A polymorphism in the 3' untranslated region of the gene encoding prostaglandin endoperoxide synthase 2 is not associated with an increase in breast cancer risk: a nested case-control study

INTRODUCTION: Prostaglandins are integral components in the cellular response to inflammation, promoting cellular proliferation and angiogenesis. The enzyme responsible for the conversion of arachidonic acid to prostaglandins in response to inflammation is prostaglandin endoperoxide synthase 2/cyclo-oxygenase 2 (PTGS2/COX2). Polymorphisms in the PTGS2 gene have been associated with various diseases, including inflammatory bowel disease and cancer of the lung, colorectum, and breast. METHODS: We genotyped the five most common polymorphisms (rs20417, rs5277, rs20432, rs5275, and rs4648298) in the Nurses' Health Study (1,270 cases, 1,762 controls) to test the hypothesis that polymorphisms in PTGS2 are associated with breast cancer risk, using logistic regression analyses. The Nurses' Health Study 2 (317 cases, 634 controls) and Harvard Women's Health Study (702 cases, 703 controls) were used to further examine putative associations. RESULTS: The rs5275 polymorphism in the 3' untranslated region of the PTGS2 gene was associated with a decrease in breast cancer risk. We therefore genotyped this single-nucleotide polymorphism in the Nurses' Health Study 2 and Harvard Women's Health Study. Similar results were observed in these subsequent analyses, with no statistically significant heterogeneity in risk estimates between studies. In pooled analyses, women homozygous for the T allele at rs5275 had a 20% lower risk of breast cancer than those homozygous for the C allele (odds ratio 0.80, 95% confidence interval 0.66 to 0.97). CONCLUSION: Although this polymorphism may be associated with a decrease in breast cancer risk among Caucasian women, we provide strong evidence that it is not associated with an increased risk of breast cancer

Migraine, vascular risk, and cardiovascular events in women: prospective cohort study

Objectives To evaluate whether the association between migraine with aura and increased risk of cardiovascular disease is modified by vascular risk groups as measured by the Framingham risk score for coronary heart disease

Socioeconomic status, blood pressure progression, and incident hypertension in a prospective cohort of female health professionals

Aims The aim of this study was to examine the association between socioeconomic status, blood pressure (BP) progression, and incident hypertension. Methods and results We included 27 207 female health professionals free of hypertension and cardiovascular disease at baseline. Participants were classified into five education and six income categories. The main outcome variables were BP progression at 48 months of follow-up and incident hypertension during the entire study period. At 48 months, 48.1% of women had BP progression. The multivariable adjusted relative risks [95% confidence intervals (CIs)] for BP progression were 1.0 (referent), 0.96 (0.92-1.00), 0.92 (0.88-0.96), 0.90 (0.85-0.94), and 0.84 (0.78-0.91) (P for trend <0.0001) across increasing education categories and 1.0 (referent), 1.01 (0.94-1.08), 0.99 (0.93-1.06), 0.97 (0.91-1.04), 0.96 (0.90-1.03), and 0.89 (0.83-0.96) across increasing income categories (P for trend = 0.0001). During a median follow-up of 9.8 years, 8248 cases of incident hypertension occurred. Multivariable adjusted hazard ratios (95% CI) were 1.0 (referent), 0.92 (0.86-0.99), 0.85 (0.79-0.92), 0.87 (0.80-0.94), and 0.74 (0.65-0.84) (P for trend <0.0001) across increasing education categories and 1.0 (referent), 1.07 (0.95-1.21), 1.07 (0.95-1.20), 1.06 (0.94-1.18), 1.04 (0.93-1.16), and 0.93 (0.82-1.06) (P for trend 0.08) across increasing income categories. In joint analyses, education but not income remained associated with BP progression and incident hypertension. Conclusion Socioeconomic status, as determined by education but not by income, is a strong independent predictor of BP progression and incident hypertension in wome

Prospective Cohort Study of Type 2 Diabetes and the Risk of Parkinson's Disease

OBJECTIVE—To evaluate the association between type 2 diabetes and newly reported Parkinson's disease

The Mitochondrial A10398G Polymorphism, Interaction with Alcohol Consumption, and Breast Cancer Risk

