Pernicious Anaemia Society
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Cancer/pernicious anemia?

When I read that people with pernicious anemia have a higher risk of developing cancer it really scared and shook me up, coming from a family that has lost many people due to cancer.

* link between damage done to the stomach’s lining by PA and gastric cancer. Regular visits and biopsies are able to check for the beginnings of cancer.*

My question is, if you are being treated for b12 and getting regular injections or tablets does this damage to the stomach lining still occur and why isn't this looked into more? or is this damage done when your b12 levels are extremely low or low?

The thought of being high risk for cancer scares me as it probably does with a lot of you guys but I am trying to fin d a silver lining in this ... are we suppose to just sit back and let it eat away our stomach living or does regular injections like I've stated take out this increased risk of cancer?

26 Replies

Yes, I'd like to know the answer to this too. I have recently been suffering from indigestion which I have never had before. Been to the docs, and even though with PA we have an increased risk of stomach cancer they won't fast track me for a gastroscopy. I have been offered one but am on the normal wait list.

Will let you know the outcome, and will ask your question too as I don't know the answer.

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You have a 2-3 times increased incidence of gastric carcinoma and gastric polyps compared with matched controls, if you have PA, and therefore in UK should be referred to a gastro if you have gastric symptoms and/or co-existent iron deficiency.


"When to refer[2]

Referral to a gastroenterologist should be considered for any patient with pernicious anaemia who has gastric symptoms and/or co-existent iron deficiency. Patients with pernicious anaemia have a 2-3 times increased incidence of gastric carcinoma and gastric polyps compared with matched controls."



When should I refer a person with vitamin B12 or folate deficiency anaemia?

•Seek urgent advice from a haematologist if the person has neurological symptoms, or is pregnant.

•Refer to a haematologist if the cause of vitamin B12 or folate deficiency is uncertain following investigations, or the suspected cause is haematological malignancy (urgently refer) or other blood disorder.

•Refer to a gastroenterologist if:

◦Malabsorption of vitamin B12 (other than due to pernicious anaemia) or folate is suspected.

◦The person has pernicious anaemia and gastrointestinal symptoms, especially if there is a suspicion of gastric cancer (for example co-existing iron deficiency). The urgency of referral will depend on the nature of the symptoms.

◦The person is folate deficient, and antibody testing suggests coeliac disease (positive for anti-endomysial or anti-transglutaminase antibodies).

•Consider referral to a dietician if vitamin B12 or folate deficiency is thought to be due to a poor diet.



In some other countries they do recommend regular endoscopies on patients with PA, but not others, the incidence is not that great, I mean getting in a car pouts you at a higher risk of getting a fatal accident, that does not mean you do not get in a car, you accept that and are vigilant. Well that is how I see it.

If you have gastric problems it is wise to see a gastro,

Kind regards,



I think the question asked, Marre was 'why?' not simply that it does.


Possible reasons; what is known (so much is still unknown, and no having B12 treatment does not alter that risk):

" Achlorhydria is associated with intestinal metaplasia, which may lead to dysplasia, and is hence considered a premalignant condition. "

"Achlorhydria may develop as a result of the following conditions:

• Antiparietal cell antibodies ◦Antibodies directed against gastric intrinsic factor results in cobalamin deficiency; this is called pernicious anemia.

◦The 2 types of anti-intrinsic factor antibodies are as follows: (1) antibodies that block attachment of cobalamin to intrinsic factor, and (2) antibodies that block attachment of the intrinsic factor-cobalamin complex to ileal receptors.

