Ovarian cancer and genetics
Ovarian cancer is a malignant growth that originates in the ovaries, which are responsible for producing eggs and female hormones. It often goes undetected until advanced stages, as symptoms may not appear until the cancer has progressed significantly. Risk factors for developing ovarian cancer include a family history of the disease, age over 50, and certain menstrual and reproductive histories. Genetic factors play a significant role, with about 10 to 15 percent of ovarian cancers being hereditary, primarily due to mutations in tumor-suppressor genes like BRCA1 and BRCA2. These genetic mutations can dramatically increase the risk of developing ovarian and breast cancers. Additionally, other hereditary syndromes, such as Lynch syndrome and Peutz-Jeghers syndrome, have been linked to ovarian cancer risks. Diagnosis typically involves a combination of medical history, physical exams, and imaging tests, while treatment may include surgery, chemotherapy, and possibly radiation therapy. Unfortunately, the prognosis is often poor due to late-stage diagnosis, highlighting the importance of awareness and regular health checkups.
Ovarian cancer and genetics
ALSO KNOWN AS: Cancer of the ovaries
DEFINITION Ovarian cancer is the growth of cancer cells in the ovaries. The ovaries make eggs for reproduction and female hormones. The most common type of ovarian cancer is epithelial.
Cancer occurs when cells in the body divide without control or order. If cells keep dividing uncontrollably, a mass of tissue forms. This is called a growth or tumor. The term “cancer” refers to malignant tumors. They can invade nearby tissue and spread to other parts of the body. Many of these tumors may grow to be very large without showing symptoms. These tumors can be hard to find during a physical exam. As a result, about 70 percent of patients are found with advanced disease. Germ cell tumors come from the reproductive tissue. They account for 20 percent of tumors. More rare are stromal cancers, which come from the connective cells of the ovary. They typically make hormones, which cause symptoms.
Risk Factors
Factors that increase a woman’s chance for ovarian cancer include a family history of ovarian cancer, especially in her mother, sister, or daughter; being fifty years of age or older; and a menstrual history of having her first period before age twelve, no childbirth or first childbirth after age thirty, and late menopause. Additional risk factors include a personal history of breast cancer or colon cancer and certain mutations in genes, including the BRCA1,BRCA2, or TP53 genes. The use of birth control pills for more than five years appears to decrease risk.
Etiology and Genetics
Only about 10 to 15 percent of ovarian cancers are inherited, while the remaining 85 to 90 percent result by chance from random mutations in the DNA of ovarian tissue in adult women. Most cases of inherited ovarian cancer result from mutations in any of several genes called tumor-suppressor genes, and these mutations can be inherited from either the male or female parent. Tumor-suppressor genes encode proteins that normally function in a variety of ways to limit or prevent cell growth and division. Mutations in these genes can lead to a loss in the ability to restrict tumor formation due to uncontrolled cell growth. When mutations occur in tumor-suppressor genes, it is not unusual to find that there is an increased risk for several different types of cancer to develop.
The two genes most commonly associated with an increased risk of ovarian cancer are BRCA1, found on the long arm of chromosome 17 at position 17q21, and BRCA2, at position 13q12.3, the same two genes that are most commonly associated with inherited breast cancer. Studies suggest that women who inherit a mutation in either of these two genes have a 15 to 40 percent chance of developing ovarian cancer and a 50 to 85 percent chance of developing breast cancer. These mutations are inherited in an autosomal dominant fashion, meaning that a single copy of the mutation is sufficient to cause the increased cancer risk. An affected individual has a 50 percent chance of transmitting the mutation to each of his or her children.
Women carrying a mutation that predisposes them to hereditary nonpolyposis colorectal cancer (Lynch syndrome) have been shown to have about a 9 to 12 percent risk of developing ovarian cancer and a 20 to 50 percent risk of developing uterine cancer, as well as smaller increased risks of developing cancers of the stomach or small intestine. Four different genes have been identified in which such mutations might occur: MLH1 (at position 3p21.3), MSH2 (at position 2p22-p21), MSH6 (at position 2p16), and PMS2 (at position 7p22).
Mutations in p53, the gene that suppresses tumors, have also been linked to ovarian and other cancers. About 96 percent of cases of high-grade serous ovarian carcinoma involve mutations of p53.
