Microbiota, Oral Microbiome, and Pancreatic Cancer

Only 30% of patients diagnosed with pancreatic cancer survive one year post-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 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

A Prospective Study of Periodontal Disease and Risk of Gastric and Duodenal Ulcer in Male Health Professionals

OBJECTIVES: Periodontal disease has been associated with higher circulating levels of inflammatory markers and conditions associated with chronic inflammation, including vascular disease, diabetes mellitus, and cancer. Limited data exist on the relationship between periodontal disease and gastric and duodenal ulcer. METHODS: We conducted a prospective cohort study of 49,120 men in the Health Professionals Follow-up Study, aged 40–75 years at enrollment in 1986. Biennially, we assessed periodontal disease, tooth loss, and other risk factors for gastric and duodenal ulcer. We validated diagnoses of gastric and duodenal ulcer through medical record review. We used Cox proportional hazards modeling, adjusting for potential confounders, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We documented 138 cases of gastric ulcer and 124 cases of duodenal ulcer with available information on Helicobacter pylori status over 24 years of follow-up. After adjustment for risk factors, including smoking and regular use of aspirin and non-steroidal anti-inflammatory drugs, men with periodontal disease with bone loss had a multivariate HR of ulcer of 1.62 (95% CI, 1.24–2.12). Periodontal disease appeared to be associated with a similar risk of developing ulcers that were H. pylori negative (HR 1.75; 95% CI, 1.26–2.43) than H. pylori positive (HR 1.40; 95% CI, 0.87-2.24), as well as ulcers in the stomach (HR 1.75; 95% CI, 1.21–2.53) than ulcers in the duodenum (HR 1.47; 95% CI, 0.98–2.19). CONCLUSIONS: Periodontal disease is associated with an increased risk of incident gastric and duodenal ulcer. This relationship may be mediated by alterations in the oral and gastrointestinal microbiome and/or systemic inflammatory factors

Meat and Components of Meat and the Risk of Bladder Cancer in the NIH-AARP Diet and Health Study

BACKGROUND: Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat-related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs). The authors comprehensively investigated the association between meat and meat components and bladder cancer. METHODS: During 7 years of follow-up, 854 transitional cell bladder-cancer cases were identified among 300,933 men and women who had completed a validated food-frequency questionnaire in the large prospective NIH-AARP Diet and Health Study. The authors estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat by using quantitative databases of measured values. Total dietary nitrate and nitrite were calculated based on literature values. RESULTS: The hazard ratios (HR) and 95% confidence intervals (CI) for red meat (HR for fifth quintile compared with first quintile, 1.22; 95% CI, 0.96-1.54; Ptrend = .07) and the HCA 2-amino-1 methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) (HR, 1.19; 95% CI, 0.95-1.48; Ptrend = .06) conferred a borderline statistically significant increased risk of bladder cancer. Positive associations were observed in the top quintile for total dietary nitrite (HR, 1.28; 95% CI, 1.02-1.61; Ptrend = .06) and nitrate plus nitrite intake from processed meat (HR, 1.29; 95% CI, 1.00-1.67; Ptrend = .11). CONCLUSIONS: These findings provided modest support for an increased risk of bladder cancer with total dietary nitrite and nitrate plus nitrite from processed meat. Results also suggested a positive association between red meat and PhIP and bladder carcinogenesis

Comparisons of oral, intestinal, and pancreatic bacterial microbiomes in patients with pancreatic cancer and other gastrointestinal diseases

Background: Oral microbiota is believed to play important roles in systemic diseases, including cancer. Methods: We collected oral samples (tongue, buccal, supragingival, and saliva) and pancreatic tissue or intestinal samples from 52 subjects, and characterized 16S rRNA genes using high-throughput DNA sequencing. Results: Bray–Curtis plot showed clear separations between bacterial communities in the oral cavity and those in intestinal and pancreatic tissue samples. PERMANOVA tests indicated that bacterial communities from buccal samples were similar to supragingival and saliva samples, and pancreatic duct samples were similar to pancreatic tumor samples, but all other samples were significantly different from each other. A total of 73 unique Amplicon Sequence Variants (ASVs) were shared between oral and pancreatic or intestinal samples. Only four ASVs showed significant concordance, and two specific bacterial species (Gemella morbillorum and Fusobacterium nucleatum subsp. vincentii) showed consistent presence or absence patterns between oral and intestinal or pancreatic samples, after adjusting for within-subject correlation and disease status. Lastly, microbial co-abundance analyses showed distinct strain-level cluster patterns among microbiome members in buccal, saliva, duodenum, jejunum, and pancreatic tumor samples. Conclusions: Our findings indicate that oral, intestinal, and pancreatic bacterial microbiomes overlap but exhibit distinct co-abundance patterns in patients with pancreatic cancer and other gastrointestinal diseases

Preventable Cancer Burden Associated With Poor Diet in the United States.