◦Clinically, highly specific anti-intrinsic factor antibodies are found in about 70% of patients with pernicious anemia. A second component of pernicious anemia is chronic atrophic gastritis that leads to a decline in intrinsic factor production. The chronic atrophic gastritis in pernicious anemia is also associated with an increased risk of intestinal gastric cancer and gastric carcinoid tumors. Clinical factors associated with autoimmune gastritis in addition to vitamin B-12 deficiency include celiac disease, neurological symptoms, and a positive family history.[10]

◦Pernicious anemia occurs in association with other autoimmune disorders.[11] In one study, autoimmune thyroid disorders were observed in 24% of 162 patients with pernicious anemia. In this condition, fundic histology is characterized by severe gland atrophy. Ninety percent of patients have antibodies directed against the H+/K+ -ATPase pump. In these patients, achlorhydria leads to pronounced hypergastrinemia (>1000 pg/mL) with subsequent hyperplasia of gastric ECL cells. Gastric carcinoid tumors develop in 3-5% of patients.

◦Parietal cell antibodies are found in 20% of patients with type 1 diabetes, denoting autoimmune gastritis, achlorhydria, and pernicious anemia. This condition may predispose to ECL cell proliferation and gastric carcinoid tumors. "


"Autoimmune atrophic gastritis

Autoimmune atrophic gastritis is associated with serum anti-parietal and anti–intrinsic factor (IF) antibodies. The gastric corpus undergoes progressive atrophy, IF deficiency occurs, and patients may develop pernicious anemia.[25]

The development of chronic atrophic gastritis (sometimes called type A gastritis) limited to corpus-fundus mucosa and marked diffuse atrophy of parietal and chief cells characterizes autoimmune atrophic gastritis. In addition to hypochlorhydria, autoimmune gastritis is associated with serum anti-parietal and anti-IF antibodies that cause IF deficiency, which, in turn, causes decreased availability of cobalamin, eventually leading to pernicious anemia in some patients. Hypochlorhydria induces G-Cell (Gastrin producing) hyperplasia, leading to hypergastrinemia. Gastrin exerts a trophic effect on enterochromaffin-like (ECL) cells and is hypothesized to be one of the mechanism leading to the development of gastric carcinoid tumors (ECL tumors).[26, 27] "



Gastric cancer may often be multifactorial, involving both inherited predisposition and environmental factors.[8] Environmental factors implicated in the development of gastric cancer include diet, Helicobacter pylori infection, previous gastric surgery, pernicious anemia, adenomatous polyps, chronic atrophic gastritis, and radiation exposure

Pernicious anemia

Pernicious anemia associated with advanced atrophic gastritis and intrinsic factor deficiency is a risk factor for gastric carcinoma.


I'm sure there is lots more, but the above shows some details and also that its not all fully known why.

I hope this helps,



Yes, the problems are that:

A) B12 deficiency, as we are well aware, is not PA. Or at least it isn't considered as being as 'important' or as 'serious' - yet that article contradicts that.

B) No one gets tested for stomach acid - there is no recognised test in Europe

C) No one gets treated for low stomach acid.

So, is it that PA is linked to increased chance of stomach cancer, or is it that B12 deficiency is linked to an increase chance of stomach cancer?

...and that article does mention that people suffering from achlorhydria also have auto immune. But the tests for auto immune, are, at best, 50% wrong.

By focusing on PA as being the most important or severe, a huge group of very sick people are getting overlooked.

Which is why, when I took my test into the doctor (in fact more than one) saying I had low stomach acid, she wrote in my notes that 'I' think I 'have something else now' and that 'I' am 'investigating it'. And it's also why I now have a doctor jumping up and down wanting to know why endoscopies and biopsies haven't been performed.

The lines between PA and B12 deficiency must be merged.

Thanks for that particular link because I hadn't seen it.


Small stomp.

Why, if Marre can nip off in a few minutes and find this research, have I been subjected to doctors sitting opposite me with a stupid smirk on their faces when I handed them the test result for low stomach acid?

Why do they simply give it me back when they clearly don't understand the implications of it?

Why have they watched my weight fall from 57kg to 42kg and still sit there grinning at me and blaming it on my diet, which there is absolutely nothing wrong with apart from the fact I can only eat little and often, when it is quite clear I have malabsorption issues and heaven only knows what else going on in my gut?

