Melanoma articles in April issue J Investigative Dermatology

Just thinking out loud here.  Maybe this won't interest you, pass on by.  But I am the type that must try to understand these technical things.

The first article discusses MC1R, which melanocortin 1 receptor.

MC1R is one of the key proteins involved in regulating mammalian skin and hair color.

In the United States, approximately 25 percent of the population are carrying the mutated Melanocortin 1 Receptor that causes red hair. The chance of two people having a child with red hair is 1-3 in every hundred (approximately 1 in 64)

In mutant yellow-orange mice and human redheads, both with non-functional MC1R, show that both genotypes display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to morphine-metabolite analgetics. These observations suggests a role for mammalian MC1R outside the pigment cell, though the exact mechanism through which the protein can modulate pain sensation is not known. People with freckles and no red hair have an 85 percent chance of carrying the defective MC1R gene that is connected to red hair. People with no freckles and no red hair have an 18 percent chance of carrying the defective MC1R gene linked to red hair.  See more from this wikipedia article about MC1R.

So, from this information in the journal article about MC1R status which is inherited (germline), what is the relationship, if any to the non-inherited (somatic) mutations NRAS and BRAF?  My interpretation is that an inherited mutation in germline makes it less likely that a person would have a BRAF mutation of the head and neck, which has a poorer prognosis.  Whereas there was an association, not statistically signficant, that such a person with inherited MCIR variant would have a melanoma of the trunk instead.  Remember that it was an article about people who all had melanomas, so one cannot  assume any relationship between MC1R and tendency to develop melanoma from this article.

So, a person like me with freckles and no red hair would have an 85% chance of carrying the defective MC1R gene, but that does not necessarily mean people like this will get a BRAF mutation melanoma of the trunk, or any melanoma.  I got a melanoma of the trunk but don't know my BRAF status.  And  this group of people is less likely to get a BRAF mutation melanoma of the head and neck.

Just how NRAS mutant melanomas connect to the inherited MC1R status is not clear from the abstract.  We would have to see the full text article to know that presumably.  Not available free. 

Largest study to date, consisted of 375 melanoma patients, and the commentary says "This suggests a fundamental difference in pathogenesis between head/neck and truncal melanomas, which could contribute to their divergent prognoses."  Head and neck worse than trunk.

From the article abstract:

"We found that NRAS-mutant melanomas were significantly more likely from older patients and BRAF-mutant melanomas were more frequent in melanomas from the trunk. We observed a nonsignificant association between germline MC1R status and somatic BRAF mutations in melanomas from trunk sites (odds ratio (OR) 1.8 (0.8–4.1), P=0.1), whereas we observed a significant inverse association between MC1R and BRAF for melanomas of the head and neck (OR 0.3 (0.1–0.8), P=0.02)."

Fell down the rabbit hole in my search for understanding.  The internet being the rabbit hole.

http://ghr.nlm.nih.gov/gene/MC1R

Started here and then just went on and on.  Need to turn this computer off and get some fresh air.

Am trying to get hold of the full text of that recent MC1R article.  At this early stage, and my status as melanoma and genetics illiterate, it appears to me that if people with certain genetic characteristics are more susceptible to "noxious" insults (presumably being a whole range of environmental things including UV, secondhand smoke, toxic chemicals, etc), then they may develop other mutations or epigenetic features that will end in cancer of some type.  Reminds me of that statement that genetics loads the gun, environment pulls the trigger.  Can't remember now if that was being said of cancer and/or other diseases.

Fell down the rabbit hole in my search for understanding.  The internet being the rabbit hole.

http://ghr.nlm.nih.gov/gene/MC1R

Started here and then just went on and on.  Need to turn this computer off and get some fresh air.

Am trying to get hold of the full text of that recent MC1R article.  At this early stage, and my status as melanoma and genetics illiterate, it appears to me that if people with certain genetic characteristics are more susceptible to "noxious" insults (presumably being a whole range of environmental things including UV, secondhand smoke, toxic chemicals, etc), then they may develop other mutations or epigenetic features that will end in cancer of some type.  Reminds me of that statement that genetics loads the gun, environment pulls the trigger.  Can't remember now if that was being said of cancer and/or other diseases.

Fell down the rabbit hole in my search for understanding.  The internet being the rabbit hole.

http://ghr.nlm.nih.gov/gene/MC1R

Started here and then just went on and on.  Need to turn this computer off and get some fresh air.

Am trying to get hold of the full text of that recent MC1R article.  At this early stage, and my status as melanoma and genetics illiterate, it appears to me that if people with certain genetic characteristics are more susceptible to "noxious" insults (presumably being a whole range of environmental things including UV, secondhand smoke, toxic chemicals, etc), then they may develop other mutations or epigenetic features that will end in cancer of some type.  Reminds me of that statement that genetics loads the gun, environment pulls the trigger.  Can't remember now if that was being said of cancer and/or other diseases.

Just thinking out loud here.  Maybe this won't interest you, pass on by.  But I am the type that must try to understand these technical things.

The first article discusses MC1R, which melanocortin 1 receptor.

MC1R is one of the key proteins involved in regulating mammalian skin and hair color.

