Polymorphisms in the estrogen receptor alpha gene (ESR1), daily cycling estrogen and mammographic density phenotypes

Background Single nucleotide polymorphisms (SNPs) involved in the estrogen pathway and SNPs in the estrogen receptor alpha gene (ESR1 6q25) have been linked to breast cancer development, and mammographic density is an established breast cancer risk factor. Whether there is an association between daily estradiol levels, SNPs in ESR1 and premenopausal mammographic density phenotypes is unknown. Methods We assessed estradiol in daily saliva samples throughout an entire menstrual cycle in 202 healthy premenopausal women in the Norwegian Energy Balance and Breast Cancer Aspects I study. DNA was genotyped using the Illumina Golden Gate platform. Mammograms were taken between days 7 and 12 of the menstrual cycle, and digitized mammographic density was assessed using a computer-assisted method (Madena). Multivariable regression models were used to study the association between SNPs in ESR1, premenopausal mammographic density phenotypes and daily cycling estradiol. Results We observed inverse linear associations between the minor alleles of eight measured SNPs (rs3020364, rs2474148, rs12154178, rs2347867, rs6927072, rs2982712, rs3020407, rs9322335) and percent mammographic density (p-values: 0.002–0.026), these associations were strongest in lean women (BMI, ≤23.6 kg/m2.). The odds of above-median percent mammographic density (>28.5 %) among women with major homozygous genotypes were 3–6 times higher than those of women with minor homozygous genotypes in seven SNPs. Women with rs3020364 major homozygous genotype had an OR of 6.46 for above-median percent mammographic density (OR: 6.46; 95 % Confidence Interval 1.61, 25.94) when compared to women with the minor homozygous genotype. These associations were not observed in relation to absolute mammographic density. No associations between SNPs and daily cycling estradiol were observed. However, we suggest, based on results of borderline significance (p values: 0.025–0.079) that the level of 17β-estradiol for women with the minor genotype for rs3020364, rs24744148 and rs2982712 were lower throughout the cycle in women with low (28.5 %) percent mammographic density, when compared to women with the major genotype. Conclusion Our results support an association between eight selected SNPs in the ESR1 gene and percent mammographic density. The results need to be confirmed in larger studies

PTSD in paramedics: history, conceptual issues and psychometric measures

Post-traumatic stress disorder (PTSD) is more common in paramedics than in the general population because of the stressful and distressing nature of their work. Forms of PTSD associated with chronic stress and repeated trauma are scarcely researched among paramedics. This is striking as this workforce is potentially more likely to be affected by these types of PTSD. Diagnostic processes are still largely based on acute rather than chronic psychological trauma. PTSD diagnosis has been influenced by sociological perceptions of mental illness and changes in diagnostic criteria. Criteria for the diagnosis of PTSD in the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases have changed in the past decade, which may facilitate more appropriate diagnoses of PTSD in paramedics. Paramedics often have a complex aetiology of PTSD resulting from experiences of both chronic and acute events. Questionnaires that cover exposure to both individual and repeated stressful events are required to enable further research in the area of PTSD in paramedics