H. pylori May Protect Against Esophageal Cancer

Major Finding: Patients with esophageal adenocarcinoma and esophagogastric junction adenocarcinoma were significantly less likely to have a history of H. pylori infection than population controls (odds ratios, 0.44 and 0.40, respectively).

Data Source: An Australian study of 269 patients with esophageal adenocarcinoma, 307 with esophagogastric junction adenocarcinoma, and 218 with esophageal squamous cell carcinoma, compared with 1,355 controls.

Disclosures: Dr. Whiteman and several of his colleagues disclosed receiving grants from the National Health and Medical Research Council of Australia. The study was supported by the Cancer Council Queensland and the National Health and Medical Research Council of Australia.

Patients with esophageal adenocarcinoma and esophagogastric junction adenocarcinoma were significantly less likely than population controls to have evidence of past Helicobacter pylori infection, Dr. David C. Whiteman and his colleagues reported.

The association persisted independently of known esophageal cancer risk factors, such as reflux and smoking, and also was independent of genetic factors, including polymorphisms in genes coding for interleukin-1B and tumor necrosis factor–alpha.

The findings add to a growing body of evidence suggesting that H. pylori might somehow be protective against esophageal cancers, even as it increases the risk of gastric cancer.

Dr. Whiteman, head of the Cancer Control Laboratory at the Queensland (Australia) Institute of Medical Research looked at 794 Australian patients aged 18-79 years with a primary invasive cancer of the esophagus or esophagogastric junction.

Overall, 269 patients had esophageal adenocarcinoma, 307 had esophagogastric junction adenocarcinoma, and 218 had esophageal squamous cell carcinoma.

The 1,355 controls were randomly selected from the Australian Electoral Roll and were roughly matched to the patients by age, sex, and state of residence.

“Patients with [esophageal adenocarcinoma, or EAC] and [esophagogastric junction adenocarcinomas, or EGJAC] were significantly less likely than were controls to have antibodies to H. pylori,” wrote Dr. Whiteman (Gastroenterology July [doi: 10.1053/j.gastro.2010.04.009]).

Among the EAC patients, the odds ratio of being seropositive was 0.44 (95% confidence interval, 0.29-0.67) after researchers adjusted for age, sex, smoking history, education, and several other environmental factors.

In the EGJAC population, the OR was 0.40 (95% CI, 0.27-0.59).

There was no association between H. pylori and esophageal squamous cell carcinoma (OR 1.08, 95% CI 0.74-1.57), they reported.

Dr. Whiteman and his colleagues also looked to see whether esophageal cancer patients shared any common mutations in the genes coding for IL-1B and TNF-alpha.

“IL-1B is among the most potent inhibitors of gastric acid yet identified,” they wrote, and “a recent meta-analysis concluded that the TNF-A-308AA genotype is associated with a moderately increased risk of gastric cancer” (Br. J. Cancer 2008;98:1443-51).

However, the authors “found no evidence that the inverse associations between H. pylori infection and [esophageal adenocarcinomas or esophagogastric junction adenocarcinomas] were modified by the presence of polymorphisms at IL-1B-31, IL-1B-511, TNF-A 308, and TNF-A 238.”

Squamous cell carcinomas also had a null association with these genotypes, they reported.

Therefore, Dr. Whiteman and his colleagues asked, “Is the inverse relationship between H. pylori infection and EAC and EGJAC evidence of a biologically protective effect?” And if so, what is the mechanism?

“Several potential mechanisms have been proposed to explain the association, including hypoacidity subsequent to prolonged infection, dysregulation of host cytokine or immune responses, disturbances to microbial flora, and changes in the expression of locally acting hormones relating to obesity pathways (notably leptin and ghrelin),” wrote the authors.

“Each of these hypotheses is plausible, and all may indeed play a role,” they commented.

As for study limitations, the authors conceded that the overall prevalence of H. pylori antibodies (23% among controls) was much lower than in other populations, including in the United States.

However, the “50-60% risk reductions we observed for EAC were remarkably similar to those reported in other studies,” they wrote.

As to the possibility of misclassification of H. pylori exposure, Dr. Whiteman and his colleagues pointed out that for such an error to have occurred “would [have] required that patients with EAC and EGJAC, but not [esophageal squamous cell carcinomas], were incorrectly categorized, a highly improbable scenario.”

