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      Periodontal disease and cancer risk: A nationwide population-based cohort study

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          Abstract

          Background

          Although emerging evidence suggests that periodontitis might increase the risk of cancer, comorbidity and lifestyle behaviors, such as smoking and body mass index (BMI), may have confounded this reported association. This study aimed to investigate whether chronic periodontitis is associated with cancer risk using a large, nationwide database.

          Methods

          We conducted a population-based, retrospective cohort study using data from the Korean National Health Insurance Cohort Database obtained between January 2003 and December 2015. We included 713,201 individuals without a history of cancer who were followed up to 10 years. Confounding factors included demographic factors (age, sex, income, and residential area), lifestyle behaviors (smoking history and BMI), and comorbidities, such as hypertension, diabetes, heart failure, and pulmonary disease, using the Charlson Comorbidity Index. Multivariable Cox regression analysis was applied to estimate the adjusted hazard ratio (aHR) for cancer risk.

          Results

          Of the 713,201 participants, 53,075 had periodontitis and were placed in the periodontitis group; the remaining 660,126 individuals were included as the control group. Overall, the cumulative incidence of cancer in the periodontitis group was 2.2 times higher than that in the control group. The periodontitis group had an increased risk of total cancer compared to the control group after adjusting for age, sex, comorbidities, BMI, and smoking history (aHR, 1.129; 95% confidence interval [CI], 1.089-1.171;  P<0.0001). When examining specific cancer types, significant associations were also observed between periodontitis and stomach cancer (aHR, 1.136; 95% CI, 1.042-1.239; P=0.0037), colon cancer (aHR, 1.129; 95% CI, 1.029-1.239;  P=0.0105), lung cancer (aHR, 1.127; 95% CI, 1.008-1.260; P=0.0353), bladder cancer (aHR, 1.307; 95% CI, 1.071-1.595; P=0.0085), thyroid cancer (aHR, 1.191; 95% CI, 1.085-1.308;  P=0.0002), and leukemia (aHR, 1.394; 95% CI, 1.039-1.872;  P=0.0270). There was no significant association between the development of secondary malignancy and periodontitis in cancer survivors who were alive 5 years after they were diagnosed with the primary malignancy.

          Conclusions

          Periodontal disease, including periodontitis, was associated with increased risk of cancer, which persisted after controlling for confounding factors. Further prospective research is warranted to establish a causal relationship.

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          Most cited references39

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          A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation

          The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
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            Oral diseases: a global public health challenge

            Oral diseases are among the most prevalent diseases globally and have serious health and economic burdens, greatly reducing quality of life for those affected. The most prevalent and consequential oral diseases globally are dental caries (tooth decay), periodontal disease, tooth loss, and cancers of the lips and oral cavity. In this first of two papers in a Series on oral health, we describe the scope of the global oral disease epidemic, its origins in terms of social and commercial determinants, and its costs in terms of population wellbeing and societal impact. Although oral diseases are largely preventable, they persist with high prevalence, reflecting widespread social and economic inequalities and inadequate funding for prevention and treatment, particularly in low-income and middle-income countries (LMICs). As with most non-communicable diseases (NCDs), oral conditions are chronic and strongly socially patterned. Children living in poverty, socially marginalised groups, and older people are the most affected by oral diseases, and have poor access to dental care. In many LMICs, oral diseases remain largely untreated because the treatment costs exceed available resources. The personal consequences of chronic untreated oral diseases are often severe and can include unremitting pain, sepsis, reduced quality of life, lost school days, disruption to family life, and decreased work productivity. The costs of treating oral diseases impose large economic burdens to families and health-care systems. Oral diseases are undoubtedly a global public health problem, with particular concern over their rising prevalence in many LMICs linked to wider social, economic, and commercial changes. By describing the extent and consequences of oral diseases, their social and commercial determinants, and their ongoing neglect in global health policy, we aim to highlight the urgent need to address oral diseases among other NCDs as a global health priority.
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              Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment.

              Increasing evidence links the gut microbiota with colorectal cancer. Metagenomic analyses indicate that symbiotic Fusobacterium spp. are associated with human colorectal carcinoma, but whether this is an indirect or causal link remains unclear. We find that Fusobacterium spp. are enriched in human colonic adenomas relative to surrounding tissues and in stool samples from colorectal adenoma and carcinoma patients compared to healthy subjects. Additionally, in the Apc(Min/+) mouse model of intestinal tumorigenesis, Fusobacterium nucleatum increases tumor multiplicity and selectively recruits tumor-infiltrating myeloid cells, which can promote tumor progression. Tumors from Apc(Min/+) mice exposed to F. nucleatum exhibit a proinflammatory expression signature that is shared with human fusobacteria-positive colorectal carcinomas. However, unlike other bacteria linked to colorectal carcinoma, F. nucleatum does not exacerbate colitis, enteritis, or inflammation-associated intestinal carcinogenesis. Collectively, these data suggest that, through recruitment of tumor-infiltrating immune cells, fusobacteria generate a proinflammatory microenvironment that is conducive for colorectal neoplasia progression. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                23 August 2022
                2022
                : 12
                : 901098
                Affiliations
                [1] 1 Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine , Seoul, South Korea
                [2] 2 College of Medicine, Yonsei University , Seoul, South Korea
                [3] 3 Department of Internal Medicine, Yonsei University College of Medicine , Seoul, South Korea
                [4] 4 Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine , Seoul, South Korea
                [5] 5 Department of Preventive Dentistry and Public Oral Health, BK21 FOUR Project, Yonsei University College of Dentistry , Seoul, South Korea
                [6] 6 Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei University College of Medicine , Seoul, South Korea
                [7] 7 Graduate School of Medical Science, Brain Korea 21 Project, Severance Biomedical Science Institute, Yonsei University College of Medicine , Seoul, South Korea
                [8] 8 Institute for Innovation in Digital Healthcare (IIDH), Severance Hospital , Seoul, South Korea
                Author notes

                Edited by: Dana Kristjansson, Norwegian Institute of Public Health (NIPH), Norway

                Reviewed by: Yan-Shen Shan, National Cheng Kung University Hospital, Taiwan; João Botelho, Egas Moniz Interdisciplinary Research Center, Portugal; Hee Sam Na, Pusan National University, South Korea; Marwa Abbass, Cairo University, Egypt; Kristina Bertl, Malmö University, Sweden; Nina Shenoy, Nitte University, India

                *Correspondence: Han Sang Kim, MODEERFHS@ 123456yuhs.ac ; Inkyung Jung, IJUNG@ 123456yuhs.ac

                †These authors share first authorship

                ‡These authors share senior authorship

                This article was submitted to Cancer Epidemiology and Prevention, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.901098
                9445882
                36081548
                ef9ef645-b136-4ed8-9ed2-6d669b0ff420
                Copyright © 2022 Kim, Nam, Park, Kim, Lee, Ahn, Shin, Park, Jung, Kim, Jung and Kim

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 21 March 2022
                : 01 August 2022
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 39, Pages: 9, Words: 4072
                Funding
                Funded by: National Research Foundation of Korea , doi 10.13039/501100003725;
                Award ID: 2022R1A2C4001879, 2022M3A9F3016364
                Funded by: Korea Health Industry Development Institute , doi 10.13039/501100003710;
                Award ID: HI21C0974
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                periodontal disease,cancer risk,cohort study,periodontitis,oral inflammation

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