Estimation of age of onset and progression of breast cancer by absolute risk dependent on polygenic risk score and other risk factors.

BACKGROUND: Genetic, lifestyle, reproductive, and anthropometric factors are associated with the risk of developing breast cancer. However, it is not yet known whether polygenic risk score (PRS) and absolute risk based on a combination of risk factors are associated with the risk of progression of breast cancer. This study aims to estimate the distribution of sojourn time (pre-clinical screen-detectable period) and mammographic sensitivity by absolute breast cancer risk derived from polygenic profile and the other risk factors. METHODS: The authors used data from a population-based case-control study. Six categories of 10-year absolute risk based on different combinations of risk factors were derived using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm. Women were classified into low, medium, and high-risk groups. The authors constructed a continuous-time multistate model. To calculate the sojourn time, they simulated the trajectories of subjects through the disease states. RESULTS: There was little difference in sojourn time with a large overlap in the 95% confidence interval (CI) between the risk groups across the six risk categories and PRS studied. However, the age of entry into the screen-detectable state varied by risk category, with the mean age of entry of 53.4 years (95% CI, 52.2-54.1) and 57.0 years (95% CI, 55.1-57.7) in the high-risk and low-risk women, respectively. CONCLUSION: In risk-stratified breast screening, the age at the start of screening, but not necessarily the frequency of screening, should be tailored to a woman's risk level. The optimal risk-stratified screening strategy that would improve the benefit-to-harm balance and the cost-effectiveness of the screening programs needs to be studied.

SARS-CoV-2 incidence among teaching staff in primary and secondary schools-Wales, 2020-2021.

BACKGROUND: During the COVID-19 pandemic, face-to-face delivery of education in schools across Wales was disrupted with repeated school closures to limit risk of infection. Evidence describing the incidence of infection amongst school staff during times when schools were open is limited. A previous research study found infection rates were higher in English primary school settings when compared with secondary. An Italian study suggested teachers weren't at greater risk of infection in comparison to the general population. The aim of this study was to identify whether educational staff had higher incidence rates than their counterparts in the general population in Wales, and secondly whether incidence rates amongst staff differed between primary and secondary school settings and by teacher age. METHODS: We performed a retrospective observational cohort study using the national case detection and contact tracing system implemented during the COVID pandemic. Age stratified person-day COVID-19 incidence rates amongst teaching staff linked to primary or secondary schools in Wales were calculated for the autumn and summer terms during 2020-2021. RESULTS: The observed pooled COVID-19 incidence rates for staff across both terms was 23.30 per 100,000 person days (95% CI: 22.31-24.33). By comparison, the rate in the general population aged 19-65, was 21.68 per 100,000 person days (95%: CI 21.53-21.84). Incidence among teaching staff was highest in the two youngest age groups (< 25 years and 25-29 years). When compared to the age matched general population, incidence was higher in the autumn term amongst primary school teachers aged ≤ 39 years, and in the summer term higher only in the primary school teachers aged < 25 years. CONCLUSION: The data were consistent with an elevated risk of COVID-19 amongst younger teaching staff in primary schools when compared to the general population, however differences in case ascertainment couldn't be excluded as a possible reason for this. Rate differences by age group in teaching staff mirrored those in the general population. The risk in older teachers (≥ 50 years) in both settings was the same or lower than in the general population. Amongst all age groups of teachers maintaining the key risk mitigations within periods of COVID transmission remain important.