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Metallic Air Pollutants and Breast Cancer Risk in a Nationwide Cohort Study

White, Alexandra J.a; O’Brien, Katie M.a,b; Niehoff, Nicole M.c; Carroll, Rachelb; Sandler, Dale P.a

doi: 10.1097/EDE.0000000000000917
Environmental Epidemiology

Background: Toxic metals show evidence of carcinogenic and estrogenic properties. However, little is known about the relationship between airborne metals and breast cancer. We evaluated the risk of breast cancer in relation to exposure to toxic metallic substances in air, individually and combined, in a US-wide cohort.

Methods: Sister Study participants (n = 50,884), breast cancer–free women who had a sister with breast cancer were recruited, from 2003 to 2009. The 2005 Environmental Protection Agency National Air Toxic Assessment’s census-tract estimates of metal concentrations in air (antimony, arsenic, cadmium, chromium, cobalt, lead, manganese, mercury, nickel, and selenium) were matched to participants’ enrollment residence. We used Cox regression to estimate the association between quintiles of individual metals and breast cancer incidence and weighted quantile sum regression to model the association between the metal mixture and breast cancer.

Results: A total of 2,587 breast cancer cases were diagnosed during follow-up (mean = 7.4 years). In individual chemical analyses comparing the highest to lowest quintiles, postmenopausal breast cancer risk was elevated for mercury (hazard ratio [HR] = 1.3, 95% confidence interval [CI], 1.1, 1.5), cadmium (HR = 1.1, 95% CI, 0.96, 1.3), and lead (HR = 1.1, 95% CI, 0.98, 1.3). The weighted quantile sum index was associated with postmenopausal breast cancer (odds ratio [OR] = 1.1, 95% CI, 1.0, 1.1). Consistent with the individual chemical analysis, the most highly weighted chemicals for predicting postmenopausal breast cancer risk were lead, cadmium, and mercury. Results were attenuated for overall breast cancer.

Conclusions: Higher levels of some airborne metals, specifically mercury, cadmium, and lead, were associated with a higher risk of postmenopausal breast cancer.

From the aEpidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC

bBiostatistics Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC

cDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Submitted January 31, 2018; accepted September 3, 2018.

This study was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01-ES044005].

The authors report no conflicts of interest.

Data and code are available for replication upon request (

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Correspondence: Alexandra J. White, Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709. E-mail:

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