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Inflammation and Breast Cancer Risk

Gierach, Gretchen Lynn (2006) Inflammation and Breast Cancer Risk. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Mammographic density is one of the strongest risk factors for breast cancer. Exactly how breast density increases breast cancer risk is unknown, although it is believed that dense breast areas may reflect exposure to estrogen. Breast cancer incidence is highest in postmenopause, when most estrogens are produced in non-ovarian tissues. Cyclooxygenase (COX)-2 and the cytokine tumor necrosis factor (TNF)-alpha may play a role in regulating estrogen synthesis in postmenopausal women. The aim of the present study was to explore the association between inflammation and breast cancer risk in two populations of postmenopausal women. Different exposures associated with inflammation (non-steroidal anti-inflammatory drug (NSAID) use, circulating receptors for TNF-alpha, and a polymorphism in the TNF receptor-II gene) were measured and tested for their association with incident breast cancer or mammographic density. In the first study, the Study of Osteoporotic Fractures (SOF), complete NSAID medication and breast cancer risk factor information was available for 6695 women, mean (SD) age 73 (5) years. During a mean (SD) of 13.2 (3.8) years of follow-up, 372 women were diagnosed with primary breast cancer. There were no differences in incident breast cancer by NSAID use, either before or after adjusting for covariates. In the second study, Mammograms and Masses (MAMS), mean mammographic density was lower among women in the highest quartiles of circulating soluble TNF receptor levels. After adjustment for body mass index, the inverse association disappeared. In evaluating the TNFR2 -196 M/R polymorphism (T>G), the unadjusted mean (SD) mammographic density was higher in women with the TT genotype (32.3% (21.0)) as compared to women with the TG/GG genotypes (26.6% (17.2)), p=0.003. The association remained statistically significant after adjustment for age and BMI (p=0.03); however, inclusion of additional covariates reduced the level of statistical significance (p=0.08). There was no observable difference in circulating sTNFR2 levels between the TNFR2 genotypes. An increased understanding of factors that affect mammographic density and their underlying mechanisms is needed, and inflammation may be involved. An association between breast cancer risk and inflammation would have important pubic health implications for screening and primary prevention of breast cancer.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Gierach, Gretchen Lynngretchengierach@gmail.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairModugno, Francesmaryfm@cs.cmedu
Committee MemberCauley, Jane AJCauley@edc.pitt.eduJCAULEY
Committee MemberWeissfeld, Joel Ljwepid@pitt.eduJWEPID
Committee MemberWilson, John Wwilson@nsabp.pitt.eduJWW
Committee MemberVogel, Victor Gvvogel@mail.magee.edu
Date: 7 June 2006
Date Type: Completion
Defense Date: 7 April 2006
Approval Date: 7 June 2006
Submission Date: 12 April 2006
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: mammographic density; postmenopause; receptors; tumor necrosis factor-alpha; breast neoplasms; cytokine; non-steroidal anti-inflammatory agents; aspirin
Other ID: http://etd.library.pitt.edu/ETD/available/etd-04122006-205122/, etd-04122006-205122
Date Deposited: 10 Nov 2011 19:36
Last Modified: 15 Nov 2016 13:39
URI: http://d-scholarship.pitt.edu/id/eprint/7046

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