Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 92
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Nat Commun ; 10(1): 4219, 2019 Sep 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.

3.
Hum Mol Genet ; 28(18): 3148-3160, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31174203

RESUMO

The keratinocyte cancers (KC), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common cancers in fair-skinned people. KC treatment represents the second highest cancer healthcare expenditure in Australia. Increasing our understanding of the genetic architecture of KC may provide new avenues for prevention and treatment. We first conducted a series of genome-wide association studies (GWAS) of KC across three European ancestry datasets from Australia, Europe and USA, and used linkage disequilibrium (LD) Score regression (LDSC) to estimate their pairwise genetic correlations. We employed a multiple-trait approach to map genes across the combined set of KC GWAS (total N = 47 742 cases, 634 413 controls). We also performed meta-analyses of BCC and SCC separately to identify trait specific loci. We found substantial genetic correlations (generally 0.5-1) between BCC and SCC suggesting overlapping genetic risk variants. The multiple trait combined KC GWAS identified 63 independent genome-wide significant loci, 29 of which were novel. Individual separate meta-analyses of BCC and SCC identified an additional 13 novel loci not found in the combined KC analysis. Three new loci were implicated using gene-based tests. New loci included common variants in BRCA2 (distinct to known rare high penetrance cancer risk variants), and in CTLA4, a target of immunotherapy in melanoma. We found shared and trait specific genetic contributions to BCC and SCC. Considering both, we identified a total of 79 independent risk loci, 45 of which are novel.

4.
Prev Med ; 124: 67-74, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31077722

RESUMO

Sunscreen when applied at the recommended concentration (2 mg/cm2) has been shown to block the harmful molecular effects of ultraviolet radiation (UVR) in vivo. In real world conditions, however, sunscreen is often not applied/reapplied sufficiently to yield protection. This field study tested the effectiveness of UV detection stickers to prevent sunburn and improve reapplication of sunscreen. During the Ashes Cricket Test match event (November 2017) in Brisbane, Australia interested spectators were recruited into the control group on DAY-1 and during subsequent days (DAY-2, DAY-3, DAY-4) new participants were recruited into the UV-Sticker group. Participants in both groups were provided with free sunscreen and participants in the UV-Sticker group were additionally provided with a UV detection sticker. Primary outcomes were self-reported sunburns and reapplication of sunscreen. Secondary endpoints included satisfaction with the UV detection stickers. 813 participants enrolled in the study, and complete data is available for 428 participants (52.6% response rate, n = 369 UV detection sticker, n = 59 control). Participants provided with a UV detection sticker were more likely to re-apply sunscreen than controls (80% vs 68%, p = 0.04); but do not reduce sunburn rates. UV detection stickers may improve sunscreen re-application in a high UV-environment. Trial registration: Australian and New Zealand clinical trials register (ACTRN12617001572358).

5.
Occup Environ Med ; 76(7): 462-466, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31113813

RESUMO

OBJECTIVES: Occupational exposure to cosmic and ultraviolet radiation may increase airline pilots' risk of cutaneous melanoma. Meta-analyses of available data show a higher than average incidence of melanoma in airline pilots, but the most recent systematic review revealed that few contemporary data are available. Moreover, all relevant studies have been conducted in Northern Hemisphere populations. We therefore aimed to examine if Australian commercial pilots have a raised incidence of melanoma compared with the general population. METHODS: We examined all melanoma histologically diagnosed among Australian-licensed commercial pilots in the period 2011-2016 by manually reviewing de-identified data in the medical records system of the Australian Civil Aviation Safety Authority. We estimated age-specific incidence rates and compared these with corresponding population rates using standardised incidence ratios (SIRs) as measures of relative risk. Expected numbers were calculated by multiplying age- and calendar period-specific person-years (PYs) with corresponding rates from the entire Australian population; 95% CI were calculated assuming a Poisson distribution of the observed cases. RESULTS: In this cohort of Australian-licensed commercial pilots observed for 91 370 PYs, 114 developed a melanoma (51 invasive, 63 in situ). More than 50% of melanomas occurred on the trunk, and the predominant subtype was superficial spreading melanoma. The SIR for invasive melanoma was 1.20 (95% CI 0.89 to 1.55) and for melanoma in situ, 1.39 (95% CI 1.08 to 1.78). CONCLUSION: Australian-licensed commercial pilots have a modestly raised risk of in situ melanoma but no elevation of invasive melanoma compared with the general population.

