Shelley Tworoger

Assistant Professor of Medicine, Harvard Medical School

My major area of research focus is on ovarian cancer with an emphasis on: (a) identifying new and modifiable risk factors, (b) evaluating heterogeneity and determining how this relates to disease etiology, and (c) discovering new biomarkers that are risk factors for this disease.  This integrative approach entails collaborations with biostatisticians, pathologists, oncologists, and basic scientists, and is a powerful method for improving our understanding of ovarian carcinogenesis.

I am the Project Leader for the Ovarian Cancer Research Project of the Nurses' Health Study.  To date, most known risk factors are not easily modifiable (e.g., pregnancy); however because ovarian cancer has a poor prognosis, it is important to identify methods for prevention.  A major interest area is the diet.  Several recent studies from my group suggest that flavonoids (compounds found in plants) and caffeine may lower risk of ovarian cancer.  New research will extend these findings, explore other dietary factors such as milk and acrylamide intake, evaluate dietary intake patterns, and explore possible mechanisms of action.  I also am investigating new potential risk factors, including shiftwork and vitamin D. Additionally, I have examined the role of several hormones in the etiology of ovarian cancer, including vitamin D, the insulin-like growth factor pathway, androgens, and anti-MUC1 antibodies in several cohorts studies.  Over the next year I plan to expand on this by examining other potential risk biomarkers (e.g., prolactin, melatonin, MMPs), markers of dietary intake (e.g., acrylamide), and am actively involved in developing an ovarian cancer cohort consortium.

A critical aspect of my research is to elucidate the heterogeneity of ovarian tumors in relation to their development.  Thus, I have created tissue microarrays to evaluate tumor protein expression. For example, hormonally-related risk factors, particularly postmenopausal hormone use, were only associated with risk of estrogen receptor positive, but progesterone receptor negative, ovarian tumors. Expansion of these analyses will help clarify how such factors may alter risk.  I also plan to explore tumor markers of inflammation as this is a key pathway in ovarian carcinogenesis.  A new approach is to examine risk factors for tumors that are fatal within three years of diagnosis.  Identifying what causes the most aggressive forms of this disease could substantially aid in prevention efforts.  Further, in conjunction with local pathologists, I am studying the epidemiology of precursor lesions and tumors based on putative cell of origin (fallopian vs. ovarian).

As Director of the NHS Biomarker Laboratory and Repository, I oversee the use and handling of nearly one million biologic specimens collected from over 120,000 NHS women.  I oversee the laboratory and data management staff, work with investigators using the repository, and now have published several papers describing the appropriate use of biomarkers in epidemiologic studies.

PhD, Epidemiology, University of Washington, Seattle, WA

1.    Tworoger SS, Eliassen AH, Sluss P, Hankinson SE. A prospective study of plasma prolactin concentrations and risk of premenopausal and postmenopausal breast cancer. J Clin Oncol.  2007;25:1482-1488.

2.    Tworoger SS, Lee IM, Buring JE, Rosner B, Hollis BW, Hankinson SE. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of incident ovarian cancer. Cancer Epidemiol Biomarkers Prev.    2007;16:783-788.

3.     Hecht JL, Kotsopoulos J, Gates MA, Hankinson SE, Tworoger SS. Validation of tissue microarray technology in ovarian cancer: results from the Nurses' Health Study. Cancer Epidemiol Biomarkers Prev. 2008;17:3043-3050.

4.    Tworoger SS, Gertig DM, Gates MA, Hecht JL, Hankinson SE. Caffeine, alcohol, smoking, and the risk of incident epithelial ovarian cancer. Cancer. 2008;112:1169-1177.

5.    Tworoger SS, Lee IM, Buring JE, Hankinson SE. Plasma androgen concentrations and risk of incident ovarian cancer. Am J Epidemiol. 2008;167:211-218.

6.    Saleemuddin A, Folkins AK, Garrett L, Garber J, Muto MG, Crum CP, Tworoger S.  Risk factors for a serous cancer precursor ("p53 signature") in women with inherited BRCA mutations. Gynecol Oncol. 2008;111:226-32.

7.    Hecht JL, Kotsopoulos J, Hankinson SE, Tworoger SS. Relationship between epidemiologic risk factors and hormone receptor expression in ovarian cancer: results from the Nurses' Health Study. Cancer Epidemiol Biomarkers Prev. 2009;18:1624-1630.

8.    Tworoger SS, Gates MA, Lee IM, Buring JE, Titus-Ernstoff L, Cramer D, Hankinson SE. Polymorphisms in the vitamin D receptor and risk of ovarian cancer in four studies. Cancer Res. 2009;69:1885-1891.

9.     Kotsopoulos J, Baer HJ, Tworoger SS. Anthropometric Measures and Risk of Epithelial Ovarian Cancer: Results from the Nurses' Health Study. Obesity 2010;18:1625-31.

10.    Gates MA, Rosner BA, Hecht JL, Tworoger SS. Risk factors for epithelial ovarian cancer by histologic subtype. Am J Epidemiol 2010;171:45-53.

11.    Gates M, Wolpin B, Cramer D, Hankinson S, Tworoger SS. ABO blood group and incidence of epithelial ovarian cancer. Int J Cancer 2010. [Epub ahead of print]