Abstract
Periodontal disease, which includes gingivitis and periodontitis, is highly prevalent in adults and disease severity increases with age. The relationship between periodontal disease and oral ...cancer has been examined for several decades, but there is increasing interest in the link between periodontal disease and overall cancer risk, with systemic inflammation serving as the main focus for biological plausibility. Numerous case-control studies have addressed the role of oral health in head and neck cancer, and several cohort studies have examined associations with other types of cancers over the past decade. For this review, we included studies that were identified from either 11 published reviews on this topic or an updated literature search on PubMed (between 2011 and July 2016). A total of 50 studies from 46 publications were included in this review. Meta-analyses were conducted on cohort and case-control studies separately when at least 4 studies could be included to determine summary estimates of the risk of cancer in relation to 1) periodontal disease or 2) tooth number (a surrogate marker of periodontal disease) with adjustment for smoking. Existing data provide support for a positive association between periodontal disease and risk of oral, lung, and pancreatic cancers; however, additional prospective studies are needed to better inform on the strength of these associations and to determine whether other cancers are associated with periodontal disease. Future studies should include sufficiently large sample sizes, improved measurements for periodontal disease, and thorough adjustment for smoking and other risk factors.
Recent evidence indicates that obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers, including those of the colon, prostate, and ...pancreas. Obesity, physical inactivity, visceral adiposity, hyperglycemia, and hyperinsulinemia are relatively consistent risk factors for colon cancer and adenoma. Also, patients with type 2 diabetes mellitus have a higher risk of colon cancer. For prostate cancer, the relationship to obesity appears more complex. Obesity seems to contribute to a greater risk of aggressive or fatal prostate cancer but perhaps to a lower risk of nonaggressive prostate cancer. Furthermore, men with type 2 diabetes mellitus are at lower risk of developing prostate cancer. Long-standing type 2 diabetes increases the risk of pancreatic cancer by approximately 50%. Furthermore, over the past 6 years, a large number of cohort studies have reported positive associations between obesity and pancreatic cancer. Together with data from prediagnostic blood specimens showing positive associations between glucose levels and pancreatic cancer up to 25 years later, sufficient evidence now supports a strong role for diabetes and obesity in pancreatic cancer etiology. The mechanisms for these associations, however, remain speculative and deserve further study. Hyperinsulinemia may be important, but the role of oxidative stress initiated by hyperglycemia also deserves further attention.
Established risk factors for pancreatic cancer, including tobacco smoking, chronic pancreatitis, obesity and type 2 diabetes, collectively account for less than half of all pancreatic cancer cases. ...Inflammation plays a key role in pancreatic carcinogenesis, but it is unclear what causes local inflammation, other than pancreatitis. Epidemiological data suggest that Helicobacter pylori may be a risk factor for pancreatic cancer, and more recently, data suggest that periodontal disease, and Porphyromonas gingivalis, a pathogen for periodontal disease, may also play a role in pancreatic carcinogenesis. Individuals with periodontal disease have elevated markers of systemic inflammation, and oral bacteria can disseminate into the blood, stomach, heart and even reach the brain. These infections may contribute to the progression of pancreatic cancer by acting jointly with other pancreatic cancer risk factors that impact the inflammation and immune response, such as smoking and obesity, and the ABO genetic variant, recently linked to pancreatic cancer through genome-wide association studies. The complex interplay between bacteria, host immune response and environmental factors has been examined closely in relation to gastric cancer, but new research suggests bacteria may be playing a role in other gastrointestinal cancers. This review will summarize the literature on epidemiological studies examining infections that have been linked to pancreatic cancer and propose mechanistic pathways that may tie infections to pancreatic cancer.
In mice, bacteria from the mouth can translocate to the pancreas and impact pancreatic cancer progression. In humans, oral bacteria associated with periodontal disease have been linked to pancreatic ...cancer risk. It is not known if DNA bacterial profiles in the pancreas and duodenum are similar within individuals.
Tissue samples were obtained from 50 subjects with pancreatic cancer or other conditions requiring foregut surgery at the Rhode Island Hospital (RIH), and from 34 organs obtained from the National Disease Research Interchange. 16S rRNA gene sequencing was performed on 189 tissue samples (pancreatic duct, duodenum, pancreas), 57 swabs (bile duct, jejunum, stomach), and 12 stool samples.