6.
Australas J Dermatol ; 2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31012087

RESUMO

BACKGROUND/OBJECTIVE: To describe the clinical settings in which keratinocyte cancers are excised in Queensland and describe the types of practitioners who excise them; to examine costs; and to identify predictors of hospital admission. METHODS: We used linked data for participants from the QSkin study (n = 43 794), including Medicare claims and Queensland hospital admissions relating to treatment episodes for incident keratinocyte cancers from July 2011 to June 2015. We used multinomial logistic regression to measure associations between demographic and clinical characteristics and treatment setting. The median costs of Medicare claims (AU$) were calculated. RESULTS: During 4 years of follow-up, there were 18 479 skin cancer excision episodes among 8613 people. Most excisions took place in private clinical rooms (89.7%), the remainder in hospitals (7.9% private; 2.4% public). Compared with other anatomical sites, skin cancers on the nose, eyelid, ear, lip, finger or genitalia were more likely to be treated in hospitals than in private clinical rooms (public hospital OR 5.7; 95%CI 4.5-7.2; private hospital OR 8.3; 95%CI 7.3-9.4). Primary care practitioners excised 83% of keratinocyte cancers, followed by plastic surgeons (9%) and dermatologists (6%). The median Medicare benefit paid was $253 in private clinical rooms and $334 in private hospitals. Out-of-pocket payments by patients treated in private hospitals were fourfold higher than those in private clinical rooms ($351 vs $80). CONCLUSIONS: Most keratinocyte cancers are excised in primary care, although more than 10% of excisions occur in hospital settings.

7.
Int J Cancer ; 145(11): 2944-2953, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30748013

RESUMO

The International Agency for Research on Cancer first concluded that alcohol causes cancer in humans in 1988. The World Cancer Research Fund has declared that alcohol causes cancer of the oral cavity, pharynx, larynx, oesophagus (squamous cell carcinoma), female breast, colon, rectum, stomach and liver. It recommended that alcohol be avoided altogether to prevent cancer. We aimed to quantify the impact of reducing alcohol consumption on future cancer incidence in Australia. We used PREVENT 3.01 simulation modelling software to estimate the proportion of cancers that could potentially be prevented over a 25-year period under two hypothetical intervention scenarios and two latency periods (20 and 30 years). Under a scenario where alcohol consumption abruptly ceases, we estimated up to 4% of alcohol-related cancers could be avoided over a 25-year period (~49,500 cancers, depending on assumed latency). If the maximum consumption of all Australian adults was ≤20 g/day (~two Australian standard drinks), up to 2% of alcohol-related cancers could be avoided (~29,600 cancers). The maximum proportions were higher for men (6% for no alcohol consumption; 5% for ≤20 g/day) than women (3%; 1%). The proportion avoidable was highest for oesophageal squamous cell carcinoma (17% no alcohol consumption; 9% ≤20 g/day), followed by cancers of the oral cavity (12%; 5%) and pharynx (11%; 5%). The cancer sites with the highest numbers of potentially avoidable cases were colon in men (11,500; 9,900) and breast in women (14,400; 4,100). Successful interventions to reduce alcohol intake could lead to significant reductions in cancer incidence.

8.
Aust N Z J Public Health ; 43(2): 171-175, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30681231

RESUMO

INTRODUCTION: Cancers of the skin are the most common cancers in humans, with Australia and New Zealand having the world's highest incidence. Primary prevention campaigns advise people to apply sunscreen to exposed body sites when outdoors. However, despite growing evidence that cumulative sub-erythemal exposures cause mutational damage, and trial data demonstrating benefit from daily sunscreen use, current policies do not consider the hazards of incidental (everyday) sun exposure. Thus, a Sunscreen Summit was convened to review the evidence and update the policies for people living in Australia and New Zealand. RESULTS: After reviewing the benefits and risks of sunscreen application, the policy group concluded that people living in Australia and New Zealand should be advised to apply sunscreen to the face/head/neck and all parts of the body not covered by clothing on all days when the ultraviolet index is forecast to reach three or greater, irrespective of their anticipated activities. For planned outdoors activities, sunscreen should be used alongside other sun protection measures. CONCLUSIONS: People living in Australia and New Zealand are now advised to apply sunscreen every day when the UV index is predicted to reach 3 or above. Implications for public health: Increased use of sunscreen as part of the daily routine to reduce incidental sun exposure will lead to decreased incidence of skin cancer in the future.


