Pilot Projects

Title: Maternal folate deficiency as a risk factor for the development of sporadic retinoblastoma among children in Mexico

Investigator: Manuela Orjuela, MD, ScM

Description: Retinoblastoma (RB) arises in the developing retina, primarily as a result of mutations in the retinoblastoma gene, RB1. Ninety percent of RB1 mutations detected in children appear to be de novo mutations whose etiology is unknown. However, the majority of mutations are C to T transitions occurring at methylated cytosines suggesting that abnormalities in methyl transfer may underlie mutation. The incidence of sporadic RB is higher in several less affluent regions of the world suggesting that environmental factors associated with poor living conditions may play a role. Folate is a key regulator of methyl transfer and folate deficiency can lead to development of mutations through uracil misincorporation. This pilot will examine whether RB 1) is associated with folate deficiency, by examining dietary intake, folate, B6, B12 and homocysteine levels in mothers in a hospital based case-control study in Mexico City; and 2) is mediated through a functional polymorphism in the methylene tetrahydrofolate reductase gene by examining maternal DNA.