Marre can find it in a few minutes...doctors won't even look!

How on earth can we possibly trust anything doctors say or do (or not do, as the case may be)

And, if you knew all the above and tried to tell doctors how important it is and why you need stuff doing - they write in your notes that you're crazy and are 'investigating it'.

Tell you what, you overpaid, lazy, obnoxious so and so's, why don't you investigate it - it's your job!!!

Stomp over.


Its not all doctors Poppet, you just have had a very bad experience. My two GP's knew, haematologist knew, gastro knew, they were all for me to see a gastro..


Three, Marre, three bad experiences - excluding the neurologist who didn't know what B12 deficiency does.

And if they do know what they are doing, why are there so many people coming to the site?

And what test did you have for stomach acid?

Considering the implications on the pancreas and bile production...

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In fact Marre let's cut through it - if the relationship between low b12 and low stomach acid is well known, how many on this site can say they've had their stomach acid levels checked - and the result - and what treatment they've had?

Me. I can tell you what test I had and what the result is and what the implications are.

Anybody else?


...and, over 100 years ago they knew about the link between B12 deficiency and low stomach acid - 100 years and the message still hasn't got through.

Every single patient with PA (and it was called PA because they didn't know what caused it NOT because of autoimmune or anything else. How I wish they'd stuck with Idiopathic) 100% had low stomach acid. At first they thought it was as a result of the PA then they discovered it was the cause.

100 YEARS!!!!

How long do they need to cotton on.

I know that later there was other research - about the 1930s - that said only 75% had low stomach acid - but that was only a small amount of research and I haven't read it so I won't comment.

100 years Marre and they are still not testing people.

It's beyond disgraceful or words....


Hi Poppet,

I think is more to do with PA, the autoimune condition than B12 def, its having the antibodies that can cause low stomach acid (Achlorhydria) and there fore an increased risk, well its what I gather from the link I supplied re Achlorhydria, see:

"Achlorhydria may develop as a result of the following conditions:

• Antiparietal cell antibodies ◦Antibodies directed against gastric intrinsic factor results in cobalamin deficiency; this is called pernicious anemia.

◦The 2 types of anti-intrinsic factor antibodies are as follows: (1) antibodies that block attachment of cobalamin to intrinsic factor, and (2) antibodies that block attachment of the intrinsic factor-cobalamin complex to ileal receptors.

◦Clinically, highly specific anti-intrinsic factor antibodies are found in about 70% of patients with pernicious anemia. A second component of pernicious anemia is chronic atrophic gastritis that leads to a decline in intrinsic factor production. The chronic atrophic gastritis in pernicious anemia is also associated with an increased risk of intestinal gastric cancer and gastric carcinoid tumors. Clinical factors associated with autoimmune gastritis in addition to vitamin B-12 deficiency include celiac disease, neurological symptoms, and a positive family history.[10]

In my case I had endoscopy and colonoscopy and biopsies to exclude chrohns, coeliac disease, H Pylori, atrophic gastritis and achlorhydria.

I was looked after well by this gastro. 30 years ago a gastro I saw3 (3 times) was a waste of my time, but time has changed, and with the B12 def diagnosis I now have meant in my case every one I saw wanted me to see a gastro, it was me who did not want the procedures..scared..

I am so sorry to read how angry you are, and what your lack of treatment has done to your life, but not every one gets the same bad treatment you had. There are good and bad people, there are good and bad Drs..I am sure it helps a lot these days if a patient is well informed and knows what to ask for. things have changed a lot over 30 years I find.

Your posts will help others who see their GP as god to think ahead though, and hopefully that will help them get better treatment than you had.



Hang on Marre -you're first para is completely contradictory.

You are talking about PA with immune. But achlorhydria has immune. So what you are saying is that anyone with low stomach acid has autoimmune therefore they have PA.

