Cancer incidence trends in New York State and associations with common population-level exposures 2010-2018: an ecological study.

The impact of common environmental exposures in combinations with socioeconomic and lifestyle factors on cancer development, particularly for young adults, remains understudied. Here, we leveraged environmental and cancer incidence data collected in New York State at the county level to examine the association between 31 exposures and 10 common cancers (i.e., lung and bronchus, thyroid, colorectal, kidney and renal pelvis, melanoma, non-Hodgkin lymphoma, and leukemia for both sexes; corpus uteri and female breast cancer; prostate cancer), for three age groups (25-49, 50-69, and 70-84 year-olds). For each cancer, we stratified by age group and sex, and applied regression models to examine the associations with multiple exposures simultaneously. The models included 642,013 incident cancer cases during 2010-2018 and found risk factors consistent with previous reports (e.g., smoking and physical inactivity). Models also found positive associations between ambient air pollutants (ozone and PM2.5) and prostate cancer, female breast cancer, and melanoma of the skin across multiple population strata. Additionally, the models were able to better explain the variation in cancer incidence data among 25-49 year-olds than the two older age groups. These findings support the impact of common environmental exposures on cancer development, particularly for younger age groups.

Psychological, behavioural, and physical aspects of caregiver strain in autism-caregivers: a cohort study.

Background: People who give care to autistic individuals (autism-caregivers) experience higher levels of caregiver strain than people who provide care for individuals with other chronic conditions (non-autism-caregivers). This places them at higher risk for psychological, behavioural and physical health concerns. The aim of this study is to delineate psychological, behavioural, and physical aspects of caregiver strain in autism-caregivers compared to non-autism-caregivers. Methods: We included 3354 adult caregivers from the general population in the Netherlands participating in the second assessment (January, 1, 2014-December, 31, 2017) of the Lifelines Cohort. In this cohort study, using multivariable regression adjusted for age, sex, and socioeconomic status, we analysed psychological (anxiety and depression based on a Mini International Neuropsychiatric Interview, and self-reported stress and perceived health), behavioural (questionnaire-assessed physical activity, alcohol use, and smoking), and physical aspects (body mass index, waist circumference, and leukocyte-counts) of caregiver strain in autism-caregivers (n = 722) compared with non-autism-caregivers (n = 2632). Findings: Autism-caregivers reported more stress (OR 3.61, 95% CI 2.60-4.99). Both anxiety (OR 1.85, 95% CI 1.37-2.49) and depressive disorders (OR 1.83, 95% CI 1.17-2.86) were more common in autism-caregivers than in non-autism-caregivers. Perceived health, physical activity, alcohol use, and smoking were not different between autism- and non-autism-caregivers. In autism-caregivers, lymphocyte- and monocyte-counts were lower than in non-autism-caregivers. Interpretation: In this large cohort, autism-caregivers had worse psychological health than non-autism-caregivers. Moreover, autism-caregiving might be associated with an altered immune balance. These findings underline the higher caregiver strain in autism-caregivers compared to other caregivers. This calls for increased support to autism-caregivers. Funding: Lifelines has been funded by the Dutch government.

Prenatal polycyclic aromatic hydrocarbons, altered ERα pathway-related methylation and expression, and mammary epithelial cell proliferation in offspring and grandoffspring adult mice.

BACKGROUND: Airborne polycyclic aromatic hydrocarbons (PAH) possess carcinogenic and endocrine disrupting properties linked to mammary tumorigenesis. These effects may be initiated during a prenatal period of susceptibility to PAH activation of the aryl hydrocarbon receptor (Ahr) and through downstream effects on estrogen receptor (Er) α. PURPOSE: We hypothesized prenatal airborne PAH exposure induces sustained effects in female adult wild type BALB/cByj mice detected in the offspring (F1) and grandoffspring (F2) generation. We hypothesized these effects would include altered expression and epigenetic regulation of Erα and altered expression of aryl hydrocarbon receptor repressor (Ahrr, Ahrr/aryl hydrocarbon receptor nuclear translocator (Arnt), and breast cancer type 1 susceptibility (Brca1). Further, we hypothesized that PAH would induce precancerous outcomes such as epithelial cell proliferation and epithelial cell hyperplasia in mammary glands of adult female offspring and grandoffspring. RESULTS: Prenatal ambient PAH exposure lowered Erα mRNA expression (F1 and F2: p<0.001 for each) and induced methylation in the Erα promoter in mammary tissue in offspring and grandoffspring mice on postnatal day (PND) 60. Prenatal PAH lowered Brca1 mRNA (F1: p=0.002, F2: p=0.02); Erα mRNA was correlated with Brca1 (F1: r=0.42, p=0.02; F2: r=0.53, p=0.005). Prenatal PAH lowered Ahrr (F1: p=0.03, F2: p=0.009) and raised Arnt mRNA expression (F1: p=0.01, F2: p=0.03). Alterations in Erα mRNA (F2: p<0.0001) and Ahrr (F2: p=0.02) in the grandoffspring mice also occured by PND 28, and similarly occurred in the dam on postpartum day (PPD) 28. Finally, prenatal PAH was associated with higher mammary epithelial cell proliferation in the offspring (p=0.02), but not grandoffspring mice, without differences in the frequency of mammary cell hyperplasia. These results did not differ after adjustment by each candidate gene expression level. CONCLUSIONS: Prenatal PAH exposure induces DNA methylation and alters gene expression in the Erα-mediated pathway across generations, and suggests that functional outcomes such as mammary cell proliferation also may occur in offspring as a result.