Abstract
Worldwide, ovarian cancer is ovarian cancer is the sixth most diagnosed cancer and is responsible for the most deaths annually than any other disease of the female reproductive system. It has a poor prognosis because the symptoms are vague even into Stage IV of the disease. Epithelial ovarian cancer constitutes about 90% of diagnosed cases. Research has demonstrated that hormone therapy, chronic pelvic inflammation, and BRCA1 and BRCA2 germline pathogenic variants are factors in the etiology of ovarian cancer. BRCA1 and BRCA2 is also associated with breast cancer, pancreatic cancer, fallopian tube cancer, prostate cancer, and primary peritoneal cancer. The clinical detection of the presence of a pathogenic variant of BRCA1 or BRAC2 begins with a review of family and personal histories. If the family history is positive, genetic testing is recommended. A prophylactic oophorectomy has proved to be highly effective. Research on ovarian cancer screening has produced tentative by encouraging findings. Keywords: ovarian cancer, pathology, etiology, genetic profiling
Worldwide, ovarian cancer is the sixth most diagnosed cancer and is responsible for the most deaths annually than any other disease of the female reproductive system (Permuth-Wey & Sellers, 2009). The incidence rate shows a wide range globally with China having the lowest rates and the United Kingdom and the Russian Federation have the highest rates (Lowe, et al., 2013). A precise epidemiology is difficult to ascertain as ovarian cancer is heterogeneous in its histopathology (Cramer, 2012). The purpose of this paper is to review the pathophysiology, etiology, prognosis, and management of ovarian cancer with a focus on genetic factors.
Epithelial ovarian cancer starts from three cell types: surface epithelial cells, stromal cells, and germ cells. Common epithelial ovarian carcinomas are responsible for 80 to 90% of ovarian cancers. In the U.S., epithelial ovarian cancer accounts for 3% of all women’s cancers and is second to uterine cancer in terms of frequency (Rosen, 2009). The relative 5-year survival rates are as follows: epithelial stage 1 is 90%, epithelial stage IV is 17%; ovarian stromal stage 1 is 95%, ovarian stroma stage IV 35%, germ cell stage 1 is 98%, germ cell stage IV is 69% (American Cancer Society, n.d.). Due to the lack of distinct symptoms, epithelial ovarian cancer is most soften detected late, which accounts for it being the most deadly of the female reproductive system cancers (Rosen, et al., 2009).
1. Pathophysiology
The more rare forms of ovarian cancer, stroma cells and germ cells respectively originate in the structural tissue of the ovaries and in the ova. The more common epithelial ovarian cancer cells typically attach themselves to organ surfaces rather than invade parenchyma. The cells implant themselves onto the peritoneal cavity lining, the mesentery of the bowel, and the liver capsule. Exfoliated cancer cells are carried along with the circulation of the peritoneal fluid to the right paracolic channel and space below the diaphragm. Therefore, the right side of the liver and diaphragm peritoneum are frequent tumour implant sites. The initial spread is direct through lymph drainage. Blood channels are more common in later stages of the disease (Green, Garcia & Ahmed, n.d.).
Hormone therapy used for the relief of menopausal symptoms has been associated with ovarian cancer (Collaborative Group on Epidemiological Studies of Ovarian Cancer, 2015) Conditions that result in inflammation of the ovaries, fallopian tubes and related ligaments have also been implicated in the etiology of ovarian cancer. Such conditions include ovarian endometriosis and chronic inflammation of the fallopian tubes (Furuya, 2013). Some of the genes that are regarded as responsible for ovarian cancer are BRCA1, BRCA2 and TP53 (Furuya, 2012). These genes have been identified as predisposing an individual to the transformation of ovarian epithelial cells into malignant tumours.
