Genetic Basis of Familial Cancer Risk: A Narrative Review

Familial cancers are caused by inherited mutations in specific genes that regulate cell growth, division, and repair. Approximately 5-10% of all cases has a hereditary character where germinal mutations in specific genes increase the susceptibility to develop cancer. Two major categories of genes involved in cancer development; tumor suppressor genes and oncogenes. Both types of genes play a crucial role in regulating cell behaviour, and when mutated, they can contribute to cancer development. In addition to genetic mutations, epigenetic changes also play a significant role in familial cancer. Epigenetics involves changes in gene expression that do not alter the underlying DNA sequence. Epigenetic changes, include DNA methylation, histone modification, and dysregulation of non-coding RNAs. There are several main inheritance patterns, each with its own characteristics. These patterns include autosomal dominant, autosomal recessive, X/Y-linked and mitochondrial inheritance. Identifying genetic mutations that increase the risk of familial cancers is a cornerstone of genetic counselling that helps families navigate the complex intersection of genetics, cancer risk, and prevention. By identifying genetic mutations early, genetic counseling can lead to better outcomes through personalized prevention, early detection, and, where appropriate, targeted treatments.