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Greys and Melanoma

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greenlich
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Greys and Melanoma
Hi, There is a discussion going on about this on another forum i am part of, so just wondering what the research says and thought this would be the best place to get the facts :) What is being said: - Homozygous greys are more likely to get melanoma and die from it young - Homozygous greys with a/a are more likely to get melanoma and die from it young - Homozygous greys go grey/white faster than heterozygous greys - Breeding homozygous grey to homozygous grey gives increased risk of melanoma and dying from it young. Looking for any research or info anyone may have or know of. Thanks, Di
RiddleMeThis
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Re: Greys and Melanoma

Hi,
There is a discussion going on about this on another forum i am part of, so just wondering what the research says and thought this would be the best place to get the facts :)

What is being said:
- Homozygous greys are more likely to get melanoma and die from it young
- Homozygous greys with a/a are more likely to get melanoma and die from it young
- Homozygous greys go grey/white faster than heterozygous greys
- Breeding homozygous grey to homozygous grey gives increased risk of melanoma and dying from it young.

Looking for any research or info anyone may have or know of.
Thanks, Di

The facts are just about true except the "die from it young" part. There was no research done (AFAIK) on death, just the melanoma part.

Homozygous grays ARE more likely to get melanomas.

Greys that are "aa" are more likely to get melanomas in general not just Homozygous ones. Though with the fact that Homozygous Grays get more melanomas already it would seem that being HZ and aa would increase it more.

Homozygous do on average gray faster than heterozygous grays.

Homozygous gray to homozygous gray will ALWAYS give you a homozygous gray which do get more melanomas, but its not because they are out of two homozygous parents but because off the fact that they themselves are homozygous gray.

Its all in the grey paper which I believe is in a stickied thread in this forum.

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lipigirl
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Re: Greys and Melanoma

Hi, we have bashed this out before but all I can tell you is that in my experience with Lipis whom are mostly Homozygous for grey and a lot are bay - very few have melanomas, they are long lived and they go grey at different rates, I had one nearly at the flebitten stage as a yearling and another still with dark mane and tail aged 10 - have seen some in late teens with a lot of colour still on them too - that's all I know.

Monsterpony
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Re: Greys and Melanoma

What RMT said. I have studied grey pretty extensively and, in one of the biggest studies, it was found that there was no difference in performance in older horses with melanomas. While there are rare instances of horses developing melanomas at young age, melanomas rarely cause any sort of problem until late teens or older.

.

greenlich
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Re: Greys and Melanoma

Thanks everyone.
So melanoma in grey horses don't cause early death?
Has there been any research done on melanomas in related horses causing early death?
Thanks, Di

rodeoratdogs
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Re: Greys and Melanoma

That grey Arab mare was starting to get some when I sold her, but from what I understand the tumors don't usually go internal and spread to other organs like in humans, so unless they get in the way of somthing fuctional like the anus(which would require surgery just to remove) then somtimes they can live a long life with them, is that true?
Just a note also, the lady I sold her too in 2005 is still in touch with the woman she sold her to, and she is still riding her and enjoying her and the mare should be about 20 now.

Third Peppermint
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Re: Greys and Melanoma

I heard that fleabitten greys were more likely to be heterozygous than homozygous. I think there was also a theory or idea that the fleabites were caused by the grey gene failing, or being corrected in those cells/areas/whatever, which was why they were more likely in heterozygotes.

Has anyone else heard this?

// fleabite derail - this thread was about melanomas

Back on track, I have heard the thing about aa greys and heterozygous vs homozygous and melanomas as well. I have heard nothing about the early death part, though!

RiddleMeThis
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Re: Greys and Melanoma

Melanomas can cause death, but they can also be completely (or at least mostly) harmless.

The gray paper didnt do any research on whether HZ grays were more likely or less likely to die from their melanomas.

And yes Third Peppermint, fleabitten grays are more likely to be heterozygous than homozygous.

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Re: Greys and Melanoma

Thanks everyone.
So melanoma in grey horses don't cause early death?
Has there been any research done on melanomas in related horses causing early death?
Thanks, Di

You can't say don't definitively, but they very rarely cause death in young horses.

That grey Arab mare was starting to get some when I sold her, but from what I understand the tumors don't usually go internal and spread to other organs like in humans, so unless they get in the way of somthing fuctional like the anus(which would require surgery just to remove) then somtimes they can live a long life with them, is that true?

