Alcohol consumption and breast cancer: a proposed mechanism for alcohol-caused breast cancer initiation, promotion, and progression
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Abstract
Breast cancer is the second leading cause of death in women in the United States. Several modifiable behaviors are known to place women at increased risk of developing breast cancer, one of which is consuming alcoholic beverages. The relationship between alcohol ingestion and breast cancer has been well established through epidemiological and experimental research; however, a mechanism describing the interaction and onset of carcinogenesis has not been determined. There are several proposed mechanisms currently being investigated, which fall into one of four general categories: DNA damage induced by alcohol metabolites, by hormone elevation, by oxidative stress, or by interfering with proper DNA methylation. An important goal is to determine how these various proposed mechanisms mediate alcohol-caused breast cancer through its initiation, promotion, and progression.
This study reviewed current breast cancer literature, looking at both epidemiological data investigating a relationship between breast cancer onset and survival, and experimental data examining the mechanisms of alcohol and cell interaction. This paper looks at alcohol-mediated breast cancer from the broader point of view of alcohol's effect on the various stages of cancer, and determines a mechanism for each step.
Data indicates that alcohol-mediated breast cancer initiation is caused by alcohol metabolites, namely acetaldehyde and its derivatives, forming DNA adducts that cause lesions in the DNA. Oxidative stress also brought on by the presence of alcohol and its metabolites initiates lipid peroxidation and the production of highly reactive aldehydes, such as trans-4-hydroxy-2-nonenal, that disrupt the DNA repair system. Together, there is DNA damage and prevention of repair, which results in the initiation of cancer. Breast cancer promotion is mediated by elevated levels of the hormones leptin and estrogen, which form complexes regulating the cell cycle and promoting cell replication and survival in these damaged cells. Cancer progression then proceeds as alcohol increases insulin sensitivity in breast cancer cells and encourages replication resulting in a mass. Furthermore, extracellular matrix proteins degrade and the cancer cells take on characteristics of migratory cells. Next, cell adhesion signals are enhanced, allowing cancer cells to follow a protein scaffold and migrate into neighboring tissue.
Although there is still much more research to be done, by determining a mechanism for how alcohol mediates breast cancer through its various stages, treatments can be developed that target various stages in the mechanism to prevent carcinogenesis or increase survival chances.
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Thesis (M.A.)--Boston University
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