4.53, P = 0.055). For BCC, top 20% PRS individuals had an absolute risk of 23%, whilst the risk in the bottom 20% was similar to that in the general non-transplantee population. Adding PRS to a model containing traditional skin cancer risk factors yielded a 3% increase in the AUC for BCC (0.73 versus 0.70); adding the PRS did not significantly increase the AUC for SCC. OTRs in the highest genetic risk quintile could benefit from more intense KC screening and preventive strategies than their counterparts. The BCC PRS improves prediction over and above traditional skin cancer risk factors by 3%.

3.
Cancer Epidemiol ; 67: 101742, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32512495

RESUMO

BACKGROUND: Cancer is a major disease burden globally and people who are socioeconomically disadvantaged have a higher incidence of many types of cancer. We investigated the potential to reduce socioeconomic disparities in cancer incidence in Australia by lowering the prevalence of exposure to four modifiable causes: smoking, alcohol, overweight/obesity and physical inactivity. METHODS: We used cancer incidence data from the Australian Cancer Database and risk factor prevalence data from the Australian National Health Survey to estimate the proportions of cancers attributable to the four factors, by area-level socioeconomic disadvantage. For the three risk factors where prevalence was lowest among the least disadvantaged (smoking, overweight/obesity, physical inactivity), we also estimated the potential impact of reducing prevalence in the most disadvantaged areas to that in the least disadvantaged areas. RESULTS: The proportion of cancer attributable to the four factors in combination ranged from 22 % in the most disadvantaged areas to 14 % in the least disadvantaged areas. If the prevalence of tobacco smoking, overweight/obesity and physical inactivity in the more disadvantaged areas were the same as that in the least disadvantaged, an estimated 19,500 cancers (4 % of all cancers diagnosed) could have been prevented in Australia between 2009 and 2013. CONCLUSIONS: Reducing the prevalence of key causal factors in areas of greater social disadvantage would prevent many cases of cancer. Strategies to achieve this in highly disadvantaged areas are needed.

4.
Lancet Glob Health ; 8(5): e613-e614, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32353298
5.
Australas J Dermatol ; 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32285436

RESUMO

BACKGROUND/OBJECTIVES: Perineural invasion within keratinocyte cancer is a hallmark of tumour aggression, and a definitive treatment paradigm for this condition remains undetermined. Our aim was to investigate the treatment and outcomes of keratinocyte cancer with incidental perineural invasion within two skin cancer databases to refine treatment protocols. METHODS: We retrospectively assessed the Queensland Perineural Invasion Registry for surgery, histopathology, adjuvant radiotherapy and recurrence of keratinocyte cancer five years post-definitive treatment. We also reviewed the Princess Alexandra Hospital Head and Neck clinical perineural invasion database, specifically looking at surgical margins and adjuvant radiotherapy of cutaneous squamous cell carcinoma (cSCC) with incidental perineural invasion in the primary lesion. RESULTS: There was no recurrence at 5 years in the Perineural Invasion Registry. Basal cell carcinoma (BCC) lesions with nerves <0.1 mm were more commonly treated with surgery alone, compared to lesions with nerves ≥0.1 mm which were offered adjuvant radiotherapy. Of the total BCC lesions with incidental perineural invasion, those with perineural margins ≥5 mm and peripheral tumour margins ≥3 mm were predominantly treated with surgery alone. Eighty-nine per cent of cSCC lesions with incidental perineural invasion were treated with surgery and adjuvant radiotherapy. CONCLUSION: Surgery alone is suitable for BCC lesions with incidental perineural invasion. The majority of BCC lesions achieved ≥5 mm perineural and ≥3 mm peripheral tumour margins. Future research can guide if adjuvant radiation is required for BCC with perineural invasion. The treatment of cSCC with incidental perineural invasion with surgery alone remains undetermined.

