Solar ultraviolet radiation exposure, and incidence of childhood acute lymphocytic leukaemia and non-Hodgkin lymphoma in a US population-based dataset.

BACKGROUND: Acute lymphocytic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) are among the commonest types of childhood cancer. Some previous studies suggested that elevated ultraviolet radiation (UVR) exposures increase ALL risk; many more indicate NHL risk is reduced. METHODS: We assessed age<20 ALL/NHL incidence in Surveillance, Epidemiology and End Results data using AVGLO-derived UVR irradiance/cumulative radiant exposure measures, using quasi-likelihood models accounting for underdispersion, adjusted for age, sex, racial/ethnic group and other county-level socioeconomic variables. RESULTS: There were 30,349 cases of ALL and 8062 of NHL, with significant increasing trends of ALL with UVR irradiance (relative risk (RR) = 1.200/mW/cm2 (95% CI 1.060, 1.359, p = 0.0040)), but significant decreasing trends for NHL (RR = 0.646/mW/cm2 (95% CI 0.512, 0.816, p = 0.0002)). There was a borderline-significant increasing trend of ALL with UVR cumulative radiant exposure (RR = 1.444/MJ/cm2 (95% CI 0.949, 2.197, p = 0.0865)), and significant decreasing trends for NHL (RR = 0.284/MJ/cm2 (95% CI 0.166, 0.485, p < 0.0001)). ALL and NHL trend RR is substantially increased among those aged 0-3. All-age trend RRs are most extreme (increasing for ALL, decreasing for NHL) for Hispanics for both UVR measures. CONCLUSIONS: Our more novel finding, of excess UVR-related ALL risk, is consistent with some previous studies, but is not clear-cut, and in need of replication.

Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial.

OBJECTIVE: To investigate whether supplementing older adults with monthly doses of vitamin D alters the incidence of major cardiovascular events. DESIGN: Randomised, double blind, placebo controlled trial of monthly vitamin D (the D-Health Trial). Computer generated permuted block randomisation was used to allocate treatments. SETTING: Australia from 2014 to 2020. PARTICIPANTS: 21 315 participants aged 60-84 years at enrolment. Exclusion criteria were self-reported hypercalcaemia, hyperparathyroidism, kidney stones, osteomalacia, sarcoidosis, taking >500 IU/day supplemental vitamin D, or unable to give consent because of language or cognitive impairment. INTERVENTION: 60 000 IU/month vitamin D3 (n=10 662) or placebo (n=10 653) taken orally for up to five years. 16 882 participants completed the intervention period: placebo 8270 (77.6%); vitamin D 8552 (80.2%). MAIN OUTCOME MEASURES: The main outcome for this analysis was the occurrence of a major cardiovascular event, including myocardial infarction, stroke, and coronary revascularisation, determined through linkage with administrative datasets. Each event was analysed separately as secondary outcomes. Flexible parametric survival models were used to estimate hazard ratios and 95% confidence intervals. RESULTS: 21 302 people were included in the analysis. The median intervention period was five years. 1336 participants experienced a major cardiovascular event (placebo 699 (6.6%); vitamin D 637 (6.0%)). The rate of major cardiovascular events was lower in the vitamin D group than in the placebo group (hazard ratio 0.91, 95% confidence interval 0.81 to 1.01), especially among those who were taking cardiovascular drugs at baseline (0.84, 0.74 to 0.97; P for interaction=0.12), although the P value for interaction was not significant (<0.05). Overall, the difference in standardised cause specific cumulative incidence at five years was -5.8 events per 1000 participants (95% confidence interval -12.2 to 0.5 per 1000 participants), resulting in a number needed to treat to avoid one major cardiovascular event of 172. The rate of myocardial infarction (hazard ratio 0.81, 95% confidence interval 0.67 to 0.98) and coronary revascularisation (0.89, 0.78 to 1.01) was lower in the vitamin D group, but there was no difference in the rate of stroke (0.99, 0.80 to 1.23). CONCLUSIONS: Vitamin D supplementation might reduce the incidence of major cardiovascular events, although the absolute risk difference was small and the confidence interval was consistent with a null finding. These findings could prompt further evaluation of the role of vitamin D supplementation, particularly in people taking drugs for prevention or treatment of cardiovascular disease. TRIAL REGISTRATION: ACTRN12613000743763.

Cancer and Ongoing Climate Change: Who Are the Most Affected?

