Causes and Risk Factors
Immune suppression and MCC are strongly linked. Individuals whose immune systems are chronically suppressed (such as HIV patients or those who have received organ transplants and must take immune-suppressing drugs) are more than 15 times likelier to develop MCC than those who are not immunosuppressed. Merkel cell carcinoma occurs at a significantly younger age in patients with organ transplants and HIV infections; about 50 percent of MCCs in immunosuppressed patients occur before age 50.
Scientific evidence also points to a strong link between MCC and ultraviolet (UV) light exposure. MCC is highly associated with squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and Bowen’s disease (an early, superficial form of SCC), which are all most frequently caused by UV exposure. Psoriasis patients treated with UVA light and psoralens (sensitizers that strengthen the effects of UV light) have about 100 times greater incidence of MCC than the general population.
UV exposure is in fact a double threat: It not only damages the skin, increasing skin cancer risk, but also suppresses the immune system, reducing its ability to repair skin damage and recognize and fight off skin cancers and other diseases.
Along with UV radiation, transplant medications and immunodeficiency viruses such as HIV, autoimmune diseases such as rheumatoid arthritis and certain malignancies such as chronic lymphocytic leukemia or lymphomas can also profoundly suppress the immune system. Patients with these different types of immune suppression are twice as likely to die of MCC as individuals with healthy immune systems. This suggests that the immune system not only helps prevent the development of MCC but also helps keep its cancerous cells from spreading.
In 2008, scientists at the University of Pittsburgh discovered a “Merkel cell polyomavirus” — a human virus present in approximately 80 percent of MCC tumors but in fewer than 10 percent of melanomas and other skin cancers. Most people have been exposed to polyomaviruses (members of a family of double-stranded DNA viruses) by age 20. When the Merkel cell polyomavirus infects a cell, it produces proteins that may cause cells to grow (divide) out of control, promoting cancer. However, about 20 percent of MCC tumors do not have this virus, indicating that it, or its continued presence, is not required in all cases of MCC. And most people have the polyomavirus all their lives without ever developing MCC. It could be that once someone has the polyomavirus, it may take other factors such as UV exposure and immunosuppression to initiate the growth of cancer.
Deborah S. Sarnoff, MD