Date of Award

Spring 5-2020

Degree Name

Master of Public Health (MPH)

Advisor(s)

ANNA V. WILKINSON, PHD

Second Advisor

COURTNEY E. BYRD-WILLIAMS, PHD

Abstract

Epithelial ovarian cancer, the most lethal of the gynecological cancers, is typically diagnosed at advanced stages. Women diagnosed with advance-staged (i.e., stage III and IV according to the International Federation of Gynecology and Obstetrics) epithelial ovarian cancer are more likely to have recurrent episodes within 18 months17. According to a 2012 2016 case analysis conducted by the surveillance, epidemiology, and end results, or SEER program, the incidence of ovarian cancer was 11.4 per 100,000 women in all races per year with the highest incidence in non-Hispanic whites, of 11.9 per 100,000 women and the lowest incidence in Asians / Pacific Islanders women, of 9.4 per 100,000 persons per year. The mortality incidence was 7.0 per 100,000 persons in all races per year in the United States. Many cancers originate from genetic mutations, including ovarian cancer. Studies indicate epithelial ovarian tumors develop in two distinctive pathways with type I arising from ovarian epithelium and inclusion germ cell layers and type II deriving from fallopian tubular epithelial origins. The mutation product of p53 results in various clinical symptoms and end points. Clinicians also have recognized the association of BRCA1 and BRCA2 genes with both of ovarian cancer and breast cancer2. A multivariate analysis conducted by Gallagher et al.14 revealed that multiple organ systems are prone to be involved during an ovarian malignancy, because there is a lack of distinct symptomatology, which allows the cancer to spread prior to detection. 2 Numerous studies also have indicated assorted risk factors contribute to the incidence and survival rate identifying racial/ethnical differences, genetic risk factors as the BRCA genes, and nongenetic risk factors including reproductive and hormonal factors, environmental and lifestyle factors. The racial differences in incidence and survival rates within the United States resemble the global pattern, with the highest incidence and mortality rates among non-Hispanic whites, followed by Hispanics, and the lowest incidence and mortality rates are among non-Hispanic blacks and Asians. The exact causes of racial disparities of epithelial ovarian cancer is still left unclear, the reasons are likely to be diverse. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) both stimulate the ovaries to produce steroids in females. Simon et al (1983) concluded, based on in vitro studies, that these hormones contribute to the malignant epithelial tumors. Aside from the oral contraceptive use research conducted by CDC32, several hormonal factors also have been associated with the development of epithelial ovarian cancer. Studies have suggested an association between lower parity and an increased risk of developing aggressive epithelial ovarian cancer6,23. Women with longer ovulatory history are exposed to a greater risk of advanced epithelial ovarian cancer as well23. Women who have had a hysterectomy or experienced early-age menopause are at reduced risk of epithelial ovarian cancer3. Menstrual cycle irregularity and younger age at menarche also have been associated with lower risk of deaths from high-grade epithelial ovarian cancer29. 3 From 1990s to 2000s, there had been seven new hormonal contraceptive regimens approved by the Federal Drug and Administration (FDA). The birth control shot, depot medroxyprogesterone acetate (DMPA) along with the arm implant were introduced in the 1990s. The intrauterine device (IUD) that releases levonorgestrel daily was approved in 2000. The following year, transdermal patch and vaginal ring were brought to the market. In 2003, combined oral contraceptive were introduced to the public and became common and popular7,39. All these various types of hormonal contraceptives differ in effectiveness and availability, but they all introduce hormones to regulate ovulation and inhibit body’s natural cyclic hormones to prevent pregnancy44. Decades of research suggest that there are many factors related to the prognostic characteristics of epithelial ovarian cancer; in fact, abundant sources have investigated the association of hormonal factors to epithelial ovarian cancer. Thigpen et al (1993) analyzed a pooled database from the Gynecologic Oncology Group and specified age as a determinant for pathological outcome in which women aged 69 and older had a poorer prognosis than younger women34. One of the early studies, conducted in the 1980s by the United States Centers for Disease Control and Prevention (CDC), the Cancer and Steroid Hormone Study (CASH), revealed that regular users of contraceptive pills for 10 years or more had a lower lifetime risk of epithelial ovarian cancer38. Based on such findings, a World Health Organization collaborative study further indicated that there were no remarkable differences in the level of protection based on the levels of dosage in contraceptive pills27. Furthermore, a meta-analysis conducted by Wheeler et al (2019) identified that any type of intrauterine device they investigated was associated with a lower incidence of ovarian cancer.

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