Cancer has become the leading cause of premature death in many counties in recent decades. Previous studies showed plenty of evidence that control of modifiable risk factors would reduce the cancer burden. Since modifiable risk factors could be eliminated by changing the lifestyles of individuals, a greater uptake of modifiable risk factors is critical to reducing cancer burden and inequality in cancer survival. However, climate change will widen cancer inequities through its complex connections with modifiable risk factors. In this perspective, complex connections between climate change and cancer risks via modifiable risk factors, including abnormal temperature, UV, air pollution, natural disasters, food (diet), water, infections, and inefficient physical activities, have been summarized. The associations between climate change and modifiable risk factors have no doubt expanded the inequities. People who face overlapping modifiable risk factors, but who are unable to change or adapt, are at the highest risk in the climate change-cancer linkage. Though individual actions to avoid exposure to modifiable risk factors have been recommended, limited benefits would be achieved unless the nations strive to ensure the basic needs of the people. No choice makes avoiding exposure to risk factors an empty phrase. Thus, government actions should be taken to reduce the expanded inequities in cancer risks.

Cutaneous melanoma, prostate-specific antigen testing and the subsequent risk of prostate cancer diagnosis: a prospective analysis of the 45 and Up Study.

BACKGROUND: The association between cutaneous melanoma and subsequent risk of prostate cancer (PC) was examined in a large population-based cohort study. METHODS: Male participants in the Sax Institute's 45 and Up Study (Australia) were recruited between 2006 and 2009. Questionnaire data and linked administrative health data from the Centre for Health Record Linkage and Services Australia identified melanomas diagnosed between 1/1/1994 and 12 months before Study recruitment (i.e., between 2005 and 2008), incident PCs, primary healthcare utilisation and prostate-specific antigen (PSA) tests. Men were excluded from the current analyses if they had a recorded PC or other cancer diagnosis other than melanoma and non-melanoma skin cancer prior to recruitment. Multivariable Cox regression was used to estimate hazard ratios (HRs) adjusting for PSA-testing frequency before PC diagnosis. RESULTS: Of 96,548 eligible men, 1899 were diagnosed with melanoma during the melanoma diagnosis period and 3677 incident PC diagnosed during follow-up (latest date 31/12/2013). Men with melanoma diagnosis had increased risk of a subsequent PC diagnoses (vs. no melanoma; fully adjusted HR = 1.32; 95% CI: 1.09-1.60). There was weak evidence of higher risks of a subsequent PC diagnosis for men diagnosed with more than one melanoma compared to men diagnosed with only one melanoma (p = 0.077), and if first melanoma diagnosis was 10 to 15 years before Study recruitment (fully adjusted HR = 2.05; 95% CI [1.35, 3.12]). CONCLUSION: Melanoma diagnosis was associated with increased risk of subsequent PC diagnosis, after adjusting for PSA testing and primary healthcare utilisation. While our ability to adjust for PC screening reduced risk of detection bias, we acknowledge that residual confounding from increased medical surveillance after melanoma diagnoses cannot be entirely ruled out.

Cancer Survivors' Long-Term Health Service Costs in Queensland, Australia: Results of a Population-Level Data Linkage Study (Cos-Q).

Worldwide, the number of cancer survivors is rapidly increasing. The aim of this study was to quantify long-term health service costs of cancer survivorship on a population level. The study cohort comprised residents of Queensland, Australia, diagnosed with a first primary malignancy between 1997 and 2015. Administrative databases were linked with cancer registry records to capture all health service utilization. Health service costs between 2013-2016 were analyzed using a bottom-up costing approach. The cumulative mean annual healthcare expenditure (2013-2016) for the cohort of N = 230,380 individuals was AU$3.66 billion. The highest costs were incurred by patients with a history of prostate (AU$538 m), breast (AU$496 m) or colorectal (AU$476 m) cancers. Costs by time since diagnosis were typically highest in the first year after diagnosis and decreased over time. Overall mean annual healthcare costs per person (2013-2016) were AU$15,889 (SD: AU$25,065) and highest costs per individual were for myeloma (AU$45,951), brain (AU$30,264) or liver cancer (AU$29,619) patients. Our results inform policy makers in Australia of the long-term health service costs of cancer survivors, provide data for economic evaluations and reinforce the benefits of investing in cancer prevention.

The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality.

