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Tran B.,QIMR Berghofer Medical Research Institute | Tran B.,Center for Research Excellence in Sun and Health | Whiteman D.C.,QIMR Berghofer Medical Research Institute | Whiteman D.C.,Center for Research Excellence in Sun and Health | And 9 more authors.
Cancer Epidemiology | Year: 2013

Background: Ecological studies showing an inverse association between pancreatic cancer incidence and mortality and levels of ultraviolet radiation (UVR), suggest that higher levels of sun exposure may reduce risks of pancreatic cancer but there has been only one individual-level study that examined this issue. We aimed to examine the association between pancreatic cancer and markers of exposure to solar UVR, namely skin type, treatment of skin lesions, ambient UVR and time outdoors on work days. Methods: We used data from an Australian case-control study. Location at birth, residential location during adulthood, outdoors work, history of skin lesion treatment and sensitivity of the skin to the sun were obtained by questionnaire. We limited the analyses to Caucasians who answered the questionnaire about UVR (controls = 589/711 recruited; cases = 496/705 recruited). We used NASA's Total Ozone Mapping Spectrometer to estimate ambient UVR. Results: Being born in or living in areas of higher ambient UVR (compared to lower ambient UVR) was associated with about 30-40% lower risk of pancreatic cancer. People with fair skin colour had 47% lower risk of pancreatic cancer than those with dark skin colour (95% CI 0.37-0.75). There was some suggestion of increased risk with increased average number of hours spent outside at work. Conclusions: This study suggests that people with light skin colour or those born or living in areas of high ambient UVR have lower risk of pancreatic cancer. Our analysis supports an association between UVR and pancreatic cancer, possibly mediated through production of vitamin D. © 2013 Elsevier Ltd.


Waterhouse M.,QIMR Berghofer Medical Research Institute | Waterhouse M.,Center for Research Excellence in Sun and Health | Tran B.,University of New South Wales | Ebeling P.R.,Center for Research Excellence in Sun and Health | And 11 more authors.
British Journal of Nutrition | Year: 2015

Observational studies have suggested that 25-hydroxyvitamin D (25(OH)D) levels are associated with inflammatory markers. Most trials reporting significant associations between vitamin D intake and inflammatory markers used specific patient groups. Thus, we aimed to determine the effect of supplementary vitamin D using secondary data from a population-based, randomised, placebo-controlled, double-blind trial (Pilot D-Health trial 2010/0423). Participants were 60- to 84-year-old residents of one of the four eastern states of Australia. They were randomly selected from the electoral roll and were randomised to one of three trial arms: placebo (n 214), 750 μg (n 215) or 1500 μg (n 215) vitamin D3, each taken once per month for 12 months. Post-intervention blood samples for the analysis of C-reactive protein (CRP), IL-6, IL-10, leptin and adiponectin levels were available for 613 participants. Associations between intervention group and biomarker levels were evaluated using quantile regression. There were no statistically significant differences in distributions of CRP, leptin, adiponectin, leptin:adiponectin ratio or IL-10 levels between the placebo group and either supplemented group. The 75th percentile IL-6 level was 2·8 pg/ml higher (95 % CI 0·4, 5·8 pg/ml) in the 1500 μg group than in the placebo group (75th percentiles:11·0 v. 8·2 pg/ml), with a somewhat smaller, non-significant difference in 75th percentiles between the 750 μg and placebo groups. Despite large differences in serum 25(OH)D levels between the three groups after 12 months of supplementation, we found little evidence of an effect of vitamin D supplementation on cytokine or adipokine levels, with the possible exception of IL-6. © 2015 The Authors.


Khalesi M.,Queensland Institute of Medical Research | Khalesi M.,Center for Research Excellence in Sun and Health | Khalesi M.,Queensland University of Technology | Whiteman D.C.,Queensland Institute of Medical Research | And 7 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2013

Epidemiologic research has shown that cutaneous markers of photo-damage are associated with risk of basal cell carcinoma (BCC). However, there has been no previous attempt to calculate pooled risk estimates. We conducted a systematic review and meta-analysis after extracting relevant studies published up to January 2013 from five electronic databases. Eligible studies were those that permitted quantitative assessment of the association between histologically confirmed BCC and actinic keratoses, solar elastosis, solar lentigines, or telangiectasia. Seven eligible studies were identified and summary odds ratios (ORs) were calculated using both random and quality effects models. Having more than ten actinic keratoses was most strongly associated with BCC, conferring up to a fivefold increase in risk (OR: 4.97; 95% CI: 3.26-7.58). Other factors, including solar elastosis, solar lentigines, and telangiectasia had weaker but positive associations with BCC with ORs around 1.5. Markers of chronic photo-damage are positively associated with BCC. The presence of actinic keratoses was the most strongly associated with BCC of the markers examined. This work highlights the relatively modest association between markers of chronic ultraviolet exposure and BCC. © 2013 AACR.