Grey horse melanomas are completely different from the common human melanomas. Human melanomas are linked to UV exposure. Grey melanomas, which are different from other horse melanomas as well, are actually more similar to the human benign blue nevi tumor. Occasionally, grey melanomas occur in areas that lead to death (spinal cord) or grow large enough to cause physical problems. I have helped in the removal off the sheath and pen-is of a gelding that was having difficulty dropping to urinate. I have also seen cases where the melanomas around the rectum were impeding defecation and had to be resected. Those are definitely in the minority and most grey horses have little difficulty compensating for the masses. The research study I mentioned earlier looked into hundreds of Lipizzaners and found no change in performance ability even in older age based on melanoma presence.

.

rodeoratdogs
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Re: Greys and Melanoma
Thanks everyone.
So melanoma in grey horses don't cause early death?
Has there been any research done on melanomas in related horses causing early death?
Thanks, Di

You can't say don't definitively, but they very rarely cause death in young horses.

That grey Arab mare was starting to get some when I sold her, but from what I understand the tumors don't usually go internal and spread to other organs like in humans, so unless they get in the way of somthing fuctional like the anus(which would require surgery just to remove) then somtimes they can live a long life with them, is that true?

Grey horse melanomas are completely different from the common human melanomas. Human melanomas are linked to UV exposure. Grey melanomas, which are different from other horse melanomas as well, are actually more similar to the human benign blue nevi tumor. Occasionally, grey melanomas occur in areas that lead to death (spinal cord) or grow large enough to cause physical problems. I have helped in the removal off the sheath and pen-is of a gelding that was having difficulty dropping to urinate. I have also seen cases where the melanomas around the rectum were impeding defecation and had to be resected. Those are definitely in the minority and most grey horses have little difficulty compensating for the masses. The research study I mentioned earlier looked into hundreds of Lipizzaners and found no change in performance ability even in older age based on melanoma presence.

Interesting, so are the grey melanomas always benign or can they become malignant? Or when a horse has a malignant tumor would it be a different kind of tumor alltogether?

Monsterpony
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Re: Greys and Melanoma

Grey melanomas are very, very rarely malignant. Most often they are benign, space occupying masses. As to your second question, malignancy is a process that occurs with cancer, so any cancerous mass can become malignant; each kind of cancer has a different likelihood of becoming malignant. Some cancers, like leukemia, are malignant by definition. Others commonly become malignant such as osteosarcoma. Non-grey melanoma in horses also has a high likelihood of developing into malignancy.

.

rodeoratdogs
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Re: Greys and Melanoma

Thanks MP, very interesting and good to know.

lipigirl
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Re: Greys and Melanoma

Wow MP where was the study done on Lipis as I had not heard of any here - but then there are only about 150 in the UK ? Also, I've found lots and lots of Fleabitten Lipis, and most I would have thought would be Homozygous so I am also now very confused ! Infact all the Lipis I owned (10) had fleabites if they had gone grey and although I knew we had a pure black Conversano stallion in the UK I don't believe he had parented any of my horses.....non-grey Lipis are flipping rare as you know. Would love to see a copy of the study if you have one anyways.

Hey What The
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Re: Greys and Melanoma

I find this very interesting reading as I recently had to PTS a 9 y/o grey arab gelding that was absolutely riddled with cancer, to the point where he could not even defecate properly. Another aged grey arab mare (20 y/o) had cancerous growths all along her neck/throat region and died out in the paddock, unsure if it was the cancer that killed her but considering the massive amount I suspect so. Another grey arab mare I have (21 y/o) is, apart from being old lol, perfectly fine. Another thing I find interesting is that from what I have read and I am a complete novice on the grey gene lol is that grey champagne horses do not appear to have the same cancer issues as one that does not carry champagne. So how does that work :)

lipigirl
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Re: Greys and Melanoma

Just wondering if the amount of Flebites makes a difference - one of my Lipi mares for instance had very few fleabites but was still fleabitten whereas the other had a lot - but as I've said before pretty sure they were homozygous. :?

Threnody
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Re: Greys and Melanoma

I've heard a theory that fleabites are likely caused by a separate modifier that only visibly expresses when gray is present. I can see homozygous gray being more likely to reduce the fleabites that are able to express.

Monsterpony
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Re: Greys and Melanoma

Lipi, this is the study I referenced:
Seltenhammer MH, Simhofer H, Scherzer P, et al. Equine melanoma in a population of 296 grey Lipizzaner horses. Equine Veterinary Journal. 2003;35(2):153-157.

Other papers I used in my thesis related to greys and melanomas:
García-Barona V, Rodríguez M, Pena L, Castano M, Rodríguez A. Grey Horse Melanotic Condition: A Pigmentary Disorder. World Equine Veterinary Meeting. 1997;17(12):677-681.

Fleury C, Bérard F, Leblond A, et al. The Study of Cutaneous Melanomas in Camargue-Type Gray-Skinned Horses (2): Epidemiological Survey. Pigment Cell Res. 13:47-51.

Fleury C, Bérard F, Balme B, Thomas L. The Study ofCutaneous Melanomas in Camargue-Type Gray-Skinned Horses (1): ClinicalPathological Characterization. Pigment Cell Res. 13:39-46.

Pielberg G, Mikko S, Sandberg K, Andersson L. Comparative linkage mapping of the Grey coat colour gene in horses1. Animal Genetics. 2005;36(5):390-395.

Rosengren Pielberg G, Golovko A, Sundström E, et al. A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse. Nat. Genet. 2008;40(8):1004-1009.

Rieder S, Stricker C, Joerg H, Dummer R, Stranzinger G. A comparative genetic approach for the investigation of ageing grey horse melanoma. J. Anim. Breed. Genet. 117:73-82.

Henner J, Poncet P, Guérin G, et al. Genetic mapping of the (G)-locus, responsible for the coat color phenotype "progressive greying with age" in horses (Equus caballus). Mammalian Genome. 2002;13:535-537.

Rieder S, Taourit S, Mariat D, Langlois B, Guérin G. Mutations in the agouti (ASIP), the extension (MC1R), and the brown (TYRP1) loci and their association to coat color phenotypes in horses (Equus caballus). Mammalian Genome. 2001;12(6):450-455.

Seltenhammer MH, Heere-Ress E, Brandt S, et al. Comparative Histopathology of Grey-Horse-Melanoma and Human Malignant Melanoma. Pigment Cell Res. 17:674-681.

LeRoy BE, Knight MC, Eggleston R, Torres-Velez F, Harmon BG. Tail-base mass from a "horse of a different color". Veterinary Clinical Pathology. 34(1).

.

Monsterpony
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Re: Greys and Melanoma

I may have posted this before, but this is the section from my thesis pertaining to grey and melanoma.

Gray: Melanoma

The gray color is found in almost every breed of horse recognized around the world. There are even breeds that are composed almost solely of gray horses, such as the Spanish Pure Bred and the Lipizzaner.1-4 Gray horses are generally born a base color such as black, bay* or chestnut*, but will eventually lose their color and become white with age (figure 1).5 This can happen quickly, with the rare foal displaying gray hairs at birth, or a horse may reach its 20s or 30s and still not be fully white. The skin of the horse will stay dark as the hair coat lightens, distinguishing this color from white markings under which the skin is pink, though gray horses often develop areas of vitiligo* (figure 2).5,6 Gray horses also commonly develop little dark spots of color throughout their coat as they gray called flea-bites (figure 2). Gray foals often have signs that they will eventually gray early in life, such as gray “goggles” of white hair around their eyes or an unusually dark base color.6 For example, black foals are normally born a mousey gray color that darkens after they shed while a black-based gray foal can be born a dark, jet black (figure 3).

The gene that is responsible for the gray coat color is located on equine chromosome (ECA) 25 and is a cis-acting regulatory mutation caused by a duplication* in intron* 6 of the STX17* gene.6 The duplication is in a highly conserved area of the chromosome and likely only occurred once in the history of the horse.5 This duplication is a mutation that has not been identified any other species.7 The gray allele* is dominant*, meaning for a foal to gray, one parent must be gray.5,6 Gray is epistatic* to all other colors except white, meaning that the actions of the mutation will mask the effects of all other coat color genes once the horse has fully grayed.8 This mutation is thought to cause excessive melanocyte proliferation, explaining why the young gray horse tends to go through a stage of a heavily darkened coat. Once the melanocyte pool has been depleted, the horse then begins to whiten from lack of pigment production. This process appears to occur faster in horses homozygous* for the gray allele, and homozygous grays are statistically more likely to develop vitiligo and melanomas. Horses that are heterozygous* for the gray allele are statistically more likely to develop the flea-bitten coat pattern (figure 4). An interesting finding by researchers involves the ASIP* allele that is responsible for the bay coat color. Bay is the result of a dominant agouti* allele (A) restricting the expression of black pigment on a horse that carries the dominant extension* allele (E). Horses that carry the mutation at the ASIP locus that codes for the non-bay coat color (a) are statistically more likely to develop melanomas, indicating that the MC1R,* the gene that codes for the extension alleles, which ASIP acts to null, promotes melanoma as it is a pro-pigment signaling gene.6,9

