Periodic Fluctuations in the Incidence of Gastrointestinal Cancer.

PURPOSE: Native stem cells can be periodically replaced during short and long epigenetic intervals. Cancer-prone new stem cells might bring about periodic (non-stochastic) carcinogenic events rather than stochastic events. We investigated the epigenetic non-stochastic carcinogenesis by analyzing regular fluctuations in lifelong cancer incidence. MATERIALS AND METHODS: Korean National Cancer Screening Program data were collected between 2009 and 2016. Non-linear and log-linear regression models were applied to comparatively evaluate non-stochastic and stochastic increases in cancer incidence. Prediction performances of regression models were measured by calculating the coefficient of determination, R2. RESULTS: The incidence of gastric and colorectal cancers fluctuated regularly during both short (8 years) and long (20 years) intervals in the non-linear regression model and increased stochastically in the log-linear regression model. In comparison between the 20-year interval fluctuation model and the stochastic model, R2 values were higher in the 20-year interval fluctuation model of men with gastric cancer (0.975 vs. 0.956), and in the stochastic model of men with colorectal cancer (0.862 vs. 0.877) and women with gastric cancer (0.837 vs. 0.890) and colorectal cancer (0.773 vs. 0.809). Men with gastric cancer showed a high R2 value (0.973) in the 8-year interval fluctuation model as well. CONCLUSION: Lifelong incidence of gastrointestinal cancer tended to fluctuate during short and long intervals, especially in men with gastric cancer, suggesting the influence of an epigenetic schedule.

Site-specific cancer risk in patients with type 2 diabetes: a nationwide population-based cohort study in Korea.

BACKGROUND/AIMS: We aimed to evaluate site-specific cancer risk in diabetic patients and to investigate causal and temporal relationships by analyzing organ-specific cancer risk according to the duration of diabetes. METHODS: Using a database provided by the Korean National Health Insurance Service, we conducted a retrospective, population-based cohort study of adults aged ≥ 30 years from January 2005 to December 2013. To verify the possibility of detection bias or reverse causation, we compared hazard ratios (HRs) for each cancer according to the following duration of diabetes: less than 6 months, 6 months to 3 years, and more than 3 years. RESULTS: The incidence of overall cancer per 1,000 person-years was higher in patients with diabetes than in those without diabetes (20.36 vs. 10.83). The overall cancer risk according to the duration of diabetes was the highest within the first 6 months after diagnosis (HR, 2.03; 95% confidence interval [CI], 1.99 to 2.07), and the HR decreased with the duration of diabetes, ranging from 1.19 (95% CI, 1.18 to 1.21) between 6 months and 3 years to 1.12 (95% CI, 1.11 to 1.13) after 3 years. Both overall cancer risk and HR remained significantly higher in patients with diabetes than in those without diabetes. The risk for prostate cancer was higher in men with diabetes than in those without diabetes (HR, 1.12; 95% CI, 1.10 to 1.14). In women, the risk for endometrial cancer was significantly higher in patients with diabetes than in those without diabetes throughout the duration of diabetes. CONCLUSION: The risk for stomach, colorectum, liver, pancreas, and kidney cancer appeared to be higher in patients with diabetes than in those without diabetes regardless of the sex or duration of diabetes.

Impaired Cortisol and Growth Hormone Counterregulatory Responses among Severe Hypoglycemic Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Elevated levels of cortisol and growth hormone are critical counterregulatory responses to severe hypoglycemia. However, the proportion and clinical characteristics of patients with type 2 diabetes mellitus (DM) who fail to show appropriate cortisol and/or growth hormone secretion in response to severe hypoglycemia have not been investigated. METHODS: We measured plasma cortisol and growth hormone levels in type 2 DM patients with severe hypoglycemia who visited the emergency department between 2006 and 2015. RESULTS: Of 112 hypoglycemic patients, 23 (20.5%) had an impaired cortisol response (<18 µg/dL) and 82 patients (73.2%) had an impaired growth hormone response (<5 ng/mL). Nineteen patients (17.0%) had impaired responses to both cortisol and growth hormone. The patients with impaired responses of cortisol, growth hormone, and both hormones were significantly older and more likely to be female, and had higher admission rates, lower growth hormone levels, and lower adrenocorticotropic hormone levels than the patients with a normal hormonal response. Multivariate logistic regression analysis indicated that an impaired growth hormone response was significantly associated with advanced age, shorter DM duration, a higher admission rate, and a higher body mass index (BMI). An impaired cortisol response was significantly associated with growth hormone levels. Patients with an impaired growth hormone response had higher admission rates than patients with a normal response. CONCLUSION: A considerable number of type 2 DM patients had impaired cortisol and/or growth hormone responses to severe hypoglycemia. Advanced age, shorter DM duration, and higher BMI were independently associated with an abnormal growth hormone response.