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 General Health

BACKGROUND: Prevention aiming at smoking, alcohol consumption, and BMI could potentially bring large gains in life expectancy (LE) and health expectancy measures such as Healthy Life Years (HLY) and Life Expectancy in Good Perceived Health (LEGPH) in the European Union. However, the potential gains might differ by region.

METHODS: A Sullivan life table model was applied for 27 European countries to calculate the impact of alternative scenarios of lifestyle behavior on life and health expectancy. Results were then pooled over countries to present the potential gains in HLY and LEGPH for four European regions.

RESULTS: Simulations show that up to 4 years of extra health expectancy can be gained by getting all countries to the healthiest levels of lifestyle observed in EU countries. This is more than the 2 years to be gained in life expectancy. Generally, Eastern Europe has the lowest LE, HLY, and LEGPH. Even though the largest gains in LEPGH and HLY can also be made in Eastern Europe, the gap in LE, HLY, and LEGPH can only in a small part be closed by changing smoking, alcohol consumption, and BMI.

CONCLUSION: Based on the current data, up to 4 years of good health could be gained by adopting lifestyle as seen in the best-performing countries. Only a part of the lagging health expectancy of Eastern Europe can potentially be solved by improvements in lifestyle involving smoking and BMI. Before it is definitely concluded that lifestyle policy for alcohol use is of relatively little importance compared to smoking or BMI, as our findings suggest, better data should be gathered in all European countries concerning alcohol use and the odds ratios of overconsumption of alcohol.

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.

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