26 February 2019 In Cancer

PURPOSE: Breast cancer (BC) risk prediction allows systematic identification of individuals at highest and lowest risk. We extend the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk model to incorporate the effects of polygenic risk scores (PRS) and other risk factors (RFs).

METHODS: BOADICEA incorporates the effects of truncating variants in BRCA1, BRCA2, PALB2, CHEK2, and ATM; a PRS based on 313 single-nucleotide polymorphisms (SNPs) explaining 20% of BC polygenic variance; a residual polygenic component accounting for other genetic/familial effects; known lifestyle/hormonal/reproductive RFs; and mammographic density, while allowing for missing information.

RESULTS: Among all factors considered, the predicted UK BC risk distribution is widest for the PRS, followed by mammographic density. The highest BC risk stratification is achieved when all genetic and lifestyle/hormonal/reproductive/anthropomorphic factors are considered jointly. With all factors, the predicted lifetime risks for women in the UK population vary from 2.8% for the 1st percentile to 30.6% for the 99th percentile, with 14.7% of women predicted to have a lifetime risk of >/=17-<30% (moderate risk according to National Institute for Health and Care Excellence [NICE] guidelines) and 1.1% a lifetime risk of >/=30% (high risk).

CONCLUSION: This comprehensive model should enable high levels of BC risk stratification in the general population and women with family history, and facilitate individualized, informed decision-making on prevention therapies and screening.

22 February 2019 In Cancer

PURPOSE: Breast cancer (BC) risk prediction allows systematic identification of individuals at highest and lowest risk. We extend the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk model to incorporate the effects of polygenic risk scores (PRS) and other risk factors (RFs).

METHODS: BOADICEA incorporates the effects of truncating variants in BRCA1, BRCA2, PALB2, CHEK2, and ATM; a PRS based on 313 single-nucleotide polymorphisms (SNPs) explaining 20% of BC polygenic variance; a residual polygenic component accounting for other genetic/familial effects; known lifestyle/hormonal/reproductive RFs; and mammographic density, while allowing for missing information.

RESULTS: Among all factors considered, the predicted UK BC risk distribution is widest for the PRS, followed by mammographic density. The highest BC risk stratification is achieved when all genetic and lifestyle/hormonal/reproductive/anthropomorphic factors are considered jointly. With all factors, the predicted lifetime risks for women in the UK population vary from 2.8% for the 1st percentile to 30.6% for the 99th percentile, with 14.7% of women predicted to have a lifetime risk of >/=17-<30% (moderate risk according to National Institute for Health and Care Excellence [NICE] guidelines) and 1.1% a lifetime risk of >/=30% (high risk).

CONCLUSION: This comprehensive model should enable high levels of BC risk stratification in the general population and women with family history, and facilitate individualized, informed decision-making on prevention therapies and screening.

27 July 2018 In Cardiovascular System

BACKGROUND: Binge drinking prevalence rates are highest in young adults; however, little is known about the effects of binge drinking on blood pressure (BP) and other cardiovascular health metrics in individuals between 18 and 45 years of age. The aim of this study was to determine the effects of regular binge drinking on BP, lipid and glucose levels and to determine if there were differences in these associations between men and women.

METHODS AND RESULTS: We analyzed data from NHANES (the US National Health and Nutrition Examination Survey) for men and women 18 to 45 years old who were non-binge drinkers, binge drank 1 to 12 times, or binge drank >12 times in the past year. After controlling for diet and physical activity, both categories of men binge drinkers compared with non-binge drinkers had higher systolic BP (121.8 and 119.0 mm Hg versus 117.5 mm Hg) and total cholesterol (215.5 and 217.9 mg/dL versus 207.8 mg/dL) values. There were no effects of binge drinking on systolic BP or total cholesterol in women. Binge drinking in men and women was associated with higher high-density lipoprotein-cholesterol values. The effects of binge drinking on glucose parameters in men and women were variable.

CONCLUSIONS: Compared with young adult women, repeated binge drinking in men was associated with an elevated systolic BP, and greater frequency of binge drinking in men was associated with a more unfavorable lipid profile. In young adults with elevated systolic BP, practitioners should consider the possible role of binge drinking and address the importance of reducing alcohol intake as an important cardiovascular risk reduction strategy.

03 May 2018 In General Health
BACKGROUND: Alcohol and in particular red wine have both immunomodulatory and neuroprotective properties, and may exert an effect on the disease course of multiple sclerosis (MS). OBJECTIVE: To assess the association between alcohol and red wine consumption and MS course. METHODS: MS patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB) who completed a self-administered questionnaire about their past year drinking habits at a single time point were included in the study. Alcohol and red wine consumption were measured as servings/week. The primary outcome was the Expanded Disability Status Scale (EDSS) at the time of the questionnaire. Secondary clinical outcomes were the Multiple Sclerosis Severity Score (MSSS) and number of relapses in the year before the questionnaire. Secondary MRI outcomes included brain parenchymal fraction and T2 hyperintense lesion volume (T2LV). Appropriate regression models were used to test the association of alcohol and red wine intake on clinical and MRI outcomes. All analyses were controlled for sex, age, body mass index, disease phenotype (relapsing vs. progressive), the proportion of time on disease modifying therapy during the previous year, smoking exposure, and disease duration. In the models for the MRI outcomes, analyses were also adjusted for acquisition protocol. RESULTS: 923 patients (74% females, mean age 47 +/- 11 years, mean disease duration 14 +/- 9 years) were included in the analysis. Compared to abstainers, patients drinking more than 4 drinks per week had a higher likelihood of a lower EDSS score (OR, 0.41; p = 0.0001) and lower MSSS (mean difference, - 1.753; p = 0.002) at the time of the questionnaire. Similarly, patients drinking more than 3 glasses of red wine per week had greater odds of a lower EDSS (OR, 0.49; p = 0.0005) and lower MSSS (mean difference, - 0.705; p = 0.0007) compared to nondrinkers. However, a faster increase in T2LV was observed in patients consuming 1-3 glasses of red wine per week compared to nondrinkers. CONCLUSIONS: Higher total alcohol and red wine intake were associated with a lower cross-sectional level of neurologic disability in MS patients but increased T2LV accumulation. Further studies should explore a potential cause-effect neuroprotective relationship, as well as the underlying biological mechanisms
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