Summary Background Data for front-line health-care workers and risk of COVID-19 are limited. We sought to assess risk of COVID-19 among front-line health-care workers compared with the general community and the effect of personal protective equipment (PPE) on risk. Methods We did a prospective, observational cohort study in the UK and the USA of the general community, including front-line health-care workers, using self-reported data from the COVID Symptom Study smartphone application (app) from March 24 (UK) and March 29 (USA) to April 23, 2020. Participants were voluntary users of the app and at first use provided information on demographic factors (including age, sex, race or ethnic background, height and weight, and occupation) and medical history, and subsequently reported any COVID-19 symptoms. We used Cox proportional hazards modelling to estimate multivariate-adjusted hazard ratios (HRs) of our primary outcome, which was a positive COVID-19 test. The COVID Symptom Study app is registered with ClinicalTrials.gov , NCT04331509 . Findings Among 2 035 395 community individuals and 99 795 front-line health-care workers, we recorded 5545 incident reports of a positive COVID-19 test over 34 435 272 person-days. Compared with the general community, front-line health-care workers were at increased risk for reporting a positive COVID-19 test (adjusted HR 11·61, 95% CI 10·93–12·33). To account for differences in testing frequency between front-line health-care workers and the general community and possible selection bias, an inverse probability-weighted model was used to adjust for the likelihood of receiving a COVID-19 test (adjusted HR 3·40, 95% CI 3·37–3·43). Secondary and post-hoc analyses suggested adequacy of PPE, clinical setting, and ethnic background were also important factors. Interpretation In the UK and the USA, risk of reporting a positive test for COVID-19 was increased among front-line health-care workers. Health-care systems should ensure adequate availability of PPE and develop additional strategies to protect health-care workers from COVID-19, particularly those from Black, Asian, and minority ethnic backgrounds. Additional follow-up of these observational findings is needed. Funding Zoe Global, Wellcome Trust, Engineering and Physical Sciences Research Council, National Institutes of Health Research, UK Research and Innovation, Alzheimer's Society, National Institutes of Health, National Institute for Occupational Safety and Health, and Massachusetts Consortium on Pathogen Readiness.

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There are well-established disparities in cancer incidence and outcomes by race/ethnicity that result from the interplay between structural, socioeconomic, socio-environmental, behavioural and biological factors. However, large research studies designed to investigate factors contributing to cancer aetiology and progression have mainly focused on populations of European origin. The limitations in clinicopathological and genetic data, as well as the reduced availability of biospecimens from diverse populations, contribute to the knowledge gap and have the potential to widen cancer health disparities. In this review, we summarise reported disparities and associated factors in the United States of America (USA) for the most common cancers (breast, prostate, lung and colon), and for a subset of other cancers that highlight the complexity of disparities (gastric, liver, pancreas and leukaemia). We focus on populations commonly identified and referred to as racial/ethnic minorities in the USA—African Americans/Blacks, American Indians and Alaska Natives, Asians, Native Hawaiians/other Pacific Islanders and Hispanics/Latinos. We conclude that even though substantial progress has been made in understanding the factors underlying cancer health disparities, marked inequities persist. Additional efforts are needed to include participants from diverse populations in the research of cancer aetiology, biology and treatment. Furthermore, to eliminate cancer health disparities, it will be necessary to facilitate access to, and utilisation of, health services to all individuals, and to address structural inequities, including racism, that disproportionally affect racial/ethnic minorities in the USA.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1 . In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P <5×10 −8 , bringing the number of known independent signals for CRC to approximately 100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs, somatic drivers, and support a role of immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of underlying biology, and impact personalized screening strategies and drug development.