The Relationship Between Cancer & Heredity

Cancer is a complex set of diseases with no single common cause or cure. However, all cancers have one thing in common: They are illnesses driven by genetic alterations. Today, scientists have access to tools, such as Next Generation Sequencing (NGS), that have provided a wide-reaching understanding of cancer’s genetic underpinnings. However, with this advanced understanding has come the realization that dangerous mutations are incredibly varied. Lung cancer is a clear example: Whereas it was once categorized as small- or non-small cell, it can now be classified according to the presence or absence of dozens of genetic biomarkers. Such granular understanding of genetic mutations is critical to advancing cancer care, as it allows for treatments, such as immunotherapies, that can be targeted to individual genetic profiles.

How and why cancer-causing genetic changes take place has been the subject of intensive research for decades and will continue to be long into the future. Here, we’ll examine a subset of these factors—inherited gene mutation.

Inherited Gene Mutation vs. Acquired Mutation

In the broadest sense, cancer is precipitated by either inherited or acquired mutations. Inherited mutations are handed down from parent to child, while acquired mutations, also known as somatic mutations, are cellular deviations that occur at any point after conception. In other words, they are not inherited from a parent. Most commonly, somatic mutations involve the exonic regions of DNA that are responsible for coding proteins. Such mutations can be driven by a wide array of factors, such as tobacco use, diet, environmental exposures, and many others. These mutations are responsible for the majority of cancers and can occur in any cell.

Inherited gene mutations, also known as germline mutations, are mutations that occur in every cell of the body. In most cases, such mutations are inherited via the sperm or egg from a parent at the time of conception. Because the mutations are global, they also affect reproductive cells, allowing them to pass from generation to generation. Researchers estimate that germline mutations are responsible for approximately 5% to 10% of all cancers.

In most cases, the germline mutations that lead to cancer affect genes responsible for tumor suppression and DNA repair. For example, the presence of inherited BRCA1 or BRCA2 mutations are associated with an elevated risk for women to develop breast or ovarian cancer and an elevated risk for men to develop prostate or breast cancer.

Identifying critical germline mutations is a vital part of advancing precision medicine. Germline sequencing can be used to detect genetic risk factors in individual patients and may allow them to take preventive measures.

Challenges Associated with Identifying Cancer-Causing Genetic Mutations

A variety of challenges remain in classifying cancers by gene mutation. In many cases, a specific cancer can’t be linked to a particular cellular change and may instead be caused by a combination of interacting mutations. Additionally, genetic mutations may interact with environmental factors in countless and unpredictable ways. It’s possible, for example, for an otherwise harmless germline mutation to impede the body’s ability to suppress a potentially harmful acquired mutation. These dynamic interactions make it impossible for researchers to precisely classify many cancers by hereditary and somatic mutations. Furthermore, both acquired and hereditary factors can impact an individual’s response to a specific treatment.