Evaluation of Early-Life Factors and Early-Onset Colorectal Cancer Among Men and Women in the UK Biobank.
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ABSTRACT:
SUBMITTER: Gausman V
PROVIDER: S-EPMC8881299 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
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Evaluation of Early-Life Factors and Early-Onset Colorectal Cancer Among Men and Women in the UK Biobank.
Gausman Valerie V Liang Peter S PS O'Connell Kelli K Kantor Elizabeth D ED Du Mengmeng M
Gastroenterology 20211127 3
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Project description: Not available
| S-EPMC11581484 | biostudies-literature
Project description:ImportanceThere is limited information on modifiable risk factors for young-onset dementia (YOD).ObjectiveTo examine factors that are associated with the incidence of YOD.Design, setting, and participantsThis prospective cohort study used data from the UK Biobank, with baseline assessment between 2006 and 2010 and follow-up until March 31, 2021, for England and Scotland, and February 28, 2018, for Wales. Participants younger than 65 years and without a dementia diagnosis at baseline assessment were included in this study. Participants who were 65 years and older and those with dementia at baseline were excluded. Data were analyzed from May 2022 to April 2023.ExposuresA total of 39 potential risk factors were identified from systematic reviews of late-onset dementia and YOD risk factors and grouped into domains of sociodemographic factors (education, socioeconomic status, and sex), genetic factors (apolipoprotein E), lifestyle factors (physical activity, alcohol use, alcohol use disorder, smoking, diet, cognitive activity, social isolation, and marriage), environmental factors (nitrogen oxide, particulate matter, pesticide, and diesel), blood marker factors (vitamin D, C-reactive protein, estimated glomerular filtration rate function, and albumin), cardiometabolic factors (stroke, hypertension, diabetes, hypoglycemia, heart disease, atrial fibrillation, and aspirin use), psychiatric factors (depression, anxiety, benzodiazepine use, delirium, and sleep problems), and other factors (traumatic brain injury, rheumatoid arthritis, thyroid dysfunction, hearing impairment, and handgrip strength).Main outcome and measuresMultivariable Cox proportional hazards regression was used to study the association between the risk factors and incidence of YOD. Factors were tested stepwise first within domains and then across domains.ResultsOf 356 052 included participants, 197 036 (55.3%) were women, and the mean (SD) age at baseline was 54.6 (7.0) years. During 2 891 409 person-years of follow-up, 485 incident YOD cases (251 of 485 men [51.8%]) were observed, yielding an incidence rate of 16.8 per 100 000 person-years (95% CI, 15.4-18.3). In the final model, 15 factors were significantly associated with a higher YOD risk, namely lower formal education, lower socioeconomic status, carrying 2 apolipoprotein ε4 allele, no alcohol use, alcohol use disorder, social isolation, vitamin D deficiency, high C-reactive protein levels, lower handgrip strength, hearing impairment, orthostatic hypotension, stroke, diabetes, heart disease, and depression.Conclusions and relevanceIn this study, several factors, mostly modifiable, were associated with a higher risk of YOD. These modifiable risk factors should be incorporated in future dementia prevention initiatives and raise new therapeutic possibilities for YOD.
| S-EPMC10751655 | biostudies-literature
Project description:This study aims to examine whether maternal smoking, birth weight, birth month and breastfeeding are associated with COVID-19 infection and hospitalisation. Maternal smoking was positively associated with COVID-19 infection. Breastfeeding was negatively associated with COVID-19 infection. The odds of being hospitalised due to COVID-19 were higher among those who had lower birthweight and mothers who were smoking during pregnancy.
| S-EPMC7860946 | biostudies-literature
Project description:BackgroundExposure early in life can influence adult disease and immunity, but the role of early life exposures in risk of systemic lupus erythematosus (SLE) is not established.MethodsWomen in a national cohort (ages 35-74) provided data on perinatal, maternal, and sociodemographic factors, longest residence to age 14, and residential farm history of at least 12?months to age 18. Cases (N?=?124) reported SLE diagnosed age 16?years or older with use of disease modifying antirheumatic drugs. Non-cases (N?=?50,465) did not report lupus. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression adjusting for age and race/ethnicity.ResultsSLE was associated with low birthweight (data on 84 cases and 36,477 non-cases; <2,500 versus 3,000 to <3,500?g OR?=?2.2; 95%CI 1.2, 3.9) and preterm birth (57 cases and 22,784 non-cases; ?1?month early versus full-term OR?=?3.4; 95%CI 1.6, 7.4). Considering longest childhood residence to age 14, SLE was associated with more frequent pesticide use (e.g., at least monthly OR?=?2.3; 95%CI 1.3, 4.1). SLE was associated with having an early and extended childhood farm residence (i.e., prenatal/maternal farm exposure and longest childhood farm residence OR?=?1.8; 95%CI 1.1, 3.0 versus neither). In those with a childhood-only farm residence of 12+ months, agricultural pesticide use was associated with SLE, with the strongest associations for direct personal exposures.ConclusionThe association of SLE with preterm birth is consistent with studies in other populations and with an observed association with low birthweight. The associations of SLE with childhood exposure to residential and agricultural pesticides warrant further study.
