We propose to continue our work identifying and validating biomarkers - particularly hormonal markers - that predict risk of invasive breast cancer in postmenopausal women. Using a prospective nested case-control design, we plan to analyze blood samples collected from the 32,826 participants in the Nurses'Health Study (NHS) who provided a blood sample in 1989-90 and, for 18,743 of these women, a second sample in 1999- 2000. We propose to evaluate markers from several inter-related pathways to determine their role in cancer risk;a number of these aims are entirely new, while others extend our work in the most promising areas from the current grant cycle. Specifically, we will evaluate the role of several matrix metalloproteins (MMPs), estrogen metabolites, prolactin as assessed by a novel bioassay, 25(OH) vitamin D, estradiol and testosterone in relation to risk;for prolactin and vitamin D, we will assess whether the plasma level / breast cancer relation varies by protein expression in tumor tissue (e.g., prolactin receptor expression). We also will assess the importance of timing of exposure in carcinogenesis using two blood samples collected ten years apart. Further, we will provide the first detailed assessment of whether plasma hormones, mammographic density and several well-confirmed gene polymorphisms contribute importantly to risk prediction models for postmenopausal estrogen receptor positive (ER+) breast cancer. Such models may be useful in identifying women at high risk of breast cancer who would most benefit from chemoprevention or increased screening - yet no prior study has evaluated this range of risk factors and few have assessed ER+ tumors specifically (although currently approved chemopreventives only decrease risk of ER+ breast cancer). The ongoing NHS Program Project grant will provide follow-up and documentation of breast cancer outcomes in addition to providing information on important covariates, substantially increasing the cost-effectiveness of the proposed project.
Cumulatively, this proposal should substantially extend knowledge of breast cancer risk prediction, and of several possible but as yet unproven etiologic pathways, that ultimately may help determine and refine ways to decrease breast cancer risk in postmenopausal women.
|Sparks, Jeffrey A; Chen, Chia-Yen; Jiang, Xia et al. (2015) Improved performance of epidemiologic and genetic risk models for rheumatoid arthritis serologic phenotypes using family history. Ann Rheum Dis 74:1522-9|
|Tworoger, Shelley S; Rice, Megan S; Rosner, Bernard A et al. (2015) Bioactive prolactin levels and risk of breast cancer: a nested case-control study. Cancer Epidemiol Biomarkers Prev 24:73-80|
|Song, Mingyang; Gong, Jian; Giovannucci, Edward L et al. (2015) Genetic variants of adiponectin and risk of colorectal cancer. Int J Cancer 137:154-64|
|Bertrand, Kimberly A; Rosner, Bernard; Eliassen, A Heather et al. (2015) Premenopausal plasma 25-hydroxyvitamin D, mammographic density, and risk of breast cancer. Breast Cancer Res Treat 149:479-87|
|Cahill, Leah E; Levy, Andrew P; Chiuve, Stephanie E et al. (2013) Haptoglobin genotype is a consistent marker of coronary heart disease risk among individuals with elevated glycosylated hemoglobin. J Am Coll Cardiol 61:728-37|
|Zhang, Xuehong; Tworoger, Shelley S; Eliassen, A Heather et al. (2013) Postmenopausal plasma sex hormone levels and breast cancer risk over 20ýýyears of follow-up. Breast Cancer Res Treat 137:883-92|
|Karlson, Elizabeth W; Ding, Bo; Keenan, Brendan T et al. (2013) Association of environmental and genetic factors and gene-environment interactions with risk of developing rheumatoid arthritis. Arthritis Care Res (Hoboken) 65:1147-56|
|Mitta, Vinod P; Christen, William G; Glynn, Robert J et al. (2013) C-reactive protein and the incidence of macular degeneration: pooled analysis of 5 cohorts. JAMA Ophthalmol 131:507-13|
|Karageorgi, Stalo; McGrath, Monica; Lee, I-Min et al. (2011) Polymorphisms in genes hydroxysteroid-dehydrogenase-17b type 2 and type 4 and endometrial cancer risk. Gynecol Oncol 121:54-8|
|Poole, Elizabeth M; Tworoger, Shelley S; Hankinson, Susan E et al. (2011) Body size in early life and adult levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3. Am J Epidemiol 174:642-51|
Showing the most recent 10 out of 166 publications