Prenatal Per- and Polyfluoroalkyl Substance Exposure in Relation to Retinoblastoma

Abstract

BackgroundPrenatal per- and polyfluoroalkyl substance (PFAS) exposure can disrupt hormonal homeostasis and induce neuro- and immunotoxicity in children. In this exploratory study, we investigated associations between PFAS levels in neonatal dried blood spots and retinoblastoma risk.Materials and MethodsThis study included 501 retinoblastoma cases born from 1983 to 2011 and 899 controls frequency-matched by birth year (20:1 matching ratio), born to 755 US-born and 366 Mexico-born mothers in California. Perfluorooctanesulfonic acid (PFOS), perflurooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) feature intensities were identified from neonatal blood spots from California newborn Genetic Disease Screening Program. Using logistic regression, we assessed whether a doubling (log2-unit increase) of PFAS levels or having above-mean levels of PFAS in blood affects retinoblastoma risk overall or its subtypes (i.e., unilateral, bilateral). We also assessed children of US-born and Mexico-born mothers, separately.Results and DiscussionAmong all children, above-mean PFOS levels at birth increased the odds of retinoblastoma overall by 29% (95% Confidence Interval (CI): 1.00, 1.67) and unilateral retinoblastoma by 42% (95% CI: 1.03, 1.97). For children of Mexico-born mothers, we estimated the highest odds of retinoblastoma overall (adjusted odds ratio (aOR): 1.67; 95% CI: 1.06, 2.66) and bilateral retinoblastoma (aOR: 2.06; 95% CI: 1.12, 3.92) with above-mean PFOS levels. Among children of US-born mothers, higher PFOS levels increased the odds of unilateral retinoblastoma by 15% (95% CI: 0.99, 1.35) for each log2-unit increase and by 71% among children with above-mean PFOS levels (95% CI: 1.04, 2.90). In addition, for children of US-born mothers, PFOA increased the odds of retinoblastoma overall (aOR: 1.41; 95% CI: 1.00, 2.02 for above-mean levels, aOR: 1.09; 95% CI: 0.98, 1.23 per log2-unit increase). PFNA was not associated with retinoblastoma risk.ConclusionsOur results suggested that PFOS and PFOA might contribute to retinoblastoma risk in children born in California.

Note:
Funding declaration: This work was supported by the National Institutes of Health grants R03CA252788, R21ES018960, R21ES019986 and the California Tobacco-Related Disease Research Program of the University of California, grant number 24RT-0033H. Ms. Yixin Chen was partially supported by National Cancer Institute, Department of Health and Human Services, Grants T32CA009142.

Conflict of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical Approval: Human subject permissions were obtained from the California Committee for the Protection of Human Subjects, the University of California, Los Angeles, and the University of North Texas.

Keywords: Per- and polyfluoroalkyl substance, Retinoblastoma, Neonatal dried blood spots, Metabolomics, Mexico-born, US-born