The melanomas that are found on gray horses were at one time thought to be non-neoplastic collections of pigment, but recent histological and immunohistochemical research has identified them as a unique, slow to metastasize, highly differentiated tumor (figure 5). These tumors most closely resemble the human blue nevi tumor rather than the human cutaneous melanoma.1,2,5,10 They are encapsulated and tumor cells are only seen in the dermal-epidermal junction in the rarely occurring ulcerated gray horse melanomas.2,10 On histology, the melanoma has central, jet black pigment cells and peripheral highly proliferating melanocytes.10 The development of gray melanomas is due to age-related pigment changes. A study of equine melanomas found there to be three forms; the benign gray horse dermal melanoma, malignant gray horse dermal melanoma and anaplastic malignant melanoma of solid-colored horses.10 The malignant form of the gray horse melanoma is uncommon as is melanoma in solid-colored horses. Anaplastic malignant melanomas experience accelerated tumor growth and metastasis, a distinct contrast to the benign gray horse melanoma.7,11,10 It is thought that, since gray horses commonly develop melanomas, but rarely have problems due to malignancy, the gray gene may be protective against malignancy.1,7

By age 15, 80% of gray horses will have developed dermal melanomas.10 Melanomas in gray horses tend to develop in specific sites, most commonly under the tail root, on and around the anus, in the perineum and on the genitals, lips, eyelids and parotid glands.1-4,10 They present as small, smooth, raised black nodules or plaque-like lesions that generally enlarge over time (figure 6).2,4,10 The common locations for tumor development are well-shielded from sunlight and are not UV-radiation exposure related.3 These tumors are fairly innocuous and were found to rarely hinder athletic performance.1 The more common complication arises due to increasing size of the benign tumor such as an anal or perineal tumor becomes so large that it hinders normal defecation. When a gray horse melanoma becomes malignant, they tend to metastasize to regional lymph nodes and occasionally to other organs such as spleen, liver and lungs (figure7).1,2,4,10

.

NZ Appaloosas
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Re: Greys and Melanoma

Thanks everyone.
So melanoma in grey horses don't cause early death?
Has there been any research done on melanomas in related horses causing early death?
Thanks, Di

From what I remember when the grey research was first released was that greys die "younger" (on average) than non-grey horses, but it wasn't as young horses, more like their expected life span (on average) was 5 or 6 years less than non-greys' expected life span (on average).

Diane

lipigirl
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Re: Greys and Melanoma

But that also does not make sense as Lipis live to a right old age on average ! :?

NZ Appaloosas
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Re: Greys and Melanoma

Except it could be that, without the grey gene, Lipis would, on average live another 5 or 6 years longer ;-). From discussions with Rebecca and Sheila when they were here about this, it was along the lines of "average horse life span around 30-32 years, greys' average life span around 25-27 years"...that's still a long overage life span.

Diane

Heather
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Re: Greys and Melanoma

our last filly born from a chestnut mare and grey stallion was born with a melanoma on her shoulder that we had removed and my other grey pony here we just PTS last year was 30 and full of melanomas all over her, genitals were a wreck to look at .

lipigirl
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Re: Greys and Melanoma

Thats what I mean...it's not at all unusual to have Lipis living to 30 odd and some perform in the Spanish Riding School in thier late twentys. ;-)

NZ Appaloosas
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Re: Greys and Melanoma

so maybe without the grey gene, they'd have lived (on average) to 40ish.

Diane

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Re: Greys and Melanoma

I'm concerned about melanomas. I checked Mist for them when we bought her, but I don't think I've ever really checked Jazz. I'm pretty sure both Mist was hetero (I dont know why I think mist was, other than she still had very dark points till she was around 8 or 9). Jazz is certainly heterozygous, unless something strange happened haha! She looks way too much like her daddy for that to be true though!
Don't they usually appear beneath the tail?

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accphotography
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Re: Greys and Melanoma

Under the tail and under the neck. Some around the cheeks.

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NZ Appaloosas
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Re: Greys and Melanoma

Thats what I mean...it's not at all unusual to have Lipis living to 30 odd and some perform in the Spanish Riding School in thier late twentys. ;-)

The other thing, aren't a fair few of the Lipis bay-base under their grey? I recall the paper pointing out that greys with agouti seemed more "immune" to the melanoma effect than non-agouti greys.

Diane

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Re: Greys and Melanoma

I thought most of the Lipi's were black based? Maybe being such a grey based breed they got a slightly better immunity bred into them, to grey cancer, than some breeds?

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Re: Greys and Melanoma

Do bad there isn't a large non-gray population of Lipi's to compare.

lipigirl
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Re: Greys and Melanoma

Yes a LOT are bay based...you do get the odd chestnut but most are bay and then black too....used to know the most stunning Black Lipi stallion - he was gorgeous !

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Greys and melanoma

Good news. My grey Arabian mare, nearly pure white and with melanoma since age 12  is now nearly 30 years old. She did lose her tail, and it's recently caused deafness, but she continues to be a trouble-free wonderful trail horse- I just don't use a bit in her mouth. I'd say it has not shortened her life yet. Very few fleabites, probably homozygous.