Abstract 4947: Objectively measured individual light exposures and risk of colorectal cancer

Abstract Introduction: The global rise in early-onset colorectal cancer underscores the urgent need to explore emerging risk factors like circadian disruption, which have become increasingly common in recent generations. Mechanistic studies showed that individual nighttime light exposure disrupts melatonin secretion and circadian rhythms, contributing to tumorigenesis. However, human studies are scarce and rely on proxies of personal light exposures. We assessed the prospective association between objectively measured individual nightlight and daylight exposures and colorectal cancer risk. Methods: A total of 80, 709 participants without prior history of shift-work and cancer in the UK Biobank who wore Axivity AX3 wrist accelerometers that contained a silicon photodiode light sensor for up to seven days between 2013-2015 were followed up to 2021. Nighttime and daytime light exposures (measured in lux) were quantified using factor analysis of 24-hour light profiles. Relative amplitude (RA) was calculated by the difference in mean activity during the highest 10-hour and lowest 5-hour active periods. Cox models were used to estimate relative risk (RRs) and 95% confidence intervals (CIs). Results: During 471, 456 person-years of follow-up, a total of 569 incident colorectal cancers occurred (378 colon cancer; 191 rectal cancer). Personal nighttime light exposure but not daytime light exposure was associated with increased risk of colorectal cancer (Ptrend = 0.07), primarily driven by rectal cancer. Compared to the lowest tertile (T1), individuals in the highest tertile (T3) of nighttime light exposure had 53% increased risk of rectal cancer (RR 1.53; 95% CI: 1.05-2.22; Ptrend = 0.003). This association was independent of putative risk factors of colorectal cancer and remained robust after adjusting for daytime light exposure as well as RA, a commonly used measure of 24-hr rest-activity rhythm. In joint analysis, individuals with the highest nighttime light exposure (T3) and high level of circadian disruption (below median RA) had the highest risk of rectal cancer (RR 2.15, 95% CI: 1.20-3.86). Conclusion: In a large prospective cohort, objectively measured individual nightlight exposure was linked to increased risk of rectal cancer, which has been rapidly increasing in younger adults. These findings underscore the need for integrative epidemiologic and mechanistic studies to validate the associations and dissect the biological pathways driving site-specific tumorigenesis, and to better inform tailored prevention and intervention strategies in younger generations. Citation Format: Melania Boker, Xiaoyu Zong, Jushawn Macon, Nick Jeschke, Charlie Bowe, Yin Cao. Objectively measured individual light exposures and risk of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4947.