Pancreatic tissue samples from both sources (RIH and National Disease Research Interchange) had diverse bacterial DNA, including taxa typically identified in the oral cavity. Bacterial DNA across different sites in the pancreas and duodenum were highly subject specific in both cancer and noncancer subjects. Presence of genus
was significantly higher in noncancer subjects compared with cancer subjects and the relative abundance of
spp., previously associated with colorectal cancer, was higher in cancer subjects compared with noncancer subjects.
Bacterial DNA profiles in the pancreas were similar to those in the duodenum tissue of the same subjects, regardless of disease state, suggesting that bacteria may be migrating from the gut into the pancreas. Whether bacteria play a causal role in human pancreatic cancer needs to be further examined.
Identifying bacterial taxa that differ in cancer patients can provide new leads on etiologically relevant bacteria.
Only 30% of patients with a diagnosis of pancreatic cancer survive 1 year after the diagnosis. Progress in understanding the causes of pancreatic cancer has been made, including solidifying the ...associations with obesity and diabetes, and a proportion of cases should be preventable through lifestyle modifications. Unfortunately, identifying reliable biomarkers of early pancreatic cancer has been extremely challenging, and no effective screening modality is currently available for this devastating form of cancer. Recent data suggest that the microbiota may play a role in the disease process, but many questions remain. Future studies focusing on the human microbiome, both etiologically and as a marker of disease susceptibility, should shed light on how to better tackle prevention, early detection, and treatment of this highly fatal disease.
While evidence is increasingly consistent with a positive association between periodontitis and cancer risk, most studies have relied on self-reported periodontitis. In this study, we prospectively ...evaluated the association of periodontal disease severity with cancer risk in black and white older adults in a cohort study that included a dental examination.
Included were 7466 participants in the Atherosclerosis Risk in Communities study cohort who at visit 4 (1996-1998) reported being edentulous or underwent the dental examination. Probing depth and gingival recession were measured at six sites on all teeth; these measurements were used to define periodontal disease severity. Incident cancers (n = 1648) and cancer deaths (n = 547) were ascertained during a median of 14.7 years of follow-up. All statistical tests were two-sided.
An increased risk of total cancer (hazard ratio HR = 1.24, 95% confidence interval CI = 1.07 to 1.44, Ptrend = .004) was observed for severe periodontitis (>30% of sites with attachment loss >3 mm) compared with no/mild periodontitis (<10% of sites with attachment loss >3 mm), adjusting for smoking and other factors. Strong associations were observed for lung cancer (HR = 2.33, 95% CI = 1.51 to 3.60, Ptrend < .001), and elevated risks were noted for colorectal cancer for severe periodontitis, which were significant among never smokers (HR = 2.12, 95% CI = 1.00 to 4.47). Associations were generally weaker, or not apparent among black participants, except for lung and colorectal cancers, where associations were similar by race. No associations were observed for breast, prostate, or hematopoietic and lymphatic cancer risk.
This study provides additional evidence that cancer risk, especially for lung and colorectal cancer, is elevated in individuals with periodontitis. Additional research is needed to understand cancer site-specific and racial differences in findings.
Summary Background Studies suggest that tooth loss and periodontal disease might increase the risk of developing various cancers; however, smoking might have confounded the reported associations. We ...aimed to assess whether periodontal disease or tooth loss is associated with cancer risk. Methods The analysis was done in a prospective study (the Health Professionals Follow-Up Study HPFS), which was initiated in 1986 when US male health professionals aged 40–75 years responded to questionnaires posted by the Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA. In addition to the baseline questionnaires, follow-up questionnaires were posted to all living participants every 2 years and dietary questionnaires every 4 years. At baseline, participants were asked whether they had a history of periodontal disease with bone loss. Participants also reported number of natural teeth at baseline and any tooth loss during the previous 2 years was reported on the follow-up questionnaires. Smoking status and history of smoking were obtained at baseline and in all subsequent questionnaires. Additionally at baseline, participants reported their mean frequency of food intake over the previous year on a 131-item semiquantitative food-frequency questionnaire. Participants reported any new cancer diagnosis on the follow-up questionnaires. Endpoints for this study were risk of total cancer and individual cancers with more than 100 cases. Multivariate hazard ratios (HRs) and 95% CIs were calculated by use of Cox proportional hazard models according to periodontal disease status and number of teeth at baseline. Findings In the main analyses, 48 375 men with median follow-up of 17·7 years (1986 to Jan 31, 2004) were eligible after excluding participants diagnosed with cancer before 1986 (other than non-melanoma skin cancer, n=2076) and those with missing data on periodontal disease (n=1078). 