Genome-wide analysis to assess if heavy alcohol consumption modifies the association between SNPs and pancreatic cancer risk.

BACKGROUND: Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk. METHODS: We conducted a genome-wide interaction analysis of single nucleotide polymorphisms (SNP) by heavy alcohol consumption (more than 3 drinks per day) for pancreatic cancer in European ancestry populations from genome-wide association studies (GWAS). Our analysis included 3,707 cases and 4,167 controls from case-control studies and 1,098 cases and 1,162 controls from cohort studies. Fixed effect meta-analyses were conducted. RESULTS: A potential novel region of association on 10p11.22, lead SNP rs7898449 (Pinteraction = 5.1 x 10-8 in the meta-analysis, Pinteraction = 2.1x10-9 in the case-control studies, Pinteraction = 0.91 cohort studies) was identified. A SNP correlated with this lead SNP is an eQTL for the NRP1 gene. Of the 17 genomic regions with genome-wide significant evidence of association with pancreatic cancer in prior studies, we observed suggestive evidence that heavy alcohol consumption modified the association for one SNP near LINC00673, rs11655237 on 17q25.1 (Pinteraction = 0.004). CONCLUSIONS: We identified a novel genomic region that may be associated with pancreatic cancer risk in conjunction with heavy alcohol consumption located near an eQTL for the NRP1, a protein that plays an important role in the development and progression of pancreatic cancer Impact: This work can provide insight into the etiology of pancreatic cancer particularly in heavy drinkers.

The epidemiology of acute pancreatitis in Tasmania over a 12-year period: Is this a disease of disadvantage?

BACKGROUND: The global incidence of acute pancreatitis (AP) is increasing, but little information exists about trends in Australia. This study aimed to describe incidence trends, along with clinical and socio-demographic associations, in the state of Tasmania over a recent 12-year period. METHODS: The study cohort was obtained by linking clinical and administrative datasets encompassing the whole Tasmanian population between 2007 and 2018, inclusive. Pancreatitis case definition was based on relevant ICD-10 hospitalization codes, or elevated serum lipase or amylase in pathology data. Age-standardised incidence rates were estimated, overall and stratified by sex, aetiology, and Index of Relative Socio-economic Disadvantage (IRSD). RESULTS: In the study period, 4905 public hospital AP episodes were identified in 3503 people. The age-standardised person-based incidence rate across the entire period was 54 per 100,000 per year. Incidence was inversely related to IRSD score; 71 per 100,000 per year in the most disadvantaged quartile compared to 32 in the least disadvantaged. Biliary AP incidence was higher than that of alcohol-related AP, although the greatest incidence was in "unspecified" cases. There was an increase in incidence for the whole cohort (average annual percent change 3.23 %), largely driven by the two most disadvantaged IRSD quartiles; the least disadvantaged quartile saw a slight overall decrease. CONCLUSION: This is the first Australian study providing robust evidence that AP incidence is increasing and is at the upper limit of population-based studies worldwide. This increased incidence is greatest in socio-economically disadvantaged areas, meriting further research to develop targeted, holistic management strategies.

Age group-specific changes in keratinocyte cancer treatment rates in Australia, 2012-2021: a retrospective cohort study based on MBS claims data.

OBJECTIVES: To examine recent changes in the numbers of Medicare-subsidised keratinocyte cancer excisions, particularly for younger people exposed to primary prevention campaigns since the early 1980s. STUDY DESIGN: Retrospective cohort study; analysis of administrative data. SETTING, PARTICIPANTS: Analysis of Medicare Benefits Schedule (MBS) claims data for procedures related to the diagnosis and treatment of keratinocyte cancer in Australia, 2012-2021. MAIN OUTCOME MEASURES: Age-standardised rates for MBS-subsidised claims for first surgical squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) excisions, Mohs surgery, surgical excisions of benign lesions, skin biopsies, and cryotherapy or serial curettage of premalignant and malignant lesions, overall, and by sex, state/territory, and age group; average annual percentage change in rate for time intervals determined by joinpoint regression. RESULTS: In men, the age-standardised rate of BCC/SCC excisions increased by 1.9% (95% confidence interval [CI], 1.4-2.4%) per year during 2012-2019 (from 2931 to 3371 per 100 000 men) and then declined by 3.8% (95% CI, 0.5-7.0%) per year during 2019-2021 (to 3152 per 100 000). In women, the age-standardised rate increased by 2.2% (95% CI, 1.7-2.8%) per year during 2012-2019 (from 1798 to 2093 per 100 000 women); the decline to 1967 excisions per 100 000 women in 2021 was not statistically significant. BCC/SCC excision rates declined for men under 55 years of age (by 1.0-3.4% per year) and women under 45 years of age (by 1.7-2.3% per year). Age-standardised biopsy rates increased during 2012-2021 in all age groups (by 2.8-6.9% per year). CONCLUSIONS: Rates of MBS-subsidised treatment for keratinocyte cancers increased during 2012-2019, but BCC/SCC treatment rates declined among younger Australians, who have probably been exposed to less sunlight than earlier generations because of public health interventions and population-wide lifestyle changes related to technology use.

