ABSTRACT
In our initial literature search for any linkages between DHA and cancer, we decided to €rst focus on any suspicious tumors in human organs with high DHA levels. At this point we ran headlong into the €eld of retinoblastoma, a good place to start because the retina has the highest levels of DHA in the body. We do not attempt to review this large €eld of literature here except to say that retinoblastoma is a childhood cancer and tumors develop from neural precursor cells in the immature retina (Classon and Harlow, 2002). About one child in 20,000 is af¦icted. Unlike other forms of cancer including colon tumors, which require roughly €ve to six separate mutations (see Figure 13.1 for relationship between age, number of mutations, and cancer), an unusually small number of mutations early in life are responsible for converting neural precursor cells to a retinoblastoma in infants (Knudson, 1971). A few individuals with retinoblastoma have inherited a deletion of the retinoblastoma (Rb) gene, which is present in all somatic cells in the body. Children carrying one defective copy of the Rb gene are predisposed to cancer. A second mutation blocking the function of the remaining good copy results in retinoblastoma. The remarkable feature of familial retinoblastoma is that once one eye is affected the other eye is likely to follow shortly. Thus, the mutation frequency of immature neural cells in the retina seems to be extraordinarily high, and this tumor might be accounted for by a pair of mutations, one in each of the Rb genes. In the familial form a single mutation triggers the cancerous state. The Rb gene was the €rst class of genes called
tumor suppressor genes to be identi€ed, and many others have followed, adding an important chapter to the cancer €eld. A genetic defect targeted to a tumor suppressor gene increases the probability of cancer, but the data on the high rates recorded for retinoblastoma suggest a specialized mechanism is at work. There is no generally accepted mechanism to account for retinoblastoma, though various ideas have surfaced, including a genetic hot spot in the Rb gene and its relatively large target size for mutations. We propose that heavy traf€cking of DHA needed for building the membranes for neurons and rods and cones subjects these cells to relatively high levels of oxidative stress directly or indirectly causing damage to chromosomal DNA. According to this scenario the window for DNA damage is open during childhood but closes later. The vulnerable period coincides with the most dynamic stage of neuron development and sculpting of the infant brain (see Chapter 3), a period when DHA circulation in retinal cells is proposed to be especially high.
