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.

25 January 2019 In Cardiovascular System

BACKGROUND: Alcohol consumption is associated with cardiovascular disease (CVD), with moderate drinkers having decreased CVD risk compared to non- and heavy drinkers. However, whether alcohol consumption is associated with ideal cardiovascular health (CVH), assessed by the American Heart Association's (AHA) Life's Simple 7 (LS7) metrics, and whether associations differ by sex, is uncertain.

HYPOTHESIS: Heavy alcohol consumption is associated with worse CVH.

METHODS: We explored associations between alcohol consumption and CVH in a multi-ethnic population including 6506 participants free of CVD, aged 45 to 84 years. Each LS7 metric was scored 0 to 2 points. Total score was categorized as inadequate (0-8), average (9-10) and optimal (11-14). Participants were classified as never, former or current drinkers. Current drinkers were categorized as 2 (heavy) drinks/day. Multinomial logistic regression models assessed associations between alcohol and CVH, adjusted for age, sex, race/ethnicity, education, income, and health insurance.

RESULTS: Mean (SD) age was 62 (10) years, 53% were women. Compared to never drinkers, those with >2 drinks/day were less likely to have average [0.61 (0.43-0.87)] and optimal CVH [0.29 (0.17-0.49)]. Binge drinking was also associated with unfavorable CVH. Overall, there was no independent association for light or moderate drinking with CVH. However, women with 1 to 2 drinks/day were more likely to have optimal CVH [1.85 (1.19-2.88)] compared to non-drinking women, which was not seen in men.

CONCLUSION: Heavy alcohol consumption was associated with unfavorable CVH. Although light or moderate drinking may be associated with a more favorable CVH in women, overall, the association was not strong.

29 October 2018 In Cardiovascular System

BACKGROUND: Alcohol-induced cardiotoxicity is incompletely understood. Specifically, the long-term impact of alcohol use on ventricular remodeling or dysfunction, its modulators, and effect thresholds among young adults remain controversial.

OBJECTIVES: The authors sought to evaluate a potential relationship between alcohol intake and cardiac remodeling, assessed by echocardiography, over 20 years of follow-up.

METHODS: Among the CARDIA (Coronary Artery Risk Development in Young Adults) study cohort, the authors studied all subjects without baseline heart disorders who provided adequate information on their drinking habits and underwent echocardiographic evaluation at years 5 and 25 of the study. The echocardiographic outcomes were left ventricular (LV) ejection fraction, indexed LV end-diastolic volume and LV mass, and left atrial diameter. Participants were grouped according to their weighted-average weekly drinking habits. An additional analysis used the estimated cumulative alcohol consumption. Regression models and multivariable fractional polynomials were used to evaluate the association between alcohol consumption and the outcomes.

RESULTS: Among the 2,368 participants, alcohol consumption was an independent predictor of higher indexed LV mass (p = 0.014) and indexed LV end-diastolic volume (p = 0.037), regardless of sex. No significant relationship between alcohol intake and LV ejection fraction was found. Drinking predominantly wine was associated with less cardiac remodeling and there was a nonsignificant trend for a harmful effect of binge drinking.

CONCLUSIONS: After 20 years of follow-up, alcohol intake was associated with adverse cardiac remodeling, although it was not related with LV systolic dysfunction in this initially healthy young cohort. Our results also suggest that drinking predominantly wine associates with less deleterious findings in cardiac structure.

Page 1 of 7

Contact us

We love your feedback. Get in touch with us.

  • Tel: +32 (0)2 230 99 70
  • Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Disclaimer

The authors have taken reasonable care in ensuring the accuracy of the information herein at the time of publication and are not responsible for any errors or omissions. Read more on our disclaimer and Privacy Policy.