Urinary 6-sulphatoxymelatonin levels and risk of breast cancer in premenopausal women : the ORDET cohort

Background: Lower urinary melatonin levels are associated with a higher risk of breast cancer in postmenopausal women. Literature for premenopausal women is scant and inconsistent. Methods: In a prospective case-control study, we measured the concentration of 6-sulphatoxymelatonin (aMT6s) in the 12-hour overnight urine of 180 premenopausal women with incident breast cancer and 683 matched controls. Results: In logistic regression models, the multivariate odds ratio (OR) of invasive breast cancer for women in the highest quartile of total overnight aMT6s output compared with the lowest was 1.43 [95% confidence interval (CI), 0.83-2.45; Ptrend = 0.03]. Among current nonsmokers, no association was existent (OR, 1.00; 95% CI, 0.52-1.94; Ptrend = 0.29). We observed an OR of 0.68 between overnight urinary aMT6s level and breast cancer risk in women with invasive breast cancer diagnosed >2 years after urine collection and a significant inverse association in women with a breast cancer diagnosis >8 years after urine collection (OR, 0.17; 95% CI, 0.04-0.71; Ptrend = 0.01). There were no important variations in ORs by tumor stage or hormone receptor status of breast tumors. Conclusion: Overall, we observed a positive association between aMT6s and risk of breast cancer. However, there was some evidence to suggest that this might be driven by the influence of subclinical disease on melatonin levels, with a possible inverse association among women diagnosed further from recruitment. Thus, the influence of lag time on the association between melatonin and breast cancer risk needs to be evaluated in further studies

Distribution of Major Health Risks: Findings from the Global Burden of Disease Study

BACKGROUND: Most analyses of risks to health focus on the total burden of their aggregate effects. The distribution of risk-factor-attributable disease burden, for example by age or exposure level, can inform the selection and targeting of specific interventions and programs, and increase cost-effectiveness. METHODS AND FINDINGS: For 26 selected risk factors, expert working groups conducted comprehensive reviews of data on risk-factor exposure and hazard for 14 epidemiological subregions of the world, by age and sex. Age-sex-subregion-population attributable fractions were estimated and applied to the mortality and burden of disease estimates from the World Health Organization Global Burden of Disease database. Where possible, exposure levels were assessed as continuous measures, or as multiple categories. The proportion of risk-factor-attributable burden in different population subgroups, defined by age, sex, and exposure level, was estimated. For major cardiovascular risk factors (blood pressure, cholesterol, tobacco use, fruit and vegetable intake, body mass index, and physical inactivity) 43%–61% of attributable disease burden occurred between the ages of 15 and 59 y, and 87% of alcohol-attributable burden occurred in this age group. Most of the disease burden for continuous risks occurred in those with only moderately raised levels, not among those with levels above commonly used cut-points, such as those with hypertension or obesity. Of all disease burden attributable to being underweight during childhood, 55% occurred among children 1–3 standard deviations below the reference population median, and the remainder occurred among severely malnourished children, who were three or more standard deviations below median. CONCLUSIONS: Many major global risks are widely spread in a population, rather than restricted to a minority. Population-based strategies that seek to shift the whole distribution of risk factors often have the potential to produce substantial reductions in disease burden

Recommendations on the measurement and the clinical use of vitamin D metabolites and vitamin D binding protein – A position paper from the IFCC Committee on bone metabolism

Vitamin D, an important hormone with a central role in calcium and phosphate homeostasis, is required for bone and muscle development as well as preservation of musculoskeletal function. The most abundant vitamin D metabolite is 25-hydroxyvitamin D [25(OH)D], which is currently considered the best marker to evaluate overall vitamin D status. 25(OH)D is therefore the most commonly measured metabolite in clinical practice. However, several other metabolites, although not broadly measured, are useful in certain clinical situations. Vitamin D and all its metabolites are circulating in blood bound to vitamin D binding protein, (VDBP). This highly polymorphic protein is not only the major transport protein which, along with albumin, binds over 99% of the circulating vitamin D metabolites, but also participates in the transport of the 25(OH)D into the cell via a megalin/cubilin complex. The accurate measurement of 25(OH)D has proved a difficult task. Although a reference method and standardization program are available for 25(OH)D, the other vitamin D metabolites still lack this. Interpretation of results, creation of clinical supplementation, and generation of therapeutic guidelines require not only accurate measurements of vitamin D metabolites, but also the accurate measurements of several other “molecules” related with bone metabolism. IFCC understood this priority and a committee has been established with the task to support and continue the standardization processes of vitamin D metabolites along with other bone-related biomarkers. In this review, we present the position of this IFCC Committee on Bone Metabolism on the latest developments concerning the measurement and standardization of vitamin D metabolites and its binding protein, as well as clinical indications for their measurement and interpretation of the results. © 2021 Elsevier B.V