Assuntos
Prevenção Primária/métodos , Neoplasias Cutâneas/prevenção & controle , Luz Solar/efeitos adversos , Protetores Solares/administração & dosagem , Administração Cutânea , Consenso , Feminino , Humanos , Masculino , Nova Zelândia
10.
Aust J Prim Health ; 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-30463662

RESUMO

Medical out-of-pocket costs paid by patients can be problematic when it adversely affects access to care. Survey research involving patients with out-of-pocket expenses may have selection biases, so accurate estimates are unknown. During 2010-11, 419 participants from the QSkin Sun and Health Study (n=43794) had a confirmed diagnosis of either melanoma, prostate, breast, colorectal or lung cancer. These were matched to a general population group (n=421) and a group of high users of GP services (n=419). Medical fees charged and out-of-pocket medical expenses for Medicare services were analysed. Over 2 years, three-quarters of individuals with cancer paid up-front provider fees of up to A$20551 compared with A$10995 for the high GP user group and A$6394 for the general population group. Out-of-pocket expenses were significantly higher for those with cancer (mean A$3514) compared with the high GP-user group (mean A$1837) and general population group (A$1245). Highest expenses were for therapeutic procedures (mean A$2062). Older individuals, those with poor perceived health or private health insurance had the highest costs. Regardless of private insurance status, patients with one of the main five cancers pay significantly higher out-of-pocket costs for health care compared with those without cancer.

11.
J Invest Dermatol ; 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30367874

RESUMO

To delineate causal pathways for melanoma, it is essential to derive unbiased estimates of risk. Extant knowledge derives largely from case-control studies with potential for bias. In a population-based prospective study (QSkin, n=38,854), we assessed melanoma risks associated with pigmentation characteristics and other phenotypes, and explored additive interactions. We fitted Cox proportional hazards models adjusting for other factors to estimate independent effects of each characteristic on melanoma risk. During a mean follow-up of 3.5 years, 642 (1.5%) participants developed melanoma (253 invasive, 389 in situ). The characteristics most strongly associated with invasive melanoma were self-reported nevus density at age 21 ('many' vs. no moles HR 4.91 [2.81-8.55]), inability to tan ('no tan' vs. 'deep tan' HR 3.39 [1.85-6.20]) and red hair color (vs. black HR 3.11 [1.50-6.43]). Notably, propensity to sunburn was not associated with melanoma after adjusting for tanning inability. People with both high nevus density and a history of multiple keratinocyte cancers had significantly higher melanoma risks than those having only one of those traits. We infer that melanoma risk is more strongly related to nevus density and inability to tan than susceptibility to sunburn.

12.
Int J Cancer ; 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30357816

RESUMO

Globally, 39% of the world's adult population is overweight or obese and 23% is insufficiently active. These percentages are even larger in high-income countries with 58% overweight/obese and 33% insufficiently active. Fourteen cancer types have been declared by the World Cancer Research Fund to be causally associated with being overweight or obese: oesophageal adenocarcinoma, stomach cardia, colon, rectum, liver, gallbladder, pancreas, breast, endometrium, ovary, advanced/fatal prostate, kidney, thyroid and multiple myeloma. Colon, postmenopausal breast and endometrial cancers have also been judged causally associated with physical inactivity. We aimed to quantify the proportion of cancer cases that would be potentially avoidable in Australia if the prevalence of overweight/obesity and physical inactivity in the population could be reduced. We used the simulation modelling software PREVENT 3.01 to calculate the proportion of avoidable cancers over a 25-year period under different theoretical intervention scenarios that change the prevalence of overweight/obesity and physical inactivity in the population. Between 2013 and 2037, 10-13% of overweight/obesity-related cancers in men and 7-11% in women could be avoided if overweight and obesity were eliminated in the Australian population. If everyone in the population met the Australian physical activity guidelines for cancer prevention (i.e. engaged in at least 300 min of moderate-intensity physical activity per week), an estimated 2-3% of physical inactivity-related cancers could be prevented in men (colon cancer) and 1-2% in women (colon, breast and endometrial cancers). This would translate to the prevention of up to 190,500 overweight/obesity-related cancers and 19,200 inactivity-related cancers over 25 years.