But I only have B12 deficiency and achlorhydria.

So what have I got...?

PA, which is seen to be more important, or B12 deficiency, which isn't.

And the immune tests are worse than useless.

So, can you see the contradiction?

There's this huge gap - the goal posts of PA changing consistently through history and people's interpretation. We should not be talking about people only being seriously ill if they have tested postitive for autoimmune. Because if you remember, only 2 or 3 years ago, only people who had 'anaemia' were ill.

PA back in the day, prior to liver treatment, was anything that caused the symptoms. Vegetarians had PA. By today's diagnostics they wouldn't even have been ill! Yet they were still dying. If they didn't have PA (by today's standard of diagnostics) then what were they dying of?? If it's only important that you have autoimmune? Yet the one thing they all had in common was low stomach acid.

It's not just me, Marre, it's nearly everybody that comes on this site who are having terrible experiences with their doctors.

Compared to most you have had good treatment - excellent treatment - and you still had to self medicate.

You are the odd one out here, not me. Martyn is another odd one out. Getting things recognised, getting things done.

I don't feel guilty anymore about being angry, because I, and many others, have every right to be. That is why they are coming to this site - because no one is doing anything.

I don't know what your stomach acid came out at. What I do know is that if you have low stomach acid then bile production will be affected. And the tests that go hand in hand with that, I'm not going to even mention - because you're happy with your treatment.

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I agree with what you write its just there are no 100% answers, so much is still unknown, new enzymes are found that are important in B12 metabolism, al sorts new is still found Poppet, its just not known. That is what the gastro said to me, she could not give me straight answers, I do not have to much bile, I do not recycle bile well as my terminal ileum is smooth not working as it should, why its smooth is not known. I do not all ways have a problem, I can have a week of no problem to months of problems, that again it is not known why, nothing food related, not stress related, but I have stuff that will help me when I do have problem and that for me is a god send!

I was not lucky initially, but learnt the hard way to make sure I was looked after and now I have very good treatment, it helps if you know what to go for investigations wise and for that you need to learn a lot about PA. I have spent 10 years reading about PA, I now know what to look for and ask for.

I also know things were missed in my case 30 years ago that now make perfect sense..but it does not help me to remember that, it helps me to move on and get things right now, for my kids and others as well.


Lipase. I put this up the other night and it was just scooted over.

It's lipase. And it's not new.

The thing is we have to got decide what actually harms people. Is it B12 deficiency or is it the antibodies. (Because it seems now that the anaemia is out of the window) If it is the antibodies then we have a huge problem because:

A) the test is at least 50% wrong

B) they have now started saying that if people have had b12 within 2 weeks of having the test that it will throw up the opposite result.

That means that all those people who tested positive, but who had b12 in the preceding fortnight, actually should have tested negative.

And should quite possibly go back to work.

While the sick folk are still working.

But it doesn't really matter about the immune problem because it's the lack of b12 which kills you. It destroys the spinal cord (and bits of the brain depending on circumstances)

If someone can prove to me how these antibodies destroy the spinal cord - I'll be more than happy to read the research.


Poppet, you want answers where there just are no answers..its just not known..

There is one called blub, have you heard of blub?

J Am Chem Soc. 2011 Mar 23;133(11):4079-91. doi: 10.1021/ja1106207. Epub 2011 Feb 23.

Intermediate-assisted multifunctional catalysis in the conversion of flavin to 5,6-dimethylbenzimidazole by BluB: a density functional theory study.


