Cancer Predisposition Syndromes - An Overview

Introduction

A genetic abnormality known as cancer predisposition syndrome raises an individual's risk of acquiring cancer relative to the general population, which could contribute to an earlier age of cancer diagnosis. It is also known as inherited cancer predisposition, hereditary cancer syndromes, or family cancer predisposition. Several gene alterations or mutations increase a person's risk of contracting the disease, which can be inherited from parents. These genetic alterations can result in early or late-onset diseases and have a dominant or recessive effect.

What Are a Few Common Hereditary Predisposition Cancers?

1. Hereditary Breast and Ovarian Cancer Syndrome (HBOC) - HBOC is the most prevalent form of inherited breast cancer—gene mutations in BRCA1 (breast cancer gene) and BRCA2 cause HBOC. A woman who carries a hereditary mutation in the BRCA genes is more likely than a woman without the mutation to develop breast and ovarian cancer in her lifetime. Breast and prostate cancer are more likely to occur in a man who has a hereditary mutation in the BRCA genes at some point in his life. Pancreatic cancer, melanoma (skin cancer), and other malignancies are also more common in certain families.

2. Lynch Syndrome or Hereditary Non-polyposis Colorectal Cancer Syndrome (HNPCC) - Early onset of colorectal cancer, uterine (endometrial) cancer, and other extracolonic cancers are characteristics of HNPCC or Lynch syndrome. Mutations in DNA (deoxyribonucleic acid) mismatch repair genes (MLH1, MSH2, MSH6, or PMS2) result in Lynch syndrome. Muir-Torre syndrome, which is a varied form of Lynch syndrome, is linked to an increased risk of developing specific skin cancers.

3. Hereditary Leukemia and Hematologic Malignancies Syndromes - As per studies, genetic causes have also been identified as potential causes of leukemia and related blood disorders, including myelodysplastic syndrome (malignancies wherein immature bone marrow blood cells fail to develop into adult, healthy blood cells), acute myeloid leukemia (malignancy involving an excessive amount of immature white blood cells in the bone marrow and blood), and aplastic anemia (body fails to produce enough red blood cells).

Although extensive research on leukemia (blood cancer) patients has not yet been finished, medical professionals believe that five percent to ten percent of leukemia cases are inherited. Patients with leukemia who have a family history of the condition should think about getting tested genetically to see if there is a hereditary component to their illness. The treatment plans of a patient may be affected by this information.

1. Von Hippel-Lindau Disease - Hemangioblastomas (a tumor that develops in the blood arteries of the retina, spinal cord, or brain. It may spread and exert pressure on nearby tissues, but it is not malignant) or angiomas are the major characteristic of Von Hippel-Lindau disease (VHL) which is a multi-system disorder. Hemangioblastomas can form in the spinal cord, brain, retina, and other nervous system sections. Tumors of different types can arise in the kidney, pancreas, and adrenal gland. Additionally, those who carry VHL are more likely to acquire several cancers, including kidney cancer. It has been discovered that almost all VHL patients have mutations in the VHL gene.

2. Multiple Endocrine Neoplasia (MEN) - It tends to cause cancers of the endocrine gland in affected individuals. The endocrine system's hormones secreted into the bloodstream regulate various bodily functions. The regulation of mood, growth and development, metabolism, sexual function, and reproductive activities are all greatly supported by the endocrine system. There are currently two different MEN syndromes: MEN1 (which is usually associated with pancreatic, parathyroid, and pituitary tumors) and MEN2 (which is usually associated with medullary thyroid cancer).

3. Cowden Syndrome - Cowden syndrome (CS) is a condition marked by a higher risk for certain malignancies and numerous tumor-like growths. Small, non-cancerous growths, called hamartomas, usually affect the skin and mucous membranes in CS patients. These growths can also form in the brain or intestinal system. Moreover, there is a higher chance of developing benign and malignant malignancies of the breast, uterus, and thyroid in those with CS. Changes in the PTEN gene are linked to CS.

4. Familial Adenomatous Polyposis (FAP) - Gardner's syndrome, also known as familial adenomatous polyposis (FAP), is a syndrome that predisposes people to colon cancer. It is characterized by the development of hundreds to thousands of adenomas, or precancerous colon polyps, throughout the gastrointestinal tract, primarily in the colon, rectum, stomach, and small intestine. A milder type of FAP called attenuated FAP (AFAP) is linked to a higher risk of colon cancer but fewer colon polyps. Mutations in the APC gene are linked to FAP. Gardner’s syndrome is also characterized by the presence of desmoid (tumors of the soft tissue) and osteoma (bone cancer).

5. Neurofibromatosis Type 1 (NF 1) - Changes in skin tone (pigmentation) and the development of tumors along nerves in the skin, brain, and other body organs are the hallmarks of neurofibromatosis type 1. Affected individuals display a wide range of symptoms indicative of this illness. Mutations in the NF1 gene bring on neurofibromatosis type 1. When the NF1 gene is mutated, a nonfunctional form of neurofibromin is produced that cannot control cell division and growth. Because of this, tumors like neurofibromas can develop along nerves all over the body. The additional characteristics of neurofibromatosis type 1, such as café-au-lait spots and learning difficulties, are not well understood to be caused by mutations in the NF1 gene.

6. Li-Fraumeni Syndrome (LFS) - Li-Fraumeni Syndrome (LFS) is characterized by an increased risk of developing numerous types of cancer. It has been identified as one of the rarest genetic conditions known. It is discovered that most people with LFS have TP53 gene mutations. The cancer types most frequently linked to LFS are soft tissue sarcomas, which are the tumors that arise in the deep skin, fat, muscle, nerve, joint, blood artery, or bone, adrenal gland tumor, brain tumor, breast cancer, and lung cancer.

7. Retinoblastoma - Retinoblastoma is a condition where cancerous cells grow in the retinal tissues. A mutation (change) in the RB1 gene is indicative of retinoblastoma. The RB1 gene mutation can arise in the egg or sperm before or shortly after conception, or the child can inherit it from one parent. Trilateral retinoblastoma, as well as other malignancies, are more common in children with heritable retinoblastoma.

What Are the Key Indicators of Cancer Predisposition Syndrome?

Several crucial markers are present in families with familial cancer syndromes, which often show different patterns. These include multiple cases of the same or rare types of cancer; cancers that start earlier than is typical for that type of cancer; multiple types of cancer in a single person; cancers that occur in paired organs, like both kidneys or both eyes; childhood cancer cases that affect siblings; cancer that occurs in less affected sexes, like breast cancer in men; and continuous history of cancer over several generations within a family lineage. Together, these markers provide essential clues to initiate more research into potential cancer familial disorders.

Conclusion

Genetic testing has improved the probability of early discovery, timely treatment, and survival rate by assisting in the identification of family members at risk of cancer predisposition syndrome. Genetic testing is used to detect germline mutations, genetic mutations, and genes linked to cancer predisposition inherited from parents to their children. However, only some benefit from genetic testing, so it is crucial to consult a genetic counselor to determine whether testing is a good fit for a person. Timely intervention improves the prognosis and patients' survival rate.