GENETICALLY RELATED DISEASES Debbie Martin: They were looking at H.O.D. (Hypotrophic Osteodystrophy), Panosteitis, Hip Dysplasia, and Elbow Dysplasia - all of them genetically inborn diseases. If there’s a relationship between them, it’s the relationship that we just talked about here. Others’ Questions: If we did a study and came up with a group of dogs where 30 or 40 percent had two diseases at the same time rather than 11 percent, then you could say… Dr. Padgett: Absolutely. But they’ve got to show that it’s higher than the expected ratio and they haven’t done that. At least I’ve never seen anyone that’s done that. If you have the data you can challenge some of these theories. If you have a breed that has 35 or 40 percent Hyperthyroidism, and they also have another disease, it’s like relating Cancer to Cadillacs - you can relate anything to it that you want it to relate to, because it’s in a high frequency. Debbie Martin: There’s a study I recently posted to the genetics group. A study that’s being done in Goldens started with one family, and then developed into sub-families. They started out studying Lymphoma in three generations. I think four or five dogs from the initial breeding produced 32 dogs with Lymphoma. As it went down the families, the cancers and the types of cancers were increasing until at the end of their study a male diagnosed with Hemangiosarcoma at two, produced another puppy that died at two that was diagnosed with Hemangiosarcoma, and the bitch also died of Hemangiosarcoma. Dr. Padgett: I would not link those two. One is a blood vessel disease and the other one is a circulating cell disease. I know of their Hemangiosarcoma study but I’ve not seen the report. I haven’t seen a report on the lymphoma study either. Debbie Martin: They found that with each generation the number of cancers and the kinds of cancers were increasing dramatically within the family… Dr. Padgett: So that would have to be a cancer gene that they’re talking about, not a cancer type. Debbie Martin: Like a suppressor. And it dramatically increased within two dogs through that family, following two dogs down through the family. Dr. Padgett: Because the data on Lymphoma in Bernese Mountain Dogs was pretty good, we can show it’s not genetic. You expect any disease, particularly a virus disease, to occur in more members of a household than one. If you had measles in your family then your brothers and sisters got measles. That’s the way it is. But the number of offspring produced by a given male does not correspond to a genetic disease despite the fact that more than one occurred within one family. Debbie Martin: If a family is missing a cancer suppressor gene, then you would see an increase in all cancers? Dr. Padgett: All cancers, yes. That’s exactly what you would expect. More on Cancer Debbie Martin: We’ve encountered problems with classifications of some of our diseases. Like, in the original survey, we have three cancers identified. We’ve now got many more identified. How do we deal with them when we’re calculating our breed risk? Do we put all the cancers together? Dr. Padgett: Cancer is a set of diseases that we know can be genetic or can be environmental. We list anything as environmental that’s not genetic, and that we don’t know what in the environment causes it. We just don’t know what causes it or why they show up, and it would do no good to track some of them like Lymphosarcoma, that in at least one way we know is not inherited. If it’s like the disease in cattle and the disease in cats, then it should be a virus. But they’ve not proven it’s a virus in dogs, because they’ve not isolated the specific virus like they have in cows and cats. My bet is that it probably is a virus. Dale Malony: So for the sake of history, we could track them by individual type and accumulate the data. Then if anything ever comes up that indicates one of those types is genetic, we can go through the data and say, "Ok now we’ve found the bloodlines," or we can periodically evaluate it… Dr. Padgett: Or you can use your data to determine whether or not it’s genetic. That’s what we’re doing in Bernese Mountain Dogs. We think now the Hemangiosarcomas are also inherited. That breed kept a record of the tumors and the families that those tumors were from so we can go back, and we’ve been doing that since about 1989. We now have about 65 Hemangiosarcomas. That’s the breed we also proved that Hemangiosarcoma and malignant histiocytosis are inherited. The only way you can prove that is to have enough data accumulated with the family associated including who the parents are, and how many are in the litters. Others’ Questions: How many cancers right now do you think are hereditary. Just the three, or are there other ones that could be added on? Dr. Padgett: Oh there will be others added on the list. Others’ Questions: But are there some now that we know of that we could add? Dr. Padgett: No. There’s not enough data. There are other breeds they’re studying cancer in. They’re doing a study on Hemangiosarcoma in Salukis, and they’re doing a study on Hemangiosarcoma in Golden Retrievers. The Salukis study is being done by Tom Bell right here at Michigan State, and the Golden Retrievers are being done at Minnesota. But, if you keep track of your cancers, you will soon be able to tell whether or not they follow a family. Debbie Martin Question: Now, what if you see a family that is producing a higher than normal frequency of cancer, say of any kind-of all kinds? If you’re looking down a line and you may see 10 different kinds of cancers but you’re seeing a lot of cancer in one line. Dr. Padgett: There are genes and then there is absence of genes. There are genes that prevent cancer in people. Now this is people data that we’re talking about, and if that gene is missing that family will have multiple cancers. That’s not being shown to occur in dogs yet, but that’s one of the things that we might have run into in this Bernese Mountain Dog study that we’ve been collecting cancers, and data on cancers in that breed for like 13 years now. When we first started out we did the first analysis at about seven years out. We did study cancer, and the spread/presence of cancer in that breed. About 25 percent of dogs were dying of cancer and that’s about what happens in people. About ¼ of all of us are going to die of cancer. So this last time we got to San Francisco to meet with the people in G.D.C. They had collected data for a long period of time and that’s where the data was stored for the Bernese Mountain Dog cancer. I’ve got some families battling 50 percent of cancer - half of the dogs - which is different from another set of dogs in the same breed. So there may be a cancer gene that is present or a cancer gene that is missing…an anti-cancer gene that is missing. We don’t know which yet. We haven’t really proven to my own satisfaction that this high frequency of cancer is not selection aboration. What we’re trying to do now is figure out what is "normal" for that breed? Did I stumble on a family that statistically has a higher frequency of cancer? In some families you’re going to have a higher influence of cancer without any genes involved- just by bad luck. Did I find bad luck? Or did we find a cancer problem?
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