2540

Introduction: Breast cancer is the most common cancer type, and the most common reason for cancer-related deaths among women worldwide. Animal and epidemiologic studies suggest that exposure to light at night may contribute to increased breast cancer risk through circadian disruption, which involves a decrease in the nocturnal secretion of melatonin followed by disturbed estrogen regulation, however, epidemiological evidence is limited. In this study, we examined the association between exposure to residential outdoor light at night (LAN) and breast cancer incidence in the Danish Nurse Cohort Study. Methods: We followed 20,404 Danish nurses from 1993 or 1999 through 2012. LAN exposure was estimated using the US Defense Meteorological Satellite Program's (DMSP) Operational Linescan System. We collected LAN data (nW/cm2/sr) for 1996, 1999, 2000, 2002, 2004, 2005, and 2010, assigned at the subject's residence during the follow-up. Data on the incidence of breast cancer was obtained from the Danish Cancer Registry. We used time-varying Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for reproductive, lifestyle and environmental factors such as residential air pollution, road traffic noise, and greenspace. Results: Of the 20,490 women, 1,081 developed breast cancer in total during 339,633 person-years of follow-up. Based on the fully adjusted model of LAN exposure divided into quintiles, where the lowest LAN quintile was reference (0-13.6 nW/cm2/sr), we found an increase in breast cancer incidence at higher LAN levels: HR: 1.01 (95% CI: 0.83-1.23, p = 0.92), 1.08 (95% CI: 0.88-1.33, p = 0.44), 1.04 (0.83-1.30, p = 0.74), and 0.87 (95% CI: 0.66-1.15, p = 0.32) for the 2nd, 3rd, 4th, and 5th quintiles, respectively. Conclusion: There was a tendency, that higher levels of exposure to LAN were associated with a higher risk of breast cancer although the statistical significance was not observed.

2548

Background: Exposure to endocrine-disrupting chemicals (EDC) may affect neurocognitive development in exposed individuals and/or offspring. Objectives: We aimed to investigate the gene-environment interactions on the associations between prenatal and postnatal exposure to EDC and children’s neurocognitive development in a prospective cohort study. Methods: We recruited midterm pregnant women between 2008 and 2011 and followed-up their children in 2012-2019 (n=574 mother-child pairs). We measured mothers’ and their children’s Bisphenol A (BPA), 3-Phenoxybenzoic acid (3-PBA), phthalates, heavy metal levels at ages 6 and 8 years, and assessed mother’s and children’s intelligence quotient (IQ) and children’s attention-deficit/hyperactivity disorder (ADHD) using the Wechsler Intelligence Scale and the Korean version of the ADHD rating scale (K-ARS), respectively. In a Genome-wide association study, we derived generic risk scores (GRS) from single nucleotide polymorphisms (SNPs) showing significant associations with children’s IQ and ADHD. We compared the associations of IQ and ADHD with EDC levels among children with low or high GRS. Results: We identified 8, 18, and 22 SNPs associated with IQ and ADHD at 6 and 8 years of age, respectively. We observed a decrease in IQ related to interquartile range increase in maternal lead and cadmium concentrations among the children with high genetic profiles: 3.0 (95% Confidence intervals [CI]: -6.0, -0.1) and 3.7 (95% CI: -6.9, -0.4). However, we did not observe significant associations between IQ and maternal exposure to EDC among children with low GRS. In addition, the associations between children’s exposure to EDC and neurocognitive functions were not modified by GRS. Discussion: The study supports that children’s genetic profiles modified the association between prenatal exposure to EDC and children’s neurocognitive development.

2524

Objectives: Evidence of the non-auditory effects of road traffic noise exposure on health is growing. We examined the association between long-term exposure to road traffic noise and incident heart failure (HF) using various exposure windows and thresholds of the road traffic noise. Methods: We used the Danish Nurse Cohort with 22,304 female nurses who at recruitment in 1993 and 1999 reported information on HF risk factors, and linked them to the Danish National Patient and Cause of Death Registries for the first hospital contact or out-of hospital death due to HF until 2014. Road traffic noise levels in 1970-2013 were estimated by Nord2000 model as the annual mean of a weighted 24h average (L_den). We examined the associations between multi-year (up to 23 years) exposures to L_den and HF incidence using time-varying Cox regression models and estimated the effects at or above the thresholds using piece-wise linear regression models after controlling for individual covariates and air pollution levels. Results: We observed a non-linear relationship between incident HF incidence (n=438) and road traffic noise. Notably, in models adjusting for individual covariates, the hazard ratio (HR) (95% confidence intervals [CI]) of incident HF was 1.22 (95% CI: 1.05, 1.42) per 10 dB of 23-year exposures at or above 37 dB. After controlling for PM_2.5, the association was attenuated (HR:1.13 [95% CI: 0.96, 1.33]), but it remained robust to adjustment for NO₂ (HR:1.21 [95% CI: 1.01, 1.46]). Associations were weaker with shorter exposure windows (1- and 3-year running mean of L_den). Conclusion: Long-term exposure to road traffic noise may increase the risk of HF.

2555

Background: Long-term exposure to particulate matter less than 2.5 μm (PM_2.5) is considered a risk factor for premature death. However, only a few studies have been conducted in areas with moderate PM_2.5 concentrations. Moreover, an aging society may be more susceptible to environmental exposure and future health impacts of PM_2.5. Methods: This study estimates hazard ratios (HRs) for all-cause and cause-specific mortality from long-term exposure to moderate PM_2.5 concentrations in the elderly populations of seven cities in South Korea. We also projected nationwide elderly mortality caused by long-term exposure to PM_2.5, accounting for population aging until 2045. Mortality in 1,720,230 elderly adults aged 65 years and older in 2008 was monitored across 2009-2016 and linked to modeled PM_2.5 concentrations. Results: A total of 421,100 deaths occurred in 2009-2016, and the mean of annual PM_2.5 concentration ranged between 21.1 μg/m³ and 31.9 μg/m³ in most regions. The overall HR for a 10 μg/m³ increase in a 36-month PM_2.5 moving average was 1.024 (95% confidence intervals: 1.009, 1.039). We estimated that 11,833 all-cause nationwide elderly deaths were attributable to PM_2.5 exposure. Annual death tolls may increase to 17,948 by 2045. However, if PM_2.5 is reduced to 5 μg/m³ by 2045, the tolls may decrease to 3,646. Conclusions: The long-term exposure to moderately high levels of PM_2.5 was associated with increased mortality risk among the elderly. Thus, PM_2.5 reduction in response to the projected aging-associated mortality in South Korea is critical.