Major Finding: Patients with esophageal adenocarcinoma and esophagogastric junction adenocarcinoma were significantly less likely to have a history of H. pylori infection than population controls (odds ratios, 0.44 and 0.40, respectively).

Data Source: An Australian study of 269 patients with esophageal adenocarcinoma, 307 with esophagogastric junction adenocarcinoma, and 218 with esophageal squamous cell carcinoma, compared with 1,355 controls.

Disclosures: Dr. Whiteman and several of his colleagues disclosed receiving grants from the National Health and Medical Research Council of Australia. The study was supported by the Cancer Council Queensland and the National Health and Medical Research Council of Australia.

Patients with esophageal adenocarcinoma and esophagogastric junction adenocarcinoma were significantly less likely than population controls to have evidence of past Helicobacter pylori infection, Dr. David C. Whiteman and his colleagues reported.

The association persisted independently of known esophageal cancer risk factors, such as reflux and smoking, and also was independent of genetic factors, including polymorphisms in genes coding for interleukin-1B and tumor necrosis factor–alpha.

The findings add to a growing body of evidence suggesting that H. pylori might somehow be protective against esophageal cancers, even as it increases the risk of gastric cancer.

Dr. Whiteman, head of the Cancer Control Laboratory at the Queensland (Australia) Institute of Medical Research looked at 794 Australian patients aged 18-79 years with a primary invasive cancer of the esophagus or esophagogastric junction.

Overall, 269 patients had esophageal adenocarcinoma, 307 had esophagogastric junction adenocarcinoma, and 218 had esophageal squamous cell carcinoma.

The 1,355 controls were randomly selected from the Australian Electoral Roll and were roughly matched to the patients by age, sex, and state of residence.

“Patients with [esophageal adenocarcinoma, or EAC] and [esophagogastric junction adenocarcinomas, or EGJAC] were significantly less likely than were controls to have antibodies to H. pylori,” wrote Dr. Whiteman (Gastroenterology July [doi: 10.1053/j.gastro.2010.04.009]).

Among the EAC patients, the odds ratio of being seropositive was 0.44 (95% confidence interval, 0.29-0.67) after researchers adjusted for age, sex, smoking history, education, and several other environmental factors.

In the EGJAC population, the OR was 0.40 (95% CI, 0.27-0.59).

There was no association between H. pylori and esophageal squamous cell carcinoma (OR 1.08, 95% CI 0.74-1.57), they reported.

Dr. Whiteman and his colleagues also looked to see whether esophageal cancer patients shared any common mutations in the genes coding for IL-1B and TNF-alpha.

“IL-1B is among the most potent inhibitors of gastric acid yet identified,” they wrote, and “a recent meta-analysis concluded that the TNF-A-308AA genotype is associated with a moderately increased risk of gastric cancer” (Br. J. Cancer 2008;98:1443-51).

However, the authors “found no evidence that the inverse associations between H. pylori infection and [esophageal adenocarcinomas or esophagogastric junction adenocarcinomas] were modified by the presence of polymorphisms at IL-1B-31, IL-1B-511, TNF-A 308, and TNF-A 238.”

Squamous cell carcinomas also had a null association with these genotypes, they reported.

Therefore, Dr. Whiteman and his colleagues asked, “Is the inverse relationship between H. pylori infection and EAC and EGJAC evidence of a biologically protective effect?” And if so, what is the mechanism?

“Several potential mechanisms have been proposed to explain the association, including hypoacidity subsequent to prolonged infection, dysregulation of host cytokine or immune responses, disturbances to microbial flora, and changes in the expression of locally acting hormones relating to obesity pathways (notably leptin and ghrelin),” wrote the authors.

“Each of these hypotheses is plausible, and all may indeed play a role,” they commented.

As for study limitations, the authors conceded that the overall prevalence of H. pylori antibodies (23% among controls) was much lower than in other populations, including in the United States.

However, the “50-60% risk reductions we observed for EAC were remarkably similar to those reported in other studies,” they wrote.

As to the possibility of misclassification of H. pylori exposure, Dr. Whiteman and his colleagues pointed out that for such an error to have occurred “would [have] required that patients with EAC and EGJAC, but not [esophageal squamous cell carcinomas], were incorrectly categorized, a highly improbable scenario.”