| S-EPMC4814765 | biostudies-literature
Project description:Men with more advantaged socioeconomic position (SEP) have been observed to have higher levels of testosterone. It is unclear whether these associations arise because testosterone has a causal impact on SEP. In 306,248 participants of UK Biobank, we performed sex-stratified genome-wide association analysis to identify genetic variants associated with testosterone. Using the identified variants, we performed Mendelian randomization analysis of the influence of testosterone on socioeconomic position, including income, employment status, neighborhood-level deprivation, and educational qualifications; on health, including self-rated health and body mass index; and on risk-taking behavior. We found little evidence that testosterone affected socioeconomic position, health, or risk-taking. Our results therefore suggest that it is unlikely that testosterone meaningfully affects these outcomes in men or women. Differences between Mendelian randomization and multivariable-adjusted estimates suggest that previously reported associations with socioeconomic position and health may be due to residual confounding or reverse causation.
| S-EPMC8318368 | biostudies-literature
Project description:ObjectivesExposures in utero and during infancy may impact the development of diseases later in life. They may be linked with development of frailty, although the mechanism is unclear. This study aims to determine the associations between early life risk factors and development of frailty among middle-aged and older adults as well as potential pathways via education, for any observed association.DesignA cross-sectional study.SettingsThis study used data from UK Biobank, a large population-based cohort.Participants502 489 individuals aged 37-73 years were included in the analysis.Primary and secondary outcome measuresEarly life factors in this study included being breast fed as a baby, maternal smoking, birth weight, the presence of perinatal diseases, birth month and birth place (in or outside the UK). We developed a frailty index comprising 49 deficits. We used generalised structural equation modelling to examine the associations between early life factors and development of frailty and whether any observed association was mediated via educational attainment.ResultsA history of breast feeding and normal birth weight were associated with a lower frailty index while maternal smoking, the occurrence of perinatal diseases and birth month with a longer day length were associated with a higher frailty index. Educational level mediated the relationship between these early life factors and frailty index.ConclusionsThis study highlights that biological and social risk occurring at different stages of life are related to the variations in frailty index in later life and suggests opportunities for prevention across the life course.
| S-EPMC9990643 | biostudies-literature
Project description:Background & aimsColorectal cancer (CRC) incidence and mortality are increasing among persons younger than 50 years old in the United States, but risk factors associated with early-onset CRC (EOCRC) have not been widely studied.MethodsWe conducted a case-control study of US veterans 18 to 49 years old who underwent colonoscopy examinations from 1999 through 2014. EOCRC cases were identified from a national cancer registry; veterans who were free of CRC at their baseline colonoscopy through 3 years of follow-up were identified as controls. We collected data on age, sex, race/ethnicity, body weight, body mass index (BMI), diabetes, smoking status, and aspirin use. Multivariate-adjusted EOCRC odds were estimated for each factor, with corresponding 95% confidence interval (CI) values.ResultsOur final analysis included 651 EOCRC cases and 67,416 controls. Median age was 45.3 years, and 82.3% were male. Higher proportions of cases were older, male, current smokers, nonaspirin users, and had lower BMIs, compared with controls (P < .05). In adjusted analyses, increasing age and male sex were significantly associated with increased risk of EOCRC, whereas aspirin use and being overweight or obese (relative to normal BMI) were significantly associated with decreased odds of EOCRC. In post hoc analyses, weight loss of 5 kg or more within the 5-year period preceding colonoscopy was associated with higher odds of EOCRC (odds ratio 2.23; 95% CI 1.76-2.83).ConclusionsIn a case-control study of veterans, we found increasing age and male sex to be significantly associated with increased risk of EOCRC, and aspirin use to be significantly associated with decreased risk; these factors also affect risk for CRC onset after age 50. Weight loss may be an early clinical sign of EOCRC. More intense efforts are required to identify the factors that cause EOCRC and signs that can be used to identify individuals at highest risk.
