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Background Individuals with major birth defects are at increased risk of developing cancer, indicating a common aetiology. However, whether the siblings of individuals with birth defects are also at an increased risk of cancer is unclear. Methods We used nationwide health registries in four Nordic countries and conducted a nested case-control study. We included 40 538 cancer cases (aged 0–46 years) and 481 945 population controls (matched by birth year and country), born between 1967 and 2014. The relative risk of cancer among individuals whose siblings had birth defects was computed with odds ratios (OR) and 95% confidence intervals (CIs), using logistic regression models. Results In the total study population (aged 0–46 years), we observed no overall difference in cancer risk between individuals whose siblings had birth defects and those who had unaffected siblings (OR 1.02; 95% CI 0.97–1.08); however, the risk of lymphoid and haematopoietic malignancies was elevated (1.16; 1.05–1.28). The overall risk of childhood cancer (0–19 years) was increased for siblings of individuals who had birth defects (1.09; 1.00–1.19), which was mainly driven by lymphoma (1.35; 1.09–1.66), neuroblastoma (1.51; 1.11–2.05) and renal carcinoma (5.03; 1.73–14.6). The risk of cancer also increased with the number of siblings with birth defects (P trend = 0.008). Conclusion Overall risk of cancer among individuals (aged 0–46 years) whose siblings had birth defects was not elevated, but the risk of childhood cancer (ages 0–19 years) was increased. Our novel findings are consistent with the common aetiologies of birth defects and cancer, such as shared genetic predisposition and environmental factors. [ABSTRACT FROM AUTHOR]

Background Childhood cancer is more common among children with birth defects, suggesting a common aetiology. Whether this association differs by sex is unclear. Methods We performed a population-based nested case-control study using nationwide health registries in four Nordic countries. We included 21 898 cancer cases (0–19 years) and 218 980 matched population controls, born 1967–2014. Associations between childhood cancer and major birth defects were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression models. Effect modification was evaluated using a counterfactual framework to estimate confidence intervals and P -values for the natural indirect effects. Results Birth defects were present for 5.1% (1117/21 898) of childhood cancer cases and 2.2% (4873/218 980) of controls; OR of cancer was higher for chromosomal (OR = 10, 95% CI = 8.6–12) than for non-chromosomal defects (OR = 1.9, 95% CI = 1.8–2.1), strongest between genetic syndromes/microdeletion and renal tumours, Down syndrome and leukaemia, and nervous system defects and central nervous system tumours. The association between birth defects and cancer was stronger among females (OR = 2.8, 95% CI = 2.6–3.1) than males (OR = 2.1, 95% CI = 1.9–2.2, P interaction <0.001). Male sex was an independent risk factor for childhood cancer, but very little of the overall association between sex and childhood cancer was mediated through birth defects (4.8%, P NIE <0.001), although more at younger ages (10% below years and 28% below 1 year). Conclusions The birth defect–cancer associations were generally stronger among females than males. Birth defects did not act as a strong mediator for the modest differences in childhood cancer risk by sex, suggesting that other biological pathways are involved. [ABSTRACT FROM AUTHOR]

Background: It is controversial whether B12 deficiency causes dementia or B12 treatment can prevent dementia.Objective: To assess associations between low plasma (P-)B12 levels, B12 treatment, and risk of Alzheimer's disease (AD; primary outcome) and all-cause or vascular dementia (secondary outcomes).Methods: We conducted a population-based cohort study using Danish registry data to assess associations between low P-B12 levels, high-dose injection or oral B12 treatment, and risk of dementia (study period 2000-2013). The primary P-B12 cohort included patients with a first-time P-B12 measurement whose subsequent B12 treatment was recorded. The secondary B12 treatment cohort included patients with a first-time B12 prescription and P-B12 measurement within one year before this prescription. For both cohorts, patients with low P-B12 levels (<200 pmol/L) were propensity score-matched 1:1 with patients with normal levels (200-600 pmol/L). We used multivariable Cox regression to compute 0-15-year hazard ratios for dementia.Results: For low P-B12 and normal P-B12 level groups, we included 53,089 patients in the primary P-B12 cohort and 13,656 patients in the secondary B12 treatment cohort. In the P-B12 cohort, hazard ratios for AD centered around one, regardless of follow-up period or treatment during follow-up. In the B12 treatment cohort, risk of AD was unaffected by low pre-treatment P-B12 levels, follow-up period and type of B12 treatment. Findings were similar for all-cause and vascular dementia.Conclusion: We found no associatio1n between low P-B12 levels and dementia. Associations were unaffected by B12 treatment. Results do not support routine screening for B12 deficiency in patients with suspected dementia. [ABSTRACT FROM AUTHOR]

Predictive factors for recurrent cancer-associated venous thromboembolism have been inconsistent across previous studies. To provide data for improved risk stratification, we described the risk of recurrent venous thromboembolism overall and across age, sex, calendar period, cancer type, Ottawa risk score, cancer stage, and cancer treatment in a nationwide cohort of patients with active cancer. Using Danish administrative registries, we identified a cohort of all adult patients with active cancer and a first-time diagnosis of venous thromboembolism during 2003–2018. We accounted for the competing risk of death and calculated absolute risks of recurrent venous thromboembolism at six months. The population included 34,072 patients with active cancer and venous thromboembolism. Recurrence risks at six months were higher for patients with genitourinary cancer (6.5%), lung cancer (6.1%), gastrointestinal cancer (5.6%), brain cancer (5.2%), and hematological cancer (5.1%) than for patients with gynecological cancer (4.7%), breast cancer (4.1%), and other cancer types (4.8%). Recurrence risks were similar for men (5.2%) and women (4.9%), with and without chemotherapy (5.1%), across Ottawa risk score group (low: 5.0%; high: 5.1%) and across calendar periods but increased with increasing cancer stage. The overall six-month all-cause mortality risk was 26%, and highest for patients with lung cancer (49%) and lowest among breast cancer patients (4.1%). Six-month recurrence risk after first-time cancer-associated venous thromboembolism was high and varied by cancer type and patient characteristics. Refining risk stratification for recurrence may improve decision-making regarding treatment duration after cancer-associated thromboembolism. • Risk factors for recurrent venous thromboembolism in cancer are not well described. • Danish nationwide cohort study on recurrent cancer-associated venous thromboembolism. • The overall risk of recurrence at 6 months was 5.2%. • Risks were similar across sex and for patients with and without chemotherapy. • Risks were higher with increasing cancer stage. [ABSTRACT FROM AUTHOR]