A study published in Cancer Prevention Research, a journal of the American Association for Cancer Research, funded by grants from the National Institutes of Health (NIH), the American Institute for Cancer Research, the American Cancer Society and others, demonstrates that periodontal disease, a disease that affects the gingiva, the supporting connective tissue, and alveolar bone, was associated with an increased risk of two precursors of colorectal cancer. [1]

According to the American Dental Association, periodontitis, the most severe form of periodontal disease.

“Periodontal disease is prevalent among adults, with periodontitis affecting more than 40 percent of the U.S. population,” explained the study’s lead author, Mingyang Song, MD, ScD, assistant professor of clinical epidemiology and nutrition at the Harvard T.H. Chan School of Public Health.

Data from the National Health and Nutrition Examination Survey (NHANES), a survey research program conducted by the National Center for Health Statistics (NCHS, now nearly a decade old, demonstrated that 46% of adults in the United States, representing 64.7 million people, had periodontitis, with 8.9% having severe periodontitis. [2]

Overall, 3.8% of all periodontal sites (10.6% of all teeth) had periodontal probing depth (PD) ≥4 mm, and 19.3% of sites (37.4% teeth) had a clinical attachment loss (AL) ≥3 mm. [2]

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The data also confirmed that the prevalence of periodontitis was positively associated with increasing age and was generally higher among males. Furthermore, the prevalence of periodontitis was highest in Hispanics (63.5%) and non-Hispanic blacks (59.1%), followed by non-Hispanic Asian Americans (50.0%), and lowest in non-Hispanic whites (40.8%). Finally, the data showed that the prevalence varied two-fold between the lowest and highest levels of socioeconomic status, whether defined by poverty or education. [2]

Photo: Mingyang Song, MD, ScD, assistant professor of clinical epidemiology and nutrition at the Harvard T.H. Chan School of Public Health. Photo courtesy: © 2020 AACR

Periodontal disease and cancer
The understanding that periodontal disease and cancer may be linked is not new.

For example, previous research has explored associations between periodontal disease and several cancer types, including breast, head, and neck, and pancreatic cancer, but little research has examined potential associations between periodontal disease and colorectal cancer.

Link with pancreatic cancer
During the 2016 annual meeting of the American Association for Cancer Research (AACR), Jiyoung Ahn, Ph.D., associate professor of population health and associate director of population sciences at the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center in New York, NY, discussed the connection between two particular strains of oral bacteria and pancreatic cancer.*

As part of their study, Ahn and her colleagues analyzed oral wash samples from 361 people who later went on to develop pancreatic cancer and from 371 matched controls. The team used genomic technologies to generate a profile of the bacterial species present in each sample and performed logistic regression analysis to study the association between individual species of bacteria and the risk of pancreatic cancer.  They also controlled for other risk factors, including age, smoking status, and body mass index.

Ahn and her team found that a bacteria called Porphyromonas gingivalis, which is acid-resistant and may migrate to the colon and change colonic functions, was associated with a 59% increased risk for pancreatic cancer and that another type of bacteria, Aggregatibacter actinomycetemcomitans, was associated with a 119% increased risk.[3][4]

However, the data Ahn and her colleagues presented did not show a causal relationship, but rather the first steps in understanding a potential risk factor for pancreatic cancer.

Almost a decade before Ahn and her team presented their study results during the 2016 annual meeting of the AACR, Dominique S Michaud, today Professor of Public Health and Community Medicine at Tufts University School of Medicine, demonstrated that compared with no periodontal disease, a history of periodontal disease was associated with increased pancreatic cancer risk (overall, multivariable RR = 1.64, 95% CI = 1.19 to 2.26; P = .002; crude incidence rates: 61 versus 25 per 100,000 person-years; among never smokers, multivariable RR = 2.09, 95% CI = 1.18 to 3.71; P = .01; crude incidence rates: 61 versus 19 per 100,000 person-years).[5]

Bothe Aha and Michaud conclude that their studies provide evidence that oral microbiota plays a role in the etiology of pancreatic cancer, and may potentially point to accessible means for the prevention of pancreatic cancer.

Photo: Chun-Han Lo, MD, MPH, a postdoctoral research fellow in the Clinical and Translational Epidemiology Unit and Division of Gastroenterology at Massachusetts General Hospital and Harvard Medical School. Photo courtesy: © 2020 AACR

Colorectal cancer
In the study published this week, researchers examined two types of colorectal neoplasms: serrated polyps** and conventional adenomas, both of which frequently develop into colorectal cancer.[1][6]

Contributing author Chun-Han Lo, MD, MPH, a postdoctoral research fellow in the Clinical and Translational Epidemiology Unit and Division of Gastroenterology at Massachusetts General Hospital and Harvard Medical School, explained that serrated polyps are often characterized by mutations in the gene BRAF and microsatellite instability, while adenomas are characterized by mutations in the gene KRAS and chromosomal instability.

