Experimental evidence suggests that omega-6 (n-6) fatty acids have mammary tumor promoting effects whereas omega-3 (n-3) fatty acids inhibit tumor growth. These two families of fatty acids may influence breast cancer development by impacting prostaglandin E2 (PGE2) formation and consequently estradiol synthesis. Whether this effect on estrogen production can be observed in the circulation or in breast tissue, as reflected on a mammogram, is unknown. Therefore, using fatty acids in erythrocytes as a biomarker of recent dietary intake, we sought to establish the relationship between the n-6 and n-3 fatty acids with both serum estradiol and mammographic breast density, two well-established modifiable breast cancer risk factors. We hypothesized that n-6 fatty acids are positively related and n-3 fatty acids negatively related to both risk factors. Nonsteroidal anti-inflammatory drugs (NSAIDs) also inhibit PGE2 formation, therefore we further hypothesized that estradiol levels would be lower among NSAID users. NSAID data was not available at the time of mammogram; hence the relationship between NSAID use and mammographic density could not accurately be assessed. To test our hypotheses we conducted several investigations ancillary to the Mammograms and Masses Study (MAMS), a case control study of the determinants of mammographic breast density. Participants were eligible for this compilation of studies if they were breast cancer-free, postmenopausal and not taking exogenous hormones. We observed significantly lower levels of serum estradiol among current users of NSAIDs as compared to non-users of NSAIDs. Further, as hypothesized, estradiol concentration decreased with increasing erythrocyte composition of total n-3 fatty acids and rose with increasing erythrocyte composition of total n-6 fatty acids. However, these findings were noted only among non-users of NSAIDs and not among NSAID users. No relationship was observed between any of the n-6 or n-3 fatty acids measures and mammographic breast density. In summary, lowering consumption of n-6 fatty acids, increasing n-3 intake, or taking a NSAID may result in reduced estradiol synthesis and potentially breast cancer risk. Further research is needed to validate our results. If confirmed, these findings could have a substantial impact on public health as it could lead to the development of chemopreventive guidelines, and ultimately prevent the development of estrogen-dependent breast cancer.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-03292008-081058 |
| Date | 25 June 2008 |
| Creators | Hudson, Alana |
| Contributors | John Wilson, Victor Vogel, MD, MHS, Joel Weissfeld, MD, MPH, Rhobert Evans, PhD |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-03292008-081058/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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