MC1R genotype may modify the effect of sun exposure on melanoma risk in the GEM study

We investigated whether MC1R genotype modifies the effect of sun exposure on melanoma risk in 1,018 cases with multiple melanomas (MPM) and 1,875 controls with one melanoma (SPM). There was some suggestion that MC1R genotype modified the effect of beach and water activities on MPM risk: ORs were 1.94 (95% CI 1.40–2.70) for any activities for no R variants and 1.39 (95% CI 1.05–1.84) with R variants (R151C, R160W, D294H, D84E) (p for interaction 0.08). MC1R modification of sun exposure effects appeared most evident for MPM of the head and neck: for early life ambient UV the OR was 4.23 (95% CI 1.76–10.20) with no R and 1.04 (95% CI 0.40–2.68) with R (p for interaction=0.01; p for three-way interaction=0.01). Phenotype modified the effect of sun exposure and MPM in a similar manner. We conclude that MC1R and pigmentary phenotype may modify the effects of sun exposure on melanoma risk on more continuously sun-exposed skin. Possible explanations include that risk may saturate with higher sun sensitivity for melanomas on continuously sun-exposed sites but continue to increase as sun exposure increases with lower sun sensitivity, or that sun sensitive people adapt their behaviour by increasing sun protection when exposed

Clinicopathologic Features of Incident and Subsequent Tumors in Patients with Multiple Primary Cutaneous Melanomas

0.6–12.7% of patients with primary cutaneous melanoma will develop additional melanomas. Pathologic features of tumors in patients with multiple primary cutaneous melanomas have not been well described. In this large international multi-center case-control study, we compared the clinicopathologic features of a subsequent melanoma with the preceding (usually the first) melanoma in patients with multiple primary cutaneous melanomas, and with those of melanomas in patients with single primary cutaneous melanomas

Ambient UV, personal sun exposure and risk of multiple primary melanomas

Sun exposure is the main cause of melanoma in populations of European origin. No previous study has examined the effect of sun exposure on risk of multiple primary melanomas compared with people who have one melanoma

Sun Exposure and Melanoma Survival: A GEM Study

We previously reported a significant association between higher ultraviolet radiation exposure before diagnosis and greater survival with melanoma in a population-based study in Connecticut. We sought to evaluate the hypothesis that sun exposure prior to diagnosis was associated with greater survival in a larger, international population-based study with more detailed exposure information

Associations of Cumulative Sun Exposure and Phenotypic Characteristics with Histologic Solar Elastosis

Solar elastosis adjacent to melanomas in histologic sections is regarded as an indicator of sun exposure although the associations of ultraviolet (UV) exposure and phenotype with solar elastosis are yet to be fully explored

The impact of disease severity adjustment on hospital standardised mortality ratios: Results from a service-wide analysis of ischaemic stroke admissions using linked pre-hospital, admissions and mortality data.

BACKGROUND:Administrative data are used to examine variation in thirty-day mortality across health services in several jurisdictions. Hospital performance measurement may be error-prone as information about disease severity is not typically available in routinely collected data to incorporate into case-mix adjusted analyses. Using ischaemic stroke as a case study, we tested the extent to which accounting for disease severity impacts on hospital performance assessment. METHODS:We linked all recorded ischaemic stroke admissions between July, 2011 and June, 2014 to death registrations and a measure of stroke severity obtained at first point of patient contact with health services, across New South Wales, Australia's largest health service jurisdiction. Thirty-day hospital standardised mortality ratios were adjusted for either comorbidities, as is typically done, or for both comorbidities and stroke severity. The impact of stroke severity adjustment on mortality ratios was determined using 95% and 99% control limits applied to funnel plots and by calculating the change in rank order of hospital risk adjusted mortality rates. RESULTS:The performance of the stroke severity adjusted model was superior to incorporating comorbidity burden alone (c-statistic = 0.82 versus 0.75; N = 17,700 patients, 176 hospitals). Concordance in outlier classification was 89% and 97% when applying 95% or 99% control limits to funnel plots, respectively. The sensitivity rates of outlier detection using comorbidity adjustment compared with gold-standard severity and comorbidity adjustment was 74% and 83% with 95% and 99% control limits, respectively. Corresponding positive predictive values were 74% and 91%. Hospital rank order of risk adjusted mortality rates shifted between 0 to 22 places with severity adjustment (Median = 4.0, Inter-quartile Range = 2-7). CONCLUSIONS:Rankings of mortality rates varied widely depending on whether stroke severity was taken into account. Funnel plots yielded largely concordant results irrespective of severity adjustment and may be sufficiently accurate as a screening tool for assessing hospital performance

Why do large breast cancers still present in a population offered screening?