Environmental plastics in the context of UV radiation, climate change, and the Montreal Protocol.

There are close links between solar UV radiation, climate change, and plastic pollution. UV-driven weathering is a key process leading to the degradation of plastics in the environment but also the formation of potentially harmful plastic fragments such as micro- and nanoplastic particles. Estimates of the environmental persistence of plastic pollution, and the formation of fragments, will need to take in account plastic dispersal around the globe, as well as projected UV radiation levels and climate change factors.

Genetic Analysis of Perceived Youthfulness Reveals Differences in How Men's and Women's Age Is Assessed.

Skin aging is a natural process that occurs over time but can be accelerated by sun exposure. Measuring skin age in a large population can provide insight into the extent of skin damage from sun exposure and skin cancer risk. Understanding the genetics of skin aging, within and across sexes (males and females), could improve our understanding of the genetic drivers of both skin aging and skin cancer. We used UK Biobank data to examine the genetic overlap between perceived youthfulness and traits relevant to actinic photoaging. Our GWAS identified 22 genome-wide significant loci for women and 43 for men. The genetic correlation (rg) between perceived youthfulness in men and women was significantly less than unity (rg = 0.75, 95% confidence interval = 0.69-0.80), suggesting a gene-by-sex interaction. In women, perceived youthfulness was modestly correlated with keratinocyte cancer (rg = -0.19) and skin tanning (rg = 0.18). In men, perceived youthfulness was correlated with male-pattern baldness (rg = -0.23). This suggests that the genetic architecture of perceived youthfulness may differ between sexes, with genes influencing skin tanning and skin cancer susceptibility driving the difference in women, whereas genes influencing male-pattern baldness and other puberty-related traits drive the difference in men. We recommend that future genetic analysis of skin aging include a sex-stratified component.

Plastics in the environment in the context of UV radiation, climate change and the Montreal Protocol: UNEP Environmental Effects Assessment Panel, Update 2023.

This Assessment Update by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) considers the interactive effects of solar UV radiation, global warming, and other weathering factors on plastics. The Assessment illustrates the significance of solar UV radiation in decreasing the durability of plastic materials, degradation of plastic debris, formation of micro- and nanoplastic particles and accompanying leaching of potential toxic compounds. Micro- and nanoplastics have been found in all ecosystems, the atmosphere, and in humans. While the potential biological risks are not yet well-established, the widespread and increasing occurrence of plastic pollution is reason for continuing research and monitoring. Plastic debris persists after its intended life in soils, water bodies and the atmosphere as well as in living organisms. To counteract accumulation of plastics in the environment, the lifetime of novel plastics or plastic alternatives should better match the functional life of products, with eventual breakdown releasing harmless substances to the environment.

The effect of three years of vitamin D supplementation on erectile dysfunction: Results from the randomized placebo-controlled D-Health Trial.