13.
Contemp Clin Trials ; 74: 61-69, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30287268

RESUMO

BACKGROUND: Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13,000 individuals with AN and ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research. METHODS: ANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire (ED100K-v1), 109 women also completed the Structured Clinical Interview for DSM-IV (SCID), Module H. RESULTS: Blood samples and clinical information were collected from 13,363 individuals with lifetime AN and from controls. Online diagnostic phenotyping was effective and efficient; the validity of the questionnaire was acceptable. CONCLUSIONS: Our multi-pronged recruitment approach was highly effective for rapid recruitment and can be used as a model for efforts by other groups. High online presence of individuals with AN rendered the Internet/social media a remarkably effective recruitment tool in some countries. ANGI has substantially augmented Psychiatric Genomics Consortium AN sample collection. ANGI is a registered clinical trial: clinicaltrials.govNCT01916538; https://clinicaltrials.gov/ct2/show/NCT01916538?cond=Anorexia+Nervosa&draw=1&rank=3.

14.
Br J Cancer ; 119(1): 114-120, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29899391

RESUMO

INTRODUCTION: Published findings on the associations between smoking and the incidence of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are inconsistent. We aimed to generate prospective evidence on these relationships overall and by anatomical site. METHODS: We followed 1,223,626 women without prior cancer by electronic linkage to national cancer registration data. Questionnaire information about smoking and other factors was recorded at recruitment (1996-2001) and every 3-5 years subsequently. Cox regression yielded adjusted relative risks (RRs) comparing smokers versus never-smokers. RESULTS: After 14 (SD4) years follow-up per woman, 6699 had a first registered cutaneous SCC and 48,666 a first BCC. In current versus never-smokers, SCC incidence was increased (RR = 1.22, 95% CI 1.15-1.31) but BCC incidence was decreased (RR = 0.80, 0.78-0.82). RRs varied substantially by anatomical site; for the limbs, current smoking was associated with an increased incidence of SCC (1.55, 1.41-1.71) and a decreased incidence of BCC (0.72, 0.66-0.79), but for facial lesions there was little association of current smoking with either SCC (0.93, 0.82-1.06) or BCC (0.92, 0.88-0.96). Findings in meta-analyses of results from this and seven other prospective studies were largely dominated by the findings in this study. CONCLUSIONS: Smoking-associated risks for cutaneous SCC and BCC are in the opposite direction to each other and appear to vary by anatomical site.

16.
JAMA Psychiatry ; 75(9): 901-910, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29936532

RESUMO

Importance: Urban life has been proposed as an environmental risk factor accounting for the increased prevalence of schizophrenia in urban areas. An alternative hypothesis is that individuals with increased genetic risk tend to live in urban/dense areas. Objective: To assess whether adults with higher genetic risk for schizophrenia have an increased probability to live in more populated areas than those with lower risk. Design, Setting, and Participants: Four large, cross-sectional samples of genotyped individuals of European ancestry older than 18 years with known addresses in Australia, the United Kingdom, and the Netherlands were included in the analysis. Data were based on the postcode of residence at the time of last contact with the participants. Community-based samples who took part in studies conducted by the Queensland Institute for Medical Research Berghofer Medical Research Institute (QIMR), UK Biobank (UKB), Netherlands Twin Register (NTR), or QSkin Sun and Health Study (QSKIN) were included. Genome-wide association analysis and mendelian randomization (MR) were included. The study was conducted between 2016 and 2018. Exposures: Polygenic risk scores for schizophrenia derived from genetic data (genetic risk is independently measured from the occurrence of the disease). Socioeconomic status of the area was included as a moderator in some of the models. Main Outcomes and Measures: Population density of the place of residence of the participants determined from census data. Remoteness and socioeconomic status of the area were also tested. Results: The QIMR participants (15 544; 10 197 [65.6%] women; mean [SD] age, 54.4 [13.2] years) living in more densely populated areas (people per square kilometer) had a higher genetic loading for schizophrenia (r2 = 0.12%; P = 5.69 × 10-5), a result that was replicated across all 3 other cohorts (UKB: 345 246; 187 469 [54.3%] women; age, 65.7 [8.0] years; NTR: 11 212; 6727 [60.0%] women; age, 48.6 [17.5] years; and QSKIN: 15 726; 8602 [54.7%] women; age, 57.0 [7.9] years). This genetic association could account for 1.7% (95% CI, 0.8%-3.2%) of the schizophrenia risk. Estimates from MR analyses performed in the UKB sample were significant (b = 0.049; P = 3.7 × 10-7 using GSMR), suggesting that the genetic liability to schizophrenia may have a causal association with the tendency to live in urbanized locations. Conclusions and Relevance: The results of this study appear to support the hypothesis that individuals with increased genetic risk tend to live in urban/dense areas and suggest the need to refine the social stress model for schizophrenia by including genetics as well as possible gene-environment interactions.

