OBJECTIVES: To assess associations between SARS-CoV-2 infection and the incidence of hospitalisation with selected respiratory and non-respiratory conditions in a largely SARS-CoV-2 vaccine-naïve population . DESIGN, SETTING, PARTICIPANTS: Self-control case series; analysis of population-wide surveillance and administrative data for all laboratory-confirmed COVID-19 cases notified to the Victorian Department of Health (onset, 23 January 2020 - 31 May 2021; ie, prior to widespread vaccination rollout) and linked hospital admissions data (admission dates to 30 September 2021). MAIN OUTCOME MEASURES: Hospitalisation of people with acute COVID-19; incidence rate ratios (IRRs) comparing incidence of hospitalisations with defined conditions (including cardiac, cerebrovascular, venous thrombo-embolic, coagulative, and renal disorders) from three days before to within 89 days of onset of COVID-19 with incidence during baseline period (60-365 days prior to COVID-19 onset). RESULTS: A total of 20 594 COVID-19 cases were notified; 2992 people (14.5%) were hospitalised with COVID-19. The incidence of hospitalisation within 89 days of onset of COVID-19 was higher than during the baseline period for several conditions, including myocarditis and pericarditis (IRR, 14.8; 95% CI, 3.2-68.3), thrombocytopenia (IRR, 7.4; 95% CI, 4.4-12.5), pulmonary embolism (IRR, 6.4; 95% CI, 3.6-11.4), acute myocardial infarction (IRR, 3.9; 95% CI, 2.6-5.8), and cerebral infarction (IRR, 2.3; 95% CI, 1.4-3.9). CONCLUSION: SARS-CoV-2 infection is associated with higher incidence of hospitalisation with several respiratory and non-respiratory conditions. Our findings reinforce the value of COVID-19 mitigation measures such as vaccination, and awareness of these associations should assist the clinical management of people with histories of SARS-CoV-2 infection.

BACKGROUND: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folates role in CRC. OBJECTIVES: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. METHODS: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). RESULTS: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. CONCLUSIONS: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.

Objectives

Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.

Methods

We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (n_snps=5) or sedentary time (n_snps=6), or accelerometer-measured (n_snps=1) or self-reported (n_snps=5) vigorous physical activity.

Results

Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).

Conclusion

Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.