6.
Aust N Z J Public Health ; 44(2): 111-115, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32190955

RESUMO

INTRODUCTION: A Melanoma Screening Summit was held in Brisbane, Australia, to review evidence regarding current approaches for early detection of melanomas and explore new opportunities. RESULTS: Formal population-based melanoma screening is not carried out in Australia, but there is evidence of considerable opportunistic screening as well as early detection. Biopsy rates are rising and most melanomas are now diagnosed when in situ. Based on evidence review and expert opinion, the Summit attendees concluded that there is currently insufficient information in terms of comparative benefits, harms and costs to support change from opportunistic to systematic screening. Assessment of gains in precision and cost-effectiveness of integrating total body imaging, artificial intelligence algorithms and genetic risk information is required, as well as better understanding of clinical and molecular features of thin fatal melanomas. CONCLUSIONS: Research is needed to understand how to further optimise early detection of melanoma in Australia. Integrating risk-based population stratification and more precise diagnostic tests is likely to improve the balance of benefits and harms of opportunistic screening, pending assessment of cost-effectiveness. Implications for public health: The Summit Group identified that the personal and financial costs to the community of detecting and treating melanoma are rising, and this may be mitigated by developing and implementing a more systematic process for diagnosing melanoma.


Assuntos
Detecção Precoce de Câncer , Programas de Rastreamento/métodos , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Austrália , Consenso , Detecção Precoce de Câncer/métodos , Política de Saúde , Humanos , Melanoma/prevenção & controle , Prática de Saúde Pública , Neoplasias Cutâneas/prevenção & controle
7.
JAMA Dermatol ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32211827

RESUMO

Importance: Men and women develop melanoma at different rates on different body sites, with variation across countries, but explanations for these disparities remain elusive. Objective: To test whether observed differences in melanoma incidence between men and women vary by population, age, or anatomic site. Design: Cross-sectional analysis of sex- and site-specific temporal trends in melanoma incidence over 3 decades was conducted for men and women diagnosed with invasive melanoma in the US (limited to white race), Canada, Australia, New Zealand, the UK, Sweden, Norway, and Denmark. Using cancer registry data, male to female incidence rate ratios (IRRs) were calculated overall and by anatomic site, and Joinpoint regression models were used to estimate the annual percentage rate changes in sex- and site-specific incidence in each population. Incidence rates were standardized to the US 2000 population. Data on the incidence between January 1, 1982, and December 31, 2015, were obtained; analysis was conducted from March 1 to October 15, 2019. Main Outcomes and Measures: Male to female IRRs and annual percentage change in rates. Results: Total melanoma incidence was higher in men than women in US individuals (limited to white race), Canada, Australia, and New Zealand, but not in Denmark, the UK, Norway, and Sweden. In all populations, men had higher rates of melanoma of the head and neck and trunk than women (male to female IRR >1), but lower melanoma rates on the lower limbs (ie, male to female IRR approximately 0.5). The male to female IRR increased log linearly with age, with excess melanomas in women younger than 45 years in all populations (eg, IRR for 20-24 y age group, 0.3 in Denmark and 0.7 in Australia), and excess melanomas in men older than 69 years (eg, IRR for 70-74 y age group, 1.1 in Denmark and 2.1 in the US white population). The age at which the melanoma incidence in men exceeded the melanoma incidence in women differed by population, being achieved the earliest in Australia (45-49 years) and latest in Denmark (65-69 years). Conclusions and Relevance: In predominantly fair-skinned populations, melanoma incidence appears to differ systematically and consistently between men and women by age and anatomic site.

8.
BMJ Open ; 10(2): e034388, 2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-32107270

RESUMO

OBJECTIVE: To compare the long-term economic impact of melanoma prevention by sun protection, with the corresponding impact of early detection of melanoma to decrease melanoma deaths. DESIGN: Cost-effectiveness analysis using Markov cohort model. Data were primarily from two population-based randomised controlled trials, epidemiological and costing reports, and included flow-on effects for keratinocyte cancers (previously non-melanoma skin cancers) and actinic keratoses. SETTING: Queensland, Australia. PARTICIPANTS: Men and women with a mean age 50 years modelled for 30 years. INTERVENTIONS: Daily sunscreen use (prevention) compared with annual clinical skin examinations (early detection) and comparing these in turn with the status quo. PRIMARY AND SECONDARY OUTCOMES: Costs, counts of melanoma, melanoma deaths, keratinocyte cancers, life years and quality-adjusted life years. RESULTS: Per 100 000 individuals, for early detection, primary prevention and without intervention, there were 2446, 1364 and 2419 new melanomas, 556, 341 and 567 melanoma deaths, 64 452, 47 682 and 64 659 keratinocyte cancers and £493.5, £386.4 and £406.1 million in economic costs, respectively. There were small differences between prevention and early detection in life years saved (0.09%) and quality-adjusted life years gained (0.10%). CONCLUSIONS: Compared with early detection of melanoma, systematic sunscreen use at a population level will prevent substantial numbers of new skin tumours, melanoma deaths and save healthcare costs. Primary prevention through daily use of sunscreen is a priority for investment in the control of melanoma.

