Tse Yen Yang

The relationship between secondary hyperparathyroidism and thyroid cancer in end stage renal disease: A population based cohort study

OBJECTIVESnWe conducted a retrospective cohort study to investigate the risk of cancer in end stage renal disease (ESRD) patients with secondary hyperparathyroidism (HPT).nnnPATIENTS AND METHODSnThis study investigated the elevated overall cancer risk in ESRD patients with secondary HPT in Taiwan. We used a population-based retrospective cohort consisting of original claims data of 1 million beneficiaries randomly sampled from the Taiwan National Health Insurance Research Database (NHIRD). We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of cancer in the ESRD with secondary HPT and comparison cohorts, using the Cox proportional hazards regression model.nnnRESULTSnWe observed that ESRD patients with secondary HPT exhibited a 10.1-fold increased risk of thyroid cancer than did ESRD patients without this parathyroid complication, after adjusting for comorbidities (95% confidence interval=1.12-91.0).nnnCONCLUSIONnThese phenomena indicate that ESRD patients with secondary HPT are at greater risk of thyroid cancer. Physicians should be alert for occult thyroid cancer in ESRD patients with secondary HPT.

Comparison of Genome-wide DNA Methylation in Urothelial Carcinomas of Patients with and without Arsenic Exposure

BACKGROUNDnArsenic is a well-documented carcinogen of human urothelial carcinoma (UC) with incompletely understood mechanisms.nnnOBJECTIVESnThis study aimed to compare the genome-wide DNA methylation profiles of arsenic-induced UC (AsUC) and non-arsenic-induced UC (Non-AsUC), and to assess associations between site-specific methylation levels and cumulative arsenic exposure.nnnMETHODSnGenome-wide DNA methylation profiles in 14 AsUC and 14 non-AsUC were analyzed by Illumina Infinium methylation27 BeadChip and validated by bisulfite pyrosequencing. Mean methylation levels (β¯) in AsUC and non-AsUC were compared by their ratio (β¯ ratio) and difference (Δβ¯). Associations between site-specific methylation levels in UC and cumulative arsenic exposure were examined.nnnRESULTSnAmong 27,578 methylation sites analyzed, 231 sites had β¯ ratio >2 or <0.5 and 45 sites had Δβ¯ >0.2 or <-0.2. There were 13 sites showing statistically significant (q<0.05) differences in β¯ between AsUC and non-AsUC including 12 hypermethylation sites in AsUC and only one hypermethylation site in non-AsUC. Significant associations between cumulative arsenic exposure and DNA methylation levels of 28 patients were observed in nine CpG sites of nine gens including PDGFD (Spearman rank correlation, 0.54), CTNNA2 (0.48), KCNK17 (0.52), PCDHB2 (0.57), ZNF132 (0.48), DCDC2 (0.48), KLK7 (0.48), FBXO39 (0.49), and NPY2R (0.45). These associations remained statistically significant for CpG sites in CTNNA2, KLK7, NPY2R, ZNF132 and KCNK17 in 20 non-smoking women after adjustment for tumor stage and age.nnnCONCLUSIONSnSignificant associations between cumulative arsenic exposure and methylation level of CTNNA2, KLK7, NPY2R, ZNF132 and KCNK17 were found in smoking-unrelated urothelial carcinoma. Arsenic exposure may cause urothelial carcinomas through the hypermethylation of genes involved in cell adhesion, proteolysis, transcriptional regulation, neuronal pathway, and ion transport. The findings of this study, which are limited by its small sample size and moderate dose-response relation, remain to be validated by further studies with large sample sizes.

Increased risk of varicella zoster virus infection in inflammatory bowel disease in an Asian population: a nationwide population-based cohort study.

Whether patients with inflammatory bowel disease (IBD) exhibit a high risk of developing varicella zoster virus (VZV) infection in Asian populations remains inconclusive. We investigated the causal relationship between two diseases by analysing the Taiwan National Health Insurance Research Database.