Polymorphisms in the mitochondrial genome are hypothesized to be associated with risk of various diseases, including cancer. However, there has been conflicting evidence for associations between a common polymorphism in the mitochondrial genome (A10398G, G10398A in some prior reports) and breast cancer risk. Reactive oxygen species, a by-product of mitochondrial energy production, can lead to oxidative stress and DNA damage in both the mitochondria and their cells. Alcohol consumption, which may also lead to oxidative stress, is associated with breast cancer risk. Therefore, we hypothesized that polymorphisms in the mitochondrial genome interact with alcohol consumption to alter breast cancer risk. We genotyped the A10398G polymorphism in a case-control study nested within the Nurses' Health Study (NHS, 1,561 cases, 2,209 controls). We observed an interaction between alcohol consumption (yes/no) and A10398G on breast cancer risk (p-int = 0.03). The risk associated with alcohol consumption was limited to carriers of the 10398G allele (Odds Ratio 1.52, 95% Confidence Interval 1.10–2.08 comparing drinkers to non-drinkers). However, we were unable to replicate these findings in the Women's Health Study (WHS, 678 cases, 669 controls), although the power to detect this interaction in the WHS was low (power = 0.57). Further examination of this interaction, such as sufficiently powered epidemiological studies of cancer risk or associations with biomarkers of oxidative stress, may provide further evidence for GxE interactions between the A10398G mitochondrial polymorphism and alcohol consumption on breast cancer risk

Revisiting the association of sedentary behavior and physical activity with all-cause mortality using a compositional approach: the Women's Health Study

This research was supported by grants from the National Institutes of Health (CA154647, CA047988, CA182913, HL043851, HL080467, and HL099355). EJS was supported by the Intramural Research Program at the National Institute on Aging. JHM was supported by a Grant from the Spanish Ministry of Education, Culture and Sport (FPU15/02645). CC-S was supported by a grant from the Spanish Ministry of Science and Innovation (FJC2018-037925-I). Additional funding was provided by the University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of Excellence; Scientific Excellence Unit on Exercise and Health (UCEES) to FBO. The funders had no role in preparing and conducting this manuscript, in interpreting and deciding to publish the results, or in drafting the manuscript. drafting this manuscript. Open Access funding provided by the National Institutes of Health (NIH).Background: While physical activity has consistently been associated with decreased mortality rates, it remains unknown if there is a single “ideal” combination of time in physical activities of different intensities and sedentary behavior (SB) associated with the lowest rate. This study examined the associations of combinations of time in moderate-to-vigorous intensity (MVPA), higher-light intensity (HLPA), lower-light intensity activities (LLPA), and SB with mortality rates in older women. Methods: This prospective cohort study included 16,676 older women from throughout the United States enrolled in the Women’s Health Study. Women wore accelerometers on their hip from 2011 to 2015 and were followed through 2017 (mean (SD) of 4.3 (1.1) years). Deaths were confirmed with medical records, death certificates, or the National Death Index. Compositional Cox regression models were used. Results: The mean (SD) age was 72 (5.7) years at accelerometer wear; 503 women died. Compared to the least active women (mean, 3 min/day MVPA, 27 min/day HLPA, 162 min/day LLPA, and 701 min/day SB): compositional models showed an inverse L-shaped dose-response association of MVPA replacing other behaviors with mortality rates mortality rates (P = .02); SB relative to LLPA, HLPA, and MVPA was directly associated with mortality rates in a curvilinear dose-response manner (P < .001); replacing 10 min of SB for MVPA (HR (95% CI) = .86 (.73–.98)) or for HLPA (HR (95% CI.94 (.88–1.00)) associated with 14 and 6% lower mortality rates, respectively; a 47% risk reduction (HR [95% CI] = .53 [.42–.64]) was observed among women meeting physical activity guidelines (mean, 36 min/day MVPA, 79 min/day HLPA, 227 min/day LLPA and 549 min/day SB); and similar mortality rate reductions of 43% (HR (95% CI) = .57 (.41–.73)) were observed with increases in HLPA and LLPA without increasing MVPA, e.g., reallocating SB to 90 min/day of HLPA plus 120 min/day of LLPA. Conclusions: There was no “ideal” combination of physical activities of different intensities and SB associated with the lowest mortality rates. Of particular relevance to older women, replacing SB with light intensity activity was associated with lower mortality rates, and “mixing and matching” times in different intensities yielded equivalent mortality risk reductions.United States Department of Health & Human Services National Institutes of Health (NIH) - USA CA154647 CA047988 CA182913 HL043851 HL080467 HL099355Intramural Research Program at the National Institute on AgingSpanish Ministry of Education, Culture and Sport FPU15/02645Spanish Government FJC2018-037925-IUniversity of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of ExcellenceScientific Excellence Unit on Exercise and Health (UCEES)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - US