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| ORIGINAL HYPOTHESIS |
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| Year : 2017 | Volume
: 8
| Issue : 1 | Page : 27-29 |
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The periodontal infection may be a contributing factor to the development of gastric cancer
Jinghua Sun1, Jie Yin2, Benxiang Hou1
1 Department of Endodontics, Beijing Stomatological Hospital, Capital Medical University, Beijing, China
2 Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center of Digestive, Beijing, China
| Date of Web Publication | 14-Mar-2017 |
Correspondence Address:
Jinghua Sun
Department of Endodontics, Beijing Stomatological Hospital, Capital Medical University, 4th Tiantan Xili, Docheng District, Beijing - 100050
China
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2155-8213.202026
Introduction: Self-reported tooth loss is highly prevalent in patients with gastric cancer, the second most common malignancy worldwide. Periodontal disease is characterized by loss of the periodontal ligament and alveolar bone, and is a major cause of tooth loss. The theories have been confirmed that chronic systemic inflammation and increased exposure to carcinogenic nitrosamines can increase the risk of cancer, and periodontal pathogens could induce the chronic inflammation. Poor oral hygiene and periodontal diseases may contribute to greater nitrosamine production. The Hypothesis: We hypothesize that periodontal diseases might be an important risk factor for gastric cancer. Major pathogens of periodontal diseases may play a more direct role through local inflammatory responses and carcinogenic transformations in the development of gastric cancer. Evaluation of the Hypothesis: It is possible that periodontal disease may be a marker of a type of immune function that has implications for tumor growth and progression in stomach. If periodontal bacteria indeed play an important role in the development of gastric cancer, the patients should be treated not only focused on the stomach disease itself but also the periodontal problems. Keywords: Gastric cancer, periodontal disease, periodontal pathogens
How to cite this article:
Sun J, Yin J, Hou B. The periodontal infection may be a contributing factor to the development of gastric cancer. Dent Hypotheses 2017;8:27-9 |
| Introduction | |  |
Gastric cancer is the second most common malignancy worldwide.[1] In 2002, 934000 cases were recorded (9% of new cancers) with 700000 deaths.[1] Although the main risk factors, including Helicobacter pylori colonization, smoking, and salt and meat consumption have been identified, it is necessary to improve our understanding of its development. Gastric cancer can be classified as either diffuse or intestinal-type.[2] A continuum of progression from chronic superficial gastritis to chronic atrophic gastritis, intestinal metaplasia, and ultimately dysplasia has been proposed for the intestinal type of gastric cancer, which accounts for more than 70% of gastric cancer cases.[3] A better understanding of factors leading to the development of cancer may extend our knowledge of the biologic basis of carcinogenesis and the natural history of the disease.
Periodontal disease is an inflammatory disease that attacks the supporting tissue around the teeth, resulting in a sustained mild systemic inflammation and elevated levels of circulating inflammatory markers.[4],[5] Periodontal disease is characterized by loss of the periodontal ligament and alveolar bone, and is a major cause of tooth loss.[6]
Tooth loss and gastric cancer
Several epidemiologic studies have found positive associations between tooth loss and upper gastrointestinal cancers.[7],[8] A previous study suggested early tooth loss to be a possible indicator of the disease.[9] Another case-control study in Japan showed the loss of more than 10 teeth increased odds of gastric cancer by two times. There was a significant dose-response relationship between the number of teeth lost and the odds ratios.[10] In 2005, a large cohort study in China investigated the relationship between tooth loss and gastric cancers. That study followed 29584 individuals since 1985. After adjusting for sex, alcohol drinking, and tobacco smoking, statistically significant associations were detected for tooth loss and the risk of dying from both noncardia and cardia gastric cancer.[11] The association was also observed in women, who were mostly (99%) never smokers. However, the influence of H. pylori status was not evaluated in this study. A prospective study of lung cancer in Finland smokers tested the infection with carcinogenic H. pylori to assess the potential confounding of previously reported associations between tooth loss and gastric noncardia cancer. Self-reported tooth lost was found to be positively correlated with gastric noncardia cancer incidence, regardless of H. pylori.[12]
Periodontal disease and Helicobacter pylori
Several studies have found that H. pylori infection in adults may be associated with poor oral hygiene, closely related to pathological deepened periodontal pockets.[13],[14] Periodontitis promotes the formation of deep pockets and increases clinical attachment loss of teeth.[14] Bacterial biofilms are not only commonly associated with a lot of chronic infections, but also more resistant to antibiotics than the non attached bacteria.
