Researchers may have found a genetic reason why people with red hair have a 10-to 100-fold higher frequency of melanoma.
Red hair and light skin is caused by a mutation in the melanocortin-1 (MC1R) gene receptor, and a mouse model suggests that the same mutation promotes an important cancer-causing pathway.
Previous work by some of the same researchers showed that MC1R plays a key role in protecting melanocytes from UV-induced DNA damage. A new study found that the mutation MC1R-RHC promotes the PI3K/Akt signaling pathway when a red-haired individual is exposed to ultraviolet radiation. PI3K/Akt is a cancer-causing pathway involved with other cancer of the breast, ovaries and lungs.
The findings appeared in Molecular Cell.
Cell cultures and mouse models showed that in normal circumstances, MC1R binds to the tumor suppressor gene PTEN. A lack of PTEN results in elevated signaling in the cancer-causing P13K/Akt pathway. MC1R-RHC mutations found in people with red hair lacked this protective mechanism, so UV-B exposure resulted in an increased destruction of PTEN in the mutated pigment cells.
Researchers also found that elevated PI3K/Akt activity in MC1R-RHC pigment cells was boosting cell proliferation and was synchronizing with another well-known cancer mutation in the BRAF gene that is found in nearly 70% of human melanomas.
Researchers said in a press release that drug inhibitors that target the PI3K/Akt signaling pathway could be used in combination with a drug that targets the BRAF oncogenic protein, to treat melanoma patients who have both BRAF and MCIR variants.