18.
Cancer Epidemiol Biomarkers Prev ; 27(8): 874-881, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29789324

RESUMO

Background: Previous studies suggest that smokers have lower risks of cutaneous melanoma than nonsmokers, but data from population-based prospective studies are scarce. We investigated associations between smoking and melanoma in a cohort study purpose-designed to investigate skin cancer outcomes.Methods: Participants with no prior history of melanoma (n = 38,697) completed a risk factor survey at baseline (2011). Patients were followed through linkage to the cancer registry. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between smoking (including intensity, duration, time since quitting) and melanoma using multivariate Cox proportional hazards regression, accounting for death as a competing event.Results: During a mean follow-up of 3.5 years, invasive melanomas developed in 247 participants. Compared with never smokers, former smokers (but not current smokers) had lower risks of invasive melanoma (HR 0.76; 95% CI, 0.57-1.01). Among former smokers, risks were lower with greater quantity of cigarettes smoked (HR 0.75; 95% CI, 0.56-0.98 per 10 cigarettes/day). No association was observed with duration of smoking while longer time since quitting was associated with a relative risk of melanoma that was not significantly different from the null (HR 1.18; 95% CI, 0.91-1.51, for every 10 years since quitting).Conclusions: We observed complex associations between smoking and melanoma, with some suggestion that former smokers had lower risks than never or current smokers. The apparent inverse association among former smokers may be due to residual confounding, although surveillance bias or biological effects cannot be excluded entirely.Impact: Smoking does not increase the risk of cutaneous melanoma. Cancer Epidemiol Biomarkers Prev; 27(8); 874-81. ©2018 AACR.

19.
J Invest Dermatol ; 138(8): 1816-1824, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29524457

RESUMO

A proportion of cutaneous melanomas display neval remnants on histologic examination. Converging lines of epidemiologic and molecular evidence suggest that melanomas arising from nevus precursors differ from melanomas arising de novo. In a large, population-based study comprising 636 cutaneous melanomas subjected to dermatopathology review, we explored the molecular, host, and environmental factors associated with the presence of neval remnants. We found that nevus-associated melanomas were significantly associated with younger age at presentation, non-brown eye color, trunk site, thickness of less than 0.5 mm, and BRAFV600E mutation. Compared with patients with de novo melanomas, those with nevus-associated tumors were more likely to self-report many moles on their skin as a teenager (odds ratio = 1.94, 95% confidence interval = 1.01-3.72) but less likely to report many facial freckles (odds ratio = 0.49, 95% confidence interval = 0.25-0.96). They also had high total nevus counts (odds ratio = 2.18, 95% confidence interval = 1.26-3.78). On histologic examination, nevus-associated melanomas exhibited less dermal elastosis in adjacent skin compared with de novo melanomas (odds ratio = 0.55, 95% confidence interval = 0.30-1.01). These epidemiologic data accord with the emerging molecular paradigm that nevus-associated melanomas arise through a distinct sequence of causal events that differ from those leading to other cutaneous melanomas.

20.
J Natl Cancer Inst ; 110(10): 1075-1083, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29538697

RESUMO

Background: Risk stratification can improve the efficacy and cost-efficiency of screening programs for early detection of cancer. We sought to derive a risk stratification tool for melanoma that was suitable for the general population using only self-reported information. Methods: We used melanoma risk factor information collected at baseline from QSKIN, a prospective cohort study of Queensland adults age 40 to 69 years at recruitment (n = 41 954). We examined two separate outcomes: 1) invasive melanomas and 2) all melanomas (invasive + in situ) obtained through data linkage to the cancer registry. We used stepwise Cox proportional hazards modeling to derive the risk models in a randomly selected two-thirds sample of the data set and assessed model performance in the remaining one-third validation sample. Results: After a median follow-up of 3.4 years, 655 (1.6%) participants developed melanoma (257 invasive, 398 in situ). The prediction model for invasive melanoma included seven terms. At baseline, the strongest predictors of invasive melanoma were age, sex, tanning ability, number of moles at age 21 years, and number of skin lesions treated destructively. The model for "all melanomas" (ie, invasive and in situ) included five additional terms. Discrimination in the validation data set was high for both models (C-index = 0.69, 95% confidence interval [CI] = 0.62 to 0.76, and C-index = 0.72, 95% CI = 0.69 to 0.75, respectively), and calibration was acceptable. Conclusions: Such a tool could be used to target surveillance activities to those at highest predicted risk of developing melanoma over a median duration of 3.4 years.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA