Significant Steps Made In Determining Susceptibility to Ovarian Cancer

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Ovarian cancer is the most lethal of all gynecological malignancies. This is in part because of the symptomology of the disease until it is at a late stage. Because of the five-year survival rate is only 45% while the actual cause of epithelial cancer of the ovary or fallopian tube is not known, studies have found about 15% are shown to be connected with the inherited genetic factors such as BRCA 1&2 mutations. The standard line of defense is surgery and treatment with platinum-based chemotherapy. Unfortunately, recurrence is high with the recurring disease resistant to further chemotherapy. Recently olaparib has shown some promise in treating BRCA 1&2 mutations that have led to ovarian cancer. It is thought this occurs along the DNA repair pathways that make the cancer cells sensitive to olaparib. The validity of the study's data was confirmed by repeated tests across different fields (Fleury et al. 2017).

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Ovarian cancer is primarily treated with chemotherapy and surgery. Recent advances in the hereditary understanding of this disease have shown a significant role for the BRCA gene. Screening for the mutations of BRCA has improved prevention and therapeutic development. Ovarian cancer is the most lethal of all gynecologic malignancies in the US. Yet despite advances in care, in 2016, 14,240 women died from the disease.

The cornerstone of chemotherapy for this cancer is platinum and taxane-based treatment. Advances in the method of administration helped to delay progression and increase survival but women sadly rarely live past five years after diagnosis. Hereditary ovarian cancer was first identified by Pierre Paul Broca in 1866 when he documented the presence of breast and ovarian cancer in his wife’s family.

Patients with mutations in either BRCA1 or BRCA 2 are at a higher risk for certain cancers compared to the general public. This study found convincing evidence of an age discrepancy for the onset of disease with BRCA 1 with the risk increased after age 40 and BRCA 2 with an increased risk after age 50. Genetic counseling should include a collection of three-generation pedigree and risk assessment based on patients’ personal and family history.

Expertise is required to give the essential elements of informed consent necessary for any cancer. Ovarian cancer screenings in high-risk populations still show relatively poor outcomes. It doesn’t help survival with the short interval between early disease and advanced stages. Improving access to genetic screening and increase in long-term treatment of patients with this insidious disease may not only help prevent the disease but also help survivability of it once it has been detected (Hodgson et al, 2018).

Those people who are carriers of the BRCA mutation face high lifetime risks of ovarian cancer. There have been a number of ovarian cancers diagnosed at the time of preventative surgery with removal of ovaries. It has been suggested in light of this information, that women before the age of 40 (preferably by 35) have their ovaries and fallopian tubes removed if they carry the BRCA 1 mutation. And the same surgery is suggested by age 45 for women with the BRCA 2 mutation. The study found the cumulative risk of ovarian cancer to age 80 was 49% for BRCA1 and 21% for BRCA 2 mutation carriers. The mean age at diagnosis was 51.6 years in women with BRCA1 mutation and 61.4 years among women with BRCA2 mutation (Kotosopoulos, 2018).

Although new mutations are described each year, few papers mention them. This study aimed to provide an overview of an important mutation of BRCA1 &2 and their importance in the fight against ovarian cancer and breast cancer. BRCA 1 & 2 are breast cancer susceptibility genes and have been shown to be indicative of high risk factors for breast cancer development. It has also been found to indicate potential occurrence of ovarian cancer in those women who carry the gene mutations.

Due to this great amount of research has been put into analyzing the degree of cancer risk associated with as many as possible BRCA mutations. However, when attempting to read the resulting research it was found many papers contained terms that result in confusion among those who are attempting to access the ever changing information. Cancer development risk adds another layer of complexity to the classification of mutations.

It has also been found with these confusing postings it makes it hard to access information of the BRCA mutations across different sources. This study identified a great need for standardization of the number of pathogenic mutations in BRCA. They also found each group of researchers developed their own methodology for cancer risk assessment with the ensuing results creating a great deal of confusion (Lopez-Urrutia et al. 2018).

Even in this day of medical breakthroughs, 14,000 women will learn they have ovarian cancer this year. And while we have made recent advances in treatment for the disease, the prognosis is still dismal. Studies have shown that less than half of newly diagnosed patients will survive five years or more. Genetic testing has found some hope in the BRCA genes in an attempt to prevent the disease from getting started.

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Mutations to genes have been found to be a major component of cancer development. Mutations can either happen spontaneously or in response to environmental damage. In some cases, this mutation can be inherited and that is why the establishment of BRCA 1 & 2 genes as indicators of an increase in ovarian cancer risk is so important. How important? Depending on the type of mutation, a woman’s risk of developing ovarian cancer before 80 years could be as high as 44% as opposed to the 1.3% lifetime risk among women without carrying one of these mutations.

But there are some misconceptions. One is that there are only BRCA 1&2 when in truth the scientists have determined there are at least 10 different mutations for BRCA 1 alone. And some of these different mutations are more likely to show up in certain patient groups. So if you have one of these 10 mutations you are considered at high risk for ovarian cancer. As for genetic testing, only one company has received FDA approval and it only searches for three of the most commonly found mutations. This means if your test is positive or negative it is best to have it double checked in a healthcare facility.

DNA inside our cells is constantly being damaged and undergoing repair. Cancer cells and tumors often occur as a result of improperly repaired DNA damage. BRCA 1and BRCA2 genes both play a part in this repair process. That is why the importance of looking for mutations of these genes to indicate patients’ risk of ovarian, breast, or other types of cancer is of such great interest (Heid, 2018).

Work cited

Fleury, H. et al. (2017). Cumulative defects in DNA repair pathways drive the PARP inhibitor response in high-grade serous epithelial ovarian cancer cell lines. Oncotarget, 8(25).

Heid, M. (2018). 7 little-known facts about ovarian cancer and the BRCA genes. Prevention. Hearst Digital Media

Hodgson, D.R. et al. (2018). Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. British Journal of Cancer.

Kotsopoulos, J. et al. (2018). Age-specific ovarian cancer risks among women with a BRCA 1 or BRCA 2 mutation. Gynecologic Oncology, 150(1).

Lopez-Urrutia et al. (2018). BRCA mutations: Is everything said? Breast Cancer Research and Treatment. Springer.

Neff, R.T. et al. (2017). BRCA mutation in ovarian cancer testing: Testing, implications and treatment considerations. Therapeutic Advances in Medical Oncology, 9(8).

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