Che-Chun Su

Possible association between nickel and chromium and oral cancer: A case–control study in central Taiwan

Oral cancer is one of the most common cancers in Taiwan. Changhua County, in central Taiwan, has an extremely high prevalence of oral cancer, along with a high concentration of metal-related industries and soil metal contamination. The aim of this study was to clarify the possible association between metals and oral cancer within this specific area. This study recruited 101 oral cancer patients and 104 controls from the Changhua Christian Hospital. All subjects completed a questionnaire that asked about demographic information; cigarette, alcohol, and betel quid use; and environmental and occupational exposure history. Blood samples were collected and tested for metal concentrations with inductively coupled plasma mass spectrometry. A multiple logistic regression model illustrated that oral cancer was significantly associated with the blood levels of nickel and chromium (both with P<0.0001) after controlling for potential confounders. This study suggested a potential role of these two metals in the mechanism of oral cancer development.

Progression of precancerous lesions to oral cancer: Results based on the Taiwan National Health Insurance Database

BACKGROUND Oral cancer (OC) is the leading cause of death from cancer in men between the ages of 25 and 44 in Taiwan. The survival rate for the last stage of OC is <20% while that for the earliest stage is >75%, which suggests the importance of the diagnosis of oral precancerous lesions (OPLs) in reducing OC mortality. The aim of this study was to analyze the time to OC event after OPL diagnosis, and to suggest the surveillance period necessary according to OPL type. MATERIALS AND METHODS This was a retrospective cohort study based on 1.0 million people randomly selected from the Taiwan National Health Insurance Database, which provided data on 3058 adult male patients aged ≥20 years who were diagnosed with OPL for the first time between 1996 and 2009. The patient population was divided into two groups according to the type of lesion: oral submucous fibrosis (OSF) or oral leukoplakia (OLE). Age-standardized incidence rate (ASIR) and hazards rate (HR) were then estimated. RESULTS The ASIR for OPL showed an increasing trend over the study period, the main contributor to this being OSF. The OSF group demonstrated a higher OC incidence rate than the OLE group. CONCLUSION Patients with both OLE and OSF carry a higher risk for OC than those with either OLE or OSF alone, and they may also experience malignant transformation at an earlier date (mostly within 5 years). The 5- and 10-year OC rate for both OLE and OSF was found to be 5% and around 10%, respectively. However, 10 years after the diagnosis of OPL, OSF carries a higher risk of developing into OC than OLE.

Quantification of betel quid chewing and cigarette smoking in oral cancer patients.

BACKGROUND Betel quid chewing and cigarette smoking are two of the risk factors for some dental diseases as well as oral cavity cancer in Taiwan. The aim of the study was to quantify these factors in oral cavity cancer patients and compare the prevalence of these factors in patients and the general population. METHODS A questionnaire was designed to evaluate betel quid chewing, cigarette smoking and alcohol drinking in 254 patients, who had squamous cell carcinoma of the oral cavity, and had received surgical excision at the Changhua Christian Hospital in Taiwan between 2005 and 2008. The results were compared with those of population of Taiwan, based on a nation-wide survey with sample of 26 744 people. RESULTS We found that more than 80% of the male patients were both betel quid chewers and smokers. Few women in the survey practiced betel quid chewing, cigarette smoking or alcohol drinking. Chewers and smokers usually started the habits in their 20s. On average, a chewer patient consumed 12 508 betel quid pieces per year, for 23.3 years before the diagnosis of oral cavity cancer, making the total amount of betel quid consumed nearly 310 000 pieces; and a smoker patient consumed 469 packs per year, for 28.5 years before diagnosis, making the total number of about 14 000 packs. Patients with both habits had the age at diagnosis 4 years earlier than the smoker-only patients, 5 years earlier than the chewer-only patients, and 6 years earlier than those with neither. CONCLUSIONS On average, it took two decades of betel quid chewing and cigarette smoking before oral cavity cancer diagnosis, making the life-time consumption of these substances an astonishing amount. Betel quid chewing and cigarette smoking patients are more likely to be diagnosed with oral cavity cancer at a younger age than those who have just one habit or none. Patients that smoke more are not only more likely to be diagnosed at a younger age, but also at an advanced stage.

Spatiotemporal trends in oral cancer mortality and potential risks associated with heavy metal content in Taiwan soil.

Central and Eastern Taiwan have alarmingly high oral cancer (OC) mortality rates, however, the effect of lifestyle factors such as betel chewing cannot fully explain the observed high-risk. Elevated concentrations of heavy metals in the soil reflect somewhat the levels of exposure to the human body, which may promote cancer development in local residents. This study assesses the space-time distribution of OC mortality in Taiwan, and its association with prime factors leading to soil heavy metal content. The current research obtained OC mortality data from the Atlas of Cancer Mortality in Taiwan, 1972–2001, and derived soil heavy metals content data from a nationwide survey carried out by ROCEPA in 1985. The exploratory data analyses showed that OC mortality rates in both genders had high spatial autocorrelation (Moran’s I = 0.6716 and 0.6318 for males and females). Factor analyses revealed three common factors (CFs) representing the major pattern of soil pollution in Taiwan. The results for Spatial Lag Models (SLM) showed that CF1 (Cr, Cu, Ni, and Zn) was most spatially related to male OC mortality which implicates that some metals in CF1 might play as promoters in OC etiology.

