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Purpose: Periodontal disease, a major cause of tooth loss in adults, may have systemic effects and has been associated with higher risk of several cancer types. However, the associations of periodontal disease or tooth loss with liver cancer have only been examined prospectively in two studies, neither of which had sufficient statistical power. In addition, no studies assessed the potential confounding by viral hepatitis or Helicobacter pylori infection status.Methods: In this study, we examined the association between tooth loss and primary liver cancer incidence in a prospective cohort of Finnish male smokers (n = 29,096). We used Cox proportional hazards models to calculate multivariable-adjusted hazard ratios (HRs) and 95% CIs. As a sensitivity analysis, we conducted a nested case-control study within the original cohort to assess confounding by hepatitis B or C virus infection and seropositivity of H. pylori.Results: A total of 213 incident primary liver cancers occurred during a mean follow-up of 17 years. Among these cases, having 11-31 permanent teeth lost (HR 1.42, 95% CI 1.01-1.98) or all 32 teeth lost (HR 1.45, 95% CI 1.00-2.10) was each associated with higher risk of liver cancer, compared to those having 0-10 teeth lost. Adjusting for H. pylori seropositivity yielded a small attenuation of the effect estimate.Conclusions: Greater number of teeth lost was associated with higher risk of primary liver cancer in our study. The role of periodontal infection in the development of liver cancer warrants further investigation. [ABSTRACT FROM AUTHOR]

BACKGROUND Debate exists about the relationship between hypovitaminosis D and cardiovascular (CVD) risk. METHODS This study investigated baseline (n=2,271) 25-hydroxyvitamin D (25(OH)D) and baseline and 4 year (n=1,957) CVD risk in a cohort of Finnish middle-aged male smokers. RESULTS The prevalences of measured hypertension, high pulse rate, diabetes, and coronary heart disease were 63%, 16%, 5%, and 10% at baseline and were 64%, 20%, 6%, and 16% at 4 years after baseline. The mean 25(OH)D was 41±18 nmol/L. At baseline, systolic blood pressure (β = −0.048; P = 0.02), and pulse rate (β = −0.043; P = 0.04) were both associated with lower 25(OH)D levels but not coronary heart disease or diabetes prevalence. On remeasuring CVD risk 4 years after baseline, the only significant association with baseline 25(OH)D levels was high pulse rate (β = −0.077; P = 0.001). In addition, a higher 25(OH)D level at baseline was associated with a change in pulse rate (β = −0.055; P = 0.01). These trends for hypertension (baseline) and high pulse rate (baseline and 4 years after baseline) were also seen on adjusted categorical analysis (Ptrend < 0.05). CONCLUSIONS Vitamin D deficiency at baseline was associated with hypertension in Finnish male smokers, but not after 4 years. These results are consistent with recent findings in other large cohort studies with measured blood pressure. Change in pulse rate over time continued to be significantly associated with lower 25(OH)D baseline levels; this new finding should be investigated further. [ABSTRACT FROM AUTHOR]

Background: Elevated systemic exposure to gut-derived bacterial products has been associated with hepatic inflammation and chronic liver diseases, potentially increasing the risk of liver cancer. However, only one prior study prospectively examined exposure to bacterial products in the circulation and risk of liver cancer, with a relatively limited coverage of biomarkers., Methods: We conducted a nested case-control study (224 liver cancer cases and 224 matched controls) in a large cohort of Finnish male smokers followed from baseline (1985-1988) to 2014. The associations between a panel of biomarkers for bacterial translocation and the risk of liver cancer were assessed using multivariable-adjusted conditional logistic regression. The biomarkers included immunoglobulin (Ig) A, IgG, and IgM against lipopolysaccharide (LPS) and flagellin, soluble CD14 (an LPS coreceptor), and the LPS-binding protein., Results: Anti-flagellin IgA [odds ratios (OR), 2.79; 95% confidence intervals (CI), 1.34-5.78; P trend = 0.01] and anti-LPS IgA (2.44; 95% CI, 1.33-4.48; P trend < 0.01) were significantly associated with risk of liver cancer. When restricting the analysis to histologically classified hepatocellular carcinoma, the ORs were 4.18 (95% CI, 1.60-10.92; P trend < 0.01) and 2.48 (95% CI, 1.16-5.29; P trend < 0.01), respectively. The results were not substantially changed after excluding cases diagnosed within the first 5 years of follow-up and those with hepatitis C virus infection., Conclusions: Antibodies to flagellin and LPS were associated with increased risk of liver cancer., Impact: Gut-derived bacterial translocation into the circulation may play a role in the development of primary liver cancer. Our findings could contribute to the understanding of primary liver cancer etiology and further prevention efforts., (©2019 American Association for Cancer Research.)

Case-cohort designs select a random sample of a cohort to be used as control with cases arising from the follow-up of the cohort. Analyses of case-cohort studies with time-varying exposures that use Cox partial likelihood methods can be computer intensive. We propose a piecewise-exponential approach where Poisson regression model parameters are estimated from a pseudolikelihood and the corresponding variances are derived by applying Taylor linearization methods that are used in survey research. The proposed approach is evaluated using Monte Carlo simulations. An illustration is provided using data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of male smokers in Finland, where a case-cohort study of serum glucose level and pancreatic cancer was analyzed., (Copyright © 2012 John Wiley & Sons, Ltd.)