Abstract 6214: Vitamin metabolites in neonatal dried blood spots and risk of retinoblastoma in California

Abstract Background: Vitamin intake may influence carcinogenesis through various pathways. In particular, vitamin B6 metabolites have been implicated in cancer development due to their involvement in processes such as oxidative stress and inflammation. However, conclusions remain inconsistent, and epidemiological studies are limited, particularly for retinoblastoma. In this exploratory study, we examined associations between vitamin metabolites in neonatal dried blood spots and retinoblastoma risk in California. Methods: This study included 497 retinoblastoma cases born between 1983 to 2011 and 893 controls matched by birth year in California. Vitamin feature intensities were measured in neonatal blood spots from the California newborn Genetic Disease Screening Program. Logistic regression was used to evaluate associations between quartiles of vitamin levels and retinoblastoma risk, adjusting for sex, birth year, maternal age, maternal race and ethnicity, maternal place of birth, and socioeconomic status. We also stratified the analyses by retinoblastoma subtypes (i.e., unilateral, bilateral), sex and maternal birthplace (U.S. vs. Mexico). Results: For vitamin B6 metabolites, the highest quartile of pyridoxamine was associated with a 32% increase in retinoblastoma risk (95% confidence interval (CI): 0.97-1.80), while the highest quartile of 4-pyridoxic acid was associated with a 32% reduction (95% CI: 0.56-1.07), compared to the lowest quartile. Additionally, the highest quartiles of NAD+ were associated with a reduced risk (adjusted odds ratio (aOR): 0.78; 95% CI: 0.57-1.06 and aOR: 0.76; 95% CI: 0.55-1.05). No overall association with retinoblastoma risk was observed for pantothenic acid (vitamin B5), vitamin A, vitamin D2, or methylcobalamin (vitamin B12). After stratification, we did not observe clear dose-response relationships, although some estimates suggested an increased risk. For example, the 3rd quartile of pantothenic acid was associated with an increased risk among female (aOR: 0.65, 95% CI: 0.40-1.04) and children with Mexican-born mothers (aOR: 0.56, 95% CI: 0.30-1.05). The 2nd quartile of methylcobalamin was associated with a 56% increase in retinoblastoma risk among males (95% CI: 1.01-2.44). Conclusion: Several vitamin metabolites showed a differential abundance in neonatal blood spots of children who later did or did not develop retinoblastoma in California. These results suggest that further research into the role of maternal vitamin intake during pregnancy may hold promise for pediatric cancer prevention. Citation Format: Chuanjie Deng, Kimberley C. Paul, Douglas I. Walker, Dean P. Jones, Beate R. Ritz, Julia E. Heck. Vitamin metabolites in neonatal dried blood spots and risk of retinoblastoma in California [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 6214.