Rates of large breast cancers should decrease in a population that is offered mammography screening, but women continue to present with them. We sought an explanation in a population-based epidemiological study of 1,459 women diagnosed with invasive breast cancer in 2002-2003 in Australia; breast cancers were 2 cm in 766 women (53%) and 11-1.9 cm in a comparison group (693, 47%). We interviewed the women about their personal, mammogram and breast histories in the years before diagnosis and collected biological characteristics of tumors and mammogram dates from medical records. The strongest correlate of breast cancer size at diagnosis was the method of detection: the odds of a 2 cm breast cancer was substantially lower for detection by a screening mammogram (OR = 0.27, 95% CI 0.21-0.34; p < 0.001) than for detection after a breast symptom. Higher BMI (ORs 1.6 for 25 kg/m2), higher cancer grade (ORs of 1.6 for moderate, 2.89 for high grade) and lobular type (OR 2.09, 95% CI 1.45-3.0) were also independent correlates (p < 0.001) of a 2 cm breast cancer. HRT use strongly reduced the odds but only in cancers detected after a breast symptom (OR = 0.49, 95% CI 0.33-0.74; p = 0.002), not in those detected by a screening mammogram. As assessed from their proportional contribution to 2 cm breast cancers in our study population, lack of mammogram detection, BMI 25 kg/m2 and moderate or high grade of the cancer were the most important factors with population attributable fractions of 42%, 11% and 29% respectively; the first 2 are amenable to intervention

Decreasing Risk of Fatal Subarachnoid Hemorrhage and Other Epidemiological Trends in the Era of Coiling Implementation in Australia

Background and purposeSubarachnoid hemorrhage (SAH) is associated with a high risk of mortality and disability in survivors. We examined the epidemiology and burden of SAH in our population during a time services were re-organized to facilitate access to evidence-based endovascular coiling and neurosurgical care.MethodsSAH hospitalizations from 2001 to 2009, in New South Wales, Australia, were linked to death registrations to June 30, 2010. We assessed the variability of admission rates, fatal SAH rates and case fatality over time and according to patient demographic characteristics.ResultsThere were 4,945 eligible patients admitted to hospital with SAH. The risk of fatal SAH significantly decreased by 2.7% on average per year (95% CI = 0.3–4.9%). Case fatality at 2, 30, 90, and 365 days significantly declined over time. The average annual percentage reduction in mortality ranged from 4.4% for 30-day mortality (95% CI −6.1 to −2.7) (P &lt; 0.001) to 4.7% for mortality within 2 days (−7.1 to −2.2) (P &lt; 0.001) (Table 3). Three percent of patients received coiling at the start of the study period, increasing to 28% at the end (P-value for trend &lt;0.001). Females were significantly more likely to be hospitalized for a SAH compared to males [incident rate ratio (IRR) = 1.33, 95% CI = 1.23–1.44] (P &lt; 0.001) and to die from SAH (IRR = 1.40, 95% CI = 1.24–1.59) (P &lt; 0.001). People born in South-East Asia and the Oceania region had a significantly increased risk of SAH, while the risk of fatal SAH was greater in South-East and North-East Asian born residents. People residing in areas of least disadvantage had the lowest risk of hospitalization (IRR = 0.83, 95% CI = 0.74–0.92) and also the lowest risk of fatal SAH (0.81, 95% CI = 0.66–1.00) (P &lt; 0.001 and P = 0.003, respectively). For every 100 SAH admissions, 20 and 15 might be avoided in males and females, respectively, if the risk of SAH in our population equated to that of the most socio-economically advantaged.ConclusionOur study reports reductions in mortality risk in SAH corresponding to identifiable changes in health service delivery and evolving treatments such as coiling. Addressing inequities in SAH risk and mortality may require the targeting of prevalent and modifiable risk factors to improve population outcomes

Impact of common genomic variants on melanoma risk prediction

Background: Genome-wide association studies have identified numerous common genomic variants associated with increased susceptibility to melanoma, but there is limited knowledge about the utility of adding them to risk prediction models for melanoma. Aim: To evaluate the contribution of common genomic variants to melanoma risk prediction, among young Australian adults. Methods: The sample included 552 cases with invasive cutaneous melanoma diagnosed between ages 18–39 years and 405 controls from an Australian population-based, case-control-family study. MC1R genotype was sequenced, and through a genome-wide association study we obtained genotype data for single nucleotide polymorphisms from 18 selected gene regions. Measures of discriminatory accuracy included the area under receiver operating characteristic curves (AUC) and net reclassification improvement (NRI), calculated based on predicted probabilities of melanoma from unconditional logistic regression models. We used 10-fold cross-validation and bootstrap methods to assess internal validation. Results: Compared to a demographic model containing age, sex and city of recruitment (AUC 0.69; 95% CI 0.65–0.72), the combined contribution to the AUC of common genomic variants was the same as that contributed from traditional self-reported risk factors for melanoma (UV exposure, pigmentation phenotype, nevi, etc) – both AUCs increased to 0.77 (95% CI 0.74–0.80). An inclusive model containing demographic, genetic and nongenetic (traditional) risk factors had an AUC of 0.81 (95% CI 0.78–0.84). Inclusion of genomic variants in the multivariate model improved the quartile classification of predicted risk (NRI) by a net 17% (95% CI 9–24) compared to the non-genetic (traditional) model. Conclusions: Our results suggest that common genomic variants could considerably improve risk prediction models for early-onset melanoma, and may have a role in primary prevention of melanoma. We are commencing pilot studies to translate these findings into potential cancer prevention strategies in general practice and in the community.1 page(s