Heartburn Causes Cancer

April 11, 2017

by Casey Graybeal MD

Surgeon at Northeast Georgia Physicians Group

Esophageal cancer isn't common.  It doesn't rank in the top 10 cancers in frequency.  It doesn't have particularly good PR.  You probably can't name a celebrity that has had esophageal cancer, unless you remember the Smothers Brothers.  It does have some distinctions, however, that make it worthy of recognition.  Only pancreatic cancer kills a higher percentage of those it affects; and, in recent years, esophageal cancer has been increasing at a rate higher than any other cancer.  Why is this?  It's simple—heartburn causes esophageal cancer, and lots of people get heartburn.

Nexium, a heartburn treatment medication called a PPI (proton pump inhibitor), is the second highest prescription expenditure in the United States.  Upon last review, over $12 billion dollars was spent annually on Nexium alone, that doesn't account for what consumers buy "over the counter", or the myriad of other drugs that do the same thing.  Surveys show that heartburn sufferers are most likely to self-treat (over a third), as compared to treatment through a family doctor, or gastroenterologist.  In part, this is due to successful direct-to-patient marketing of drugs, a practice only allowed in the United States. 

There are many PPI drugs to choose from, but they fundamentally work the same way.  They permanently disable the pumps in the stomach that produce acid.  Older drugs, such as Zantac and Pepcid are different. They are called H2-blockers, and they simply turn down the activity of the pumps.  They're faster (as the fireman on the Zantac commercial will tell you), but less potent.  What both drug types have in common is that they reduce acid production with the goal of relieving heartburn.  There is still acid, but if it is reduced a bit, you probably won't notice the burning—and that's the rub.  Since these drugs simply mask the symptoms, and don't address the gastroesophageal reflux disease (GERD) that actually causes heartburn and regurgitation, the esophagus is still exposed to other dangerous gastric contents like enzymes and bile salts.  Coincidentally, when the acidity of the gastric contents is decreased by medication, the bile becomes more dangerous because now it is soluble enough in to concentrate inside the cells of the esophagus lining.

With the number of GERD patients growing, the risk also continues to rise.  About forty percent of our adult population experiences some type of GERD monthly, many of those much more commonly.  That translates into millions of GERD patients in the United States.   According to The Healthcare Cost and Utilization Project (HCUP), primary or secondary GERD diagnosis increased by an unprecedented 216% from 1998 to 2005.   The reasons for this explosion of GERD sufferers are many, but the single most important culprit probably won't surprise—it is likely obesity.

GERD results in chronic exposure to refluxed gastric content, and can result in an intestinal metaplasia, which is premalignant damage to the esophagus’ tissue, commonly referred to as “Barrett’s esophagus”.  There is lab based evidence that suggests acid is not enough to cause Barrett’s esophagus; bile must also be present to produce such injury.  Once formed, Barrett's esophagus has an increased risk of turning into esophageal adenocarcinoma (cancer).  Once Barrett’s esophagus is present, the risk of esophageal cancer is about the same as the risk of developing colon cancer from a colon polyp—around 0.5% per year. That means one in 200 Barrett’s patients will be diagnosed with cancer each year.

 There are two types of esophageal cancer.  Squamous cell cancer occurs more frequently with exposure to alcohol, cigarettes and perhaps viral influences.  Adenocarcinoma is usually associated with Barrett's esophagus, which comes from GERD.  It is the adenocarcinoma that has been increasing in frequency in recent years.  Barrett's esophagus is found in approximately 15% of GERD patients undergoing an upper endoscopic exam (think colonoscopy, but from the other end and with a shorter scope).  It is most likely to occur in patients with long-standing reflux, and more severe symptoms.  Once Barrett's esophagus has formed, it's progression to cancer can be interrupted, but we cannot treat what we don't know about.  It is necessary to biopsy the tissue during endoscopy to identify any esophageal changes in need of treatment.

The risk that Barrett's esophagus will progress to cancer is considered by most gastroenterologists to be adequately managed by PPI medications.  However, there is conflicting data from some very large studies in Europe.  These studies suggest that PPI drugs my actually increase the risk of progression to cancer, depending on how they are used.  But let's not go so far, yet, to say these drugs are part of the cancer problem; the current standard of care in the U.S. (and my practice) is to use PPI drugs as needed for heartburn symptom management.  It is vitally important to GERD sufferers, however, to recognize that these drugs do not affect the underlying disease process, other than reducing the acidity of the stomach contents.  The implications are huge for someone who regurgitates at night and repeatedly develops aspiration pneumonia from their reflux; their heartburn is controlled, but the contamination of the airways continues while all their doctors scratch their heads.

PPI drugs are a double-edge sword. After all, isn't there acid in the stomach for a reason?  We now know that reducing the acidity of the stomach impacts the absorption of dietary minerals and vitamins; but lower acid levels can also allow some pretty nasty organisms to get past what should have been the first line of defense against contaminating our normal gut flora with unwelcome inhabitants like clostridium difficile.  Here in Georgia, that's like kudzu in your roses.  Wouldn't it be better to just stop the GERD?  It turns out, as expected, the answer is "yes".

There are multiple therapies for GERD whose aim is to stop the regurgitation of gastric contents, and allow for normal acid function. However, every medical therapy—pills or procedures—is ultimately a compromise with normal physiologic function.  We attempt to modify a disease state favorably without excessive side effects.  Every treatment has a profile of risks and benefits to be considered in the individual patient.  Most importantly, managing GERD treatment requires expertise in areas crossing several specialties, and a variety of testing platforms. Newer procedures can control reflux while introducing fewer side effects, but this is not an arena for the casual esophagologist.   

April is Esophageal Cancer Awareness Month. The first goal is to make heartburn sufferers—millions of them—aware that "Heartburn Causes Cancer".  Less than 1% of GERD sufferers in the US are referred for treatment beyond PPI drugs, despite evidence that surgery improves quality of life, and the risk of Barrett's progressing to cancer is reduced.  Additionally, endoscopic ablation can destroy Barrett's and reduce cancer risk, but first we have to identify those at risk.  The current guidelines published by the gastroenterology societies do not aggressively address the risks associated with GERD.  

Since Barrett's esophagus is not a diagnosis made by inspection alone; anyone with 5 years of symptoms, or more, should undergo an endoscopic exam, with biopsies.  Anyone with difficult or painful swallowing, or who has altered their diet to avoid these symptoms, should be evaluated.  Evaluation is particularly important for those with a higher risk of esophageal cancer: more than five years of heartburn or more severe symptoms, patients over 50, men and Caucasians.  I strongly suggest patients in these categories have endoscopic exam.  The good news is, it can be combined with your colonoscopy, reducing costs and inconvenience; but you may have to insist—financial incentives in medicine favor doing the two procedure separately.

Esophageal cancer is a heartbreaking disease.  I commonly see esophageal cancer patients in their 50's and 40's, most of whom knew they had GERD and were being treated by a physician with medication, but were not evaluated for cancer risk.  Many times we can intervene with extensive treatment, including surgery.  Most times the esophageal cancer cannot be cured.  The only way to really make an impact with esophageal cancer is earlier identification of those at risk, and then managing that risk appropriately.  We can treat Barrett's, but we have to start earlier, much farther upstream, with heartburn.


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