Cancer is caused by the gradual accumulation of mutations in genes that regulate normal cell growth, proliferation, differentiation, and death. The risk of developing cancer is high in individuals who have specific mutations in important regulatory genes. Individuals who have inherited mutations in cancer associated genes have a significantly higher risk of developing cancer than the average individual. Such cancers are called hereditary cancers. Approximately ten percent of all cancers globally are caused attributed to inheriting these mutations in these specific cancer causing genes.

A cancer that is caused by a specific mutation in a gene that controls an important regulatory function is called a syndrome. Some examples of cancer syndromes and the associated mutations are:

Infection with HPV is responsible for almost all cervical cancers, 90% and 70% of anal and oropharyngeal cancers, respectively. There are 13 different types of HPV that can cause cancers. The USFDA has approved a vaccine called Gardasil 9, which protects against 9 different types of HPV. It has been shown that vaccination against HPV can significantly reduce the risk of developing cervical cancer by 90%.

  • Leukemias and lymphomas- Ataxia telangiectasia syndrome [ATM gene]

  • All cancers- Bloom syndrome [BLM gene]

  • Breast, ovarian, pancreatic, and prostate cancers- Breast-ovarian cancer syndrome [BRCA1, BRCA2 genes]

  • Colorectal cancer, medulloblastoma- Familial adenomatous polyposis [APC gene]

  • Retinal cancer, pineoblastoma, and bone and soft tissue sarcomas- Retinoblastoma predisposition syndrome [RB1 gene]

  • Pancreatic cancer- Hereditary pancreatitis/familial pancreatitis [PRSS1, SPINK1 genes]

  • Leukemias, breast cancer, glioblastoma, choroid plexus carcinoma, adrenocortical carcinoma,and bone and soft tissue cancers- Li-Fraumeni syndrome [TP53 gene]

  • Glioblastoma, colorectal cancer, and endometrial cancer- Brain tumor polyposis type I [MLH1, PMS2 genes]

  • Subependymal giant cell astrocytoma, renal angiolipomas, and cardiac rhabdomyomas- Tuberous sclerosis complex [TSC1 and TSC2 genes]

  • Tumors of the spinal cord, cerebellum, retina, adrenals, and kidneys- von Hippel-Lindau syndrome [VHL gene]

The National Cancer Institute (NCI) has issued a guideline for identifying people who are at a high risk for developing inherited cancers.

Author:Ramesh Jayaraman-Chief Scientific Officer, OncoDynamiX Lifesciences.