Using Family History Data to Improve the Power of Association Studies: Application to Cancer in UK Biobank.

In large cohort studies the number of unaffected individuals outnumbers the number of affected individuals, and the power can be low to detect associations for outcomes with low prevalence. We consider how including recorded family history in regression models increases the power to detect associations between genetic variants and disease risk. We show theoretically and using Monte-Carlo simulations that including a family history of the disease, with a weighting of 0.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Evaluating the performance of the BOADICEA model in predicting 10-year breast cancer risks in UK Biobank.

Background: The BOADICEA model predicts breast cancer risk using cancer family history, epidemiological and genetic data. We evaluated its validity in a large prospective cohort.

Methods: We assessed model calibration, discrimination and risk classification ability in 217,885 women (6,838 incident breast cancers) aged 40-70 years old of self-reported White ethnicity with no previous cancer from the UK Biobank.

Polygenic risk scores stratify breast cancer risk among women with benign breast disease.

Purpose: Most breast biopsies are diagnosed as benign breast disease (BBD), with 1.5- to fourfold increased breast cancer (BC) risk. Apart from pathologic diagnoses of atypical hyperplasia, few factors aid in BC risk assessment of these patients.

Evaluation of chlorine dioxide exposure in an Australian gnotobiotic mouse research facility.

Exposure to chlorine dioxide by staff working in a gnotobiotic mouse facility at an Australian research institute was measured to determine whether current controls were sufficient to ensure their exposure remains below the current Australian workplace exposure standard. A combination of workplace surveys, interviews with workers, and personal sampling was undertaken to understand the workplace, identify higher-risk tasks, and measure the concentration of chlorine dioxide in the air where the workers conduct routine tasks involving the use of a chlorine dioxide-based disinfectant. Personal sampling utilized the validated Occupational Safety and Health Administration (OSHA) method ID-202, with minor alterations.

Validation of the BOADICEA model for epithelial tubo-ovarian cancer risk prediction in UK Biobank.

Background: The clinical validity of the multifactorial BOADICEA model for epithelial tubo-ovarian cancer (EOC) risk prediction has not been assessed in a large sample size or over a longer term.

Methods: We evaluated the model discrimination and calibration in the UK Biobank cohort comprising 199,429 women (733 incident EOCs) of European ancestry without previous cancer history. We predicted 10-year EOC risk incorporating data on questionnaire-based risk factors (QRFs), family history, a 36-SNP polygenic risk score and pathogenic variants (PV) in six EOC susceptibility genes (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1 and PALB2).

Protein-truncating and rare missense variants in and and associations with cancer in UK Biobank whole-exome sequence data.

Background: Deleterious germline variants in and have been associated with a moderately increased risk of breast cancer. Risks for other cancers remain unclear.

Methods: Cancer associations for coding variants in and were evaluated using whole-exome sequence data from UK Biobank linked to cancer registration data (348 488 participants), and analysed both as a retrospective case-control and a prospective cohort study.

The impact of breaking up sitting during simulated nightshifts on musculoskeletal pain: A randomised controlled trial.

Objectives: Prolonged sitting is associated with an increased risk of musculoskeletal pain, especially in nightshift workers. However, research investigating effects of breaking up sitting on musculoskeletal pain during nightshifts is lacking. This study evaluated effects of prolonged sitting or breaking up sitting with short bouts of light-intensity physical activity on pain in healthy adults during simulated nightshifts.

Polio, public health memories and temporal dissonance of re-emerging infectious diseases in the global north.

Social science research on polio has been centred in the global south, where countries that remain endemic or vulnerable to outbreaks are located. However, closely-related strains of poliovirus were detected in the sewage systems of several New York State counties and London boroughs in 2022. These detections constituted the first encounters with polio in the United States and United Kingdom for a generation - for both public health agencies and publics alike.

BOADICEA model: updates to the breast cancer risks for ages 60 years and older.

Breast cancer risks in older pathogenic variant carriers are understudied. Recent studies show a marked decline in the relative risk at older ages. We used data from two large studies to update the breast cancer risks in the BOADICEA model for carriers 60 years and older.

Implementing Multifactorial Risk Assessment with Polygenic Risk Scores for Personalized Breast Cancer Screening in the Population Setting: Challenges and Opportunities.

Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population setting to inform the implementation of risk-stratified screening. Recruited females aged 40-69 unaffected by breast cancer, with a previous mammogram, underwent multifactorial breast cancer risk assessment.

Disentangling the relationships of body mass index and circulating sex hormone concentrations in mammographic density using Mendelian randomization.

Purpose: Mammographic density phenotypes, adjusted for age and body mass index (BMI), are strong predictors of breast cancer risk. BMI is associated with mammographic density measures, but the role of circulating sex hormone concentrations is less clear. We investigated the relationship between BMI, circulating sex hormone concentrations, and mammographic density phenotypes using Mendelian randomization (MR).

Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk.

Background: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS).

Methods: We analyzed >22 million variants for 398,238 women.

Move the night way: how can physical activity facilitate adaptation to shift work?

Shift work, involving night work, leads to impaired sleep, cognition, health and wellbeing, and an increased risk of occupational incidents. Current countermeasures include circadian adaptation to phase shift circadian biomarkers. However, evidence of real-world circadian adaptation is found primarily in occupations where light exposure is readily controlled.

Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction.

The 313-variant polygenic risk score (PRS) provides a promising tool for breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed. Here, we explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 225,105 female participants from the UK Biobank.

Age-specific breast and ovarian cancer risks associated with germline or pathogenic variants - an Asian study of 572 families.

Background: Clinical management of Asian and pathogenic variants (PV) carriers remains challenging due to imprecise age-specific breast (BC) and ovarian cancer (OC) risks estimates. We aimed to refine these estimates using six multi-ethnic studies in Asia.

Methods: Data were collected on 271 and 301 families from Malaysia and Singapore, ascertained through population/hospital-based case-series (88%) and genetic clinics (12%).