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5 d Including acral lentiginous melanoma, melanoma in junctional nevus, malignant melanoma not otherwise specified, etc. 6 e As per the study design, fatal and non-fatal cases were similar regarding median thickness. While the individual case fatality rate from thin melanoma is low, overall, thin melanomas contribute a large proportion of total melanoma deaths. [Extracted from the article]

Objectives: Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio). Design, Setting, Participants, and Intervention: Participants were Australians aged 60–84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation. Results: The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was −0.001 (95% CI −0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration. Conclusion: In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length. [ABSTRACT FROM AUTHOR]

Observational studies suggest that people with a high serum 25-hydroxyvitamin D (25(OH)D) concentration may have reduced risk of chronic diseases such as osteoporosis, multiple sclerosis, type 1 diabetes, cardiovascular disease, and some cancers. The AusD Study (A Quantitative Assessment of Solar UV Exposure for Vitamin D Synthesis in Australian Adults) was conducted to clarify the relationships between ultraviolet (UV) radiation exposure, dietary intake of vitamin D, and serum 25(OH)D concentration among Australian adults residing in Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S), and Hobart (42.8°S). Participants aged 18–75 years were recruited from the Australian Electoral Roll between 2009 and 2010. Measurements were made of height, weight, waist:hip ratio, skin, hair, and eye color, blood pressure, and grip strength. Participants completed a questionnaire on sun exposure and vitamin D intake, together with 10 days of personal UV dosimetry and an associated sun-exposure and physical-activity diary that was temporally linked to a blood test for measurement of 25(OH)D concentration. Ambient solar UV radiation was also monitored at all study sites. We collected comprehensive, high-quality data from 1,002 participants (459 males, 543 females) assessed simultaneously across a range of latitudes and through all seasons. Here we describe the scientific and methodological issues considered in designing the AusD Study. [ABSTRACT FROM PUBLISHER]

Background: In both Sweden and Australia high incidence rates of skin cancer have become a major health problem. In prevention and risk communication, it is important to have reliable ways for identifying people with risky sun habits. In this study the validity and reliability of the questionnaire Sun Exposure Protection Index (SEPI), developed to assess individual's sun habits and their propensity to increase sun protection during routine, often brief, clinical encounters, has been evaluated. The aim of our study was to evaluate validity and reliability of the proposed SEPI scoring instrument, in two countries with markedly different ultraviolet radiation environments (Sweden and Australia).Method: Two subpopulations in Sweden and Australia respectively were asked to fill out the SEPI together with the previously evaluated Readiness to Alter Sun Protective Behaviour questionnaire (RASP-B) and the associated Sun-protective Behaviours Questionnaire. To test reliability, the SEPI was again filled out by the subjects one month later.Results: Comparison between SEPI and the questions in the Sun-protective Behaviours Questionnaire, analyzed with Spearman's Rho, showed good correlations regarding sun habits. Comparison between SEPI and RASP-B regarding propensity to increase sun protection showed concurrently lower SEPI mean scores for action stage, but no difference between precontemplation and contemplation stages. The SEPI test-retest analysis indicated stability over time. Internal consistency of the SEPI, assessed with Cronbach's alpha estimation showed values marginally lower than the desired >0.70 coefficient value generally recommended, and was somewhat negatively affected by the question on sunscreen use, likely related to the classic "sunscreen paradox". There were some differences in the performance of the SEPI between the Swedish and Australian samples, possibly due to the influence of "available" sunlight and differing attitudes to behaviour and protection "at home" and on vacation.Conclusions: SEPI appears to be a stable instrument with an overall acceptable validity and reliability, applicable for use in populations exposed to different UVR environments, in order to evaluate individual sun exposure and protection. [ABSTRACT FROM AUTHOR]