BACKGROUND: The effect of supplementing unscreened adults with vitamin D3 on mortality is unclear. We aimed to determine whether monthly doses of vitamin D3 influenced mortality in older Australians. METHODS: We did a randomised, double-blind, placebo-controlled trial of oral vitamin D3 supplementation (60 000 IU per month) in Australians 60 years or older who were recruited across the country via the Commonwealth electoral roll. Participants were randomly assigned (1:1), using automated computer-generated permuted block randomisation, to receive one oral gel capsule of either 60 000 IU vitamin D3 or placebo once a month for 5 years. Participants, staff, and investigators were blinded to study group allocation. The primary endpoint was all-cause mortality assessed in all participants who were randomly assigned. We also analysed mortality from cancer, cardiovascular disease, and other causes. Hazard ratios (HRs) and 95% CIs were generated using flexible parametric survival models. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000743763. FINDINGS: Between Feb 14, 2014, and June 17, 2015, we randomly assigned 21 315 participants, including 10 662 to the vitamin D group and 10 653 to the placebo group. In 4441 blood samples collected from randomly sampled participants (N=3943) during follow-up, mean serum 25-hydroxy-vitamin D concentrations were 77 (SD 25) in the placebo group and 115 (SD 30) nmol/L in the vitamin D group. Following 5 years of intervention (median follow-up 5·7 years [IQR 5·4-6·7]), 1100 deaths were recorded (placebo 538 [5·1%]; vitamin D 562 [5·3%]). 10 661 participants in the vitamin D group and 10 649 participants in the placebo group were included in the primary analysis. Five participants (one in the vitamin D group and four in the placebo group) were not included as they requested to be withdrawn and their data to be destroyed. The HR of vitamin D3 effect on all-cause mortality was 1.04 [95% CI 0·93 to 1·18]; p=0·47)and the HR of vitamin D3 effect on cardiovascular disease mortality was 0·96 (95% CI 0·72 to 1·28; p=0·77). The HR for cancer mortality was 1·15 (95% CI 0·96 to 1·39; p=0·13) and for mortality from other causes it was 0·83 (95% CI 0·65 to 1·07; p=0·15). The odds ratio for the per-protocol analysis was OR 1·18 (95% CI 1·00 to 1·40; p=0·06). In exploratory analyses excluding the first 2 years of follow-up, those randomly assigned to receive vitamin D had a numerically higher hazard of cancer mortality than those in the placebo group (HR 1·24 [95% CI 1·01-1·54]; p=0·05). INTERPRETATION: Administering vitamin D3 monthly to unscreened older people did not reduce all-cause mortality. Point estimates and exploratory analyses excluding the early follow-up period were consistent with an increased risk of death from cancer. Pending further evidence, the precautionary principle would suggest that this dosing regimen might not be appropriate in people who are vitamin D-replete. FUNDING: The D-Health Trial is funded by National Health and Medical Research Council.

Vitamin D supplementation and risk of falling: outcomes from the randomized, placebo-controlled D-Health Trial.

BACKGROUND: Falls cause considerable morbidity and mortality in older people. It is unclear how vitamin D supplementation affects falls risk, particularly when taken at high doses. We sought to determine whether monthly high-dose vitamin D supplementation reduces risk and incidence of falls. METHODS: We used data from the randomized, double-blind, placebo-controlled D-Health Trial conducted in Australia. Between February 2014 and May 2015, 21 315 participants aged 60-84 years were randomized (1:1) to monthly doses of either 60 000 IU of colecalciferol or placebo for a maximum of 5 years. People who reported a history of osteomalacia, sarcoidosis, hyperparathyroidism, hypercalcaemia or kidney stones or who were taking >500 IU/day supplementary vitamin D were ineligible. Each year, we collected blood samples from ~450 randomly sampled participants from each trial arm and measured 25-hydroxyvitamin D [25(OH)D]. Falls, a prespecified tertiary outcome, were ascertained using annual surveys and, for a subset of participants, 3-month falls diaries. The primary outcome for this analysis was any fall in the month before completing an annual survey. As part of our process to maintain blinding, we used random samples of participants (surveys, n = 16 000; diaries, n = 2400), with equal numbers per group. Participants with no outcome data were excluded. Following an intention-to-treat approach, we analysed outcomes using logistic, ordinal and negative binomial regression. Registration: Australian New Zealand Clinical Trials Registry (ACTRN12613000743763); registered 4 July 2013. RESULTS: Mean treatment duration was 4.3 years (standard deviation [SD] = 1.4 years). Mean serum 25(OH)D concentrations during the trial were 114.8 (SD 30.3) nmol/L and 77.5 (SD 25.2) nmol/L in the vitamin D and placebo groups, respectively. Survey and diary analytic sets included 15 416 and 2200 participants, respectively; approximately half were randomized to vitamin D (surveys: 50.1%; diaries: 50.4%). Vitamin D had no effect on falling in the past month (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.95-1.10). There was an interaction with body mass index (BMI) (P-interaction = 0.001); vitamin D increased risk in participants with BMI < 25 kg/m2 (OR 1.25, 95% CI 1.09-1.43), but there was no effect in those with BMI ≥ 25 kg/m2 (OR 0.95, 95% CI 0.87-1.04). Analyses of diary data were consistent with these findings. The incidence of hypercalcaemia and kidney stones did not differ between groups. CONCLUSIONS: Monthly high-dose vitamin D supplementation did not reduce risk of falling. A possible increased risk of falling with vitamin D supplementation in people with normal BMI warrants further investigation.