Sun J.,Queensland University of Technology | Sun J.,Center for Research Excellence in Sun and Health | Lucas R.M.,Australian National University | Lucas R.M.,University of Western Australia | And 7 more authors.
Photochemical and Photobiological Sciences | Year: 2014

Despite the widespread use of ambient ultraviolet radiation (UVR) as a proxy measure of personal exposure to UVR, the relationship between the two is not well-defined. This paper examines the effects of season and latitude on the relationship between ambient UVR and personal UVR exposure. We used data from the AusD Study, a multi-centre cross-sectional study among Australian adults (18-75 years), where personal UVR exposure was objectively measured using polysulphone dosimeters. Data were analysed for 991 participants from 4 Australian cities of different latitude: Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S) and Hobart (42.8°S). Daily personal UVR exposure varied from 0.01 to 21 Standard Erythemal Doses (median = 1.1, IQR: 0.5-2.1), on average accounting for 5% of the total available ambient dose. There was an overall positive correlation between ambient UVR and personal UVR exposure (r = 0.23, p < 0.001). However, the correlations varied according to season and study location: from strong correlations in winter (r = 0.50) and at high latitudes (Hobart, r = 0.50; Canberra, r = 0.39), to null or even slightly negative correlations, in summer (r = 0.01) and at low latitudes (Townsville, r = -0.06; Brisbane, r = -0.16). Multiple regression models showed significant effect modification by season and location. Personal exposure fraction of total available ambient dose was highest in winter (7%) and amongst Hobart participants (7%) and lowest in summer (1%) and in Townsville (4%). These results suggest season and latitude modify the relationship between ambient UVR and personal UVR exposure. Ambient UVR may not be a good indicator for personal exposure dose under some circumstances. This journal is © The Royal Society of Chemistry and Owner Societies.


Waterhouse M.,QIMR Berghofer Medical Research Institute | Tran B.,QIMR Berghofer Medical Research Institute | Tran B.,Center for Research Excellence in Sun and Health | Armstrong B.K.,University of Sydney | And 16 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context and Objective: Suboptimal vitamin D status can be corrected by vitamin D supplementation, but individual responses to supplementation vary. We aimed to examine genetic and nongenetic determinants of change in serum 25-hydroxyvitamin D (25(OH)D) after supplementation. Design and Participants: We used data from a pilot randomized controlled trial in which 644 adults aged 60 to 84 years were randomly assigned to monthly doses of placebo, 30 000 IU, or 60 000 IU vitamin D3 for 12 months. Baseline characteristics were obtained from a self-administered questionnaire. Eighty-eight single-nucleotide polymorphisms (SNPs) in 41 candidate genes were genotyped using Sequenom MassArray technology. Serum 25(OH)D levels before and after the intervention were measured using the Diasorin Liaison platform immunoassay. We used linear regression models to examine associations between genetic and nongenetic factors and change in serum 25(OH)D levels. Results: Supplement dose and baseline 25(OH)D level explained 24% of the variability in response to supplementation. Body mass index, self-reported health status, and ambient UV radiation made a small additional contribution. SNPs in CYP2R1, IRF4, MC1R, CYP27B1, VDR, TYRP1, MCM6, and HERC2 were associated with change in 25(OH)D level, although only CYP2R1 was significant after adjustment for multiple testing. Models including SNPs explained a similar proportion of variability in response to supplementation as models that included personal and environmental factors. Conclusion: Stepwise regression analyses suggest that genetic variability may be associated with response to supplementation, perhaps suggesting that some people might need higher doses to reach optimal 25(OH)D levels or that there is variability in the physiologically normal level of 25(OH)D. Copyright © 2014 by the Endocrine Society.


Khalesi M.,Queensland Institute of Medical Research | Khalesi M.,Queensland University of Technology | Khalesi M.,Center for Research Excellence in Sun and Health | Whiteman D.C.,Queensland Institute of Medical Research | And 8 more authors.
Cancer Epidemiology | Year: 2013