Microbial flora of dental plaque is very complex. There are more than 500 kinds of bacteria in plaque samples detected. Bacterial species that inhabiting the biofilm formation do not choose neighbor passively, but through specific interactions with other bacterial species.[15] These interactions, as well as the biofilm structure, bring the resident bacterial species numerous advantages such as increasing the host defense mechanism and antibiotic resistance. For H. pylori positive people, H. pylori may still exist in the oral cavity, even after successful eradication from the stomach. Therefore, it may serve as a possible source to infect and colonize the stomach again. Periodontal pocket provides a reservoir for H. pylori and many other bacteria.[16]
| The Hypothesis | | |
Up until now, several studies have reported the strongest associations between tooth loss and upper gastrointestinal cancers. Because H. pylori is only associated with noncardia gastric cancer, according to the observed increase in risk with tooth loss, we hypothesized that:
- Periodontal diseases might be an important risk factor for gastric cancer.
- Major pathogens of periodontal diseases may play a more direct role through local inflammatory responses and carcinogenic transformations in the development of gastric cancer.
| Evaluation of the Hypothesis | | |
The observed relationships between periodontal diseases and gastric cancer might be explained by chronic systemic inflammation and increased exposure to carcinogenic nitrosamines through smoking or diet.
Inflammation is thought to induce cancer by increasing production of free radicals,[17] increasing apoptotic and necrotic epithelial cell death,[18] and augmenting cell proliferation.[19] Periodontal pathogens may induce chronic inflammation that is promoted by the initiation of cells, leading to the collapse of normal cell growth control, and potential carcinogenic effects.[20] Certain oral bacteria, especially major pathogens of periodontal diseases, may play a more direct role through local inflammatory responses and carcinogenic transformations. A typical cause of periodontitis, Aggregatibacter actinomycetemcomitans, is a Gram-negative bacterium that inhabits the oral cavity of one-third or more of the population.[21] In addition to the oral cavity, A. actinomycetemcomitans has also been isolated from many other lesions in different parts of the body, and hence is regarded as a systemic pathogen.[22],[23],[24] Increased production of carcinogenic nitrosamines is another plausible mechanism which may explain the observed relationships between periodontal diseases and gastric cancer. In the oral cavity, poor oral hygiene and periodontal disease, as well as tobacco use and certain dietary factors, could promote the formation of endogenous nitrosamines by nitrate-reducing bacteria.[25],[26],[27] Tooth loss resulting from poor oral hygiene and periodontal diseases may also contribute to greater nitrosamine production.[12] The link between oral and systemic health is well known. Nitrosamines have been shown to cause a wide range of tumors in animal studies and may be specifically involved in the etiology of cancer. Chronic periodontitis may indicate that the individual’s immune system defects in clearing the infection, and subsequently defects in monitoring the growth of tumor. It is possible that periodontal disease may be a marker of a type of immune function that has implications for tumor growth and progression in stomach. Considering other sources of bias, well-designed epidemiologic studies are needed to establish the strength and temporality of the association between stomach cancer and periodontal diseases/tooth loss. Bacteria in the mouth infect tissue surrounding the tooth, causing inflammation around the tooth and leading to periodontal disease.[28] Few studies have in fact examined the shifts in oral microbial species that occur in gastric cancer individuals. Based on the information above, we hypothesize that the oral microbial diversity shifts in gastric cancer individuals compared with that in healthy ones. The strongest possibility could be that there is a different bacterial community in the oral cavity of individuals harboring gastric cancer. To test this hypothesis, we could conduct an exploratory hospital-based case-control study. In that study, high-throughput sequencing could be chosen as a tool for analyzing the microbial populations obtained from both oral salivary and subgingival plaque samples from patients harboring gastric cancer and control. If periodontal bacteria indeed play an important role in the development of gastric cancer, the patients’ treatment should be focused not only on the stomach disease itself but also the periodontal problems.
Acknowledgement
Funded by the National Natural Science Foundation of China (81400515), the Natural Science Foundation of Beijing, China (7142068), and Beijing Municipal Administration of Hospitals’ Youth Programme (QML20161502).
Financial support and sponsorship
Nil.
Conflict of Interest
There are no conflicts of interest.
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