Impact of personal genomic risk information on melanoma prevention behaviors and psychological outcomes: a randomized controlled trial.

PURPOSE: We evaluated the impact of personal melanoma genomic risk information on sun-related behaviors and psychological outcomes. METHODS: In this parallel group, open, randomized controlled trial, 1,025 Australians of European ancestry without melanoma and aged 18-69 years were recruited via the Medicare database (3% consent). Participants were randomized to the intervention (n = 513; saliva sample for genetic testing, personalized melanoma risk booklet based on a 40-variant polygenic risk score, telephone-based genetic counseling, educational booklet) or control (n = 512; educational booklet). Wrist-worn ultraviolet (UV) radiation dosimeters (10-day wear) and questionnaires were administered at baseline, 1 month postintervention, and 12 months postbaseline. RESULTS: At 12 months, 948 (92%) participants completed dosimetry and 973 (95%) the questionnaire. For the primary outcome, there was no effect of the genomic risk intervention on objectively measured UV exposure at 12 months, irrespective of traditional risk factors. For secondary outcomes at 12 months, the intervention reduced sunburns (risk ratio: 0.72, 95% confidence interval: 0.54-0.96), and increased skin examinations among women. Melanoma-related worry was reduced. There was no overall impact on general psychological distress. CONCLUSION: Personalized genomic risk information did not influence sun exposure patterns but did improve some skin cancer prevention and early detection behaviors, suggesting it may be useful for precision prevention. There was no evidence of psychological harm.

Lifetime Ambient UV Radiation Exposure and Risk of Basal Cell Carcinoma by Anatomic Site in a Nationwide U.S. Cohort, 1983-2005.

BACKGROUND: Cutaneous basal cell carcinoma (BCC) has long been associated with UV radiation (UVR) exposure, but data are limited on risks by anatomic site. METHODS: We followed 63,912 cancer-free White U.S. radiologic technologists from cohort entry (1983-1989/1994-1998) to exit (date first BCC via 2003-2005 questionnaire). We estimated associations between cumulative ambient UVR and relative/absolute risks of self-reported BCC by anatomic location via Poisson models. RESULTS: For incident first primary BCC in 2,124 subjects (mean follow-up, 16.9 years) log[excess relative risks] (ERR) of BCC per unit cumulative ambient UVR = 1.27/MJ cm-2 [95% confidence interval (CI): 0.86-1.68; P trend < 0.001] did not vary by anatomic site (P = 0.153). However, excess absolute risks of BCC per unit cumulative ambient UVR were large for the head/neck = 5.46/MJ cm-2/104 person-year (95% CI: 2.92-7.36; P trend < 0.001), smaller for the trunk (2.56; 95% CI: 1.26-3.33; P trend = 0.003), with lesser increases elsewhere. There were lower relative risks, but higher absolute risks, for those with Gaelic ancestry (P < 0.001), also higher absolute risks among those with fair complexion, but relative and absolute risks were not generally modified by other constitutional, lifestyle or medical factors for any anatomic sites. Excess absolute and relative risk was concentrated 5-15 years before time of follow-up. CONCLUSIONS: BCC relative and absolute risk rose with increasing cumulative ambient UVR exposure, with absolute risk highest for the head/neck, to a lesser extent in the trunk. IMPACT: These associations should be evaluated in other White and other racial/ethnic populations along with assessment of possible modification by time outdoors, protective, and behavioral factors.