Helicobacter pylori infection and the risk of acute coronary syndrome: a nationwide retrospective cohort study

Helicobacter pylori infection (HPI) imposes substantial social costs and is of major etiological importance in peptic ulcer disease, gastric cancer, and accelerated cardiovascular diseases. This study determined the risk of acute coronary syndrome (ACS) associated with HPI in a nationwide retrospective cohort study. By using the Taiwan National Health Insurance Research Database (NHIRD), we identified patients diagnosed with HPI from 1998 to 2010. In addition, we randomly selected non-HPI controls frequency-matched by age, sex, and index year from the general population free of HPI. The risk of ACS was analyzed using Cox proportional hazards regression models in which sex, age, and comorbidities were included as variables. We identified 17,075 participants for the HPI group and selected 68,300 participants for the comparison group. The incidence rates were increased in the patients in the HPI group compared with those in the comparison group. Overall, the HPI patients exhibited a 1.93-fold high crude hazard ratio for ACS, and a 1.48-fold adjusted hazard ratio after age, sex, and comorbidities were adjusted. However, the overall adjusted hazard ratio of ACS increased with increasing age with a 3.11 to 8.24 adjusted hazard ratio among the various age groups. Several comorbidities, such as diabetes, hyperlipidemia, and COPD exhibited synergistic effects for ACS risk. We determined a significant association between ACS and comorbidities and provide evidence to encourage clinicians to observe ACS-related comorbidities.

Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan

Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1), reactive oxygen species (ROS) related metabolic genes (NQO1, EPHX1, and HO-1), and DNA repair genes (XRCC1, XPD, hOGG1, and ATM) together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR) and 95% confidence interval (CI) using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01–8.83; OR = 2.04, 95% CI = 0.99–4.27; OR = 1.74, 95% CI = 1.00–3.02, resp.). However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated.

Helicobacter pylori infection increases the risk of adult-onset asthma: a nationwide cohort study

Helicobacter pylori infection (HPI) appears to reduce risk of childhood-onset asthma, but the relationship between HPI and adult-onset asthma is inconclusive. This study explored the potential association between HPI and risk of adult-onset asthma. We conducted a national insurance retrospective cohort study using the longitudinal health insurance database (LHID 2000) in Taiwan. We enrolled the HPI group consisting of 1664 patients with HPI diagnosis between 2000 and 2007, and the non-HPI group consisting of 6,656 age- and sex-matched subjects without HPI. All study participants had been followed up from index date to the diagnostic date of asthma, withdrawal from the National Health Insurance program, or the end of 2011, which came first. We analyzed risk of adult-onset asthma with respect to sex, age, and comorbidities by using Cox models. Cigarette smoking status, which could not be obtained from the program, was adjusted indirectly by considering chronic obstructive pulmonary diseases in our statistical models because the disease is related to heavy smoking. After adjustment for sex, age, and comorbidities, HPI was significantly associated with an increased 1.38-fold risk of adult-onset asthma. Moreover, among people without comorbidities, the 1.85-fold risk of adult-onset asthma remained higher for the HPI population compared with the non-HPI population. In this study, patients with HPI exhibited a significantly higher risk of adult-onset asthma than did the subjects without HPI.

Correlation between use of simvastatin and lovastatin and female lung cancer risk: a nationwide case–control study

The objective of this study was to determine the association between statin use and female lung cancer in Taiwan.

Leptin signaling axis specifically associates with clinical prognosis and is multifunctional in regulating cancer progression

Leptin is a peptide hormone that has been characterized as the ligand of leptin receptor (LEPR). The observation of leptin secretion and leptin receptor expression beyond the normal tissues suggests the potentially critical roles other than its physiological function. In addition to the original function in controlling appetite and energy expenditure, leptin-mediated signaling axis through leptin receptor is multifunctional which plays role in the regulation toward broad types of cancer. Emerging evidences has indicated leptins function in promoting several processes which are relevant to cancer progression including cell proliferation, metastasis, angiogenesis and drug resistance. We relatively display leptin and leptin receptor expression levels in pan-cancer panel based on the transcriptome analysis via dataset The Cancer Genome Atlas (TCGA), and show the clinical association of the axis in predicting cancer prognosis. The results indicate the pathological impacts of this axis on many types of cancer. This review mainly focuses on leptin-mediated effects and its downstream signaling related to the progression of cancers, and displays the clinical significance of this axis including the impact on cancer patient survival.