BACKGROUND & AIMS: Erectile dysfunction is common among older men and has been associated with low serum 25-hydroxy vitamin D concentration. However, this association may be due to uncontrolled confounding, and there is a paucity of evidence from interventional studies. We aimed to examine the effect of vitamin D supplementation on the prevalence of erectile dysfunction, in an exploratory analysis using data from a large randomized controlled trial. METHODS: The D-Health Trial recruited Australians aged 60-84 years between January 2014 and May 2015 and randomly assigned them to supplementation with 60,000 IU of vitamin D or placebo per month for up to 5 years. Blood samples were collected annually from randomly selected participants (total N = 3943). We assessed erectile dysfunction at the end of the third year of follow-up. We used log-binomial regression to examine the effect of vitamin D on the prevalence of erectile dysfunction overall, and within sub-groups. RESULTS: Of the 11,530 men enrolled, 8920 (77.4 %) completed the erectile dysfunction question and were included in the analysis. After three years of supplementation, the mean serum 25-hydroxy vitamin D concentration was 76 nmol/L (standard deviation (SD) 24.94) in the placebo group and 106 nmol/L (SD 26.76) in the vitamin D group (p < 0.0001). The prevalence of erectile dysfunction was 58.8 % and 59.0 % in the vitamin D and placebo groups, respectively (prevalence ratio 1.00, 95 % CI 0.97, 1.03); there was no evidence of an effect of vitamin D in any subgroup analyses. CONCLUSION: Supplementing older men with vitamin D is unlikely to prevent or improve erectile dysfunction. CLINICAL TRIALS REGISTRY: (ACTRN12613000743763).

Predicting the risk of pancreatic cancer in women with new-onset diabetes mellitus.

BACKGROUND AND AIM: People with new-onset diabetes mellitus (diabetes) could be a possible target population for pancreatic cancer surveillance. However, distinguishing diabetes caused by pancreatic cancer from type 2 diabetes remains challenging. We aimed to develop and validate a model to predict pancreatic cancer among women with new-onset diabetes. METHODS: We conducted a retrospective cohort study among Australian women newly diagnosed with diabetes, using first prescription of anti-diabetic medications, sourced from administrative data, as a surrogate for the diagnosis of diabetes. The outcome was a diagnosis of pancreatic cancer within 3 years of diabetes diagnosis. We used prescription medications, severity of diabetes (i.e., change/addition of medication within 2 months after first medication), and age at diabetes diagnosis as potential predictors of pancreatic cancer. RESULTS: Among 99 687 women aged ≥ 50 years with new-onset diabetes, 602 (0.6%) were diagnosed with pancreatic cancer within 3 years. The area under the receiver operating curve for the risk prediction model was 0.73. Age and diabetes severity were the two most influential predictors followed by beta-blockers, acid disorder drugs, and lipid-modifying agents. Using a risk threshold of 50%, sensitivity and specificity were 69% and the positive predictive value (PPV) was 1.3%. CONCLUSIONS: Our model doubled the PPV of pancreatic cancer in women with new-onset diabetes from 0.6% to 1.3%. Age and rapid progression of diabetes were important risk factors, and pancreatic cancer occurred more commonly in women without typical risk factors for type 2 diabetes. This model could prove valuable as an initial screening tool, especially as new biomarkers emerge.

Balancing the risks and benefits of sun exposure: A revised position statement for Australian adults.

OBJECTIVE: To describe the development of a new position statement regarding balancing the risks and benefits of sun exposure for Australian adults. METHODS: We conducted a Sun Exposure Summit in March 2021, with presentations from invited experts and a workshop including representation from academic, clinical, policy, and patient stakeholder organisations. The group considered advice about balancing the risks and benefits of sun exposure for Australian adults and developed a revised consensus position statement. RESULTS: The balance of risks and benefits of sun exposure is not the same for everybody. For people at very high risk of skin cancer, the risks of exposure likely outweigh the benefits; sun protection is essential. Conversely, people with deeply pigmented skin are at low risk of skin cancer but at high risk of vitamin D deficiency; routine sun protection is not recommended. For those at intermediate risk of skin cancer, sun protection remains a priority, but individuals may obtain sufficient sun exposure to maintain adequate vitamin D status. CONCLUSIONS: The new position statement provides sun exposure advice that explicitly recognises the differing needs of Australia's diverse population. IMPLICATIONS FOR PUBLIC HEALTH: Mass communication campaigns should retain the focus on skin cancer prevention. The new position statement will support the delivery of personalised advice.

Association between unstable diabetes mellitus and risk of pancreatic cancer.

