Common breast cancer risk alleles and risk assessment: a study on 35 441 individuals from the Danish general population

Abstract

Common breast cancer risk alleles are associated with incidence and mortality of breast cancer in the general population, but not with other cancers. After including breast cancer allele sum in risk assessment, 25% of women currently being offered screening mammography had an absolute 5-year risk below the cutoff of average risk for a 50-year-old woman.

Validation of the BOADICEA model and a 313-variant polygenic risk score for breast cancer risk prediction in a Dutch prospective cohort

“…Another prospective study also reported no association between other types of cancer and a sum of breast cancer risk alleles at 72 loci. 29 Because we only analyzed all other tumors combined, we cannot exclude that the PRS 313 has an association with one specific type of other cancer.…”

Development and Validation of a Clinical Polygenic Risk Score to Predict Breast Cancer Risk

“…Modification of risk estimates by PRS-based stratification has been shown in a variety of clinical settings, including women who carry a pathogenic variant, high-risk women, and population cohorts. 11 , 15 - 17 These novel tools, however, are of particular interest to women who present for genetic risk assessment with increased risk due to a FH of breast cancer. FH and susceptibility variants contribute independently to risk prediction, yet the approximately 13% reduction in the OR for FH when adjusted for the PRS77 (or PRS313) indicates an overlapping contribution to risk.…”

Lolland-Falster Health Study: Study protocol for a household-based prospective cohort study

“…Previous population-based health studies in Denmark have primarily focused on urbanized populations. This is the case for the Diet, Cancer and Health study recruiting participants from Copenhagen and Aarhus [16], the Copenhagen City Heart Study [17] and the Copenhagen General Population Study [19]. To make research findings generalizable for the general public and use the results in public-health planning and precision medicine, these studies do not only need to be large, but also represent the underlying diversity in the population.…”

“…The burden of diseases in the Lolland-Falster population is hypothesized to result from a combination of socioeconomic, genetic, lifestyle-related, familial and environmental factors, and the combination and weight of these factors are expected to differ from the pattern seen in previous studies of populations in the capital and larger cities of Denmark [17][18][19].…”

“…The Copenhagen General population study [19], the Danish General suburban population study [18] and LOFus include similar datasets. Therefore, it will be possible to correlate the profiles of their measures and compare the morbidity and mortality of these respective populations.…”