SNP Shot: Genomic Insights

Parathyroid cancer is a rare malignancy that typically arises in individuals in their 40s and 50s. It develops in one of the four parathyroid glands, which are located in the neck. These glands produce parathyroid hormone, which plays a crucial role in regulating calcium levels in the blood by increasing its release.

Approximately 90% of parathyroid cancer cases are characterized by elevated levels of parathyroid hormone (hyperparathyroidism) and calcium (hypercalcemia) in the blood. These cases are classified as hormonally functional because the cancerous parathyroid glands overproduce the hormone.

Many individuals with hormonally functional parathyroid cancer experience hypercalcemic crisis, a condition marked by severely high calcium levels in the blood. This can lead to neurological issues like mood alterations and depression. About 30% of hypercalcemic patients caused by parathyroid cancer develop kidney and skeletal problems. These include increased urination (polyuria), calcium deposits in the kidneys (nephrocalcinosis) leading to kidney stone formation (nephrolithiasis), bone pain, bone density loss, and increased susceptibility to fractures. Other common symptoms are abdominal pain, inflammation of the pancreas (pancreatitis), digestive tract sores (ulcers), nausea, vomiting, weight loss, and fatigue.

The remaining 10% of parathyroid cancer cases are classified as hormonally nonfunctional, meaning that parathyroid hormone and calcium levels are within the normal range. Symptoms in these cases arise from the tumor's physical obstruction of nearby structures in the neck, causing difficulty swallowing (dysphagia), slurred speech (dysarthria), a hoarse voice, shortness of breath (dyspnea), or vocal cord paralysis.

Up to 85% of individuals diagnosed with parathyroid cancer survive for at least 5 years after diagnosis. However, the cancer recurs in about half of these individuals. If recurrence occurs, it typically happens within 3 years of the initial diagnosis, and approximately 78% of those with recurrent cancer survive at least 5 years. Hormonally nonfunctional parathyroid cancer has a lower survival rate as it is often detected at a later stage due to the absence of early warning signs like elevated calcium and parathyroid hormone levels.

In hormonally functional parathyroid cancer, death is usually a consequence of organ failure, most often kidney failure, resulting from prolonged hypercalcemia rather than directly from the tumor itself. Conversely, in hormonally nonfunctional parathyroid cancer, death typically results from the tumor's direct effects, such as its impact on the function of adjacent structures or its spread to distant tissues (metastasis).

Inheritance:

Most parathyroid cancer cases are not linked to inherited genetic factors. These cancers are usually associated with somatic mutations, which occur during a person's lifetime and are not passed down through families.

A predisposition to parathyroid cancer caused by a germline mutation is generally inherited in an autosomal dominant manner. This means that inheriting just one copy of the altered gene in each cell is enough to increase a person's risk of developing the tumor. It is important to understand that individuals inherit a higher chance of developing cancer, not the disease itself. Not everyone who inherits a cancer-predisposing gene mutation will ultimately develop cancer.