Background: Melanoma develops as the result of complex interactions between sun exposure and genetic factors. However, data on these interactions from prospective studies are scant., Objectives: To quantify the association between ambient and personal ultraviolet exposure and incident melanoma in a large population-based prospective study of men and women residing in a setting of high ambient ultraviolet radiation, and to examine potential gene-environment interactions., Methods: Data were obtained from the QSkin Sun and Health Study, a prospective cohort study of men and women aged 40-69 years, randomly sampled from the Queensland population in 2011. Participants were genotyped and assessed for ultraviolet exposure., Results: Among participants with genetic data (n = 15 373), 420 (2·7%) developed cutaneous melanoma (173 invasive, 247 in situ) during a median follow-up time of 4·4 years. Country of birth, age at migration, having > 50 sunburns in childhood or adolescence, and a history of keratinocyte cancer or actinic lesions were significantly associated with melanoma risk., Conclusions: An interaction with polygenic risk was suggested: among people at low polygenic risk, markers of cumulative sun exposure (as measured by actinic damage) were associated with melanoma. In contrast, among people at high polygenic risk, markers of high-level early-life ambient exposure (as measured by place of birth) were associated with melanoma (hazard ratio for born in Australia vs. overseas 3·16, 95% confidence interval 1·39-7·22). These findings suggest interactions between genotype and environment that are consistent with divergent pathways for melanoma development. What's already known about this topic? The relationship between sun exposure and melanoma is complex, and exposure effects are highly modified by host factors and behaviours. The role of genotype on the relationship between ultraviolet radiation exposure and melanoma risk is poorly understood. What does this study add? We found that country of birth, age at migration, sunburns in childhood or adolescence, and history of keratinocyte cancer or actinic lesions were significantly associated with melanoma risk, while other measures of continuous or more intermittent patterns of sun exposure were not. We found evidence for gene-environment interactions that are consistent with divergent pathways for melanoma development. Linked Comment: Cust. Br J Dermatol 2020; 183:205-206. Plain language summary available online., (© 2019 British Association of Dermatologists.)

Background: Thin cutaneous melanomas (≤ 1·00 mm) are increasing worldwide, causing around a quarter of all melanoma deaths in the U.S.A. and Australia. Identification of predictive factors for potentially fatal thin melanomas could allow better use of resources for follow-up., Objectives: To identify the clinicopathological factors associated with fatal thin melanomas., Methods: This large, nested case-case study extracted data from the population-based Queensland Cancer Registry, Australia. Our cohort consisted of Queensland residents aged 0-89 years who were diagnosed with a single, locally invasive thin melanoma (≤ 1·00 mm) between 1995 and 2014. Fatal cases (eligible patients who died from melanoma) were individually matched to three nonfatal cases (eligible patients who were not known to have died from melanoma) according to sex, age, year of diagnosis and follow-up interval. Using conditional logistic regression, we calculated odds ratios (ORs) for melanoma-specific death, adjusting for all collected clinicopathological variables., Results: In the cohort, 27 660 eligible patients were diagnosed with a single, thin melanoma. The final case-case series included 424 fatal cases and 1189 nonfatal cases. Fatal cases were sixfold as likely to arise on the scalp as on the back [OR 6·39, 95% confidence interval (CI) 2·57-15·92] and six times as likely to be of thickness 0·80-1·00 mm as of < 0·30 mm (OR 6·00, 95% CI 3·55-10·17)., Conclusions: Scalp location is a strong prognostic factor of death from thin melanoma. Further, this study provides support that melanomas with a thickness of 0·80-1·00 mm are the more hazardous thin lesions. Patients with these tumour characteristics require specific attention during follow-up. What's already known about this topic? Thin invasive melanomas (≤ 1·00 mm) contribute a substantial proportion of melanoma fatalities, owing to the high volume of disease. There is a need to find prognostic factors that will better identify fatal thin melanomas at the time of diagnosis. What does this study add? In this large population-based study, fatal thin tumours were sixfold as likely to be located on the scalp as on the back. Thin melanomas of 0·80-1·00 mm thickness were six times as likely to be associated with death as tumours < 0·30 mm. Scalp location and increasing thickness are strong predictive factors of fatal thin melanomas, indicating that patients with these tumour characteristics require close follow-up., (© 2019 British Association of Dermatologists.)

