Already in the sixties the appearance of fetal proteins in cancer patients was discovered Abelev GI 1965, and
described for cancer of the liver. Up to now for many cancers fetal or embryonic proteins are described, and for
many of them it is known that they are made under the influence of progesterone, which is the typical steroid
hormone of pregnancy. But this did not lead to a search for progesterone in patients with cancer most of whom
are outside the age of pregnancy men or children.

A hint to the origin of the progesterone comes from the well known observation that many types of cancer,
most prominent breast, prostate and colon cancer were extremely rare in peoples which did not use milk as food.
That are the East Asians. Even Japanese who reach an age comparable or higher than those of Western
industrialized countries did not get much of these diseases before picking up the use of milk-based food.

That is very naive. It is possible to gain milk during pregnancy, too. And as it is possible, it is done. About 70% of the today produced milk comes from pregnant cows Rollinger M 2004 and this is the origin of the ingested progesterone Sato A 2006. Additionally to progesterone there are estrogenes in the same foodCourant F 2008 which often act synergistically in induction of tumor promoting markers.

After eating food like ice cream, cheese or butter a big increase in progesterone levels can become
demonstrated a day later in the saliva Goodson WH 2007. In rats it was shown that the mRNA, a precursor of
igf-1, a hormone linked to many kinds of tumors gets produced in the liver of rats feed with casein instead of
plant protein Miura Y 1992. But not only rats, human breast cancer tissue to start to produce igf-1 under the
influence of progesterone Milewicz T 2002.

We take it up with milk products like milk, cheese, butter or cream in cakes, sweets, drinks and so on and so it comes that children, not pregnant women and man produce fetal proteins. Not only in cancer, but especially for cancer patients the progesterone is dangerous because progesterone is an immune modulation hormone which stops the immune reactions against the embryo. Natural killer cells have progesterone receptors and the contact

J Tatarinov discoverd
alpha fetoprotein as an
antigen of hepatomas and
embryos described by

discover the Carcino
Embryonic Antigen CEA
and describe that it is a
fetal protein expressed
between the second and
sixth month of fetal life

The tumor marker CA15-3 mostly used to follow breast cancer is an embryonic protein called MUC1. MUC1 is produced under the influence of progesterone McGuckin et al. 1998, Horne AW 2006 and and protects the embryo Braymann MJ 2007

, by inhibiting cell lysis by natural killer cells Zhang K 1997. In cancer patients it stops the immune reaction against cancer cells and so the tumor is not disturbed to proliferate. CA15-3 is also up in other cancers but breast cancer for example prostate cancer where it is better known as MUC1 Li Y 2007. In Japan it is called Kl-6 and is used to monitor non small cell lung cancer Ishikawa N 2008 among others.

The more recently discovered progesterone induced blocking factor PIBF another tumor marker found not only
in cancers but also in leukemia cells, too blocks the natural killer cells Check JH 2007. Here like with other
tumor markers one finds a hint to their fetal or embryonic origin writing or reading the full name. For example
CEA the often used tumor marker in colon cancer patients is the Carcino-Embryonic Antigen.

Letter to Naomi Allen
corresponding author of
the the Epic study

many diseases like colon cancer with antibodies like bevacizumab. But as these antibodies work only against
one of many progesterone dependent proteins, the success is limited. The same VEGF associated process occurs
during late diabetes where patients suffer from aberrant vascularization of the retina resulting in blindness or
aberrant vascularization of kidney tissue resulting in the dependency on dialysis.

Of cause this process is not limited to diabetes or cancer patients which often do not live long enough to
experience it. We see the same process in the eye of otherwise healthy people. There it is called wet age-related
macular degeneration or macular edema and treated with a lot of VEGF directed antibodies Tremolada G 2007.

Others progesterone induced proteins might provoke the insulin resistance known as diabetes type 2 which we
often see in breast cancer patients during disease progression. The today produced milk is so rich in
progesterone that it induces insulin resistance, hyperglycemia and glucosuria in calves Hostettler-Allen RL

In the pregnant women this change in metabolism may be necessary to keep the glucose in the blood in favor of the fetus. But, may be, even for the pregnant women the additional progesterone from food is deleterious. Many women on Western diet develop gestational diabetes and keep it after pregnancy.

To find the diseases which might be involved one should look for progesterone dependent proteins. One easily finds VEGF in the medulloblastoma of children, of cause in breast cancer, in colon cancer, where anti-VEGF antibodies are approved for treatment and there is a wide array of other diseases. For example in the skin of persons with atopic disease there it a 25 fold increase in VEGF Zhang Y 2006

A further new discovered protein trying to make a career as a tumor marker for mesothelioma the osteopontin
is progesterone inducible too Mo SX 2007, Qu X 2008. In lung cancer its expression is linked to disease
progression Guy SY 2007

Like VEGF osteopontin is not only elevated in cancer, but in diabetes type 2 Belovici M 2007 where it is linked
to calcification of blood vessels. Prednisolone probably competing for progesterone binding sites provides a
certain relieve to osteopontin linked conditions like Erdheim-Chester disease Taguchi T 2008.