Predicting deseasonalised serum 25 hydroxy vitamin D concentrations in the D-Health Trial: An analysis using boosted regression trees.

BACKGROUND: The D-Health Trial aims to determine whether monthly high-dose vitamin D supplementation can reduce the mortality rate and prevent cancer. We did not have adequate statistical power for subgroup analyses, so could not justify the high cost of collecting blood samples at baseline. To enable future exploratory analyses stratified by baseline vitamin D status, we developed models to predict baseline serum 25 hydroxy vitamin D [25(OH)D] concentration. METHODS: We used data and serum 25(OH)D concentrations from participants who gave a blood sample during the trial for compliance monitoring and were randomised to placebo. Data were partitioned into training (80%) and validation (20%) datasets. Deseasonalised serum 25(OH)D concentrations were dichotomised using cut-points of 50, 60 and 75 nmol/L. We fitted boosted regression tree models, based on 13 predictors, and evaluated model performance using the validation data. RESULTS: The training and validation datasets had 1788 (10.5% <50 nmol/L, 23.1% <60 nmol, 48.8 <75 nmol/L) and 447 (11.9% <50 nmol/L, 25.7% <60 nmol/L, and 49.2% <75 nmol/L) samples, respectively. Ambient UV radiation and total intake of vitamin D were the strongest predictors of 'low' serum 25(OH)D concentration. The area under the receiver operating characteristic curves were 0.71, 0.70, and 0.66 for cut-points of <50, <60 and <75 nmol/L respectively. CONCLUSIONS: We exploited compliance monitoring data to develop models to predict serum 25(OH)D concentration for D-Health participants at baseline. This approach may prove useful in other trial settings where there is an obstacle to exhaustive data collection.

High-dose vitamin D supplementation to prevent prostate cancer progression in localised cases with low-to-intermediate risk of progression on active surveillance (ProsD): protocol of a phase II randomised controlled trial.

INTRODUCTION: Active surveillance (AS) for patients with prostate cancer (PC) with low risk of PC death is an alternative to radical treatment. A major drawback of AS is the uncertainty whether a patient truly has low risk PC based on biopsy alone. Multiparametric MRI scan together with biopsy, appears useful in separating patients who need curative therapy from those for whom AS may be safe. Two small clinical trials have shown short-term high-dose vitamin D supplementation may prevent PC progression. There is no substantial evidence for its long-term safety and efficacy, hence its use in the care of men with PC on AS needs assessment. This protocol describes the ProsD clinical trial which aims to determine if oral high-dose vitamin D supplementation taken monthly for 2 years can prevent PC progression in cases with low-to-intermediate risk of progression. METHOD AND ANALYSIS: This is an Australian national multicentre, 2:1 double-blinded placebo-controlled phase II randomised controlled trial of monthly oral high-dose vitamin D supplementation (50 000 IU cholecalciferol), in men diagnosed with localised PC who have low-to-intermediate risk of disease progression and are being managed by AS. This trial will assess the feasibility, efficacy and safety of supplementing men with an initial oral loading dose of 500 000 IU cholecalciferol, followed by a monthly oral dose of 50 000 IU during the 24 months of AS. The primary trial outcome is the commencement of active therapy for clinical or non-clinical reason, within 2 years of AS. ETHICS AND DISSEMINATION: This trial is approved by Bellberry Ethics Committee (2016-06-459). All results will be reported in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12616001707459.

County-level variation in the long-term association between PM2.5 and lung cancer mortality in China.

INTRODUCTION: The relative risk (RR) of long-term exposure to PM2.5 in lung cancer mortality (LCM) may vary spatially in China. However, previous studies applying global regression have been unable to capture such variation. We aimed to employ a geographically weighted Poisson regression (GWPR) to estimate the RRs of LCM among the elderly (≥65 years) related to long-term exposure to PM2.5 and the LCM attributable to PM2.5 at the county level in China. METHODS: We obtained annual LCM in the elderly between 2013 and 2015 from the National Death Surveillance. We linked annual mean concentrations of PM2.5 between 2000 and 2004 with LCM using GWPR model at 148 counties across mainland China, adjusting for smoking and socioeconomic covariates. We used county-specific GWPR models to estimate annual average LCM in the elderly between 2013 and 2015 attributable to PM2.5 exposure between 2000 and 2004. RESULTS: The magnitude of the association between long-term exposure to PM2.5 and LCM varied with county. The median of county-specific RRs of LCM among elderly men and women was 1.52 (range: 0.90, 2.40) and 1.49 (range: 0.88, 2.56) for each 10 µg/m3 increment in PM2.5, respectively. The RRs were positively significant (P < 0.05) at 95% (140/148) of counties among both elderly men and women. Higher RRs of PM2.5 among elderly men were located at Southwest and South China, and higher RRs among elderly women were located at Northwest, Southwest, and South China. There were 99,967 and 54,457 lung cancer deaths among elderly men and women that could be attributed to PM2.5, with the attributable fractions of 31.4% and 33.8%, respectively. CONCLUSIONS: The relative importance of long-term exposure to PM2.5 in LCM differed by county. The results could help the government design tailored and efficient interventions. More stringent PM2.5 control is urgently needed to reduce LCM in China.