Reduction in arsenic intake from water has different impacts on lung cancer and bladder cancer in an arseniasis endemic area in Taiwan.

BackgroundExcessive arsenic intake has a detrimental effect on human health, as reflected in an increase in cancer incidence. In an area on the southwest coast of Taiwan, arsenic intake from well water since the 1920s had caused an exceptionally high mortality from cancer. Municipal water has become available to people living in the arseniasis endemic area since the early 1970s. This study explored the impacts of reduction in arsenic intake from water on lung cancer and bladder cancer in the arseniasis endemic area in Taiwan.MethodsChart records of 23,013 patients diagnosed with bladder cancer and 93,633 patients with lung cancer from 1979 to 2003 were retrieved from the Taiwan Cancer Registry Center. We used the age-period-cohort model to study the changes in the incidence of lung cancer and bladder cancer in the arseniasis endemic area and the rest of Taiwan.ResultsThree decades after municipal water supply to the arseniasis and black foot disease endemic area (BFDEA), we saw a marked decrease in the incidence of both bladder cancer and lung cancer in the area, especially for those in the later cohorts. The relative risk (RR) of getting a bladder cancer for people living in BFDEA when compared with those in the rest of Taiwan has dropped from 20 for the early cohorts to 5 for the late cohorts. As to lung cancer, the RR has decreased from 8 to between 1.5 and 2.ConclusionReduction in arsenic intake from water has a positive impact on the incidence of both lung and bladder cancer; however, while RR for lung cancer has dropped to below 2, RR for bladder cancer remained at around 5. The difference may be because (1) there are other risk factors beside the well-water intake or (2) bladder cancer may have longer latency period for excessive arsenic exposure than lung cancer. More studies are required to understand the causes behind the difference in RR for these two types of cancer.

Risk of Diabetes in Patients with Rheumatoid Arthritis: A 12-year Retrospective Cohort Study

Objective. The incidence of type 2 diabetes (T2D) in adults with rheumatoid arthritis (RA) was investigated, and the results were compared with non-RA controls to confirm whether RA is a risk factor for diabetes mellitus (DM) in Taiwan. Methods. We used a databank of 1 million individuals randomly selected from 23 million Taiwanese citizens covered by the National Health Insurance plan in 2005. All persons older than age 20 years in 1998 and not diagnosed with either RA or T2D before 1998 were included. They were divided into 2 cohorts, 1 with RA and the other without. Those who had T2D before RA were excluded. Each patient in the RA cohort was followed from the RA diagnosis until the end of 2009, or until dropping out of the insurance coverage. RA was ascertained by at least 3 visits using ICD-9 code 714.0, plus at least 2 visits with prescription of antirheumatic drugs in a period of 12 months. T2D was ascertained by at least 3 visits with diabetes codes within 1 year, while hypertension (HTN) and disorders of lipid metabolism (DLM) were determined by at least 3 visits using corresponding ICD codes during the study period. Kaplan-Meier plots, log-rank tests, and Cox regression were used to study the effects of age, sex, glucocorticoid use, HTN, DLM, and RA on T2D risk. Results. The subjects include 600,695 adults. Of these, 4193 were diagnosed with RA, and among them 799 were diagnosed with T2D. The RA to non-RA risk ratio for T2D was 1.68 (95% CI 1.53–1.84) in men and 1.46 (95% CI 1.39–1.54) in women. Conclusion. RA appears to be associated with an increased risk for T2D in Taiwan.

Supplement of 5-hydroxytryptophan before induction suppresses inflammation and collagen-induced arthritis

BackgroundEvidence is accumulating that a preclinical phase is present before the onset of clinical signs and symptoms of rheumatoid arthritis (RA). This phase represents an important therapeutic window within which interventions can dramatically modulate outcomes. An agent able to prevent RA for high risk individuals in this phase is therefore desired. In this study, we investigated whether tryptophan metabolite, 5-hydroxytryptophan (5-HTP) or 5-methoxytryptophan (5-MTP), can act as such an agent for primary prevention of collagen-induced arthritis (CIA).MethodsMouse splenocytes were pretreated with 5-HTP or 5-MTP and activated by anti-CD3 plus anti-CD28 antibodies in vitro. The percentages of interferon-γ (IFNγ)+CD4+ T cells and interleukin-17 (IL-17)+CD4+ T cells were measured by flow cytometry. The production of pro-inflammatory cytokines, serotonin and kynurenine was measured by enzyme-linked immunosorbent assay. A CIA model was used to investigate the in vivo effects of 5-HTP on the prevention of arthritis.Results5-HTP decreased the percentages of IFNγ+CD4+ T cells and IL-17+CD4+ T cells and suppressed the production of IL-2, IL-4, IL-6, IL-17, tumor necrosis factor-α (TNFα) and IFNγ in activated splenocytes. 5-HTP administered before induction decreased the disease activities in CIA mice and suppressed the production of TNFα, IL-6 and cyclooxygenase-2 in arthritic joints. 5-HTP also increased serotonin, but decreased kynurenine in the CIA mice.Conclusions5-HTP suppresses inflammation and arthritis through decreasing the production of pro-inflammatory mediators. 5-HTP supplement before induction ameliorates arthritis in a CIA model.

Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper

BACKGROUND/PURPOSE Heavy metal pollution in farm soils is a problem in some parts of Taiwan. Copper can be a factor associated with increased disease activities of rheumatoid arthritis (RA). Thus, the aim of this study was to investigate whether copper pollution in farm soils is associated with worsened RA. METHODS Clinical parameters from 122 RA patients were collected from a medical center in central Taiwan. Levels of heavy metals in the blood were measured using inductively coupled plasma mass spectrometry. Levels of copper in farm soils were retrieved from a national survey. These data were analyzed to find the factors related to RA disease activities. RESULTS RA patients living where farm soils contained high levels of copper had increased white blood cell counts, erythrocyte sedimentation rate, and disease activity score 28, compared with patients living where copper levels were low. Among the nine types of heavy metal measured in the study, blood levels of copper and nickel correlated with erythrocyte sedimentation rate. CONCLUSION Our cross-sectional data suggest a correlation between RA disease activity and the level of copper at township farm soils samples. Further longitudinal studies using more rigorous methodologies are warranted to examine whether this correlation is causal.

Environmental heavy metal as a potential risk factor for the progression of oral potentially malignant disorders in central Taiwan

OBJECTIVE Oral cancer (OC) is a leading cause of death from cancer in men between the ages of 25 and 44 years in Taiwan. The overall 5-year survival rates for the four OC stages (I-IV) in Taiwan are approximately 70%, 30%, 20%, and 10%, respectively, indicating the importance of the early diagnosis of oral potentially malignant disorders (OPMDs). Previous studies indicated an association between the OC incidence and certain environmental heavy metal concentrations. If these associations do exist for OC, they may also be observed for OPMD. The purpose of this study is to explore the association between the development of OPMD to OC and environmental heavy metals. Oral submucous fibrosis (OSF) and oral leukoplakia (OL) are two major types of OPMD in Taiwan. MATERIALS AND METHODS A retrospective cohort study was conducted by Changhua Christian Hospital, the sole medical center in Changhua County, where 2725 male adult patients diagnosed with either OSF or OL between 2000 and 2014 were recruited. Data were analyzed by Cox regression and adjusted for smoking and betel-quid chewing. RESULTS AND DISCUSSION OPMD patients who resided in areas with high nickel concentrations (polluted levels) exhibited hazard ratios of 1.8-2 for OC relative to those who lived in areas with low nickel levels (P<0.01). Meanwhile, smokers with OPMDs had a hazard ratio of 2.8-2.9 relative to non-smokers. Betel-quid chewers had a 2.2-2.3 hazard ratio relative to non-chewers. Smoking, betel-quid chewing, and environmental nickel exposure are associated with an increased risk of OC development in OPMD patients. This study provides valuable findings on the environmental effects of heavy metals on human health. Enhanced surveillance of the condition of OPMD patients who have been exposed to high nickel concentrations may be crucial for OC prevention.

Increased Prevalence of Esophageal Cancer in Areas with High Levels of Nickel in Farm Soils.

Background: Heavy metal pollution in farm soils is a grave concern in Taiwan. Previously, we found the incidence of oral cancer (OC) correlated positively with levels of nickel and arsenic in farm soils. Many OC patients have a second malignancy, among which esophageal cancer (EC) is the most common one in Taiwan. Objectives: We aimed to investigate whether these two cancers share some common risk factors. Methods: Taiwan began a compulsory national health insurance program in 1995. We used a database from this program to calculate the prevalence of EC and OC in Taiwan. We compared the prevalence of EC with prevalence of betel nut chewers in adults and the information of heavy metal in farm soils to look for any association. Results: The prevalence of OC and prevalence of EC were strongly correlated. The prevalence of betel nut chewing correlated with OC prevalence, but not with EC prevalence. An increased prevalence (1.9 fold) of EC was found where the farm soils contained high levels of nickel. Meanwhile, among the eight heavy metals studied, only the levels of nickel in the farm soils correlated statistically with the prevalence of EC. Conclusion: Nickel is probably a common environmental risk factor for esophageal cancer and oral cancer.