Objective: To calculate pooled risk estimates of the association between pigmentary characteristics and basal cell carcinoma (BCC) of the skin. Methods: We searched three electronic databases and reviewed the reference lists of the retrieved articles until July 2012 to identify eligible epidemiologic studies. Eligible studies were those published in between 1965 and July 2012 that permitted quantitative assessment of the association between histologically-confirmed BCC and any of the following characteristics: hair colour, eye colour, skin colour, skin phototype, tanning and burning ability, and presence of freckling or melanocytic nevi. We included 29 studies from 2236 initially identified. We calculated summary odds ratios (ORs) using weighted averages of the log OR, using random effects models. Results: We found strongest associations with red hair (OR 2.02; 95% CI: 1.68, 2.44), fair skin colour (OR 2.11; 95% CI: 1.56, 2.86), and having skin that burns and never tans (OR 2.03; 95% CI: 1.73, 2.38). All other factors had weaker but positive associations with BCC, with the exception of freckling of the face in adulthood which showed no association. Conclusions: Although most studies report risk estimates that are in the same direction, there is significant heterogeneity in the size of the estimates. The associations were quite modest and remarkably similar, with ORs between about 1.5 and 2.5 for the highest risk level for each factor. Given the public health impact of BCC, this meta-analysis will make a valuable contribution to our understanding of BCC. © 2013 Elsevier Ltd.


Tran B.,Queensland Institute of Medical Research | Tran B.,Center for Research Excellence in Sun and Health | Armstrong B.K.,University of Sydney | McGeechan K.,University of Sydney | And 13 more authors.
Clinical Endocrinology | Year: 2013

Objective There has been a dramatic increase in vitamin D testing in Australia in recent years, prompting calls for targeted testing. We sought to develop a model to identify people most at risk of vitamin D deficiency. Design and Participants This is a cross-sectional study of 644 60- to 84-year-old participants, 95% of whom were Caucasian, who took part in a pilot randomized controlled trial of vitamin D supplementation. Measurements Baseline 25(OH)D was measured using the Diasorin Liaison platform. Vitamin D insufficiency and deficiency were defined using 50 and 25 nmol/l as cut-points, respectively. A questionnaire was used to obtain information on demographic characteristics and lifestyle factors. We used multivariate logistic regression to predict low vitamin D and calculated the net benefit of using the model compared with 'test-all' and 'test-none' strategies. Results The mean serum 25(OH)D was 42 (SD 14) nmol/1. Seventy-five per cent of participants were vitamin D insufficient and 10% deficient. Serum 25(OH)D was positively correlated with time outdoors, physical activity, vitamin D intake and ambient UVR, and inversely correlated with age, BMI and poor self-reported health status. These predictors explained approximately 21% of the variance in serum 25(OH)D. The area under the ROC curve predicting vitamin D deficiency was 0·82. Net benefit for the prediction model was higher than that for the 'test-all' strategy at all probability thresholds and higher than the 'test-none' strategy for probabilities up to 60%. Conclusion Our model could predict vitamin D deficiency with reasonable accuracy, but it needs to be validated in other populations before being implemented. © 2013 John Wiley & Sons Ltd.


Xiang F.,Australian National University | Xiang F.,Center for Research Excellence in Sun and Health | Lucas R.,Australian National University | Lucas R.,University of Western Australia | And 2 more authors.
JAMA Dermatology | Year: 2014

IMPORTANCE Nonmelanoma skin cancers (NMSCs) are the most common cancers in fair-skinned populations. Their incidence continues to increase in many countries. Exposure to UV radiation (UVR) is the primary cause of NMSC, although the pattern of exposure that gives rise to different types of NMSC appears to vary. Copyright 2014 American Medical Association. All rights reserved.OBJECTIVE To examine dose-response relationships between ambient UVR levels and NMSC incidence at the population level.DESIGN, SETTING, AND PARTICIPANTS Peer-reviewed literature published from January 1, 1978, through December 31, 2012, that provided age- and sex-specific incidence of NMSC in white populations worldwide was systematically reviewed.EXPOSURES Mean erythemally weighted daily ambient UVR levels for each study location were derived from satellite data.MAIN OUTCOMES AND MEASURES The incidence of NMSC in white populationsworldwide as reported in population-based studies.RESULTS Forty eligible publications were included in the analysis. Analysis models that contained age group, sex, study year, mean daily UVR, and day-to-day variability of UVR explained most of the variability in NMSC incidence: 82%for basal cell carcinoma (BCC) and 85%for squamous cell carcinoma (SCC). Exclusion of studies in which imputation of age-specific incidence data from standardized rates was required improved the model fit to 85%for BCC and 88%for SCC. Higher mean daily UVR was associated with higher NMSC incidence rates; this was greater in men than women for BCC (70% vs 60%) but greater in women for SCC (99% vs 92%). Incidence rates for BCC and SCC were higher among those older than 60 years, but the increase with age was steeper for those younger than 60 years.CONCLUSIONS AND RELEVANCE Our models highlight the etiologic differences between BCC and SCC and allow prediction of NMSC incidence for data-poor regions and under changing demographic and environmental conditions.

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