[dlaxague]

I don't know why it happens but again, I wrote a long reply and when I hit submit, I was re-directed to sign in before posting (but I had already signed in), and the post disappeared. Sigh. Usually I give up at that point but this topic is really intriguing so I'll try again.

I am confused by the discussions. My understanding is that there is fairly good evidence that something about ESA's decreases survival in at least some cancer patients. The reason for that could be related to the increase in Hg, to the possible growth-stimulating effect if there are epoetin receptors on the cancer cells, or to something not-yet-understood.

The best evidence for the above seems to come from studies that took the observation that cancer cells that were operating in a hypoxic manner were resistant to chemo and rads, and they looked at the possibility that increasing Hg. might counteract that resistance. But weren't those cancer cells choosing hypoxia? Weren't they choosing not to use the already-available oxygen? Then why would increasing Hg (which is not necessarily the same as increasing oxygen) change the way they functioned? The reason that they thought that might make a difference is my first area of confusion.

Then there's my anemia/hypoxia confusion. Anemia is not the same thing as hypoxia. Anemia is less-than-normal numbers of red blood cells. Hypoxia is decreased oxygen levels in tissue. Red blood cells carry oxygen to the tissues, so sometimes these two things correlate, sometimes not. I do not think that people who are mildly anemic (Hg 10 to 12) have decreased oxygen delivery to their tissues - the body adapts pretty well, especially when the changes are gradual. Otoh, the people who DO have significantly decreased levels of oxygen in blood and tissue are those with chronic lung disease, and they typically do not raise their Hg much, to try to compensate (hmm - 'wonder why not?). Nor, to my knowledge, do they have a difference in their incidence of cancer.

So if the link in decreased survival were r/t purely to Hg levels, surely by now this would have been noticed, r/t Hg levels or to oxygenation, independent of ESA administration.

It seems possible that ESA's, while stimulating red cell production, might also stimulate angiogenesis. That could be one factor in this phenomenon.

And then there's the altitude discussion. There is less oxygen in the air at higher altitude and so over time (not days - I think it's more like months), people living at altitude produce a few more red blood cells, to compensate. This compensation, however, means that they that have exactly the same oxygen levels in their blood and available to their tissues - so why would that make a difference to cancer? Someone posted that it's well know that there's less cancer at altitude. I didn't know that. Can you post references, please?

I have more to ramble about but this is too long already. I'll save further comments for responses to other's thoughts on this.

Debbie Laxague