BACKGROUND: Deterioration of glycaemic control in people with long-standing diabetes mellitus (diabetes) may be a possible indicator of pancreatic cancer. However, the magnitude of the association between diabetes deterioration and pancreatic cancer has received little attention. METHODS: We conducted a matched cohort study, nested within a population-based cohort of Australian women with diabetes. Women with unstable diabetes, defined as a change in medication after a 2-year period of stable medication use, were matched by birth year to those with stable diabetes, in a 1:4 ratio. We used flexible parametric survival models to estimate hazard ratios (HRs) and 95% confidence intervals (CI). RESULTS: We included 134,954 and 539,789 women in the unstable and stable diabetes cohorts, respectively (mean age 68 years). In total, 1,315 pancreatic cancers were diagnosed. Deterioration of stable diabetes was associated with a 2.5-fold increased risk of pancreatic cancer (HR 2.55; 95% CI 2.29-2.85). The risk was particularly high within the first year after diabetes deteriorated. HRs at 3 months, 6 months and 1 year were: 5.76 (95% CI 4.72-7.04); 4.56 (95% CI 3.81-5.46); and 3.33 (95% CI 2.86-3.89), respectively. The risk was no longer significantly different after 7 years. CONCLUSIONS: Deterioration in glycaemic control in people with previously stable diabetes may be an indicator of pancreatic cancer, suggesting investigations of the pancreas may be appropriate. The weaker longer-term (3-7 years) association between diabetes deterioration and pancreatic cancer may indicate that poor glycaemic control can be a risk factor for pancreatic cancer.

Vitamin D status during and after treatment and ovarian cancer survival.

PURPOSE: Five-year relative survival for ovarian cancer remains below 50%. Strategies to improve outcomes are needed. Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations [measure of vitamin D status] at and before diagnosis have been associated with longer survival in cancer patients; however, data for ovarian cancer are limited. We aimed to determine if 25(OH)D concentrations during and after primary treatment were associated with ovarian cancer-specific survival. METHODS: We used data from a nationwide prospective cohort study of women with ovarian cancer. Among 886 participants treated with chemotherapy, 700 (79%) had a blood sample collected during (n = 591) and/or after (n = 458) primary treatment. These were tested for 25(OH)D. Clinical and survival data were abstracted from medical records. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between 25(OH)D and ovarian cancer-specific survival. RESULTS: Mean 25(OH)D concentrations were lower during than after primary treatment (82 and 91 nmol/L, respectively); only 14% and 8% had concentrations below 50 nmol/L during and after primary treatment, respectively. There was no association between 25(OH)D and ovarian cancer-specific survival during five years of follow-up [HR 1.10 (95% CI: 0.76, 1.61) and 0.95 (0.54, 1.68) for the highest vs. lowest quintile during and after treatment, respectively]. CONCLUSIONS: We did not observe any association between serum 25(OH)D concentration and ovarian cancer-specific survival. Our results suggest that, in the absence of vitamin D deficiency, vitamin D supplementation to improve ovarian cancer survival is not warranted.

International patterns and trends in the incidence of melanoma and cutaneous squamous cell carcinoma, 1989-2020.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) and melanoma have different associations with sun exposure. OBJECTIVES: To compare trends in the incidence rates of cSCC and melanoma, to provide insight into changing patterns of exposure to ultraviolet radiation (UVR). METHODS: We compared trends in the incidence of cSCC and melanoma in seven susceptible populations residing at mid-to-high latitudes: Finland, Norway, Sweden, Denmark, Scotland, the Netherlands and Tasmania (Australia). We fitted Joinpoint models to describe trends in age-standardized incidence rates for melanoma and cSCC and calculated the average annual percentage rate of change for the period 1989-2020 (1989-2018 for Tasmania). We calculated the incident rate ratio (IRR) as the ratio of the age-standardized rates (European Standard Population) for cSCC to melanoma and conducted age-period-cohort modelling to compare age, period and cohort effects. RESULTS: The ratio of cSCC-to-melanoma incidence increased with proximity to the equator and over time. In the most recent time period, the incidence of cSCC was higher than the incidence of melanoma for men and women in all seven populations. While the ratio of cSCC-to-melanoma incidence was higher for men vs. women, in most countries the cSCC-to-melanoma IRR increased over time to a greater extent in women than in men. Melanoma incidence was higher among younger people and cSCC incidence was higher among older people; the age at which the incidence of cSCC overtook the incidence of melanoma was progressively younger with proximity to the equator. CONCLUSIONS: Despite concerted international efforts to preserve the ozone layer over the past four decades resulting in significant reductions in surface ultraviolet B at mid-latitudes, the incidence of skin cancer, particularly cSCC, continues to rise in those regions. Our findings are consistent with a stronger association with age-associated cumulative sun exposure for cSCC vs. melanoma and suggest that women are currently receiving greater UV radiation exposure than in the past.

