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.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04122006-205122 |
| Date | 07 June 2006 |
| Creators | Gierach, Gretchen Lynn |
| Contributors | Victor G. Vogel III, MD MHS, Jane A. Cauley, DrPH MPH, Joel L. Weissfeld, MD MPH, John W. Wilson, PhD, Francesmary Modugno, PhD MPH |
| 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-04122006-205122/ |
| Rights | unrestricted, 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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