BluB is a distinct flavin destructase that catalyzes a complex oxygen-dependent conversion of reduced flavin mononucleotide (FMNH(2)) to form 5,6-dimethylbenzimidazole (DMB), the lower ligand of vitamin B(12). The catalyzed mechanism remains a challenge due to the discrepancy between the complexity of the conversion and the relative simplicity of the active site of BluB. In this study, we have explored the detailed conversion mechanism by using the hybrid density functional method B3LYP on an active site model of BluB consisting of 144 atoms. The results indicate that the conversion involves more than 14 sequential steps in two distinct stages. In the first stage, BluB catalyzes the incorporation of dioxygen, and the fragmentation of the isoalloxazine ring of FMNH(2) to form alloxan and the ribityl dimethylphenylenediimine (DMPDI); in the second stage, BluB exploits alloxan as a multifunctional cofactor, such as a proton donor, a proton acceptor, and a hydride acceptor, to catalyze the remaining no fewer than 10 steps of the reaction. The retro-aldol cleavage of the C1'-C2' bond of DMPDI is the rate-determining step with a barrier of about 21.6 kcal/mol, which produces D-erythrose 4-phosphate (E4P) and the ring-closing precursor of DMB. The highly conserved residue Asp32 plays critical roles in multiple steps of the conversion by serving as a proton acceptor or a proton shuttle, and another conserved residue Ser167 plays its catalytic role mainly in the rate-determining step by stabilizing the protonated retro-aldol precursor. These results are consistent with the available experimental observations. More significantly, the novel intermediate-assisted mechanism not only provides significant insights into understanding the mechanism underlying the power of the simple BluB catalyzing the complex conversion of FMNH(2) to DMB, but also represents a new type of intermediate-assisted multifunctional catalysis in an enzymatic reaction.

There are more new ones, I just remember this one as I can remember the name blub!

Edited to add and then there are other factors such as magnetic fields that can influence B12, there really is so much more..see:


There's lots. But since lipase is the primary one relating to degrading fats, then that is the one to examine first.


That is tested for I believe in biopsies when undergoing colo/endoscopy, and it looks like to me in stool sample, which I expect most that go to GP with bowel issues will have done, I had it done twice, they test serum amylase cryptosporidium etc besides e coli , bacterial infections/ microbiology etc.


Isolated co-lipase deficiency in two brothers.


Two normally developed Assyrian brothers with isolated pancreatic co-lipase deficiency are described. They presented at the age of 5-6 years with loose stools. They had steatorrhoea, and analysis of exocrine pancreatic enzymes in the small intestine showed co-lipase deficiency, while amylase, chymotrypsin, trypsin and lipase were normal. Intraduodenal infusion of purified co-lipase improved fat digestion measured by the triolein breath test. Their steatorrhoea diminished on treatment with enteric-coated pancreatic enzymes


Generally speaking lipase deficiency can be identified by the symptoms - which is the undigested fats. So you get weight loss, pale stools in toilet, floating stools, and sometimes a greasy residue around the waterline in the toilet.

You can't buy lipase as an enzyme on it's own (I don't think - and certainly not in the US) It has to be on prescription. However you can buy it in blends of enzymes.

...and then there is the cholesterol issue - which opens the whole thing up even further.


stomach acid not tested, also have low folate and ferritin, never seen a gastro. Recently started having occaisional acid reflux type things when going through a stressful period. As it passed, I have not seen a doc.. maybe I should.


Firstly you're not at high risk for cancer if you have PA, you just have an increased risk which happens with a lot of different health conditions. There are other risk factors for stomach cancer such as being male, being over 50 and I think drinking and smoking is too. If you have these risk factors then I think doctors will be extra cautious with any gastric symptoms. I've even heard that after a certain age you can get some sort of check like an endoscopy every 5 years or so to check for stomach cancer but I'm not sure how you have to qualify for this. As far as I'm aware it doesn't matter how much b12 you have, if you have PA then the damage has been done, your body is attacking yoir stomach and b12 injections are just to help the symptoms, they dont cure PA. However I'm not a doctor so I'm not 100%, its probably a good idea to see your GP and fnd out what are some good steps to lookout for cancer if your worried about it


Hi Poppet, - took GP's and specialists 10 years to diagnose my gastric atrophy. Gastro Specilaist advised regular Endoscopies every two years to keep an eye on any changes that may be occurring as he said I am a candidate for stomach cancer. I had a fight with my GP to get this instigated but now its a routine procedure. Its on my medical file from the Specialist so GP doesnt question.

