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The most representative indicator of vitamin D status in clinical practice is 25(OH)D3, but new biomarkers could improve the assessment of vitamin D status and metabolism. The objective of this study is to investigate the association of serum vitamin D metabolites and vitamin D metabolite ratios (VMRs) with potentially influential factors in premenopausal women. This is a cross-sectional study based on 1422 women, aged 39-50, recruited from a Madrid Medical Diagnostic Center. Participants answered an epidemiological and a food frequency questionnaire. Serum vitamin D metabolites were determined using an SPE-LC-MS/MS platform. The association between participant's characteristics, vitamin D metabolites, and VMRs was quantified by multiple linear regression models. Mean 25(OH)D3 concentration was 49.2 + 18.9 nmol/L, with greater deficits among obese, nulliparous, dark-skinned women, and with less sun exposure. A lower R2 ratio (1,25(OH)2D3/25(OH)D3) and a higher R4 (24,25(OH)2D3/1,25(OH)2D3) were observed in nulliparous women, with high sun exposure, and those with low caloric intake or high consumption of calcium, vitamin D supplements, or alcohol. Nulliparous women had lower R1 (25(OH)D3/Vit D3) and R3 (24,25(OH)2D3/25(OH)D3), and older women showed lower R3 and R4. Vitamin D status modified the association of the VMRs with seasons. VMRs can be complementary indicators of vitamin D status and its endogenous metabolism, and reveal the influence of certain individual characteristics on the expression of hydroxylase enzymes. This study was funded by the Spanish Ministry of Health (EC11–273) and by the Carlos III Institute of Health (PI15CIII/0029). The article presents independent research. The views expressed are those of the authors and not necessarily those of the Carlos III Institute of Health. Sí

The role of vitamin D in mammographic density is still unclear. This study examines the association between serum 25-hydroxyvitamin D (25(OH)D) and mammographic density, overall and by specific women characteristics. DDM-Madrid is a cross-sectional study that recruited 1403 premenopausal women in a breast radiodiagnosis unit of Madrid City Council. Information was collected with a questionnaire and plasma 25(OH)D was measured by solid-phase extraction on-line coupled to liquid chromatography–tandem mass spectrometry. Percent mammographic density was assessed using a semi-automated computer tool (DM-Scan). Multivariable linear regression models were used to quantify the associations, categorizing 25(OH)D levels (nmol/L) into 3 groups according to the cut-offs established by the US Endocrine Society. Models were adjusted for age, education, body mass index, age at menarche, parity, previous breast biopsies, family history of breast cancer, physical activity, energy intake, use of corticoids, hypercholesterolemia and day of sample extraction. Mean serum 25(OH)D level was 49.4 + 18.9 nmol/L. Women with sufficient concentrations of 25(OH)D showed a slight decrease in mammographic density (β >75nmol/L=-3.40; p = 0.037). No differences were observed according to women characteristics except for parity, where the protective effect of 25(OH)D was only seen among nulliparous (β >75nmol/L=-13.00; p-heterogeneity = 0.006). In light of the protective effect of vitamin D on mammographic density and the high prevalence of vitamin D insufficiency in our population, improving these levels could be an effective measure for the prevention of health problems related to the lack of this essential vitamin.

[EN] Introduction: Mammographic density (MD), the proportion of radiologically dense breast tissue, is a strong risk factor for breast cancer. Our objective is to investigate the influence of occupations and occupational exposure to physical, chemical, and microbiological agents on MD in Spanish premenopausal women. Methods: This is a cross-sectional study based on 1362 premenopausal workers, aged 39-50, who attended a gynecological screening in a breast radiodiagnosis unit of Madrid City Council. The work history was compiled through a personal interview. Exposure to occupational agents was evaluated using the Spanish job-exposure matrix MatEmESp. MD percentage was assessed using the validated semi-automated computer tool DM-Scan. The association between occupation, occupational exposures, and MD was quantified using multiple linear regression models, adjusted for age, educational level, body mass index, parity, previous breast biopsies, family history of breast cancer, energy intake, use of oral contraceptives, smoking, and alcohol consumption. Results: Although no occupation was statistically significantly associated with MD, a borderline significant inverse association was mainly observed in orchard, greenhouse, nursery, and garden workers (beta = -6.60; 95% confidence interval (95%CI) = -14.27; 1.07) and information and communication technology technicians (beta = -7.27; 95%CI = -15.37; 0.84). On the contrary, a positive association was found among technicians in art galleries, museums, and libraries (beta = 8.47; 95%CI = -0.65; 17.60). Women occupationally exposed to fungicides, herbicides, and insecticides tended to have lower MD. The percentage of density decreased by almost 2% for every 5 years spent in occupations exposed to the mentioned agents. Conclusions: Although our findings point to a lack of association with the occupations and exposures analyzed, this study supports a deeper exploration of the role of certain occupational agents in MD, such as pesticides., This work was supported by the Carlos III Institute of Health (AESI PI15CIII/00029 and AESI PI15CIII/00013). The article presents independent research. The views expressed are those of the authors and not necessarily those of the Carlos III Institute of Health.