Global, regional, and national burden of lung cancer and its attributable risk factors, 1990 to 2017.

BACKGROUND: China's lung cancer (LC) burden plays a pivotal role in the global cancer epidemic. Comparing LC burden and population attributable fractions (PAFs) of risk factors between China and other countries/regions is essential to inform effective intervention. The Global Burden of Disease (GBD) study provides a unique opportunity for such comparisons. METHODS: We extracted the number of LC deaths, age-standardized death rates (ASDRs), age-standardized disability-adjusted life-year (DALY) rates, and PAFs of risk factors for LC deaths between 1990 and 2017 from GBD 2017. The annual percentage change (APC) was used to quantify the trends of LC ASDRs and age-standardized DALY rates. The relationship between the APC of LC ASDR and Socio-demographic Index was assessed among China and other countries. RESULTS: Globally, the ASDR for LC decreased in men (APC, -0.66% [95% CI, -0.69 to -0.62]) but increased in women (APC, 0.31% [95% CI, 0.26 to 0.36]) from 1990 to 2017. The ASDRs in China increased both for men (APC, 1.12% [95% CI, 1.03 to 1.20]) and women (APC, 0.80% [95% CI, 0.70 to 0.89]). The increased LC death numbers among men (312,798) and women (139,115) in China accounted for 59.39% and 43.01% of global increases. LC years of life lost accounted for the majority of LC DALYs globally and in China. The risk factors with the highest PAFs of LC death in China were smoking and ambient particulate matter. The ASDRs for LC associated with ambient particulate matter in China ranked second globally. CONCLUSIONS: The trends of LC ASDRs and age-standardized DALY rates and the PAFs of risk factors vary markedly by region, indicating a need for tailored measures to reduce LC burden and improve health equality. China's LC ASDRs are among the highest in the world, and the primary intervention priorities in China should be control of ambient particulate matter and tobacco usage.

Post-treatment levels of plasma 25- and 1,25-dihydroxy vitamin D and mortality in men with aggressive prostate cancer.

Vitamin D may reduce mortality from prostate cancer (PC). We examined the associations of post-treatment plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations with PC mortality. Participants were PC cases from the New South Wales Prostate Cancer Care. All contactable and consenting participants, at 4.9 to 8.6 years after diagnosis, were interviewed and had plasma 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) measured in blood specimens. Cox regression allowing for left-truncation was used to calculate adjusted mortality hazards ratios (HR) and 95% confidence intervals (95% CI) for all-cause and PC-specific mortality in relation to vitamin D levels and other potentially-predictive variables. Of the participants (n = 111; 75·9% response rate), there were 198 deaths from any cause and 41 from PC in the study period. Plasma 25(OH)D was not associated with all-cause or PC-specific mortality (p-values > 0·10). Plasma 1,25(OH)2D was inversely associated with all-cause mortality (HR for highest relative to lowest quartile = 0·45; 95% CI: 0·29-0·69), and PC-specific mortality (HR = 0·40; 95% CI: 0·14-1·19). These associations were apparent only in men with aggressive PC: all-cause mortality HR = 0·28 (95% CI·0·15-0·52; p-interaction = 0·07) and PC-specific mortality HR = 0·26 (95% CI: 0·07-1.00). Time spent outdoors was also associated with lower all-cause (HR for 4th relative to 1st exposure quartile = 0·42; 95% CI: 0·24-0·75) and PC-specific (HR = 0·48; 95% CI: 0·14-1·64) mortality, although the 95% CI for the latter was wide. The inverse association between post-treatment plasma 1,25(OH)2D levels and all-cause and PC-specific mortality in men with aggressive PC, suggest a possible beneficial effect of vitamin D supplementation in these men.

