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The Omega-6 and Omega-3 Polyunsaturated Fatty Acids and Modifiable Breast Cancer Risk Factors

Hudson, Alana (2008) The Omega-6 and Omega-3 Polyunsaturated Fatty Acids and Modifiable Breast Cancer Risk Factors. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWeissfeld, Joeljwepid@pitt.eduJWEPID
Committee MemberWilson, Johnwilson@nsabp.pitt.eduJWW
Committee MemberEvans, RhobertEvansR@edc.pitt.eduRWE2
Committee MemberVogel,
Date: 25 June 2008
Date Type: Completion
Defense Date: 28 November 2007
Approval Date: 25 June 2008
Submission Date: 29 March 2008
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: estradiol; nonsteroidal anti-inflammatory agents; mammographic breast density; polyunsaturated fatty acids
Other ID:, etd-03292008-081058
Date Deposited: 10 Nov 2011 19:33
Last Modified: 15 Nov 2016 13:37


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