ArticleCancer2012
Risk of retinoblastoma is associated with a maternal polymorphism in dihydrofolatereductase (DHFR) and prenatal folic acid intake.
Article in Cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Review
- Folate from probiotic bacteria and its therapeutic applications.Archives of microbiology · 2025Review
- Article
- Association Between Vitamin Deficiencies and Ophthalmological Conditions.Clinical ophthalmology (Auckland, N.Z.) · 2023Review
- Epidemiological aspect of retinoblastoma in the world: a review of recent advance studies.International journal of ophthalmology · 2023Review
- Overview of Neural Tube Defects: Gene-Environment Interactions, Preventative Approaches and Future Perspectives.Biomedicines · 2022Review
- Sunlight exposure in infancy decreases risk of sporadic retinoblastoma, extent of intraocular disease.Cancer reports (Hoboken, N.J.) · 2021Article
- Association between Predictors of Vitamin D Serum Levels and Risk of Retinoblastoma in Children: A Case-Control Study.Nutrients · 2021Article
- Dihydrofolate Reductase (DHFR) del19bp Polymorphism and Down Syndrome Offspring.Journal of molecular neuroscience : MN · 2020Article
- Discovery of a transcriptomic core of genes shared in 8 primary retinoblastoma with a novel detection score analysis.Journal of cancer research and clinical oncology · 2020Article
- Eag1 Gene and Protein Expression in Human Retinoblastoma Tumors and its Regulation by pRb in HeLa Cells.Genes · 2020Article
- Article
- Maternal Haplotypes inGenes · 2019Article
- Article
- Influence of dihydrofolate reductase gene polymorphisms rs408626 (-317A>G) and rs442767 (-680C>A) on the outcome of methotrexate-based maintenance therapy in South Indian patients with acute lymphoblastic leukemia.European journal of clinical pharmacology · 2015Article
- Article
- Maternal diet during pregnancy and unilateral retinoblastoma.Cancer causes & control : CCC · 2015Article
- Folic acid supplementation in pregnancy and implications in health and disease.Journal of biomedical science · 2014Review
- Diagnostic delay and sociodemographic predictors of stage at diagnosis and mortality in unilateral and bilateral retinoblastoma.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2014Article
- Folate.Advances in nutrition (Bethesda, Md.) · 2013Article
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundThe incidence of unilateral retinoblastoma varies globally, suggesting possible environmental contributors to disease incidence. Maternal intake of naturally occurring folate from vegetables during pregnancy is associated inversely with the risk of retinoblastoma in offspring.
methodsThe authors used a case-control study design to examine the association between retinoblastoma risk and maternal variations in the folate-metabolizing genes methylenetetrahydrofolate reductase (MTHFR) (a cytosine-to-thymine substitution at nucleotide 677 [MTHFR677C→T]; reference single nucleotide polymorphism rs1801133) and dihydrofolate reductase (DHFR) (a 19-base-pair deletion of intron 1a [DHFR19bpdel]; rs70991108). In central Mexico, 103 mothers of children with newly diagnosed unilateral retinoblastoma were enrolled in an institutional review board-approved study along with a control group of 97 mothers who had healthy children. Mothers were interviewed regarding perinatal characteristics, including use of prenatal vitamin supplements, and gave peripheral blood samples, which were used for polymerase chain reaction-based genotyping of rs1801133 and rs70991108.
resultsThe risk of having a child with unilateral retinoblastoma was associated with maternal homozygosity for DHFR19bpdel (odds ratio, 3.78; 95% confidence interval, 1.89-7.55; P = .0002), even after controlling for the child's DHFR19bpdel genotype (odds ratio, 2.81; 95% confidence interval, 1.32-5.99; P = .0073). In a subgroup of 167 mothers with data on prenatal intake of supplements containing folic acid (a synthetic form of folate), DHFR19bpdel-associated risk was elevated significantly only among those who reported taking folic acid supplements. Maternal MTHFR genotype was unrelated to the risk of having a child with retinoblastoma.
conclusionsMaternal homozygosity for a polymorphism in the DHFR gene necessary for converting synthetic folic acid into biologic folate was associated with an increased risk for retinoblastoma. Prenatal ingestion of synthetic folic acid supplements may be associated with increased risk for early childhood carcinogenesis in a genetically susceptible subset of the population.
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