In the United States, approximately 25 percent of the population are carrying the mutated Melanocortin 1 Receptor that causes red hair. The chance of two people having a child with red hair is 1-3 in every hundred (approximately 1 in 64)

In mutant yellow-orange mice and human redheads, both with non-functional MC1R, show that both genotypes display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to morphine-metabolite analgetics. These observations suggests a role for mammalian MC1R outside the pigment cell, though the exact mechanism through which the protein can modulate pain sensation is not known. People with freckles and no red hair have an 85 percent chance of carrying the defective MC1R gene that is connected to red hair. People with no freckles and no red hair have an 18 percent chance of carrying the defective MC1R gene linked to red hair.  See more from this wikipedia article about MC1R.

So, from this information in the journal article about MC1R status which is inherited (germline), what is the relationship, if any to the non-inherited (somatic) mutations NRAS and BRAF?  My interpretation is that an inherited mutation in germline makes it less likely that a person would have a BRAF mutation of the head and neck, which has a poorer prognosis.  Whereas there was an association, not statistically signficant, that such a person with inherited MCIR variant would have a melanoma of the trunk instead.  Remember that it was an article about people who all had melanomas, so one cannot  assume any relationship between MC1R and tendency to develop melanoma from this article.

So, a person like me with freckles and no red hair would have an 85% chance of carrying the defective MC1R gene, but that does not necessarily mean people like this will get a BRAF mutation melanoma of the trunk, or any melanoma.  I got a melanoma of the trunk but don't know my BRAF status.  And  this group of people is less likely to get a BRAF mutation melanoma of the head and neck.

Just how NRAS mutant melanomas connect to the inherited MC1R status is not clear from the abstract.  We would have to see the full text article to know that presumably.  Not available free. 

Largest study to date, consisted of 375 melanoma patients, and the commentary says "This suggests a fundamental difference in pathogenesis between head/neck and truncal melanomas, which could contribute to their divergent prognoses."  Head and neck worse than trunk.

From the article abstract:

"We found that NRAS-mutant melanomas were significantly more likely from older patients and BRAF-mutant melanomas were more frequent in melanomas from the trunk. We observed a nonsignificant association between germline MC1R status and somatic BRAF mutations in melanomas from trunk sites (odds ratio (OR) 1.8 (0.8–4.1), P=0.1), whereas we observed a significant inverse association between MC1R and BRAF for melanomas of the head and neck (OR 0.3 (0.1–0.8), P=0.02)."

Just thinking out loud here.  Maybe this won't interest you, pass on by.  But I am the type that must try to understand these technical things.

The first article discusses MC1R, which melanocortin 1 receptor.

MC1R is one of the key proteins involved in regulating mammalian skin and hair color.

In the United States, approximately 25 percent of the population are carrying the mutated Melanocortin 1 Receptor that causes red hair. The chance of two people having a child with red hair is 1-3 in every hundred (approximately 1 in 64)

In mutant yellow-orange mice and human redheads, both with non-functional MC1R, show that both genotypes display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to morphine-metabolite analgetics. These observations suggests a role for mammalian MC1R outside the pigment cell, though the exact mechanism through which the protein can modulate pain sensation is not known. People with freckles and no red hair have an 85 percent chance of carrying the defective MC1R gene that is connected to red hair. People with no freckles and no red hair have an 18 percent chance of carrying the defective MC1R gene linked to red hair.  See more from this wikipedia article about MC1R.

So, from this information in the journal article about MC1R status which is inherited (germline), what is the relationship, if any to the non-inherited (somatic) mutations NRAS and BRAF?  My interpretation is that an inherited mutation in germline makes it less likely that a person would have a BRAF mutation of the head and neck, which has a poorer prognosis.  Whereas there was an association, not statistically signficant, that such a person with inherited MCIR variant would have a melanoma of the trunk instead.  Remember that it was an article about people who all had melanomas, so one cannot  assume any relationship between MC1R and tendency to develop melanoma from this article.

So, a person like me with freckles and no red hair would have an 85% chance of carrying the defective MC1R gene, but that does not necessarily mean people like this will get a BRAF mutation melanoma of the trunk, or any melanoma.  I got a melanoma of the trunk but don't know my BRAF status.  And  this group of people is less likely to get a BRAF mutation melanoma of the head and neck.

Just how NRAS mutant melanomas connect to the inherited MC1R status is not clear from the abstract.  We would have to see the full text article to know that presumably.  Not available free. 

Largest study to date, consisted of 375 melanoma patients, and the commentary says "This suggests a fundamental difference in pathogenesis between head/neck and truncal melanomas, which could contribute to their divergent prognoses."  Head and neck worse than trunk.

From the article abstract:

"We found that NRAS-mutant melanomas were significantly more likely from older patients and BRAF-mutant melanomas were more frequent in melanomas from the trunk. We observed a nonsignificant association between germline MC1R status and somatic BRAF mutations in melanomas from trunk sites (odds ratio (OR) 1.8 (0.8–4.1), P=0.1), whereas we observed a significant inverse association between MC1R and BRAF for melanomas of the head and neck (OR 0.3 (0.1–0.8), P=0.02)."