5720 incident cancer cases were documented (excluding non-melanoma skin cancer and non-aggressive prostate cancer). The five most common cancers were colorectal (n=1043), melanoma of the skin (n=698), lung (n=678), bladder (n=543), and advanced prostate (n=541). After adjusting for known risk factors, including detailed smoking history and dietary factors, participants with a history of periodontal disease had an increased risk of total cancer (HR 1·14 95% CI 1·07–1·22) compared with those with no history of periodontal disease. By cancer site, significant associations for those with a history of peridontal disease were noted for lung (1·36 1·15–1·60), kidney (1·49 1·12–1·97), pancreas (1·54 1·16–2·04; findings previously published), and haematological cancers (1·30 1·11–1·53). Fewer teeth at baseline (0–16) was associated with an increase in risk of lung cancer (1·70 1·37–2·11) for those with 0–16 teeth versus those with 25–32 teeth. In never-smokers, periodontal disease was associated with significant increases in total (1·21 1·06–1·39) and haematological cancers (1·35 1·01–1·81). By contrast, no association was noted for lung cancer (0·96 0·46–1·98). Interpretation Periodontal disease was associated with a small, but significant, increase in overall cancer risk, which persisted in never-smokers. The associations recorded for lung cancer are probably because of residual confounding by smoking. The increased risks noted for haematological, kidney, and pancreatic cancers need confirmation, but suggest that periodontal disease might be a marker of a susceptible immune system or might directly affect cancer risk. Funding National Cancer Institute, National Institutes of Health, Bethesda, MD, USA (grant number P01CA055075).
Recent studies have investigated the association between periodontal disease, tooth loss, and several systemic diseases including cancer, cardiovascular disease, and preterm birth. Periodontal ...disease, a chronic inflammatory condition, is highly prevalent in adult populations around the world, and may be preventable. Estimates of prevalence vary between races and geographic regions, with a marked increase in the occurrence of periodontal disease with advancing age. Worldwide estimates for the prevalence of severe periodontal disease generally range from 10 to 15%. The relationship between oral health and cancer has been examined for a number of specific cancer sites. Several studies have reported associations between periodontal disease or tooth loss and risk of oral, upper gastrointestinal, lung, and pancreatic cancer in different populations. In a number of studies, these associations persisted after adjustment for major risk factors, including cigarette smoking and socioeconomic status. This review provides a summary of these findings, discusses possible biological mechanisms involved, and raises methodological issues related to studying these relationships.
Abstract The relation between Schistosomiasis and bladder cancer is well-established and accounts for the high rates of bladder cancer in a number of developing countries, including Egypt. In ...developed countries, transitional cell carcinoma is the predominant type of bladder cancer, whereas in Schistosomiasis-endemic regions, squamous cell carcinoma is the most common type. In this review, experimental and observational data on infection, inflammation, and bladder cancer are summarized with special emphasis on transitional cell carcinoma. Findings from numerous studies suggest that inflammation is likely to have an important role in bladder carcinogenesis in developed countries. Future studies need to focus in greater detail on risk factors that increase inflammation of the bladder, examine genetic susceptibility to inflammatory pathways, and include markers of inflammation measured prior to cancer diagnosis. Understanding the role of inflammation on transitional cell carcinogenesis may provide important insights on how to prevent the sixth most common cancer in the United States.
To quantify disparities in health and economic burdens of cancer attributable to suboptimal diet among US adults.
Using a probabilistic cohort state-transition model, we estimated the number of new ...cancer cases and cancer deaths, and economic costs of 15 diet-related cancers attributable to suboptimal intake of 7 dietary factors (a low intake of fruits, vegetables, dairy, and whole grains and a high intake of red and processed meats and sugar-sweetened beverages) among a closed cohort of US adults starting in 2017.
Suboptimal diet was estimated to contribute to 3.04 (95% uncertainty interval UI = 2.88, 3.20) million new cancer cases, 1.74 (95% UI = 1.65, 1.84) million cancer deaths, and $254 (95% UI = $242, $267) billion economic costs among US adults aged 20 years or older over a lifetime. Diet-attributable cancer burdens were higher among younger adults, men, non-Hispanic Blacks, and individuals with lower education and income attainments than other population subgroups. The largest disparities were for cancers attributable to high consumption of sugar-sweetened beverages and low consumption of whole grains.
Suboptimal diet contributes to substantial disparities in health and economic burdens of cancer among young adults, men, racial/ethnic minorities, and socioeconomically disadvantaged groups. (
. 2021;111(11):2008-2018. https://doi.org/10.2105/AJPH.2021.306475).
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