From the Guidelines
Cancer does not skip generations in a genetic sense, and the appearance of skipping is often due to factors such as incomplete penetrance, variable expressivity, or chance. The concept of cancer skipping a generation is a common misconception, and it is essential to understand the genetic basis of hereditary cancer syndromes. According to the study by Kleihues et al 1, Li-Fraumeni syndrome, which is caused by germline mutations in the TP53 tumor suppressor gene, is characterized by an increased risk of developing multiple primary malignancies, including soft tissue sarcomas, osteosarcomas, breast cancer, leukemia, brain tumors, and adrenocortical carcinoma. However, this does not mean that cancer skips a generation, but rather that the risk is inherited in an autosomal-dominant pattern.
Some key points to consider:
- Hereditary cancer syndromes, such as BRCA mutations for breast and ovarian cancer, Lynch syndrome for colorectal cancer, and familial adenomatous polyposis, follow standard inheritance patterns 1.
- If a person inherits a cancer predisposition gene, they have an increased risk regardless of their parents' cancer history.
- The perception of "skipping" often results from factors like early death from other causes, preventive measures, or simply chance.
- Anyone with a strong family history of cancer should consider genetic counseling and testing to understand their personal risk, regardless of which relatives had cancer.
It is crucial to note that genetic counseling and testing can help individuals understand their personal risk and make informed decisions about their health. The study by Pasini et al 1 highlights the importance of genetic testing in identifying germline mutations associated with hereditary cancer syndromes, such as Carney-Stratakis syndrome. Therefore, it is essential to prioritize genetic counseling and testing for individuals with a strong family history of cancer, rather than relying on the concept of cancer skipping a generation.
From the Research
Cancer Skipping a Generation
- Li-Fraumeni syndrome (LFS) is a rare inherited cancer susceptibility disorder that can be passed down from generation to generation 2, 3, 4, 5, 6.
- The syndrome is associated with mutations in the TP53 tumor suppressor gene, which can increase the risk of developing certain types of cancer, including breast cancer, soft tissue sarcoma, brain tumors, and osteosarcoma 2, 3, 4, 5, 6.
- The cancer risk associated with LFS can skip a generation, as seen in a case report of a 40-year-old female who underwent genetic testing and was found to be a carrier of the TP53 gene mutation, despite her brothers and sisters' genetic tests being normal 6.
- This suggests that LFS can be inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to increase the risk of developing cancer, and that the risk can be passed down from parent to child, even if the child's siblings do not inherit the mutation 2, 3, 4, 5, 6.
Types of Cancer Associated with LFS
- Breast cancer is a common type of cancer associated with LFS, particularly in young women 2, 3, 4, 5, 6.
- Other types of cancer associated with LFS include soft tissue sarcoma, brain tumors, osteosarcoma, leukemia, and adrenocortical carcinoma 2, 3, 4, 5, 6.
- The risk of developing these types of cancer can be increased in individuals with LFS, and the cancer can occur at a younger age than in the general population 2, 3, 4, 5, 6.
Genetic Testing and Diagnosis
- Genetic testing can be used to diagnose LFS and identify individuals who are at increased risk of developing cancer 2, 3, 4, 5, 6.
- The diagnosis of LFS is typically confirmed by the presence of a TP53 gene mutation, which can be detected through genetic testing 2, 3, 4, 5, 6.
- Individuals who are found to have a TP53 gene mutation may be at increased risk of developing cancer, and may require regular surveillance and screening to detect cancer at an early stage 2, 3, 4, 5, 6.