Citation
Mazul, Angela L.; Weinberg, Clarice R.; Engel, Stephanie M.; Siega-Riz, Anna Maria; Zou, Fei; Carrier, Kathryn S.; Basta, Patricia V.; Vaksman, Zalman; Maris, John M.; & Diskin, Sharon J., et al. (2019). Neuroblastoma in Relation to Joint Effects of Vitamin A and Maternal and Offspring Variants in Vitamin A-Related Genes: A Report of the Children's Oncology Group. Cancer Epidemiology, 61, 165-171. PMCID: PMC6730673Abstract
BACKGROUND: There is evidence vitamin A plays a role in neuroblastoma. Not only is 13-cis-retinoic acid used as maintenance therapy for high-risk cases, but prenatal vitamin intake use may decrease neuroblastoma risk. We hypothesized that single nucleotide polymorphisms (SNPs) in vitamin A-related genes are may be associated with neuroblastoma risk and potentially be modified by vitamin A intake.METHODS: The Neuroblastoma Epidemiology in North America (NENA) study recruited 563 case-parent sets through the Children's Oncology Group's Childhood Cancer Research Network. We ascertained dietary nutrient intake through questionnaires and genotyped 463 SNPs in vitamin A-related genes from saliva DNA. Offspring and maternal log-additive risk ratios (RR) and stratum-specific RR for gene-environment interaction were estimated with a log-linear model. We avoided false positives due to multiple testing by using the false discovery rate (FDR).
RESULTS: When all neuroblastoma cases were considered together, no offspring variants met the significance criteria (FDR Q-value < 0.2). One maternal SNP (rs12442054) was associated with decreased risk of neuroblastoma (RR: 0.61; 95% Confidence Interval (CI): 0.47-0.79, Q = 0.076). When the cases were categorized according to prognostic risk category and age at onset, nine offspring SNPs were significantly associated with intermediate-risk neuroblastoma. Maternal rs6776706 was associated with (RR: 0.49; 95% CI: 0.33-0.72, Q = 0.161) high-risk neuroblastoma and maternal rs11103603 (RR: 0.60; 95% CI: 0.45-0.79, Q = 0.127) was associated with neuroblastoma aged <1 year. For gene-environment interaction, maternal rs729147 was associated with decreased risk of neuroblastoma among mothers with vitamin A consumption above the recommendation.
CONCLUSIONS: Although there is biologic plausibility for the role of vitamin A in neuroblastoma, we found weak evidence of a relationship between vitamin A related genes and neuroblastoma.
URL
http://dx.doi.org/10.1016/j.canep.2019.06.009Reference Type
Journal ArticleYear Published
2019Journal Title
Cancer EpidemiologyAuthor(s)
Mazul, Angela L.Weinberg, Clarice R.
Engel, Stephanie M.
Siega-Riz, Anna Maria
Zou, Fei
Carrier, Kathryn S.
Basta, Patricia V.
Vaksman, Zalman
Maris, John M.
Diskin, Sharon J.
Maxen, Charlene
Naranjo, Arlene
Olshan, Andrew F.