Mithua Ghosh, Director – Clinical Diagnostics, HOD- Molecular and Clinical Genomics (HCG), Strand life Sciences gives an insight on how genetic testing can help estimate the risk of developing ovarian cancer
Dipti (name changed), a 29-year-old woman presented herself with persistent pelvic pain. Further examinations revealed that she had a large mass in her right ovary. With appropriate investigations, it was diagnosed to be ovarian cancer. She was immediately admitted to the hospital for surgery and subsequent treatment to manage the condition. During her treatment, she was counselled by the genetic counsellor who found a history of ovarian cancer in her family. On the maternal side, her grandmother and great grandmother were diagnosed with ovarian cancer. Based on the family history and early onset of the disease, the counsellor recommended genetic testing for Hereditary Breast and Ovarian Cancer syndrome (HBOC). The report revealed a pathogenic heterozygous mutation in the BRCA1 gene (BReast CAncer one gene). After Dipti’s reports revealed the BRCA1 mutation, her family members were also advised to undergo genetic counselling and confirmatory tests as precautionary measures towards inherited disorders. Her mother and brother were screened, and the same mutation in the BRCA1 gene was detected in them too. As a preventive measure, Dipti’s mother opted for a risk-reducing mastectomy, while her other family members were suggested to be under stringent monitoring and surveillance and report any persistent symptoms.
Germline mutations, also known as hereditary mutations, in BRCA1 and BRCA2 genes are associated with Hereditary Breast and Ovarian Cancer Syndrome (HBOC) predisposition. Individuals with mutated BRCA1 and BRCA2 genes have an increased risk of developing breast cancer, ovarian cancer (including fallopian and primary peritoneal cancers) and to a lesser extent, other cancers as well. It should be noted that HBOC caused due to pathogenic mutation in the BRCA1 gene shows an autosomal mode of inheritance, i.e. one copy of the faulty gene in an individual is sufficient to increase the risk of developing cancer. These mutations may pass from parents to the next generation, and each first-degree relative (siblings and offspring) has a 50 per cent chance of having this gene alteration.
In India, most of the ovarian cancer cases are diagnosed after they have progressed to advanced stages. Initial symptoms are mistaken and overlooked as regular feminine health issues. Studies show that the survival rate of patients diagnosed with ovarian cancer is approximately 45 per cent. Such low success rates attributed to ovarian cancer is due to late diagnosis. Almost 56.per cent of the ovarian cancer cases are diagnosed when the disease has progressed to advanced stages, which makes it difficult to manage.
A number of tests have been evaluated as potential methods of screening for ovarian cancer. Screening is recommended to start at 30-35 years of age with transvaginal ultrasounds and the blood test for the serum marker CA-125 every 6-12 months. Screening for ovarian cancer in women with family history plays an important role in identifying high-versus average-risk women. An individual’s lifetime risk of developing ovarian cancer is influenced by many factors, which include the age, family history, relationship to an already diagnosed family member, etc. In those cases, risk-reducing salpingo-oophorectomy (removal of ovaries and fallopian tubes) is recommended around 35-40 years of age or once childbearing is completed.
Genetic counselling provides a flawless knowledge about the disease condition, surveillance, genetic testing availability and implications along with proper management and risk mitigation strategies. Genetic testing helps to detect gene mutations that predispose an individual to develop ovarian cancer, and thus identify ‘at-risk’ individuals who require effective monitoring, surveillance and risk management strategies. Creating ovarian cancer awareness among women and encouraging them to go for regular screening can lead to early diagnosis of the disease, which in turn can significantly improve the survival rates with a good quality of life.
Therefore, genetic counselling and genetic testing should be strongly considered in patients with ovarian cancers, particularly if it is an early-onset disease and in the case of family history. This approach unfolds the genetic background of the patient as well the family members to a greater extent and identifies the risk of predisposition to the disease. It also enables the expanded collaborative role in patient care to support the patients and their family members through effective monitoring and surveillance programme and adoption of simple lifestyle changes, and mitigate the risk significantly.
Cancer is no longer a deadly disease; rather, it is a chronic lifestyle disease, which can be treated and effectively managed through early detection.