9.
Int J Cancer ; 147(5): 1391-1396, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32067220

RESUMO

There is little long-term follow-up information about how the number of melanoma deaths and case fatality vary over time according to the measured thickness of melanoma at diagnosis. This population-based longitudinal cohort study examines patterns and trends in case fatality among 44,531 people in Queensland (Australia) diagnosed with a single invasive melanoma (International Classification of Diseases for Oncology, third revision [ICD-O-3], C44, Morphology 872-879) between 1987 and 2011, including 11,883 diagnosed between 1987 and 1996, with up to 20 years follow-up (to December 2016). The 20-year case fatality increased by thickness, with the percentage of melanoma deaths within 20 years of diagnosis being up to 4.8% for melanomas with measured thickness <0.80 mm, 10.6% for tumors 0.8 to <1.0 mm and generally more than 30% for melanomas measuring 3 mm and more. For melanomas <1.0 mm, most deaths occurred between 5 and 20 years after diagnosis, whereas for thicker melanomas the reverse was true with most deaths occurring within the first 5 years. Five-year case fatality decreased over successive calendar time periods for melanomas <1.0 mm, but not for melanomas ≥1.0 mm. These findings demonstrate that the time course for fatal melanomas varies markedly according to tumor thickness at diagnosis. Improved understanding of the patient factors and characteristics of melanomas, in addition to tumor thickness, which increase the likelihood of progression, is needed to guide clinical diagnosis, communication with patients and ongoing surveillance pathways of patients with potentially fatal lesions.

10.
Int J Epidemiol ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068838

RESUMO

BACKGROUND: Height and body mass index (BMI) have both been positively associated with melanoma risk, although findings for BMI have been less consistent than height. It remains unclear, however, whether these associations reflect causality or are due to residual confounding by environmental and lifestyle risk factors. We re-evaluated these associations using a two-sample Mendelian randomization (MR) approach. METHODS: We identified single nucleotide polymorphisms (SNPs) for BMI and height from separate genome-wide association study (GWAS) meta-analyses. We obtained melanoma SNPs from the most recent melanoma GWAS meta-analysis comprising 12 874 cases and 23 203 controls. We used the inverse variance-weighted estimator to derive separate causal risk estimates across all SNP instruments for BMI and height. RESULTS: Based on the combined estimate derived from 730 SNPs for BMI, we found no evidence of an association between genetically predicted BMI and melanoma [odds ratio (OR) per one standard deviation (1 SD) (4.6 kg/m2) increase in BMI 1.00, 95% confidence interval (CI): 0.91-1.11]. In contrast, we observed a positive association between genetically-predicted height (derived from a pooled estimate of 3290 SNPs) and melanoma risk [OR 1.08, 95% CI: 1.02-1.13, per 1 SD (9.27 cm) increase in height]. Sensitivity analyses using two alternative MR methods yielded similar results. CONCLUSIONS: These findings provide no evidence for a causal association between higher BMI and melanoma, but support the notion that height is causally associated with melanoma risk. Mechanisms through which height influences melanoma risk remain unclear, and it remains possible that the effect could be mediated through diverse pathways including growth factors and even socioeconomic status.

11.
Australas J Dermatol ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32017030

RESUMO

BACKGROUND/OBJECTIVES: Basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs) are the most commonly encountered cancers in fair-skinned populations worldwide. Perineural invasion is associated with worse outcomes for patients with BCC or SCC. Estimates of perineural invasion prevalence range widely, likely reflecting non-representative patient samples. We sought to determine the prevalence of perineural invasion in BCC and SCC in the general population, as well as among cancers arising in solid organ transplant recipients. METHODS: We retrospectively analysed histopathology reports of BCC and SCC from patients enrolled in the QSkin Study (a population-based cohort of 43 794 Queensland residents recruited 2010-2011) and the Skin Tumours in Allograft Recipients (STAR) study (a cohort of 509 high-risk kidney or liver transplant recipients at the Princess Alexandra Hospital, Brisbane, recruited 2012-2014.) We estimated the prevalence of perineural invasion (and 95% confidence interval) in BCC and SCC, respectively, and identified clinical factors associated with perineural invasion. RESULTS: In QSkin, we observed 35 instances of perineural invasion in 9850 histopathologically confirmed BCCs (0.36%) and 9 instances of perineural invasion in 3982 confirmed SCC (0.23%) lesions. In the STAR cohort, we identified 4 lesions with perineural invasion in 692 BCCs (0.58%) and 16 reports of perineural invasion in 875 SCC lesions (1.9%). CONCLUSIONS: These data suggest that the overall prevalence of perineural invasion in keratinocyte cancer is low, although perineural invasion prevalence may be slightly higher among organ transplant recipients when compared to the general population.

