Source/Disclosures
Disclosures: American Cancer Society, American Institute for Cancer Research, Bennett Family Foundation, Entertainment Industry Foundation’s National Colorectal Cancer Research Alliance, NIH, Project P Fund for Colorectal Cancer Research and Siteman Investment Program supported this study. Song reports no relevant financial disclosures. One author reports prior consultant roles with Bayer Healthcare and Pfizer for work unrelated to this study.
July 21, 2020
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Gum disease linked to higher risk for gastric, esophageal cancers

Source/Disclosures
Disclosures: American Cancer Society, American Institute for Cancer Research, Bennett Family Foundation, Entertainment Industry Foundation’s National Colorectal Cancer Research Alliance, NIH, Project P Fund for Colorectal Cancer Research and Siteman Investment Program supported this study. Song reports no relevant financial disclosures. One author reports prior consultant roles with Bayer Healthcare and Pfizer for work unrelated to this study.
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A history of gum disease appeared associated with significantly elevated risks for two types of gastrointestinal cancer, according to prospective study results published in Gut.

Multivariable analyses showed individuals with periodontal disease were 43% more likely to develop esophageal adenocarcinoma and 52% more likely to develop gastric adenocarcinoma.

Infographic showing link between periodontal disease and cancer

A history of gum disease appeared associated with significantly elevated risks for two types of gastrointestinal cancer.

The results confirmed what had been proposed in prior studies but had not yet been established by large-scale epidemiologic evidence, researchers wrote.

“Our findings support a possible role of oral health in the development of upper GI cancer,” Mingyang Song, MD, ScD, assistant professor of clinical epidemiology and nutrition at Harvard T.H. Chan School of Public Health, told Healio. “Based on our findings, people with periodontal disease should be encouraged to modify their lifestyle — for example, quit smoking and lower alcohol intake — in order to reduce their cancer risk.”

Mingyang Song, MD, ScD
Mingyang Song

Prior studies into the association between periodontal disease or tooth loss with gastric and esophageal cancers have been limited by considerable variations in study design, exposure ascertainment and confounding adjustment, according to study background.

“We conducted this study because the association of periodontal disease and tooth loss with these two types of cancer has been inconsistent and sometimes goes against evidence from microbiome studies,” said Song, who also serves as assistant professor of medicine in the clinical and translational epidemiology unit in the division of gastroenterology at Massachusetts General Hospital and Harvard Medical School. “Recent studies showed a presence of dysbiotic oral microbiome in patients with esophageal and gastric cancer, suggesting a link between oral health and these cancers.”

Song and colleagues — including first author Chun-Han Lo, MD, of the department of epidemiology at Harvard T.H. Chan School of Public Health and the division of gastroenterology at Massachusetts General Hospital and Harvard Medical School — used data from the Nurses’ Health Study (n = 98,459 women) and Health Professionals Follow-up Study (n = 49,685 men) to prospectively assess the association of periodontal disease and tooth loss with risk for esophageal or gastric adenocarcinoma.

Researchers used validated follow-up questionnaires to assess dental measures, lifestyle, diet and demographics, and they reviewed medical records to confirm self-reported cancer diagnoses.

Follow-up ranged from 22 to 28 years. During that time, researchers documented 199 esophageal adenocarcinoma cases and 238 gastric adenocarcinoma cases.

Multivariable analyses adjusted for smoking showed periodontal disease history significantly increased risk for esophageal adenocarcinoma (adjusted HR [aHR] = 1.43; 95% CI, 1.05-1.96) and gastric adenocarcinoma (aHR = 1.52; 95% CI, 1.13-2.04).

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Researchers also analyzed the effect of tooth loss.

Among all study participants, those who lost two or more teeth had numerically elevated risks for esophageal adenocarcinoma (aHR = 1.42; 95% CI, 1-2.03) and gastric adenocarcinoma (aHR = 1.33; 95% CI, 0.95-1.86), but the differences did not reach statistical significance.

Among those with periodontal disease history, researchers reported higher risk for esophageal adenocarcinoma among those who had no tooth loss (aHR = 1.59; 95% CI, 1.04-2.41) and those who lost at least one tooth (aHR = 1.59; 95% CI, 1.04-2.44) compared with those who had no periodontal disease history and no tooth loss.

Further analysis of the cohort with periodontal disease history showed higher risk for gastric adenocarcinoma among those who had no tooth loss (aHR = 1.5; 95% CI, 1.01-2.23) and those who lost at least one tooth (aHR = 1.68; 95% CI, 1.13-2.5) compared with those who had no periodontal disease history and no tooth loss.

“We are confident that these findings are robust because we had a large sample size and were able to prospectively follow participants’ cancer status,” Song told Healio. “We also performed rigorous control of lifestyle factors that might have confounded the results, particularly smoking.”

Researchers provided potential explanations for associations between oral bacteria and these two malignancies.

Evidence from prior studies suggested the periodontal pathogens Tannerella forsythia and Porphyromonas gingivalis may affect esophageal cancer risk. It also is possible that poor oral hygiene and periodontal disease may promote formation of endogenous nitrosamines, which promote gastric cancer via nitrate-reducing bacteria.

Researchers acknowledged no firm conclusions can be made from this observational study, noting the potential for confounding factors. Additional research in this area is “certainly needed,” Song said.

“We expect more microbiome studies nested within long-running cohorts to be carried out over the next few years,” Song told Healio. “These studies would leverage the rich data in large prospective cohorts and directly assess the role of microbiome data in esophageal and gastric adenocarcinoma. Also ... further studies are needed to assess the predictive capability of oral health for these malignancies.”

For more information:

Mingyang Song, MD, ScD, can be reached at mis911@mail.harvard.edu.