Abstract DPOC-008: LIFESTYLE AND REPRODUCTIVE RISK FACTORS AND OVARIAN CANCER RISK BY p53 AND MAPK EXPRESSION

Abstract

Abstract BACKGROUND: One recent model of ovarian cancer development divides ovarian cancer into two types. Type II tumors are fast growing, potentially arising from the fallopian tubes, and characterized by tubal precursor lesions with p53 mutations. Type I tumors are slow–growing, arising from the ovary, and characterized by KRAS, BRAF, and PTEN mutations. The purpose of this study was to evaluate the association between selected lifestyle and reproductive risk factors and risk of ovarian cancer defined by expression of p53 (as a marker of Type II disease) and mitogen–activated protein kinase (MAPK), which is upregulated by KRAS and BRAF (as a marker of Type I disease). METHODS: Epithelial ovarian cancer cases with available tumor blocks and cancer–free controls were identified from the Nurses' Health Study (NHS) and NHS II prospective cohorts, and from the population–based New England Case–Control (NECC) study of ovarian cancer. We performed immunohistochemical assays for p53 and MAPK expression. Age– and multivariable–adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the association between each lifestyle or reproductive risk factor (e.g. parity, oral contraceptive use, tubal ligation, age at menarche, menopausal status, age at menopause, hormone therapy use, and family history of ovarian cancer) and ovarian cancer using polytomous logistic regression. RESULTS: 249 cases and 1051 controls from the NHS/NHS II and 77 cases and 857 controls from the NECC study were included in the analyses. Overall there were few significant differences in lifestyle or reproductive risk factors by p53 or MAPK tumor expression. Increasing parity was associated with a greater decreased risk of p53 negative tumors (OR=0.40; 95% CI=0.26–0.62) than p53 positive tumors (OR=0.85; 95% CI=0.46–1.57) (pheterogeneity=0.03). Family history of ovarian cancer was associated with risk of developing MAPK negative (OR=1.87; 95% CI=1.28–2.74) but not MAPK positive tumors (OR=0.76; 95% CI=0.46–1.23) (pheterogeneity<0.01). When p53 and MAPK expression were cross–classified family history was most strongly associated p53+/MAPK– expression (OR=2.46; 95% CI=1.42–4.28). CONCLUSIONS: These findings provide evidence that parity and family history may be associated with tumor subtypes defined by p53 and MAPK expression. However, in future studies other immunohistochemical markers that more clearly define these subtypes should be considered. Citation Format: Holly R. Harris, Megan S. Rice, Amy L. Shafrir, Elizabeth M. Poole, Jonathan L. Hecht, Kathryn L. Terry, Shelley S. Tworoger. LIFESTYLE AND REPRODUCTIVE RISK FACTORS AND OVARIAN CANCER RISK BY p53 AND MAPK EXPRESSION [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr DPOC-008.