The Unmet Needs of Pancreatic Cancer Carers Are Associated with Anxiety and Depression in Patients and Carers.

Pancreatic cancer has one of the lowest survival rates, and patients experience debilitating symptoms. Family carers provide essential daily care. This study determined the prevalence of and risk factors for unmet supportive care needs among carers for pancreatic cancer patients and examined which carer needs were associated with anxiety and depression in carers and patients. Eighty-four pancreatic cancer patients and their carers were recruited. The carers completed a needs survey (SCNS-P&C). Both carers and patients completed the Hospital Anxiety and Depression Scale. Log binomial regression was used to identify associations between carer needs and anxiety and depression among carers and patients. The top 10 moderate-to-high unmet needs reported by ≥28% of carers were related to healthcare (e.g., discussing concerns with doctors) and information need domains (e.g., information about a patient's physical needs), plus one other item related to hospital parking. Being male or caring for a patient within 4 months of their diagnosis were associated with greater unmet needs. Some unmet needs, including 'accessing information about treatments' and 'being involved in patient care', were associated with both carers and patients having anxiety and depression. Carers should be involved in health care consultations and provided with information and opportunities to discuss concerns.

Uncovering the complex relationship between balding, testosterone and skin cancers in men.

Male-pattern baldness (MPB) is related to dysregulation of androgens such as testosterone. A previously observed relationship between MPB and skin cancer may be due to greater exposure to ultraviolet radiation or indicate a role for androgenic pathways in the pathogenesis of skin cancers. We dissected this relationship via Mendelian randomization (MR) analyses, using genetic data from recent male-only meta-analyses of cutaneous melanoma (12,232 cases; 20,566 controls) and keratinocyte cancers (KCs) (up to 17,512 cases; >100,000 controls), followed by stratified MR analysis by body-sites. We found strong associations between MPB and the risk of KC, but not with androgens, and multivariable models revealed that this relationship was heavily confounded by MPB single nucleotide polymorphisms involved in pigmentation pathways. Site-stratified MR analyses revealed strong associations between MPB with head and neck squamous cell carcinoma and melanoma, suggesting that sun exposure on the scalp, rather than androgens, is the main driver. Men with less hair covering likely explains, at least in part, the higher incidence of melanoma in men residing in countries with high ambient UV.

Genetic variants for smoking behaviour and risk of skin cancer.

Observational studies have suggested that smoking may increase the risk of cutaneous squamous cell carcinoma (cSCC) while decreasing the risks of basal cell carcinoma (BCC), and melanoma. However, it remains possible that confounding by other factors may explain these associations. The aim of this investigation was to use Mendelian randomization (MR) to test whether smoking is associated with skin cancer, independently of other factors. Two-sample MR analyses were conducted to determine the causal effect of smoking measures on skin cancer risk using genome-wide association study (GWAS) summary statistics. We used the inverse-variance-weighted estimator to derive separate risk estimates across genetic instruments for all smoking measures. A genetic predisposition to smoking initiation was associated with lower risks of all skin cancer types, although none of the effect estimates reached statistical significance (OR 95% CI BCC 0.91, 0.82-1.01; cSCC 0.82, 0.66-1.01; melanoma 0.91, 0.82-1.01). Results for other measures were similar to smoking initiation with the exception of smoking intensity which was associated with a significantly reduced risk of melanoma (OR 0.67, 95% CI 0.51-0.89). Our findings support the findings of observational studies linking smoking to lower risks of melanoma and BCC. However, we found no evidence that smoking is associated with an elevated risk of cSCC; indeed, our results are most consistent with a decreased risk, similar to BCC and melanoma.

Does genetic risk modify the effect of skin screening on melanoma detection rates?

