Ovarian Cancer Mutations: How Genetic Changes Influence Risk and Treatment

At Not These Ovaries, we understand the critical importance of genetic factors in ovarian cancer. We’re committed to helping all women understand ovarian cancer mutations and how they significantly influence both cancer risk and treatment decisions.

The reality? Your genes can be your greatest ally in the fight against ovarian cancer when you know what you’re dealing with.

What Does It Mean to Have a Gene Mutation?

A genetic mutation (also sometimes called genetic alteration) is a permanent change in your DNA sequence. Think of DNA as an instruction manual written with four letters: adenine (A), thymine (T), guanine (G), and cytosine (C). When these letters get scrambled, deleted, or duplicated, it creates a mutation.

But here’s what matters most: Not all mutations spell trouble.

Mutations fall into two critical categories:

Inherited mutations (germline): These are present from birth in every cell of your body. These can be passed to your children and significantly impact cancer risk.

Acquired mutations (somatic): These develop during your lifetime in specific cells only. These aren’t inherited but can still drive cancer development.

While some mutations cause no health problems, others disrupt crucial processes like DNA repair, creating a perfect storm for cancer development. Mutations in tumor suppressor genes, oncogenes, or DNA repair genes can lead to uncontrolled cell growth and tumor formation.

Understanding Ovarian Cancer Mutations: Why Genetics Matter

Every year, tens of thousands of women face an ovarian cancer diagnosis. And while there are multiple ovarian cancer risk factors, genetic mutations play a role in determining who develops this disease and how they might respond to treatment.

Germline Mutations and Somatic Mutations

The genetic mutations discussed in this article are primarily germline mutations, meaning they are inherited and can be passed down from parent to child. These mutations can be identified through genetic blood tests or saliva tests. 

However, not all genetic mutations associated with ovarian cancer are germline; many are somatic mutations that occur within the tumor cells themselves and are not inherited. 

One example of a somatic mutation in ovarian cancer is the RB1 mutation, which is not typically included in the list of inherited mutations. It’s worth noting that some mutations, like TP53, can be either germline or somatic, depending on the individual case.

It’s crucial to understand that even if a woman tests negative for germline mutations, she may still develop ovarian cancer due to somatic mutations, which cannot be detected through standard genetic tests used for assessing hereditary cancer risk.

Somatic mutations: These are genetic changes that occur within the cells of the tumor itself. They are not present in the person’s normal, healthy cells and cannot be passed down to their children. 

Somatic mutations are acquired during a person’s lifetime and can be caused by various factors, such as exposure to carcinogens or random errors during cell division. Tumor testing, such as molecular profiling or genomic sequencing, is designed to detect these specific mutations within the tumor cells. 

Keep in mind that in most cases, a representative sample of the tumor is tested only once for somatic mutations — unless there are specific reasons to repeat the test (insufficient or low-quality sample or heterogeneity within the tumor).

Germline mutations: These are genetic changes that are inherited from a parent and are present in every cell of the body, including the tumor cells. 

Germline mutations can be identified through genetic blood tests or saliva tests, as they are present in all cells of the body, not just the tumor. While tumor testing may incidentally detect germline mutations, it is not the primary purpose of such tests. 

The distinction between somatic and germline mutations is important because they have different implications for cancer treatment and hereditary cancer risk assessment. Somatic mutations can help guide targeted therapy decisions and provide information about the tumor’s characteristics.

In contrast, germline mutations can inform a person’s risk of developing certain cancers and may prompt genetic testing for family members to determine their risk as well. 

While genetic testing for germline mutations can provide valuable information about a woman’s risk of developing ovarian cancer, it does not provide a complete picture of all possible genetic factors involved in the disease. Both germline and somatic mutations play crucial roles in the development and progression of ovarian cancer, and understanding both types is essential for comprehensive cancer care.

Common Ovarian Cancer Gene Mutations

Let’s take a closer look at different types of germline mutations associated with ovarian cancer. 

BRCA Mutations: The Most Significant Risk Factor

BRCA1 and BRCA2 genes are your cellular repair crew. When functioning normally, they fix dangerous DNA breaks that could lead to cancer. But when these genes carry harmful mutations, your repair system fails.

The numbers are striking:

• BRCA1 mutations: 39-46% lifetime ovarian cancer risk (compared to 1.3% in the general population)
• BRCA2 mutations: 10-27% lifetime ovarian cancer risk
• Recent 2024 data shows that approximately 1 in 400 women carry BRCA mutations

Learn more about BRCA testing for ovarian cancer.

Ovarian Cancer and BRCA Mutations: Practical Advice for Women

Know your family history. If ovarian, breast, or related cancers run in your family, genetic testing could be life-saving.

