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Etiology

Gastroesophageal reflux disease symptoms were associated with increased risk for adenocarcinomas of the esophagus and gastric cardia

ACP J Club. 1999 Sept-Oct;131:52. doi:10.7326/ACPJC-1999-131-2-052


Source Citation

Lagergren J, Bergström R, Lindgren A, Nyrén O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med. 1999 Mar 18;340:825-31.


Abstract

Question

Are symptoms of gastroesophageal reflux disease (GERD) associated with an increased risk for adenocarcinomas of the esophagus and gastric cardia?

Design

Population-based case-control study.

Setting

Sweden.

Participants

Of 529 eligible persons, 451 (85%) were studied as cases. They were < 80 years of age and had adenocarcinomas of the esophagus (n = 189, median age 69 y, 87% men) or gastric cardia (n = 262, median age 66 y, 85% men). 167 persons with esophageal squamous-cell carcinoma (median age 67 y, 72% men) were also studied. A random sample of 820 persons (median age 68 y, 83% men) was matched by sex and age to case-participants.

Assessment of risk factors

Interviews were used to assess cardinal symptoms of GERD during the previous ≥ 5 years. Potential confounding variables were also assessed: age, sex, body mass index, tobacco smoking, alcohol use, educational level, dietary intake of fruits and vegetables, energy intake, a stooped posture at work, physical activity at work, and physical activity during leisure time. Interviewers were blinded to study hypotheses.

Main outcome measures

Adenocarcinomas of the esophagus and gastric cardia.

Main results

Heartburn, regurgitation, or both that occurred one or more times per week were associated with increased risks for esophageal adenocarcinoma (odds ratio [OR] 7.5, 95% CI 5.4 to 10.6) and adenocarcinoma of the gastric cardia (OR 2.0, CI 1.5 to 2.8) but not esophageal squamous-cell carcinoma (OR 0.9, CI 0.6 to 1.4). Results were similar after adjustment for potential confounding variables; the risk for esophageal adenocarcinoma was greater than the risk for adenocarcinoma of the gastric cardia (Table).

Conclusions

Symptoms of gastroesophageal reflux disease were associated with an increased risk for adenocarcinomas of the esophagus and gastric cardia. The risk for esophageal adenocarcinoma was greater than the risk for adenocarcinoma of the gastric cardia.

Sources of funding: National Cancer Institute; Swedish Cancer Society; Dalarna Research Institute.

For correspondence: Dr. J. Lagergren, Department of Medical Epidemiology, Karolinska Institute, Box 281, S-171 77 Stockholm, Sweden. FAX 46-8-31-4957.


Table. Associations between symptoms of gastroesophageal reflux disease and cancer

Outcomes Adjusted odds ratio (95% CI)*
Esophageal adenocarcinoma 7.7 (5.3 to 11.4)
Adenocarcinoma of the gastric cardia 2.0 (1.4 to 2.9)
Esophageal squamous-cell carcinoma 1.2 (0.7 to 2.0)†

*Odds ratios adjusted for age, sex, body mass index, tobacco smoking, alcohol use, educational level, energy intake, intake of fruits and vegetables, stooped posture at work, physical activity at work, and physical activity during leisure time.
†Not significant.


Commentary

More than 10% of Americans have symptoms of GERD on a weekly basis (1). Although GERD has been postulated to be a risk factor for adenocarcinoma of the esophagus, data linking the 2 entities have been lacking. This case-control study has many strengths, including a high participation rate, strict case definition, well-chosen controls, and patients with squamous-cell cancer of the esophagus as a second comparison group.

The strong "dose-dependent" relation reported between GERD and risk for cancer will certainly trouble both patients and physicians. Although this work emphasizes that GERD is not a symptom to be ignored, it may be unduly alarming to some. Despite the impressive odds ratios, the absolute risk for cancer is the more important issue. Because the incidence rate of this type of cancer was low—216 cases in a population > 8 million over a 2-year interval—the absolute risk was small, even in patients with increased risk secondary to GERD.

These data make a persuasive argument that GERD is associated with adenocarcinomas of the esophagus and cardia. However, because GERD is so common, better methods of stratifying the risk for cancer among patients with GERD are needed. Although the current practice of following only patients with Barrett esophagus by using serial endoscopy may increase the yield of cases of cancer that are detected early, incidence rates of cancer in this group are still < 0.5% per patient-year (2). Until better risk stratification tools are developed, effective prevention of this type of cancer may be difficult.

Nicholas Shaheen, MD, MPH
University of North CarolinaChapel Hill, North Carolina, USA


References

1. Gallup Organization National Survey. Heartburn across America. Princeton, NJ: The Gallup Organization; 1988.

2. Drewitz DJ, Sampliner RE, Garewal HS. The incidence of adenocarcinoma in Barrett's esophagus: a prospective study of 170 patients followed 4.8 years. Am J Gastroenterol. 1997;92:212-5.