BACKGROUND: Skin screening is associated with higher melanoma detection rates, a potential indicator of overdiagnosis, but it remains possible that this effect is due to confounding by genetic risk. OBJECTIVES: To compare melanoma incidence among screened vs. unscreened participants within tertiles of genetic risk. METHODS: We investigated melanoma incidence in the QSkin study, a prospective cohort study which for this analysis comprised 15 283 participants aged 40-69 years with genotype data and no prior history of melanoma. We calculated a polygenic score (PGS) for melanoma. We first calculated the age-standardized rate (ASR) of melanoma within PGS tertiles, and then measured the association between skin examination and melanoma detection by calculating the hazard ratio (HR) and 95% confidence interval (95% CI), overall and within PGS tertiles. RESULTS: Melanoma incidence increased with PGS (ASR per 100 000 per year): tertile 1 = 442; tertile 2 = 519; tertile 3 = 871. We found that the HRs for all melanomas (i.e. in situ and invasive) associated with skin examination differed slightly across PGS tertiles [age- and sex-adjusted tertile 1 HR 1.88 (95% CI 1.26-2.81); tertile 2 HR 1.70 (95% CI 1.20-2.41); tertile 3 HR 1.96 (95% CI 1.43-2.70); fully adjusted tertile 1 HR 1.14 (95% CI 0.74-1.75); tertile 2 HR 1.21 (95% CI 0.82-1.78); tertile 3 HR 1.41 (95% CI 1.00-1.98)], but these differences were not statistically significant. HRs for in situ melanoma associated with skin examination were similar across PGS tertiles. For invasive melanomas, the point estimates appeared to be highest in PGS tertile 3 in both the minimally adjusted (age, sex) and fully adjusted models; however, these apparent differences were also not statistically significant. CONCLUSIONS: Genetic risk predicts subsequent melanoma incidence, and is weakly associated with screening behaviour, but it does not explain the higher rate of melanoma detection between screened and unscreened people.

The Effect of Vitamin D Supplementation on Hypothyroidism in the Randomized Controlled D-Health Trial.

Background: Hypothyroidism is common, and in iodine-sufficient areas, it is primarily caused by autoimmune destruction of the thyroid gland. Observational studies have consistently shown an inverse association between serum 25-hydroxyvitamin D concentration and autoimmune diseases; however, there is a lack of evidence from randomized controlled trials to support a benefit of vitamin D supplementation, particularly for autoimmune thyroid diseases. We, therefore, aimed to assess the effect of vitamin D supplementation on the incidence of hypothyroidism. Methods: We analyzed data from the D-Health Trial (n = 21,315), a randomized double-blind placebo-controlled trial of 60,000 international units per month of supplemental vitamin D3 among Australians aged 60 years and over. Hypothyroidism, a tertiary outcome of the D-Health Trial, was defined by treatment with levothyroxine, ascertained through linkage with the Australian Pharmaceutical Benefits Scheme. The outcome was time to first prescription of levothyroxine. We began follow-up at 12 months after randomization; people who had died or who had been dispensed levothyroxine during the first year were excluded. Flexible parametric survival models were used to assess the effect of vitamin D supplementation on hypothyroidism, overall and within strata defined by age, sex, body mass index, and predicted baseline vitamin D status. Results: We included 17,851 participants in the main analysis (vitamin D = 8939; placebo = 8912). During a median follow-up of 4.1 years (interquartile range 4.1-4.1), 293 participants developed hypothyroidism (vitamin D = 138 [1.5%]; placebo = 155 [1.7%]). Vitamin D supplementation did not significantly reduce the incidence of hypothyroidism (overall hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.71-1.12). There was some suggestion of an effect in females (overall HR 0.78; CI 0.58-1.06) but not in males (overall HR 1.06; CI 0.74-1.50; p interaction 0.20). Conclusions: Vitamin D supplementation did not reduce the incidence of hypothyroidism overall; however, the possible beneficial effect observed in females warrants further investigation. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12613000743763.

Making the sunshine vitamin - How much sun exposure is needed to maintain 25-hydroxy vitamin D concentration?