Consider enhanced screening. While no perfect ovarian cancer screening exists, women with BRCA mutations benefit from:

• More frequent breast imaging (mammograms and MRIs)
• Regular gynecologic exams with CA-125 testing
• Transvaginal ultrasound monitoring

Explore prevention options:

• Oral contraceptives can reduce ovarian cancer risk by up to 50% in BRCA carriers
• Risk-reducing surgery: Oophorectomy surgery or bilateral salpingo-oophorectomy can reduce risk by 85 to 95%
• Enhanced surveillance with gynecologic oncologist care

Seek support. Learning about a BRCA mutation can be emotionally challenging. Remember that this does not mean you will definitely develop ovarian or breast cancer. However, understanding your risk and exploring risk-reducing options can help you take proactive steps to protect your health.

CHEK2 Mutations: An Emerging Risk Factor

The CHEK2 gene acts as a cellular quality control manager, stopping damaged cells from dividing. When mutated, this safety system fails.

Risk profile:

• 6% lifetime ovarian cancer risk (versus 1.3% general population)
• 20 to 30% breast cancer risk (versus 12% general population)
• Often found in families with multiple cancer types

Lynch Syndrome: Beyond Colorectal Cancer

Lynch syndrome affects DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2). While known for colorectal cancer risk, it also significantly impacts ovarian cancer likelihood.

Ovarian cancer risk by gene:

• MLH1/MSH2 mutations: 6-12% lifetime risk
• MSH6 mutations: 1-2% lifetime risk
• PMS2 mutations: Risk still being studied

Women with Lynch syndrome typically develop ovarian cancer at younger ages and may benefit from early ovarian cancer hysterectomy and bilateral salpingo-oophorectomy.

Additional Risk Genes

BRIP1 mutations: 2.6 times higher ovarian cancer risk 

ATM mutations: 1.7% lifetime risk (2-3 times general population) 

RAD51C, RAD51D, PALB2: Less common but still significant risk factors

Multiple genetic mutations can increase the risk of ovarian cancer because several genes play crucial roles in maintaining the normal function of ovarian cells. Mutations in these genes can disrupt critical cellular processes, leading to uncontrolled cell growth and tumor formation. Additionally, the combined effect of multiple genetic variants, genetic heterogeneity, and gene-environment interactions can contribute to the complexity of ovarian cancer risk.

Ovarian Cancer Mutations and Genetic Testing: Your Roadmap to Risk Assessment

Keep in mind that the risk of ovarian cancer is not determined by genetic factors alone. Environmental and lifestyle factors like age, reproductive history, and hormone use can also influence risk. These factors may interact with genetic mutations to modify an individual’s overall risk of developing ovarian cancer.

When should you consider genetic testing?

• Family history of ovarian, breast, pancreatic, or colorectal cancer
• Ashkenazi Jewish ancestry
• Personal history of breast cancer before age 50
• Male relatives with breast cancer
• Triple-negative breast cancer diagnosis

Types of Genetic Testing Available

There are several types of genetic testing available for women who want to assess their risk of ovarian cancer based on genetic mutations. The choice of test depends on factors such as personal and family history of cancer, ancestry, and specific gene mutations of interest.

Single gene testing: Focuses on specific genes like BRCA1/BRCA2 when family mutations are known

Multigene panels: Test multiple ovarian cancer genes simultaneously — ideal when family history suggests hereditary cancer but no specific mutation is identified

Comprehensive cancer panels: Examine genes for multiple cancer types

Tumor testing: Analyzes cancer tissue for somatic mutations that might guide treatment

Treatment Implications: How Mutations Guide Therapy

Recent research has brought significant advances in targeted treatments for women with specific mutations:

PARP Inhibitors: These are approved for maintenance therapy in high-grade ovarian cancers with BRCA mutations, showing significant improvement in progression-free survival. However, these treatments are less effective for low-grade serous ovarian cancer.

Immunotherapy combinations: Emerging research shows the promise of immunotherapy for ovarian cancer for certain mutation types.

Targeted drug combinations: Therapies specifically designed for mutation-positive cancers are in clinical trials.

Moving Forward: Hope Through Understanding

Genetic mutations don’t determine your destiny — they inform your strategy.

Genetic testing can provide valuable information about ovarian cancer risk, but it is not perfect. Some women with mutations may never develop ovarian cancer, while others without identified mutations may still develop the disease. It’s important to note that even without ANY genetic mutations or known lifestyle risk factors, ovarian cancer can still occur. 

If it does, and you never had any risk factors or genetic predispositions, it’s not your fault. This means that testing should be combined with other risk assessment tools, such as family history and lifestyle factors, to guide individualized prevention and management strategies. However, the absence of known risk factors does not eliminate the possibility of developing ovarian cancer.

At Not These Ovaries, we’re committed to advancing genetic research for all ovarian cancer types, with special focus on the under-researched subtypes that affect younger women. Through our ovarian cancer research fund, we’re working to ensure that every woman with ovarian cancer — regardless of her specific mutation profile — has access to effective, personalized treatment.