| S-EPMC7343609 | biostudies-literature
Project description:Background Cardiorespiratory fitness may moderate the association between obesity and all-cause mortality (ie, the "fat-but-fit" hypothesis), but unaddressed sources of bias are a concern. Methods and Results Cardiorespiratory fitness was estimated as watts per kilogram from a submaximal bicycle test in 77 169 men and women from the UK Biobank cohort and combined with World Health Organization standard body mass index categories, yielding 9 unique fitness-fatness combinations. We also formed fitness-fatness combinations based on bioimpedance as a direct measure of body composition. All-cause mortality was ascertained from death registries. Multivariable-adjusted Cox regression models were used to estimate hazard ratios and 95% CIs. We examined the association between fitness-fatness combinations and all-cause mortality in models with progressively more conservative approaches for accounting for reverse causation, misclassification of body composition, and confounding. Over a median follow-up of 7.7 years, 1731 participants died. In our base model, unfit men and women had higher risk of premature mortality irrespective of levels of adiposity, compared with the normal weight-fit reference. This pattern was attenuated but maintained with more conservative approaches in men, but not in women. In analysis stratified by sex and excluding individuals with prevalent major chronic disease and short follow-up and using direct measures of body composition, mortality risk was 1.78 (95% CI, 1.17-2.71) times higher in unfit-obese men but not higher in obese-fit men (0.94 [95% CI, 0.60-1.48]). In contrast, there was no increased risk in obese-unfit women (1.09 [95% CI, 0.44-1.05]) as compared with the reference. Conclusions Cardiorespiratory fitness modified the association between obesity and mortality in men, but this pattern appeared susceptible to biases in women.
| S-EPMC8174221 | biostudies-literature
Project description:Substantial evidence shown that the age at onset (AAO) of Parkinson's disease (PD) is a major determinant of clinical heterogeneity. However, the mechanisms underlying heterogeneity in the AAO remain unclear. To investigate the risk factors with the AAO of PD, a total of 3156 patients with PD from the UK Biobank were included in this study. We evaluated the effects of polygenic risk scores (PRS), nongenetic risk factors, and their interaction on the AAO using Mann-Whitney U tests and regression analyses. We further identified the genes interacting with nongenetic risk factors for the AAO using genome-wide environment interaction studies. We newly found physical activity (P < 0.0001) was positively associated with AAO and excessive daytime sleepiness (P < 0.0001) was negatively associated with AAO, and reproduced the positive associations of smoking and non-steroidal anti-inflammatory drug intake and the negative association of family history with AAO. In the dose-dependent analyses, smoking duration (P = 1.95 × 10-6), coffee consumption (P = 0.0150), and tea consumption (P = 0.0008) were positively associated with AAO. Individuals with higher PRS had younger AAO (P = 3.91 × 10-5). In addition, we observed a significant interaction between the PRS and smoking for AAO (P = 0.0316). Specifically, several genes, including ANGPT1 (P = 7.17 × 10-7) and PLEKHA6 (P = 4.87 × 10-6), may influence the positive relationship between smoking and AAO. Our data suggests that genetic and nongenetic risk factors are associated with the AAO of PD and that there is an interaction between the two.
| S-EPMC10762149 | biostudies-literature
Project description:Background: Despite overall incidence reduction in colorectal cancer (CRC) the past 32 years, unexplained incidence and mortality rates have increased significantly in younger adults ages 20-49. To improve understanding of sex-specific differences among this population, we aimed to determine the variance in early-onset CRC (EOCRC) survival among US men diagnosed with CRC before age 50, while considering individual- and county-level CRC outcome determinants. Methods: Hotspots (i.e., counties with high EOCRC mortality rates) were derived from Centers for Disease Control and Prevention data from 1999-2017, and linked to SEER data for men aged 15-49 years with CRC. Cox proportional hazards models were used to compare CRC-specific survival probability and hazard in hotspots versus non-significant counties. A generalized R2 was used to estimate the total variance in EOCRC survival explained by clinicodemographic and county-level determinants. Results: We identified 232 hotspot counties for EOCRC-214 (92%) of which were in the South. In hotspots, 1,009 men were diagnosed with EOCRC and 31,438 in non-significant counties. After adjusting for age, race, tumor stage and grade, surgery, chemotherapy, radiation therapy, and marital status, men residing in hotspot counties had higher hazard of CRC-specific death (HR 1.24, 95% CI, 1.12-1.36). Individual/county-level factors explained nearly 35% of the variation in survival, and adult smoking served as the strongest county-level determinant of EOCRC survival. Conclusion: Distinct geographic patterns of EOCRC were predominantly located in the southern US. Survival after EOCRC diagnosis was significantly worse among men residing in hotspot counties.
| S-EPMC7269786 | biostudies-literature