Lifetime Costs of Surviving Cancer-A Queensland Study (COS-Q): Protocol of a Large Healthcare Data Linkage Study.

Australia-wide, there are currently more than one million cancer survivors. There are over 32 million world-wide. A trend of increasing cancer incidence, medical innovations and extended survival places growing pressure on healthcare systems to manage the ongoing and late effects of cancer treatment. There are no published studies of the long-term health service use and cost of cancer survivorship on a population basis in Australia. All residents of the state of Queensland, Australia, diagnosed with a first primary malignancy from 1997-2015 formed the cohort of interest. State and national healthcare databases are linked with cancer registry records to capture all health service utilization and healthcare costs for 20 years (or death, if this occurs first), starting from the date of cancer diagnosis, including hospital admissions, emergency presentations, healthcare costing data, Medicare services and pharmaceuticals. Data analyses include regression and economic modeling. We capture the whole journey of health service contact and estimate long-term costs of all cancer patients diagnosed and treated in Queensland by linking routinely collected state and national healthcare data. Our results may improve the understanding of lifetime health effects faced by cancer survivors and estimate related healthcare costs. Research outcomes may inform policy and facilitate future planning for the allocation of healthcare resources according to the burden of disease.

Parametric human modelling to determine body surface area covered by sun-protective clothing.

Solar ultraviolet radiation (UVR) is the main environmental risk-factor for cancer of the skin. Sun-protective clothing provides a physical barrier that reduces the UVR dose reaching the skin and European and Australian standards for sun-protective clothing set minimum clothing coverage requirements. Body Surface Area Coverage by clothing (BSAC) is calculated by means of indirect or direct methods, which are laborious and do not support computer-based apparel design. To support the sun-safe specification and design of garments, parametric digital human models and protective clothing mesh covering the minimum Body Surface Area specified in AS/NZS 4399:2017, were created making use of MakeHuman v1.1.1 and Blender software. The Whole Body Surface Area (WBSA) and the BSAC were calculated employing code developed in Blender. Thus, different groups of subjects were analysed to explore BSAC. The method assists in the evaluation of exposed body areas in a wider spectrum of different occupations. Practitioner summary: Sun-protective clothing provides a physical barrier that reduces the UVR dose reaching the skin's surface. Body Surface Area Coverage (BSAC) by clothing is an important determinant of the sun protective capabilities of a garment. In this study, BSAC is calculated using parametric digital human modelling. Abbreviation: UVR: (Solar) ultraviolet radiation; DHM: digital human modeling; BSA: body surface area; BSAC: body surface area coverage (by clothing); BSANC: body surface area not covered (by clothing); WBSA: whole body surface area; BCC: basal cell carcinoma; SCC: squamous cell carcinoma; UPF: ultraviolet protection factor; GPF: garment protection factor.

Multiple interaction nodes define the postreplication repair response to UV-induced DNA damage that is defective in melanomas and correlated with UV signature mutation load.

Ultraviolet radiation-induced DNA mutations are a primary environmental driver of melanoma. The reason for this very high level of unrepaired DNA lesions leading to these mutations is still poorly understood. The primary DNA repair mechanism for UV-induced lesions, that is, the nucleotide excision repair pathway, appears intact in most melanomas. We have previously reported a postreplication repair mechanism that is commonly defective in melanoma cell lines. Here we have used a genome-wide approach to identify the components of this postreplication repair mechanism. We have used differential transcript polysome loading to identify transcripts that are associated with UV response, and then functionally assessed these to identify novel components of this repair and cell cycle checkpoint network. We have identified multiple interaction nodes, including global genomic nucleotide excision repair and homologous recombination repair, and previously unexpected MASTL pathway, as components of the response. Finally, we have used bioinformatics to assess the contribution of dysregulated expression of these pathways to the UV signature mutation load of a large melanoma cohort. We show that dysregulation of the pathway, especially the DNA damage repair components, are significant contributors to UV mutation load, and that dysregulation of the MASTL pathway appears to be a significant contributor to high UV signature mutation load.

Cumulative solar ultraviolet radiation exposure and basal cell carcinoma of the skin in a nationwide US cohort using satellite and ground-based measures.

