Bile acids in esophageal cancer?

[Guest guest]

Hi All,

CRers seem to generally have fewer difficulties with stomach acid reflux and

bile

acid abnormalities.

Previously, it had been suggested that bile acids may be implicated in colon

cancer

generation via a mechanism involving oxidative stress, in the post:

http://lists.calorierestriction.org/cgi-bin/wa?A2=ind0210 & L=crsociety & P=R56313 & X\

=3C3DD37AEF7B57A97A & Y=old542000

Now, the pdf-available below seems to implicate bile acids and reflux in

esophageal

cancer.

Stomach " acid suppression therapy should be restricted, not promoted " ?

See:

Stamp DH.

Bile acids aided by acid suppression therapy may be associated with the

development

of esophageal cancers in westernized societies.

Med Hypotheses. 2005 Aug 24; [Epub ahead of print]

PMID: 16125332

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=16125332 & query_hl=36

It was postulated that bile acids can interact with esophageal epithelia of

rats,

either by the gastro-duodeno-esophageal anastomosis operation, or by adding bile

concentrate to the diet. These interactions would cause reflux diseases and

eventually esophageal cancer. Rats gastrectomized and jejunostomized to allow

bile

acids to reflux into the esophagus developed many carcinomas in 50 weeks, while

other modifications that kept bile out of the esophagus did not produce any

carcinogenesis, thus supporting the hypothesis. Therefore, we conclude that bile

acids refluxing into the esophagus of humans should also cause cancers,

especially

in Westernized societies with their high fat diets, which provide an abundant

supply

of bile. Bile acids can enter the model OE33 cells and activate the oncogene

c-myc

at pH 4, the gene complex NF-kappaB at pH 6.5, and start proliferation at

neutral

pH. 50% of Barrett's metaplasia contained activated c-myc, and 40% of Barrett's

Esophagus patients contain activated NF-kappaB. Since normal human esophageal

epithelia contained neither activated c-myc nor NF-kappaB, these activations

must

also occur in Barrett's patients. Acid suppression therapy is used to treat

these

patients, and will solubilize free bile acids and some of the glycine

conjugates,

allowing them to enter the epithelia. Taurine conjugates (20% of bile) will also

enter the epithelia unaffected by acid suppression therapy. All these

internalized

bile acids will start carcinogenesis. Therefore, techniques to keep bile acids

out

of the stomach, or prevent them from reacting, must be developed, but until

then,

acid suppression therapy should be restricted, not promoted.

Al Pater, PhD; email: old542000@...

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