12.
Dig Dis Sci ; 65(4): 1172-1179, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31493039

RESUMO

BACKGROUND: Retrospective studies observe an increased risk of keratinocyte carcinomas (KCs) in patients with inflammatory bowel disease (IBD) on thiopurine (TP) medication. The role of traditional risk factors such as skin type and sun protection behavior has not been studied in this population. This study aimed to examine traditional KC risk factors and thiopurine use on skin cancer development in an IBD cohort. METHODS: Consecutive IBD patients were recruited from four specialist centers in Australia and New Zealand, each with varying UV exposure indices. Data pertaining to race, skin color, freckling and sun protection behavior, dose of TP therapy, and skin cancer development were elicited through a self-reported questionnaire. RESULTS: A total of 691 IBD patients were included with 62 reporting KC development. Thiopurine usage was similar among patients who developed skin cancer compared with those who did not (92% vs. 89%, p = 0.3). There was no statistically significant association between KC development and TP dose or 6-thioguanine nucleotide levels. In multivariate modeling, four factors were independently and significantly associated with KC: age over 61 years old versus less than 30 years old (OR 6.76; 95% CI 2.38-19.18), residing in Brisbane versus Christchurch (OR 3.3; 95% CI 1.6-6.8), never staying in the shade versus staying in the shade ≥ 50% of the time (OR 3.8; 95% CI 1.4-10.5), and having a skin type that never tanned versus other skin types (OR 6.9; 95% CI 2.9-16.0). CONCLUSION: Skin type, age, and sun protection behavior are more important risk factors for KC development than thiopurine medication use in this IBD population.

14.
Cancer Epidemiol Biomarkers Prev ; 29(2): 427-433, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31748258

RESUMO

BACKGROUND: Obesity is a major risk factor for esophageal adenocarcinoma (EA) and its precursor Barrett's esophagus (BE). Research suggests that individuals with high genetic risk to obesity have a higher BE/EA risk. To facilitate understanding of biological factors that lead to progression from BE to EA, the present study investigated the shared genetic background of BE/EA and obesity-related traits. METHODS: Cross-trait linkage disequilibrium score regression was applied to summary statistics from genome-wide association meta-analyses on BE/EA and on obesity traits. Body mass index (BMI) was used as a proxy for general obesity, and waist-to-hip ratio (WHR) for abdominal obesity. For single marker analyses, all genome-wide significant risk alleles for BMI and WHR were compared with summary statistics of the BE/EA meta-analyses. RESULTS: Sex-combined analyses revealed a significant genetic correlation between BMI and BE/EA (rg = 0.13, P = 2 × 10-04) and a rg of 0.12 between WHR and BE/EA (P = 1 × 10-02). Sex-specific analyses revealed a pronounced genetic correlation between BMI and EA in females (rg = 0.17, P = 1.2 × 10-03), and WHR and EA in males (rg = 0.18, P = 1.51 × 10-02). On the single marker level, significant enrichment of concordant effects was observed for BMI and BE/EA risk variants (P = 8.45 × 10-03) and WHR and BE/EA risk variants (P = 2 × 10-02). CONCLUSIONS: Our study provides evidence for sex-specific genetic correlations that might reflect specific biological mecha-nisms. The data demonstrate that shared genetic factors are particularly relevant in progression from BE to EA. IMPACT: Our study quantifies the genetic correlation between BE/EA and obesity. Further research is now warranted to elucidate these effects and to understand the shared pathophysiology.