The researchers collected data on periodontal disease and tooth loss from the Nurses’ Health Study and the Health Professionals Follow-up Study. Study enrollees reported whether they had ever been diagnosed with colorectal polyps or adenomas, and the researchers confirmed diagnoses via medical records.

Study design
In all, the study enrolled 42,486 people and used data from 84,714 person-endoscopies. Overall, those who had periodontal disease had a 17% higher risk of developing serrated polyps and an 11% higher risk of developing conventional adenomas. Those who had lost four or more teeth had a 20% higher risk of developing serrated polyps.

Among participants with periodontal disease, the more teeth a person lost, the higher their risk of advanced conventional adenomas. Those who had periodontal disease and had lost one to three teeth had a 28% higher chance of developing advanced conventional adenomas, while those who had periodontal disease and lost four or more teeth had a 36% higher risk.

The researchers pointed out that the association between tooth loss and small serrated polyps and advanced conventional adenomas was not observed for large serrated polyps. Song said this finding was somewhat surprising, as large serrated polyps are known predictors of cancer risk. He said the small sample size of large serrated polyps may have limited the statistical power for detecting that association.

Increased risk
While smoking is a known cause of both periodontal disease and colorectal cancer, the authors noted that even nonsmokers with tooth loss had higher rates of serrated polyps and conventional adenomas.

“Having ever been diagnosed with periodontal disease puts a person at risk of colorectal cancer precursor lesions, some of which may eventually lead to colorectal cancer,” Song said.

“Regular screening colonoscopy and lifestyle modifications are particularly important in this population.”

The authors said these study results contribute to a growing body of research on how the oral microbiome, a collection of bacteria that affects the progression of health and disease, may influence the development of cancer.

“The oral cavity harbors a wide array of microbial communities,” Song said.

“Various factors, including poor oral hygiene, genetic susceptibility, smoking, diabetes, and obesity can result in an excess of oral pathogens that may induce host inflammation and immune dysregulation,” he added.

Good oral health
Song said the results of this study, combined with previous research linking periodontal disease to some types of cancer, reinforce the importance of good oral health to ensure a healthy oral microbiome.

Also, people who have experienced tooth loss may benefit from more intensive cancer screening measures.

Study limitations
Song noted that the study’s limitations include the self-reporting of tooth loss and the small sample size for large serrated polyps. Also, most respondents were white, and he cautioned that results should be confirmed in more diverse populations.

* With just 7.7% of patients surviving five years or more after their diagnosis, pancreatic cancer is considered one of the deadliest types of cancer.
** Historically, serrated polyps have long been thought to lack malignant potential in the human colorectum. However, based on molecular biology, scientists have identified the serrated pathway linked to colorectal cancer. This finding improved the general understanding of the pathogenesis of colorectal cancers and leading to the belief that serrated polyps such as traditional serrated adenoma and sessile serrated adenoma/polyps (SSA/P) should be considered to be precursor lesions of the serrated pathway. Furthermore, it has been suggested that SSA/P in the proximal colon is a precursor lesion of the pathogenesis of colorectal cancer and is characterized by BRAF mutation and a CpG island methylator phenotype with or without microsatellite instability.[6]

[1] Lo C-H, Nguyen LH, Wu K, Ogino S, Chan AT, Giovannucci EL, Song M. Periodontal Disease, Tooth Loss, and Risk of Serrated Polyps and Conventional Adenomas. Cancer Prev Res 2020;13:699–706
doi: 10.1158/1940-6207.CAPR-20-0090
[2] Eke PI, Dye BA, Wei L, et al. Update on Prevalence of Periodontitis in Adults in the United States: NHANES 2009 to 2012. J Periodontol. 2015;86(5):611-622. doi:10.1902/jop.2015.140520
[3] Fan X, Alekseyenko AV, Wu J, Jacobs EJ, Gapstur SM, Purdue MP, Abnet CC, Stolzenberg-Solomon R, et al. Human oral microbiome and prospective risk for pancreatic cancer: a population-based, nested case-control study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl): Abstract nr 4350.
[4] Walker MY, Pratap S, Southerland JH, Farmer-Dixon CM, Lakshmyya K, Gangula PR. Role of oral and gut microbiome in nitric oxide-mediated colon motility. Nitric Oxide. 2018;73:81-88. doi:10.1016/j.niox.2017.06.003
[5] Michaud DS, Joshipura K, Giovannucci E, Fuchs CS. A prospective study of periodontal disease and pancreatic cancer in US male health professionals. J Natl Cancer Inst. 2007;99(2):171-175. doi:10.1093/jnci/djk021
[6] Sweetser S, Smyrk TC, Sinicrope FA. Serrated colon polyps as precursors to colorectal cancer. Clin Gastroenterol Hepatol. 2013;11(7):760-e55. doi:10.1016/j.cgh.2012.12.004

Featured image: Woman; dental surgery close-up. Photo courtesy © 2016 – 2020 Fotolia/Adobe

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