BACKGROUND: Basal cell carcinoma of the skin (BCC) is the most common cancer in populations of European ancestry. Although consistently linked with basal cell carcinoma of the skin in case-control studies, few prospective cohort studies have evaluated the shape of the exposure-response of basal cell carcinoma associated with cumulative radiant solar ultraviolet exposure (UVR). METHODS: We followed 63,912 white cancer-free US radiologic technologists from entry (1983-1998) to exit (2003-2005) with known ultraviolet irradiance at up to 5 residential locations. Using generalized-additive and relative risk models we analyzed the exposure-response of basal cell carcinomas associated with ambient cumulative ultraviolet radiant exposure using ground-based National Solar Radiation database Average Daily Total Global data and satellite-based National Aeronautics and Space Administration Total Ozone Mapping Spectrometer data. RESULTS: There were 2151 technologists with an incident primary basal cell carcinoma. Risk of basal cell carcinoma rose with increasing cumulative ultraviolet radiation exposure using both measures, such that 1 MJ cm- 2 increased basal cell carcinoma risk by 8.48 (95% CI 5.22, 11.09, p < 0.001) and by 10.15 (95% CI 6.67, 13.10, p < 0.001) per 10,000 persons per year using the Average Daily Total Global and Total Ozone Mapping Spectrometer ultraviolet data, respectively; relative risk was likewise elevated. There was some evidence of upward curvature in the cumulative ultraviolet exposure response using both exposure measures with a greater increase in risk of basal cell carcinoma at higher levels of ultraviolet radiation exposure, but less evidence for curvature in relative risk. There are indications of substantial variation of relative risk with time after exposure and age at exposure, so that risk is highest for the period 10-14 years after ultraviolet radiation exposure and for those exposed under the age of 25. CONCLUSIONS: We observed increases in risk of basal cell carcinoma and a similar exposure-response for ground-based and satellite ultraviolet radiation measures. Our observations suggest that interventions should concentrate on persons with higher levels of ultraviolet radiation exposure.

Short-term association between ambient air pollution and lung cancer mortality.

RATIONALE: Long-term exposure to air pollution has been associated with increased lung cancer incidence and mortality. However, the short-term association between air pollution and lung cancer mortality (LCM) remains largely unknown. METHODS: We collected daily data on particulate matter with diameter <2.5 µm (PM2.5), particulate matter with diameter < 10 µm (PM10), sulfur dioxide (SO2), and ozone (O3), and LCM in three of the biggest cities in China, i.e. Beijing, Chongqing, and Guangzhou, from 2013 to 2015. We first estimated city-specific relationships between air pollutants and LCM using time-series generalized linear models, adjusting for potential confounders. A classification and regression tree (CART) model was used to stratify LCM risk based on combinations of air pollutants and meteorological factors in each city. Then we pooled the city-specific associations using random-effects meta-analysis. Meta regression was used to explore if city-specific characteristics modified the air pollution-LCM association. Finally, we stratified the analyses by season, age, and sex. RESULTS: Over the entire period, the current-day concentrations of PM2.5 and PM10 in Chongqing and PM2.5, PM10, and SO2 in Guangzhou were positively associated with LCM (Excess risk ranged from 0.72% (95% CI 0.27%-1.17%) to 6.06% (95% CI 0.76%-11.64%) with each 10 µg/m3 increment in different pollutants), but the association between current-day air pollution and LCM in Beijing was not significant (P > 0.05). When considering the environmental and weather factors simultaneously, current-day PM2.5, relative humidity, and PM10 were the most important factors associated with LCM in Beijing, Chongqing, and Guangzhou, respectively. LCM risk related with daily PM2.5, PM10, and SO2 significantly increased with the increasing annual mean temperature and humidity of the city, while LCM risk related with daily O3 significantly increased with the increases of latitude, annual mean O3 concentration, and socioeconomic level. After stratification, the current-day PM2.5, PM10, and O3 during the warm season in Beijing and PM2.5, PM10, and SO2 during the cool season in Chongqing and Guangzhou were positively associated with LCM (Excess risk ranged from 0.93% (95% CI 0.42%-1.45%) to 7.16% (95% CI 0.64%-14.09%) with each 10 µg/m3 increment in different pollutants). Male and the elderly lung cancer patients were more sensitive to the short-term effect of air pollution. CONCLUSIONS: Lung cancer patients should enhance protection measures against air pollution. More attentions should be paid for the high PM2.5, PM10, and O3 during the warm season in Beijing, and high PM2.5, PM10, and SO2 during the cool season in Chongqing and Guangzhou.