Do Aspirin and Reflux-Promoting Drugs Change Esophageal and Stomach Cancer Risk?

Aspirin and corticosteroids were linked to lower risk. Drugs that relax the esophageal sphincter were not linked to higher risk. People with pharmacy records of aspirin use had 40% to 60% lower odds of esophageal adenocarcinoma, gastric cardia cancer and non-cardia stomach cancer. As a group, sphincter-relaxing drugs showed no increase in any of the four cancers studied (esophageal adenocarcinoma: odds ratio 1.1, 95% CI 0.7 to 1.7).

This was a case-control study using pharmacy records from two US health systems in Seattle and Detroit. It compared 773 people with esophageal or stomach cancer against 3,996 matched people without cancer.

Dr. Kumar’s Take

The common worry is that drugs which loosen the valve at the bottom of the esophagus cause more reflux and, over years, more esophageal cancer. In this study that did not show up. As a group, these drugs were not linked to higher risk of any of the four cancers. The more striking signal was the other way: aspirin and corticosteroids were tied to lower risk, with less cancer at higher numbers of prescriptions. This is observational pharmacy data. It cannot prove that aspirin prevents these cancers, and aspirin has its own bleeding risks. I read it as a reason not to panic about these medications, not as a reason to start one.

What the Research Shows

Researchers at Memorial Sloan-Kettering and two US health systems (Group Health Cooperative in Seattle and Henry Ford Health System in Detroit) identified every new case of four cancers diagnosed between 1980 and 2002 in Seattle and 1993 and 2002 in Detroit:

Esophageal adenocarcinoma (163 cases)
Esophageal squamous cell carcinoma (114 cases)
Gastric cardia adenocarcinoma, at the top of the stomach (176 cases)
Gastric non-cardia adenocarcinoma, in the rest of the stomach (320 cases)

Each case was matched with up to 5 controls of the same age, sex, health plan and length of membership. The team then compared prescription records for corticosteroids, aspirin, other NSAIDs and sphincter-relaxing drugs (beta agonists, theophylline and related drugs, anticholinergics, antihistamines, benzodiazepines, calcium channel blockers, nitrates and tricyclic antidepressants).

How This Works (Biological Rationale)

NSAIDs may influence cancer risk through multiple pathways including anti-inflammatory effects that could reduce cancer-promoting inflammation, but also through direct tissue toxicity and interference with protective prostaglandin production. The net effect depends on the specific drug, dose, and duration of use. Corticosteroids are also strong anti-inflammatory drugs, which fits the idea that inflammation helps drive cancers of the digestive tract.

Sphincter-relaxing medications have been thought to raise esophageal adenocarcinoma risk by promoting reflux, since chronic acid exposure can damage the lining and lead to Barrett’s esophagus. This study did not find that increase. The authors note that reflux-driven cancer probably takes many years to develop, and their exposure window may have been too short to detect it.

Key Results

Figures are odds ratios compared with people who never filled a prescription for that drug class. An odds ratio of 0.6 means about 40% lower odds.

Corticosteroids (ever used): esophageal adenocarcinoma 0.6 (0.4 to 0.9), esophageal squamous cell carcinoma 0.4 (0.2 to 0.6), non-cardia stomach cancer 0.4 (0.3 to 0.6). Gastric cardia cancer 0.7 (0.5 to 1.0), not significant.
Aspirin (ever used): esophageal adenocarcinoma 0.6 (0.4 to 0.9), gastric cardia cancer 0.4 (0.3 to 0.7), non-cardia stomach cancer 0.5 (0.4 to 0.7). Esophageal squamous cell carcinoma 0.7 (0.4 to 1.1), not significant.
Aspirin, heaviest use (top third of prescriptions): odds ratios of 0.3 to 0.4 for all four cancers, with a significant trend of lower risk as prescriptions increased.
Other NSAIDs: no clear link, except lower non-cardia stomach cancer in the heaviest users (0.5).
Sphincter-relaxing drugs as a group: esophageal adenocarcinoma 1.1 (0.7 to 1.7), gastric cardia 0.8 (0.5 to 1.2), esophageal squamous cell 0.7 (0.4 to 1.3). Non-cardia stomach cancer was lower, 0.6 (0.4 to 0.8).
Individual drugs: the highest cumulative dose of diazepam was linked to more esophageal adenocarcinoma (2.2) and squamous cell carcinoma (2.8). Theophylline was linked to more squamous cell carcinoma (2.2), which the authors think smoking may partly explain. Numbers for single drugs were small.

Safety, Limits, and Caveats

The study was observational and cannot definitively establish causation between medication use and cancer risk. Confounding by indication is possible, as patients taking these medications may have underlying conditions that independently affect cancer risk. The records had no data on smoking, weight or reflux symptoms. The authors ran sensitivity analyses and judged that these factors were unlikely to explain the aspirin and corticosteroid findings, but some confounding is possible.

Pharmacy records also miss aspirin bought elsewhere over the counter, and the study had limited power to judge individual sphincter-relaxing drugs. Many comparisons were run, so some findings may be due to chance.

Practical Takeaways

In this study, drugs that relax the lower esophageal sphincter were not linked to higher esophageal or stomach cancer risk as a group.
Aspirin and corticosteroid prescriptions were linked to lower risk of these cancers, but an observational study cannot show that the drugs caused the drop.
Aspirin and steroids carry real side effects, including stomach bleeding. Do not start either one for cancer prevention without talking to your doctor.
If you take a sphincter-relaxing drug and have frequent heartburn, the reflux itself is worth raising with your doctor.

FAQs

Should I stop taking NSAIDs because of cancer risk?

This study gives no reason to. Aspirin prescriptions were linked to lower risk of esophageal and stomach cancer, and other NSAIDs showed no clear link either way. Discuss the overall risk-benefit profile with your healthcare provider based on your individual situation.

Which medications are considered sphincter-relaxing drugs?

Common sphincter-relaxing medications include calcium channel blockers, nitrates, some antispasmodics, and certain blood pressure medications.

How long does medication use need to continue to affect cancer risk?

This study counted the number of prescriptions filled, not years of use. For aspirin and corticosteroids, more prescriptions went with lower risk. The authors note that reflux-related cancers take many years to develop, so their records may have been too short to capture a long-term effect of sphincter-relaxing drugs.

Can I reduce cancer risk while still taking necessary medications?

Strategies may include using the lowest effective dose, shortest duration possible, and combining with lifestyle modifications to reduce overall cancer risk.

Should I have more frequent cancer screening if I take these medications?

Screening recommendations should be individualized based on your overall risk profile, family history, and medication use. Discuss appropriate screening with your healthcare provider.

Bottom Line

In this case-control study of 773 people with esophageal or stomach cancer and 3,996 without, drugs that relax the lower esophageal sphincter were not linked to higher cancer risk as a group. Aspirin and corticosteroid prescriptions were linked to 40% to 60% lower odds of several of these cancers. These are associations from pharmacy records, not proof that the drugs protect.

Do Aspirin and Reflux-Promoting Drugs Change Esophageal and Stomach Cancer Risk?