I have been having regular endoscopies for 10 years with no changes in my stomach which is very encouraging.

I have multiple auto immune problems and work on trying to reverse antibodies. I am reading Joyce Myers book "The Autoimmune Solution" which I find very helpful and have gone gluten and dairy free with huge improvements in my general well being.

I wish you well in your search for answers.



One of the suspected causes of a B12 deficiency and also of stomach cancer is a bacterial infection from heliobacter pylori. This bacterial contributes to (or even causes) peptic and duodenal ulcers. IT may also attack the parietal cells where Intrinsic Factor and stomach acid are both made.

There is a breath test now for it. Previously an endoscopy and a biopsy were made. The cure is simple, a couple of antibiotics and Pepto-Bismol.

I don't think the connection between a B12D and stomach cancer has been made. The idea is really that there might be a common cause for both.

I find that for my heartburn, having some acid like orange juice or salsa gets rid of it. If I take antacid tablets, it gets much worse.

Although I don't have the genetic version of PA, my stomach surgery 23 years ago. When my duodenal ulcer was repaired, the biopsy showed that I had H-Pylori infection. The procedure on my stomach was a partial vagotomy, where the branch nerves of the vagus nerve on the stomach were cut in an attempt to decrease my stomach acid. Eventually this resulted in a Vit B12 Deficiency which was diagnosed about 8 years ago.


You know when we've just spent a couple of days putting up links proving there is a link between b12d and stomach cancer - why have you come on and said there isn't?

...and links indicating that H Pylori quite possibly isn't the cause of diddly.

...and that low stomach acid is alkaline pH and you suggest the 'cure' for all his is antibiotics and an alkaline antacid.


Then you go on to say an acid treats your heartburn - which would indicate low stomach acid, which you actually say.

So your heartburn is caused by low stomach acid not high - so the doctors made a mistake when they decided to cut a nerve and decrease the stomach acid production and caused an alkaline stomach. Your doctors never proved that H Pylori caused anything - just that it was there at the same time as you got a duodenal ulcer.

Tell me, when are we going to cotton on that some people actually don't think B12d is 'important'?

When are we going to get b12d taken seriously and not just PA?

Because by my reckoning this nonsense has been going on for over 100 years - and no sign of it getting any better.

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I'll just add this bit because I am very angry: from Medscape

"Achlorhydria is associated with intestinal metaplasia, which may lead to dysplasia, and is hence considered a premalignant condition."

Now, since I've been walking around for 3.5 years with a test result trying to get doctors to take it seriously and understand it. Would somebody, anybody, mind explaining to me why on a B12 'support' forum - this condition has just been poo-poohed again?

Now can you see why I've not had anything whatsoever done to help me - why nothing that has happened or continues to happen has been taken seriously - because it isn't even taken seriously here.

How would you feel if they had told you that your ulcer wasn't a problem and sent you home without treatment or time off work?


Next Wednesday I'm Scheduled For Both A Endoscopy & Colonoscopy...Last August My B-12 Levels Were A Little Over 300...I Became Extremely Ill...November I Had Mohs Surgery For Skin Cancer Of My Nose...My Immunity Was Extremely Low...I Showed That My Red Blood Cells Are Oddly Shaped Through Bloodwork...After The Tests I'm Going To Eat A Bland Diet


Hi everyone. I was diagnosed with pernicious anemia in 2012 at the Mayo Clinic. I’ve been on vitamin b12 injections since and my b12 is still low. Upper gi’s Constantly don’t know what else to do. On top of that I have Ruminating Syndrome with a bunch of other diagnoses. Anyway, do any of you have any suggestions of how to get your vitamin b12 up? Help please


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