Major Finding: Patients with esophageal adenocarcinoma and esophagogastric junction adenocarcinoma were significantly less likely to have a history of H. pylori infection than population controls (odds ratios, 0.44 and 0.40, respectively).

Data Source: An Australian study of 269 patients with esophageal adenocarcinoma, 307 with esophagogastric junction adenocarcinoma, and 218 with esophageal squamous cell carcinoma, compared with 1,355 controls.

Disclosures: Dr. Whiteman and several of his colleagues disclosed receiving grants from the National Health and Medical Research Council of Australia. The study was supported by the Cancer Council Queensland and the National Health and Medical Research Council of Australia.

Patients with esophageal adenocarcinoma and esophagogastric junction adenocarcinoma were significantly less likely than population controls to have evidence of past Helicobacter pylori infection, Dr. David C. Whiteman and his colleagues reported.

The association persisted independently of known esophageal cancer risk factors, such as reflux and smoking, and also was independent of genetic factors, including polymorphisms in genes coding for interleukin-1B and tumor necrosis factor–alpha.

The findings add to a growing body of evidence suggesting that H. pylori might somehow be protective against esophageal cancers, even as it increases the risk of gastric cancer.

Dr. Whiteman, head of the Cancer Control Laboratory at the Queensland (Australia) Institute of Medical Research looked at 794 Australian patients aged 18-79 years with a primary invasive cancer of the esophagus or esophagogastric junction.

Overall, 269 patients had esophageal adenocarcinoma, 307 had esophagogastric junction adenocarcinoma, and 218 had esophageal squamous cell carcinoma.

The 1,355 controls were randomly selected from the Australian Electoral Roll and were roughly matched to the patients by age, sex, and state of residence.

“Patients with [esophageal adenocarcinoma, or EAC] and [esophagogastric junction adenocarcinomas, or EGJAC] were significantly less likely than were controls to have antibodies to H. pylori,” wrote Dr. Whiteman (Gastroenterology July [doi: 10.1053/j.gastro.2010.04.009]).

Among the EAC patients, the odds ratio of being seropositive was 0.44 (95% confidence interval, 0.29-0.67) after researchers adjusted for age, sex, smoking history, education, and several other environmental factors.

In the EGJAC population, the OR was 0.40 (95% CI, 0.27-0.59).

There was no association between H. pylori and esophageal squamous cell carcinoma (OR 1.08, 95% CI 0.74-1.57), they reported.

Dr. Whiteman and his colleagues also looked to see whether esophageal cancer patients shared any common mutations in the genes coding for IL-1B and TNF-alpha.

“IL-1B is among the most potent inhibitors of gastric acid yet identified,” they wrote, and “a recent meta-analysis concluded that the TNF-A-308AA genotype is associated with a moderately increased risk of gastric cancer” (Br. J. Cancer 2008;98:1443-51).

However, the authors “found no evidence that the inverse associations between H. pylori infection and [esophageal adenocarcinomas or esophagogastric junction adenocarcinomas] were modified by the presence of polymorphisms at IL-1B-31, IL-1B-511, TNF-A 308, and TNF-A 238.”

Squamous cell carcinomas also had a null association with these genotypes, they reported.

Therefore, Dr. Whiteman and his colleagues asked, “Is the inverse relationship between H. pylori infection and EAC and EGJAC evidence of a biologically protective effect?” And if so, what is the mechanism?

“Several potential mechanisms have been proposed to explain the association, including hypoacidity subsequent to prolonged infection, dysregulation of host cytokine or immune responses, disturbances to microbial flora, and changes in the expression of locally acting hormones relating to obesity pathways (notably leptin and ghrelin),” wrote the authors.

“Each of these hypotheses is plausible, and all may indeed play a role,” they commented.

As for study limitations, the authors conceded that the overall prevalence of H. pylori antibodies (23% among controls) was much lower than in other populations, including in the United States.

However, the “50-60% risk reductions we observed for EAC were remarkably similar to those reported in other studies,” they wrote.

As to the possibility of misclassification of H. pylori exposure, Dr. Whiteman and his colleagues pointed out that for such an error to have occurred “would [have] required that patients with EAC and EGJAC, but not [esophageal squamous cell carcinomas], were incorrectly categorized, a highly improbable scenario.”