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Does Melanoma skin cancer only affect people without P53 gene?

P53 is a tumour suppressor gene that destroys cells that become cancerous. Normally people have 2 copies of this gene.
Is it true that people who are born with 2 active functioning copies of P53 can never get malignant melanoma even if they get regular sun exposure and sun burn as the p53 instantly destroys any cancer that forms?

Reply 1

Original post
by Ambitious1999
P53 is a tumour suppressor gene that destroys cells that become cancerous. Normally people have 2 copies of this gene.
Is it true that people who are born with 2 active functioning copies of P53 can never get malignant melanoma even if they get regular sun exposure and sun burn as the p53 instantly destroys any cancer that forms?

I am no oncologist (studying oncology in my next semester) but I'll try answer this the best I can, as simply as I can...

Spontaneous mutations can happen to the P53 tumour suppressor gene AFTER birth, so no people born with functioning copies of P53 may develop cancer due to defects in the P53 system later in life.

Mutations in the P53 tumour suppressor gene are not the only cause of skin melanoma, for example "FAMMM syndrome" (CDKN2A mutation) is also a risk factor for the development of melanoma and several other cancers.

With regards to melanoma and many other cancers, environmental factors can produce damage to DNA overtime (for example, UV exposure duration and intensity in melanoma) which becomes either unrepairable or may be missed or only partially repaired by the nucleotide excision based-repair system and with time may lead to the development of cancer.

Cancer is multifaceted and we do not really know all the causes of every type of cancer unfortunately, if you want a cancer book or specific PPTs (for doctors, so its complicated even for me) I would be more than happy to share my digital copies with you.
(edited 1 year ago)

Reply 2

Original post
by $hadow
I am no oncologist (studying oncology in my next semester) but I'll try answer this the best I can, as simply as I can...
Spontaneous mutations can happen to the P53 tumour suppressor gene AFTER birth, so no people born with functioning copies of P53 may develop cancer due to defects in the P53 system later in life.
Mutations in the P53 tumour suppressor gene are not the only cause of skin melanoma, for example "FAMMM syndrome" (CDKN2A mutation) is also a risk factor for the development of melanoma and several other cancers.
With regards to melanoma and many other cancers, environmental factors can produce damage to DNA overtime (for example, UV exposure duration and intensity in melanoma) which becomes either unrepairable or may be missed or only partially repaired by the nucleotide excision based-repair system and with time may lead to the development of cancer.
Cancer is multifaceted and we do not really know all the causes of every type of cancer unfortunately, if you want a cancer book or specific PPTs (for doctors, so its complicated even for me) I would be more than happy to share my digital copies with you.

Thank you for your reply. That makes sense that both copies of p53 could be mutated throughout life meaning cancer is still possible. Since my post I also read that a protein called MDM2 increases when tissues are exposed to stress such as UV exposure or chemical carcinogens. MDM2 activates the p53 gene but too much MDM2 can block the p53 gene from being transcripted thus reducing p53’s ability to repair damage or cause apoptosis, if that makes any sense?

Reply 3

Original post
by Ambitious1999
Thank you for your reply. That makes sense that both copies of p53 could be mutated throughout life meaning cancer is still possible. Since my post I also read that a protein called MDM2 increases when tissues are exposed to stress such as UV exposure or chemical carcinogens. MDM2 activates the p53 gene but too much MDM2 can block the p53 gene from being transcripted thus reducing p53’s ability to repair damage or cause apoptosis, if that makes any sense?

Sounds about right to me, MDM2 regulates p53. My understanding of p53 and MDM2 is that the later is a negative regulator of p53 when levels are too high, preventing it from activating the transcription of its target genes involved in repair of damage and apoptosis as you already said. I always thought when DNA is damaged, p53 becomes activated and levels increase.

As I know, when p53 increases, MDM2 increases (same is true when they decrease) as a result to act as a negative feedback loop to induce degradation of p53 to regulate its function. This is a basic explanation, but the diagram I attached explains it in pictural format.

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