The Association between Outdoor Artificial Light at Night and Breast Cancer Risk in Black and White Women in the Southern Community Cohort Study

Qian Xiao,1 Gretchen L. Gierach,2 Cici Bauer,3 William J. Blot,4 Peter James,5,6 and Rena R. Jones7 Department of Epidemiology, Human Genetics and Environmental Health, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, USA Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA Department of Biostatistics and Data Science, University of Texas Health Science Center at Houston, Houston, Texas, USA Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA


Introduction
Black women in the United States are more likely to develop breast cancer at a younger age and to be diagnosed with more aggressive subtypes and more advanced stage disease, both contributing to higher rates of breast cancer mortality among Black women. 1 Light at night (LAN) has been proposed as a breast cancer risk factor because it inhibits nighttime production of melatonin, a hormone that may modulate biological pathways involved in breast cancer carcinogenesis. 2,3 Several epidemiologic studies have linked higher outdoor LAN estimated from satellite imagery to elevated incidence of breast cancer, including in cohorts predominantly comprised of White women with relatively high socioeconomic status (SES). 4,5,6 However, it remains unclear whether LAN is associated with breast cancer risk among Black women and women of lower SES.

Methods
We examined the relationship between LAN and incident breast cancer in the Southern Community Cohort Study (SCCS). 7,8 The vast majority of participants (86%) were recruited from community health centers in the southeastern United States that primarily served uninsured and underinsured populations, and ∼ 2=3 were Black. Our analytic cohort included 30,518 Black and 12,982 White women who were cancer free and reported residential addresses at baseline. LAN exposures were estimated by linking geocoded baseline addresses (2002-2009) with satellite images in 2004 obtained by the U.S. Defense Meteorological Satellite Program's Operational Linescan System, and we used the highdynamic range data to avoid saturation in high-LAN areas. 9 Incident breast cancer cases were identified via linkage to state cancer registries and vital status was ascertained from the Social Security Administration-both through 31 December 2017. Data on estrogen receptor (ER) status and cancer stage were obtained from cancer registries and supplemented by pathology reports and medical records. Race was self-reported at baseline. Institutional review boards at Vanderbilt University (Nashville, TN) and Meharry Medical College (Nashville, TN) approved the study and participants provided informed consent at the time of enrollment. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) comparing higher quintiles of LAN (Q2-Q5) with the lowest quintile, as well as for each 10-unit increase in LAN. Models were adjusted for multiple covariates as listed in table footnotes.

Results
Among all women in the cohort, we found a statistically significant increased risk of breast cancer overall in association with increasing levels of LAN [HR Q5 vs: Q1 = 1.27 (95% CI: 1.00, 1.60), p trend = 0.05] and for ER + breast cancer specifically [HR Q5 vs: Q1 = 1.37 (95% CI: 1.02, 1.84), p trend = 0.01] ( Table 1). For Black women, the highest quintile was associated with a 28% increase in overall and ER + breast cancer risk [HR Q5 vs: Q1 = 1.28 (95% CI: 0.98, 1.68), p trend = 0.05 and 33% (1.33 (95% CI: 0.94, 1.88), p trend = 0.02), respectively] with borderline statistical significance. The patterns of association appeared similar in White women, but the effect estimates were relatively less precise owing to smaller sample sizes and the p trend values were not statistically significant. For ERbreast cancer in Black women, breast cancer incidence appeared higher for women in Q2-Q5 of LAN compared to Q1 but did not show a clear exposureresponse relationship. Results from the analysis stratified by tumor stage were mixed ( Table 2): in Black women, the relationship between LAN and increased breast cancer risk was observed for localized breast cancer only, whereas in White women, the relationship was observed for regional/distant stages.

Discussion
Our findings corroborate the previously reported positive association between LAN and breast cancer risk and extend prior work by characterizing this relationship among both Blacks and Whites in a large cohort of women recruited from disadvantaged communities. Several previous cohort investigations, including in the California Teachers Study, 4 the Nurses' Health Study II, 5 and the National Institutes of Health-AARP Diet and Health Study, 6 reported a modest increase in breast cancer risk associated with higher outdoor LAN levels (10-14%, comparing the highest to the lowest quintile). In our SCCS analysis, the effect sizes appeared larger compared with those in previous cohorts 4,5,6 although the distribution of LAN was similar and the confidence intervals overlap. We speculate that the large proportion of low SES and Black women in the SCCS may have partially contributed to the larger effect sizes. Compared with those in more advantaged populations, low SES individuals are more likely to have sleep disturbances and shorter sleep duration due to poor housing conditions, high stress, and irregular and unpredictable daily schedules, 10 and therefore they may be more likely to The authors declare they have no actual or potential competing financial interests.
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Acknowledgments
This work was supported by the Intramural Research Program of the National Cancer Institute (G.L.G. and R.R.J.) as well as extramural funding (R00 CA201542 from the National Cancer Institute, P.J.; 80NSSC21K0510 from the National Aeronautics and Space Administration Health and Air Quality Applied Science Team, Q.X. and C.B.).