Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 190

The exact mechanisms by which any given cancer has arisen are difficult to pinpoint. However, many studies have shown that primary cancer develops in the brain because cells, possibly stem cells, have acquired mutations in their DNA which allow them to undergo unchecked and uncontrollable division. Secondary cancers (cancers that develop elsewhere, for example, the lungs and then spreading to the brain), are far more common compared to primary brain cancers.

Multiple risk factors are known to play a role in enhancing the chance of developing a brain tumor or accelerating the process. Some people with several risk factors may never develop a brain cancer. Conversely, some people with no known risk factors have presented with brain tumors. Complex interactions between environmental and genetic factors contribute to the development of brain tumors.

Environmental triggers for the brain tumor have been identified through epidemiologic studies that examine patterns of distribution of cancer in patients. Although brain tumors can develop at any age, they are more common in children and older adults. Men are more likely to develop brain tumors, however, meningiomas are more common in women. Recent investigations of mortality among workers employed in petroleum refineries and petrochemical plants have revealed an association between increased brain tumor risk and employment in the chemical industries and petroleum. Occupational groups having an elevated risk of brain tumors are suggested by literature review. The most eminent associations have been noted among white-collar professional groups and workers in occupations in which there is potential contact with lubricating oils, polycyclic aromatic hydrocarbons, organic solvents, polyvinyl chloride, formaldehyde, acrylonitrile, and phenolic compound. Moreover, employment in textile industry maintenance jobs and exposure to wool products may also be associated with an increased risk of brain tumor as suggested by another study. Exposure to radiation at an early age increases the risk of brain tumor. Ionizing radiation appears to be more strongly associated with meningioma risk than with glioma risk.

Genetics also play an important role as a risk factor. The genetic syndromes including neurofibromatosis, tuberous sclerosis, and Turcot’s and Li-Fraumeni syndromes are important risk factors in the development of brain cancers. In these syndromes, individuals inherit a germ-line mutation in a tumor suppressor gene. Tumor is initiated when the remaining copy of the gene is spliced or mutated, giving rise to uncontrolled growth of cells.

Because every cell in these individuals has a preexisting mutation the risk of tumorogenesis through the accumulation of other mutations is greatly increased.

Li-Fraumeni syndrome is caused by mutations in the cell checkpoint genes CHEK2 and TP53. Mutations in genes involved in DNA repair results in Turcot’s syndrome. It is plausible that in Li-Fraumeni syndrome and Turcot’s syndrome that the risk for brain tumors is increased by an accelerated rate of DNA mutation, leading to uncontrolled growth. Tuberous sclerosis is caused by mutations in TSC1 or TSC2, and neurofibromatosis is caused by mutations in NF1 or NF2. NF1, NF2, TSC1, and TSC2 are all involved in down-regulation of growth-promoting signal transduction pathways in the cell. It is therefore likely that, in tuberous sclerosis and neurofibromatosis, the risk for brain tumors is increased because brain cells are prepared for excessive growth and then develop additional mutations that allow cancer to form.

In addition, it has also been observed that brain tumors can cluster within families with no known risk factors, suggesting that these families might be carrying unknown susceptibility genes.

Meta-analyses have shown that people with HIV or AIDS have around double the risk of being diagnosed with a brain tumor in comparison with the general population.