Heartburn Raises Cancer Risk, Antacids May Offer Protection

Roxanne Nelson

May 29, 2013

Common antacids might help protect against the development of squamous cancers of the pharynx and larynx, according to data from a large study evaluating the association between heartburn and the use of medications. Although gastric reflux was a strong independent risk factor for laryngopharyngeal squamous cell carcinoma (LPSCC), there was also a consistent inverse association between antacid use and the development of LPSCC in individuals with a history of heartburn symptoms.

The study was published online May 23 in Cancer Epidemiology, Biomarkers & Prevention.

Individuals without a history of heavy tobacco use or alcohol consumption but with a history of frequent heartburn had a 78% increased risk for malignancies of the larynx and pharynx. However, for those who used antacids instead of prescription drugs to treat their symptoms, there was a 41% reduced risk for these cancers.

This apparent chemopreventive effect of antacids was consistent, regardless of smoking status, alcohol consumption, human papillomavirus (HPV) type 16 status, and tumor site.

"Previous studies examining gastric reflux and cancers of the head and neck have generated mixed results," said study author Scott M. Langevin, PhD, a postdoctoral research fellow at Brown University in Providence, Rhode Island. "Most of those studies had few cases or were not adjusted for confounding factors."

In contrast, this is a large population-based study with "robust parameters that strongly suggest that gastric reflux, which causes frequent heartburn, is an independent risk factor for cancers of the pharynx and larynx," Dr. Langevin said in a statement.

Smoking, alcohol consumption, and HPV 16 infection are the major risk factors for these cancers, but other factors, such as occupational exposures, oral hygiene, gastroesophageal reflux, and inherited cancer syndromes, have also been linked to an increased risk for this disease.

Gastric reflux can reach into the upper airway, the authors note, which can then induce cellular damage in the epithelial lining. Although this process is believed to be a risk factor for LPSCC, results from the literature are mixed.

Heartburn Increases Risk

In this study, Dr. Langevin and colleagues sought to clarify the association between gastric reflux and LPSCC. They evaluated the association between self-reported heartburn symptoms and the use of medications in 631 patients with LPSCC and 1234 matched controls. All participants were enrolled as part of a population-based case–control study of head and neck squamous cell carcinoma in the greater Boston area in Massachusetts.

Case subjects tended to be heavier smokers (P < .001), were more likely to consume more than 14 alcoholic beverages per week (P < .001), had a higher prevalence of the HPV 16 L1 antibody, and were more likely to have a body mass index (BMI) in normal range than control subjects. They were also less likely to be obese (P <.001), and were generally less educated (P < .001).

There was a significant relation between the frequency of symptom occurrence and the type of medication used to relieve heartburn. As expected, patients who reported symptoms occurring often or extremely often were far more likely to use a proton pump inhibitor or histamine H2-receptor antagonist than those who reported only rare occurrences of heartburn.

After adjustment for age, sex, race, smoking, alcohol consumption, HPV 16 seropositivity, education, and BMI, patients with a history of frequent heartburn who were not heavy smokers or heavy drinkers had a significantly elevated risk for LPSCC (odds ratio [OR], 1.78). Of those with a history of heartburn, there was an inverse association between antacid use and LPSCC (OR, 0.59). This association remained consistent when analyzed by smoking/drinking status, HPV 16 status, or primary tumor site.

Only Antacids Lowered Cancer Risk

However, for participants with a history of heartburn, the use antacids only to relieve symptoms was significantly inversely associated with LPSCC (OR, 0.59) and laryngeal carcinoma (OR, 0.33). In addition, there was an inverse but nonsignificant point estimate for the association with pharyngeal carcinoma (OR, 0.71).

Dr. Langevin pointed out that a potential protective effect of antacids could have clinical implications. However, further studies are needed to clarify the possible chemopreventive role of antacid use.

"The finding that acid reflux is a risk factor for throat and vocal cord cancers...is now better established with the addition of our large, well-controlled study," he noted.

This study was supported by the National Cancer Institute and National Institute of Environmental Health Sciences. The authors have disclosed no relevant financial relationships.

Cancer Epidemiol Biomarkers Prev. Published online May 23, 2013. Abstract

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