Background: Ultraviolet radiation causes cutaneous melanoma. Sunscreen prevents sunburn and protects skin cells against mutations. High-quality epidemiological studies suggest regular sunscreen use prevents melanoma., Objectives: To calculate the potential impact fraction (PIF) for melanoma in the U.S.A. and Australia assuming a range of different intervention scenarios intended to increase sunscreen use., Methods: We calculated the PIF, the proportional difference between the observed number of melanomas arising under prevailing levels of sunscreen use compared with the number expected under counterfactual scenarios. We used published melanoma incidence projections for Australia and the white population in the U.S.A. from 2012 through to 2031 as the baseline condition, with estimates for protective effects of 'regular sunscreen use' from the literature. Sunscreen prevalence was sourced from national or state surveys., Results: Under a plausible public health intervention scenario comprising incremental increases in sunscreen prevalence over a 10-year implementation programme, we estimated that cumulatively to 2031, 231 053 fewer melanomas would arise in the U.S. white population (PIF 11%) and 28 071 fewer melanomas would arise in Australia (PIF 10%). Under the theoretical maximum model of sunscreen use, almost 797 000 (PIF 38%) and approximately 96 000 (PIF 34%) melanomas would be prevented in the U.S.A. and Australia, respectively between 2012 and 2031. A sensitivity analysis using weaker effect estimates resulted in more conservative PIF estimates., Conclusions: Overall, interventions to increase use of sunscreen would result in moderate reductions in melanoma incidence, assuming no compensatory overexposure to the sun. Countries with a high incidence of melanoma should monitor levels of sunscreen use in the community., (© 2017 British Association of Dermatologists.)

Background: During the past four decades, the incidence of esophageal adenocarcinoma (EAC) has increased markedly in Western populations. Recent reports have suggested that the rate of increase has slowed or plateaued., Patients and Methods: Using data from cancer registries in Australia, the United States and Sweden, we examined incidence trends for esophageal and gastric cardia tumors between 1984 and 2008 using joinpoint analyses and age-period-cohort models., Results: EAC incidence continues to undergo statistically significant annual increases in Australia and the United States, although the rate of increase has slowed. Among men, incidence increased annually by 2.2% [95% confidence interval (CI) 1.5% to 2.9%] between 1994 and 2008 in Australia and 1.5% (95% CI 0.2% to 2.8%) between 1998 and 2008 in the United States. EAC incidence among men remained unchanged in Sweden between 2001 and 2008 (P = 0.52). EAC incidence among women showed significant linear increases between 1984 and 2008. Age-period-cohort models suggested strong effects for both period and birth cohort on EAC incidence in Australia and the United States, and a strong period effect for Sweden., Conclusions: EAC incidence continues to increase in Australia and the United States. The continued increases, even among more recent birth cohorts, suggest that EAC incidence will continue to rise during coming decades.

Background: Concern about skin cancer is a common reason for people from predominantly fair-skinned populations to present to primary care doctors., Objectives: To examine the frequency and body-site distribution of malignant, pre-malignant and benign pigmented skin lesions excised in primary care., Methods: This prospective study conducted in Queensland, Australia, included 154 primary care doctors. For all excised or biopsied lesions, doctors recorded the patient's age and sex, body site, level of patient pressure to excise, and the clinical diagnosis. Histological confirmation was obtained through pathology laboratories., Results: Of 9650 skin lesions, 57·7% were excised in males and 75·0% excised in patients ≥ 50 years. The most common diagnoses were basal cell carcinoma (BCC) (35·1%) and squamous cell carcinoma (SCC) (19·7%). Compared with the whole body, the highest densities for SCC, BCC and actinic keratoses were observed on chronically sun-exposed areas of the body including the face in males and females, the scalp and ears in males, and the hands in females. The density of BCC was also high on intermittently or rarely exposed body sites. Females, younger patients and patients with melanocytic naevi were significantly more likely to exert moderate/high levels of pressure on the doctor to excise., Conclusions: More than half the excised lesions were skin cancer, which mostly occurred on the more chronically sun-exposed areas of the body. Information on the type and body-site distribution of skin lesions can aid in the diagnosis and planned management of skin cancer and other skin lesions commonly presented in primary care., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.)