BACKGROUND: Diet is an important risk factor for cancer that is amenable to intervention. Estimating the cancer burden associated with diet informs evidence-based priorities for nutrition policies to reduce cancer burden in the United States. METHODS: Using a comparative risk assessment model that incorporated nationally representative data on dietary intake, national cancer incidence, and estimated associations of diet with cancer risk from meta-analyses of prospective cohort studies, we estimated the annual number and proportion of new cancer cases attributable to suboptimal intakes of seven dietary factors among US adults ages 20 years or older, and by population subgroups. RESULTS: An estimated 80 110 (95% uncertainty interval [UI] = 76 316 to 83 657) new cancer cases were attributable to suboptimal diet, accounting for 5.2% (95% UI = 5.0% to 5.5%) of all new cancer cases in 2015. Of these, 67 488 (95% UI = 63 583 to 70 978) and 4.4% (95% UI = 4.2% to 4.6%) were attributable to direct associations and 12 589 (95% UI = 12 156 to 13 038) and 0.82% (95% UI = 0.79% to 0.85%) to obesity-mediated associations. By cancer type, colorectal cancer had the highest number and proportion of diet-related cases (n = 52 225, 38.3%). By diet, low consumption of whole grains (n = 27 763, 1.8%) and dairy products (n = 17 692, 1.2%) and high intake of processed meats (n = 14 524, 1.0%) contributed to the highest burden. Men, middle-aged (45-64 years) and racial/ethnic minorities (non-Hispanic blacks, Hispanics, and others) had the highest proportion of diet-associated cancer burden than other age, sex, and race/ethnicity groups. CONCLUSIONS: More than 80 000 new cancer cases are estimated to be associated with suboptimal diet among US adults in 2015, with middle-aged men and racial/ethnic minorities experiencing the largest proportion of diet-associated cancer burden in the United States.This work was supported by NIH/ NIMHD 1R01MD011501 (FFZ), NIH/ NHLBI R01HL115189 (DM), United Kingdom Medical Research Council Epidemiology Unit Core Support (MC_UU_12015/5) (FI), and American Heart Association postdoctoral fellowship (JXL)

Understanding the Role of the Immune System in the Development of Cancer: New Opportunities for Population-Based Research

Understanding the precise role of the immune system in cancer has been hindered by the complexity of the immune response and challenges in measuring immune cell types in health and disease in the context of large epidemiologic studies. In this review, we present the rationale to study immunity in cancer and highlight newly available tools to further elucidate the epidemiologic factors driving individual variation in the immune response in cancer. Here, we summarize key studies that have evaluated the role of immunological status on risk of cancer, discuss tools that have been used in epidemiological studies to measure immune status, as well as new evolving methodologies where application to epidemiology is becoming more feasible. We also encourage further development of novel emerging technologies that will continue to enable prospective assessment of the dynamic and complex role played by the immune system in cancer susceptibility. Finally, we summarize characteristics and environmental factors that impact the immune response, as these will need to be considered in epidemiological settings. Overall, we consider the application of a systems biologic approach and highlight new opportunities to understand the immune response in cancer risk.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Association for Cancer Research and can be found at: http://cebp.aacrjournals.org/content/24/12/181

History of Periodontitis Diagnosis and Edentulism as Predictors of Cardiovascular Disease, Stroke, and Mortality in Postmenopausal Women

BACKGROUND: Few studies have reported associations between periodontitis and cardiovascular disease (CVD) risk in older women, which is the objective of the present investigation. METHODS AND RESULTS: Participants were 57 001 postmenopausal women ages 55 to 89 years (mean 68 years; \u3e 85% 60 and older) who were enrolled (1993-1998) in the Women\u27s Health Initiative Observational Study, and were without known CVD when history of periodontitis and edentulism was assessed by questionnaire at study Year-5 (1998-2003). There were 3589 incident CVD events and 3816 total deaths during a mean follow-up of 6.7 years. In multivariable analysis, periodontitis was not associated with CVD events, but was associated with higher total mortality (hazard ratio (HR)=1.12, 95% CI: 1.05-1.21). Edentulism was associated with higher age- and smoking-adjusted risks of CVD (HR=1.42, 95% CI: 1.27-1.59) and mortality (HR=1.47, 95% CI: 1.32-1.63). Further adjustment eliminated the association with CVD, but mortality remained significantly increased (HR=1.17, 95% CI: 1.02-1.33). Stratification on age, race-ethnicity, smoking, and diabetes mellitus yielded comparable results; however, edentulism was more strongly associated with CVD in women reporting \u3e /=1 dental visit (HR=1.57) compared with (HR 1.03, interaction P=0.004) annually. CONCLUSIONS: In community-dwelling older women, edentulism was associated with increased risks of CVD and total mortality, and presence of periodontitis, which is more prevalent than edentulism, was associated with 17% higher mortality rate. These findings suggest that improving periodontal condition of the general population could reduce overall mortality