Peutz-Jeghers syndrome (PJS) is a rare condition in which affected individuals have multiple polyps in the digestive tract. Women with PJS have about a 20 percent risk of developing ovarian cancer, as well as an increased risk for skin, uterine, breast, and lung cancers. Mutations in a single gene called STK11 (at position 19p13.3) are responsible for PJS. Another rare autosomal dominant genetic condition, Gorlin syndrome, predisposes affected women to developing multiple benign fibrous tumors in the ovaries. There is a small risk that these tumors could become cancerous. The associated gene is called PTCH1 and is found on the long arm of chromosome 9 at position 9q22.3.
Symptoms
Symptoms often appear only in the later stages and include abdominal discomfort and/or pain; gas, indigestion, pressure, swelling, bloating, or cramps; ascites; nausea, diarrhea, constipation, or frequent urination; loss of appetite; a feeling of fullness even after eating only a light meal; and unexplained weight gain or loss. Other symptoms include abnormal bleeding from the vagina, hair growth, voice deepening, acne, and loss of menstrual periods in some rare stromal tumors. These symptoms may also be caused by other, less serious health conditions. Anyone with these symptoms should see a doctor.
Screening and Diagnosis
The doctor will ask about a patient’s symptoms and medical history, and a physical exam will be done. Tests may include a pelvic exam, in which the doctor will use a gloved finger to check a woman’s uterus, vagina, ovaries, fallopian tubes, bladder, and rectum. The doctor will also check for lumps or changes in size or shape.
Imaging tests that create pictures of the ovaries and surrounding tissues will show if there is a tumor. These tests include an ultrasound, a test that uses radiation to take a picture of structures inside the body; a computed tomography (CT) scan, a type of X-ray that uses a computer to make pictures of structures inside the body; a magnetic resonance imaging (MRI) scan, a test that uses magnetic waves to make pictures of structures inside the body; a lower GI (gastrointestinal) series or barium enema, an injection of fluid into the rectum that makes the colon show up on an X-ray so the doctor can see abnormal spots; and a CA-125 assay, a blood test to measure the level of CA-125, a substance in the blood that may be elevated if ovarian cancer is present.
Treatment and Therapy
Treatment depends on the extent of the cancer and a woman’s general health. If ovarian cancer is found, staging tests are done. They will help to find out if the cancer has spread and, if so, to what extent. Surgery is often the first step. Afterward, a patient will receive chemotherapy. Sometimes, radiation therapy of the abdomen is given.
In surgery, the cancerous tumor and nearby tissue will be removed. Nearby lymph nodes may also be removed. Chemotherapy is the use of drugs to kill cancer cells. It may be given in many forms, including pill, injection, and via a catheter. The drugs enter the bloodstream and travel through the body, killing mostly cancer cells. Some healthy cells are also killed. Radiation therapy (radiotherapy) uses radiation to kill cancer cells and shrink tumors. Radiation may be external radiation therapy, in which radiation is directed at the abdomen from a source outside the body. Radiation may also be intra-abdominal P32, in which a radioactive solution may sometimes be introduced into the abdomen as part of the treatment.
The more advanced the tumor at diagnosis, the poorer the prognosis. Unfortunately, 75 percent of all epithelial tumors are stage 3 or 4 at the time of diagnosis. The overall five-year survival rate is about 50 percent.
Prevention and Outcomes
There are no guidelines for preventing ovarian cancer because the cause is unknown. Symptoms also are not present in the early stages. A woman who thinks she is at risk for ovarian cancer should talk to her doctor and schedule checkups with her doctor if needed. All women should have regular physical exams, which should include vaginal exams and palpation of the ovaries.
Bibliography
Dizon, Don S., Nadeem R. Abu-Rustum, and Andrea Gibbs Brown. One Hundred Questions and Answers About Ovarian Cancer. Boston: Jones and Bartlett, 2004.
EBSCO Publishing. Health Library: Ovarian Cancer. Ipswich, Mass.: Author, 2009. Available through http://www.ebscohost.com.
Mogos, Raluca Ana-Maria, et al. "New Approaches in Ovarian Cancer Based on Genetics and Carcinogenesis Hypotheses (Review)." Experimental and Therapeutic Medicine, vol. 23, no. 6, 2022, doi.org/10.3892/etm.2022.11351. Accessed 5 Sept. 2024.
Montz, F. J., and Robert E. Bristow. A Guide to Survivorship for Women with Ovarian Cancer. Baltimore: Johns Hopkins University Press, 2005.
Wallis, Bryce, Katherine Redd Bowman, Phong Lu, and Carol S. Lim. "The Challenges and Prospects of p53-Based Therapies in Ovarian Cancer." Biomolecules, vol. 13, no. 1, 2023, doi.org/10.3390/biom13010159. Accessed 5 Sept. 2024.