Effects of Arsenic in Drinking Water on Risk of Hepatitis or Cirrhosis in Persons With and Without Chronic Viral Hepatitis

BACKGROUND & AIMSnArsenic in drinking water is associated with hepatomegaly and death from liver cancer. However, confounding factors related to liver diseases have not been carefully studied. We examined associations between exposure of arsenic in drinking water and risk of hepatitis and cirrhosis, and the interaction with chronic viral hepatitis, in people living in the Lanyang Basin of northeastern Taiwan, where well water has an arsenic content that ranges from undetectable to 3590 μg/L.nnnMETHODSnWe tested blood samples from 4387 people who lived in arseniasis-endemic areas in northeastern Taiwan from 1991 through 1994 for hepatitis B virus DNA, hepatitis B surface antigen (HBsAg), and antibodies against hepatitis C virus (anti-HCV). We measured arsenic concentrations in well water and collected information on residents histories of major chronic diseases. Reports of chronic hepatitis or cirrhosis were ascertained using the Taiwan National Health Insurance database. Reports of liver cancer were ascertained using the Taiwan National Cancer Registry.nnnRESULTSnPrevalence odds ratios in the overall study population for chronic hepatitis or cirrhosis for well water arsenic concentrations of ≤10 μg/L were 1.00 (reference), 0.93 for 10.1-49.9 μg/L (95% confidence interval [CI], 0.57-1.52), 1.24 for 50.0-99.9 μg/L (95% CI, 0.68-2.23), 0.98 for 100.0-299.9 (95% CI, 0.52-1.85), and 1.86 for ≥300.0 μg/L (95% CI, 1.08-3.20). Increasing levels of arsenic in drinking water were associated with increasing prevalence of chronic hepatitis or cirrhosis in residents who were seronegative for HBsAg and seronegative for anti-HCV, but not for seropositive for either HBsAg or anti-HCV. In individuals who were seropositive for HBsAg or anti-HCV, we observed an inverse association between hepatitis or cirrhosis and consumption of water with levels of arsenic ≥100.0 μg/L. Among participants who were seropositive for HBsAg or anti-HCV, consumption of water with levels of arsenic ≥100.0 μg/L was associated with a reduced risk of liver cancer (multivariate-adjusted hazard ratio, 0.29;xa095% CI, 0.09-0.95; P < .05). A higher proportion of individuals exposed to cumulative arsenic level >14,000 μg/Lxa0×year were carriers of inactive hepatitis B virus (DNA <10,000 copies/mL) and were positive for HBsAg (60%) than individuals exposed to water below this arsenic level (35%).nnnCONCLUSIONSnConcentrations of arsenic concentration in drinking water ≥300.0 μg/L significantly increase risk of hepatitis or cirrhosis in people without chronic viral hepatitis. However, in people with chronic viral hepatitis, levels of arsenic ≥100.0 μg/L in drinking water significantly reduce the risk of chronic hepatitis or cirrhosis.

Dry eye syndrome and the subsequent risk of chronic fatigue syndrome—a prospective population-based study in Taiwan

Background and Aim The clinical association between dry eye syndrome (DES) and chronic fatigue syndrome (CFS) remain unclear with less evidences. We aimed to investigate the relationship between CFS and DES using a national insurance and prospective cohort study. Methods Data from the Longitudinal Health Insurance Database 2000 was applied to estimate the incidence of CFS among patients with DES, and their age- and sex-matched controls without DES over a long-term follow-up period. All participants were CFS free at baseline, before the interval (2005–2007), but were later diagnosed with CFS. DES patients and its relative matched controls were excluded prevalent CFS before the same interval. Results We identified 884 patients with DES and 3,536 matched controls in baseline and estimated the hazard ratios for incident CFS in the follow-up period. Patients with DES had a 2.08-fold considerably increasing risk of developing CFS, compared to non-DES group. An elevated risk of developing CFS remained (1.61-fold risk) even after adjusting for age, sex, and comorbidities. There was a presence of increasing risk in DES-related CFS when CFS-related comorbidities existing (adjusted hazard ratio, 1.98, 95% confidence interval, 1.19–3.29; p < 0.01). The subsequent risk for CFS between DES and non-DES patients was significant increased with three or more annual medical visits, the adjusted risk for CFS was 4.88-fold risk (95% CI, 2.26–10.58, p < 0.001). Conclusion We recommended that physicians should be aware of the increased risk of CFS among DES patients and adequately assess the health impacts among these patients.