Genetic modifiers of CHEK2*1100delC-associated breast cancer risk

Purpose: CHEK2*1100delC is a founder variant in European populations that confers a two-to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC). Methods: Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction. Results: The PRS conferred odds ratios (OR) of 1.59 (95% CI: 1.212.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average. Conclusion: Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.Peer reviewe

Genetic modifiers of CHEK2*1100delC-associated breast cancer risk.

PurposeCHEK2*1100delC is a founder variant in European populations that confers a two- to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC).MethodsUsing genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction.ResultsThe PRS conferred odds ratios (OR) of 1.59 (95% CI: 1.21-2.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average.ConclusionOur results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.Genet Med advance online publication 06 October 2016

Strategic R&D Programme on Technologies for Future Experiments - Annual Report 2021

This report summarises the activities and main achievements of the CERN strategic R&D programme on technologies for future experiments during the year 2021

Annual Report 2022

This report summarises the activities and main achievements of the CERN strategic R&D programme on technologies for future experiments during the year 202

Extension of the R&D Programme on Technologies for Future Experiments

we have conceived an extension of the R&D programme covering the period 2024 to 2028, i.e. again a 5-year period, however with 2024 as overlap year. This step was encouraged by the success of the current programme but also by the Europe-wide efforts to launch new Detector R&D collaborations in the framework of the ECFA Detector R&D Roadmap. We propose to continue our R&D programme with the main activities in essentially the same areas. All activities are fully aligned with the ECFA Roadmap and in most cases will be carried out under the umbrella of one of the new DRD collaborations. The program is a mix of natural continuations of the current activities and a couple of very innovative new developments, such as a radiation hard embedded FPGA implemented in an ASIC based on System-on-Chip technology. A special and urgent topic is the fabrication of Al-reinforced super-conducting cables. Such cables are a core ingredient of any new superconducting magnet such as BabyIAXO, PANDA, EIC, ALICE-3 etc. Production volumes are small and demands come in irregular intervals. Industry (world-wide) is no longer able and willing to fabricate such cables. The most effective approach (technically and financially) may be to re-invent the process at CERN, together with interested partners, and offer this service to the community