Objective: To measure the extent to which risks of oesophageal cancers associated with gastro-oesophageal reflux (GOR) are modified by common factors including smoking, non-steroidal anti-inflammatory drugs (NSAIDs) and acid suppressant medications., Design and Setting: Population-based case-control study., Participants: Cases were patients with oesophageal (OAC; n = 365) or gastro-oesophageal junction (GOJAC; n = 426) adenocarcinomas, or squamous cell carcinomas (OSCC; n = 303). Controls were sampled from a population register (n = 1580)., Main Outcome Measure: Odds ratio and 95% confidence interval., Results: Frequent (at least weekly) symptoms of GOR were associated with significant 6.4-fold, 4.6-fold and 2.2-fold increased risks of OAC, GOJAC and OSCC, respectively. Under models examining effects of combined exposure, patients with frequent GOR symptoms who were also heavy smokers had markedly higher OAC risks (OR = 12.3, 95% CI 6.3 to 24.0) than those with frequent GOR who did not smoke (OR = 6.8, 95% CI 3.6 to 12.9). Similar patterns were observed for GOJAC and OSCC. Among people with frequent GOR symptoms, regular use of aspirin/NSAIDs was associated with almost two-thirds lower OAC risks (OR = 4.8, 95% CI 2.5 to 9.2) than non-users (13.9, 95% CI 6.5 to 30.0). In contrast, among those with frequent GOR symptoms, users of acid suppressants had similar OAC risks (OR 7.8, 95% CI 5.2 to 11.8) to non-users (OR 5.3, 95% CI 3.2 to 9.0)., Conclusions: People experiencing frequent GOR symptoms have markedly increased risks of OAC and GOJAC, and this effect may be greater amongst smokers. Use of aspirin and NSAIDs, but not acid suppressants, significantly reduced the risks of oesophageal cancers associated with GOR.

Background and Methods: Prevailing hypotheses about the causes of ovarian carcinogenesis predict that women with a history of multiple births (twins, triplets, etc.) should be at increased risk of epithelial ovarian cancer. However, the scant available evidence suggests that they may actually be at lower risk. To resolve this issue, we pooled data from eight studies involving 2859 parous women with epithelial ovarian cancer (case patients) and 7434 parous women without ovarian cancer (control women). In addition to assessing their history of multiple births (and the sex of the children, where available), we obtained information on age, parity, oral contraceptive use, and other reproductive factors for each woman. Details of tumor histology were available for all case patients. We estimated the relative risks of various histologic types of ovarian cancers associated with multiple births by using multivariable logistic regression analysis, adjusting for matching and confounding variables., Results: Among these parous women, 73 case patients (2. 6%) and 257 control women (3.5%) had a history of multiple births. The adjusted summary odds ratio (OR) for developing all types of epithelial ovarian cancer that are associated with multiple births was 0.81 (95% confidence interval [CI] = 0.61-1.08). We found no evidence that risks associated with multiple births differed among women with borderline or invasive tumors and among women with same-sex and opposite-sex offspring from multiple births. The risk reductions appeared specific for nonmucinous tumors (n = 2453; summary adjusted OR = 0.71 [95% CI = 0.52-0.98]); in contrast, associations with mucinous tumors (n = 406) were heterogeneous across studies., Conclusions: Parous women with nonmucinous ovarian cancer are no more likely to have a history of multiple births than other parous women, counter to the predictions of current hypotheses for causes of ovarian cancer.