Our objective was to calculate the time in the sun necessary to maintain existing 25-hydroxyvitamin D (25(OH)D) concentration at locations across Australia and New Zealand. We used a microsimulation model to estimate changes in monthly 25(OH)D concentration using data on standard erythemal dose, solar zenith angle, and climatological ozone. We estimated the number of standard vitamin D doses per 10-min interval and used a dose-response equation to determine the average time in the sun to maintain existing 25(OH)D concentration according to month and time of day. Across all locations in summer, 5-10 min outdoors between 8 a.m. and 4 p.m. on most days of the week, with 35% of the body surface area exposed, is sufficient to maintain existing 25(OH)D concentration. In winter, at mid-to-high latitudes, time outdoors during the middle of the day is required. In winter, with 10% of the body surface area exposed, greater than 45 min in the middle of the day is required in most locations to maintain existing 25(OH)D concentration. These data can be used to inform guidelines regarding maintaining vitamin D via sun exposure and may help health practitioners identify patients who may be vitamin D deficient.

It is time to update sun safety campaigns to recognise population diversity: Findings from two citizens' juries in Australia.

ISSUE ADDRESSED: While the links between sun exposure and skin cancer are well known, the benefits of sun exposure, particularly as a source of vitamin D, are less well known. This paper reports on a deliberative study exploring public perspectives about sun exposure harms and benefits. METHODS: Two citizens' juries were conducted in Brisbane and Adelaide to consider questions about sun exposure, vitamin D and health promotion. Members of the general population (jurors) listened to evidence from expert witnesses about the harms and benefits of sun exposure. Most witness sessions extended for 60 min, with 6 sessions over 2 days. At each citizens' jury, jurors were asked to listen to expert testimony, consider the evidence and make policy recommendations. The planning and design of the citizens' juries were informed by well-established citizens' jury methods. RESULTS: Jurors proposed that Australia needs improved public information about the harms and benefits of sun exposure. They argued for information that supports personal decision-making that accounts for differences in skin tone and geographical region. Jurors agreed that Australia needs an updated sun safety campaign that reflects new research and addresses diversity. A one-size-fits-all approach to sun protection may no longer be appropriate. CONCLUSIONS: While a new campaign should address both harms and benefits, jurors felt the need for skin cancer prevention outweighs the desirability of generating vitamin D through sun exposure. More nuanced public health messages are needed, which balance the need for skin protection and vitamin D, and acknowledge the diversity of Australia's population. SO WHAT?: Previous research studies are typically siloed into the separate areas of vitamin D or skin cancer research. This study incorporated both topics and pooled the views of participants in two citizens' juries who agreed on the need for improved information about the harms and benefits of sun exposure to reflect a modern Australian population.

Health Effects of Vitamin D Supplementation: Lessons Learned From Randomized Controlled Trials and Mendelian Randomization Studies.

Vitamin D plays an important role in calcium homeostasis and many cellular processes. Although vitamin D supplements are widely recommended for community-dwelling adults, definitive data on whether these supplements benefit clinically important skeletal and extraskeletal outcomes have been conflicting. Although observational studies on effects of vitamin D on musculoskeletal and extraskeletal outcomes may be confounded by reverse causation, randomized controlled studies (RCTs) and Mendelian randomization (MR) studies can help to elucidate causation. In this review, we summarize the recent findings from large RCTs and/or MR studies of vitamin D on bone health and risk of fractures, falls, cancer, and cardiovascular disease, disorders of the immune system, multiple sclerosis, and mortality in community-dwelling adults. The primary analyses indicate that vitamin D supplementation does not decrease bone loss, fractures, falls, cancer incidence, hypertension, or cardiovascular risk in generally healthy populations. Large RCTs and meta-analyses suggest an effect of supplemental vitamin D on cancer mortality. The existence of extraskeletal benefits of vitamin D supplementations are best documented for the immune system especially in people with poor vitamin D status, autoimmune diseases, and multiple sclerosis. Accumulating evidence indicates that vitamin D may reduce all-cause mortality. These findings, in mostly vitamin D-replete populations, do not apply to older adults in residential communities or adults with vitamin D deficiency or osteoporosis. The focus of vitamin D supplementation should shift from widespread use in generally healthy populations to targeted vitamin D supplementation in select individuals, good nutritional approaches, and elimination of vitamin D deficiency globally. © 2023 American Society for Bone and Mineral Research (ASBMR).