16.
BMJ Open ; 9(11): e032969, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31712348

RESUMO

INTRODUCTION: Melanoma is Australia's fourth most common cancer. Early detection is fundamental in maximising health outcomes and minimising treatment costs. To date, population-based screening programmes have not been justified in health economic studies. However, a skin surveillance approach targeting high-risk individuals could improve the cost-benefit ratio. METHODS AND ANALYSIS: This paper describes a 2-year longitudinal randomised controlled trial (RCT) to compare routine clinical care (control) with an intensive skin surveillance programme (intervention) consisting of novel three-dimensional (3D) total-body photography (TBP), sequential digital dermoscopy and melanoma-risk stratification, in a high-risk melanoma cohort. Primary outcomes will evaluate clinical, economic and consumer impact of the intervention. Clinical outcomes will evaluate differences in the rate of lesion excisions/biopsies per person, benign to malignant ratio for excisions and thickness of melanomas diagnosed. A health economic analysis using government data repositories will capture healthcare utilisation and costs relating to skin surveillance. Consumer questionnaires will examine intervention acceptability, the psychological impact, and attitudes towards melanoma risk and sun protective behaviour. Secondary outcomes include the development of a holistic risk algorithm incorporating clinical, phenotypic and genetic factors to facilitate the identification of those most likely to benefit from this surveillance approach. Furthermore, the feasibility of integrating the intervention with teledermatology to enhance specialist care in remote locations will be evaluated. This will be the first RCT to compare a targeted surveillance programme utilising new 3D TBP technology against current routine clinical care for individuals at high risk of melanoma. ETHICS AND DISSEMINATION: This study has received Human Research Ethics Committee (HREC) approval from both Metro South Health HREC (HREC/17/QPAH/816) and The University of Queensland HREC (2018000074). TRIAL REGISTRATION NUMBER: ANZCTR12618000267257; Pre-results.

17.
BMJ Open ; 9(11): e029360, 2019 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-31678937

RESUMO

OBJECTIVES: We aimed to estimate the annual pharmaceutical costs for patients with stable coronary artery disease, using Australian administrative data, comparing patients who had undergone interventional treatment with those had not. We also aimed to compare the duration of dual antiplatelet therapy (DAPT) prescription in the real-world, with recommended guidelines. DESIGN: An observational study using administrative data. PARTICIPANTS: We used data from the QSkin study, a population-based prospective study assessing skin cancer risk. Participants were invited from the Queensland population, not based on perceived skin cancer risk, and had consented to future use of their data for approved research projects. MAIN OUTCOME MEASURES: We calculated 12-month costs of pharmaceutical therapy for coronary artery disease for patients in each of three clinically relevant groups: medical therapy only, following coronary stent implantation and following coronary artery bypass graft surgery. We measured the duration of DAPT following stent implantation and total duration of DAPT, where it was prescribed, in the medical therapy only group. RESULTS: Estimated mean annual pharmaceutical costs were highest in the stent group at AUD$1920, compared with AUD$1481 in the medical therapy group, and AUD$881 in the coronary artery bypass group. There were similar rates of prescriptions of symptom relief drugs following stent insertion, compared with the medical therapy only group. The median duration of DAPT in the stent group was 16, and 31 months in the medical therapy group. CONCLUSIONS: Our results suggest that despite the common expectation that the burden of medical therapy is reduced following coronary stent insertion for stable coronary artery disease, this does not occur in practice. Many patients also appear to continue DAPT longer than guidelines recommend, which may put them at unnecessarily elevated risk of bleeding events.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31756444

RESUMO

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.

19.
Cancer ; 125(23): 4210-4223, 2019 12 01.
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.

20.
Nat Commun ; 10(1): 4219, 2019 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527586

RESUMO

Gastroesophageal reflux disease (GERD) is caused by gastric acid entering the esophagus. GERD has high prevalence and is the major risk factor for Barrett's esophagus (BE) and esophageal adenocarcinoma (EA). We conduct a large GERD GWAS meta-analysis (80,265 cases, 305,011 controls), identifying 25 independent genome-wide significant loci for GERD. Several of the implicated genes are existing or putative drug targets. Loci discovery is greatest with a broad GERD definition (including cases defined by self-report or medication data). Further, 91% of the GERD risk-increasing alleles also increase BE and/or EA risk, greatly expanding gene discovery for these traits. Our results map genes for GERD and related traits and uncover potential new drug targets for these conditions.


Assuntos
Doenças do Esôfago/genética , Refluxo Gastroesofágico/genética , Estudo de Associação Genômica Ampla , Feminino , Loci Gênicos , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
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