2. Contribution to Etiology of Cancer
BRCA1 and BRCA2 have also been associated with Hereditary Breast and Ovarian Cancer Syndrome (Appel & Clement, 2016; Petrucelli, Daly & Feldman, 2013). Hereditary Breast and Ovarian Cancer Syndrome (HBOC) is regarded as the result of a germline variant of BRCA1 or BRCA. This pathogenic variant of BRCA1 or BRCA2 is associated with an increased risk for ovarian cancer, breast cancer, pancreatic cancer, fallopian tube cancer, prostate cancer, and primary peritoneal cancer (Petrucelli, Daly & Feldman, 2013). For individuals with a pathogenic variant of BRCA1 or BRAC2, the life time risk of developing cancer is: 11-40% for ovarian cancer, 40-80% for breast cancer, 1-10% for male breast cancer, 1-7% for pancreatic cancer, and up to 39% for prostate cancer (Petrucelli, Daly & Feldman, 2013). BRCA2 pathogenic variations may also be responsible for melanoma (Petrucelli, Daly & Feldman, 2013). Women with a BRCA1 germline variant are at higher risk for ovarian cancer than those with a BRCA 2 variant (Petrucelli, Daly & Feldman, 2013).
3. Detection of the Ovarian Cancer
Early diagnosis is the key as the difference in the 5-year survival rate is 90% for early detection and 20% for late detection. However, detection tools for ovarian cancer are not well developed and even late stage symptoms can be vague (Jacobs, et al, 2016; Langhe, 2015). The clinical detection of the presence of a pathogenic variant of BRCA1 or BRAC2 begins with a review of family and personal histories. The individual and family history encompasses up to the third degree blood relative on either the maternal or paternal side and includes the following characteristics: diagnosis of breast cancer at the age of 50 or less, multiple breast cancers in the same individual, triple-negative breast cancer, more than one relative with breast cancer with one under the age of 50, three of relatives diagnosed with breast cancer at any age, ovarian cancer, ovarian and breast cancer, male breast cancer, pancreatic cancer plus ovarian or breast cancer in one individual or on solely on the maternal or paternal side of the family, Ashkenazi heritage, and a previous diagnosis of HBOC in the family (Petrucelli, Daly & Feldman, 2013) .
Langhe (2015) reviews microRNAs in the pathophysiology in all human cancers, specifically those caused by the expression of a pathogenic gene. The genetic profiling has shown that deregulated microRNA is associated with ovarian cancer (Langhe, 2015). A diagnosis of HBOC is made after genetic testing has been conducted on the family or individual. However, the current status of genetic testing does not guarantee the identification of all of the pathogenic variants of BRCA1 or BRAC2 (Petrucelli, Daly & Feldman, 2013).
4. Prevention of the Ovarian Cancer
BRAC1 and BRAC2 are autosomal dominant which means that if one parent has the aberrant gene, there is a 50% chance that the offspring carry the gene (Petrucelli, Daly & Feldman, 2013). Once a diagnosis of HBOC has been established in a first to third degree blood relative, genetic counselling and surveillance are recommended to other members of the family as the family-specific gene mutation can be detected with accuracy. Prenatal testing can determine the child has inherited HBOC, however prenatal testing for conditions with an adult onset is not common and genetic counseling is highly recommended (Petrucelli, Daly & Feldman, 2013).
A prophylactic oophorectomy reduces the risk of ovarian cancer by 80 – 90% (Rutter, et al, 2003) and a 53% risk reduction for breast cancer (Kauff et al., 2008). The use of oral contraceptives has also been found to reduce the risk of ovarian cancer (Petrucelli, Daly & Feldman, 2013). For those who have decided not to have prophylactic oophorectomy, ovarian cancer screening, transvaginal ultrasound and serum CA-125 concentration, is available and is recommended starting at the earliest onset age in the family (Petrucelli, Daly & Feldman, 2013). In a large randomized controlled study of postmenopausal women, Jacobs et al., (2016) have found some encouraging evidence for transvaginal ultrasound and serum CA-125 concentration ovarian cancer screening for those without the BRCA 1 and BRCA 2 variants.
5. Conclusion
In conclusion, ovarian cancer has a poor prognosis due to the vague symptoms, even at Stage 1V of the disease. Studies have found that hormone therapy, chronic pelvic inflammation, and germline pathogenic variants of BRCA 1 and BRCA 2 are associated with ovarian cancer. For those with BRCA1 and BRCA2 gene mutations, a prophylactic oophorectomy is available. Recent research from Jacobs et al. (2016) suggests that ovarian cancer screening could prove efficacious for all women regardless of genetic makeup, however further studies are required.
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