Heavy metal exposure linked to metabolic syndrome in Korean male firefighters: FRESH cohort cross-sectional analysis.

This study aimed to identify the relationship between blood lead and Cadmium (Cd) concentrations and metabolic syndromes (MetS), including its components (central obesity, hypertriglyceridemia, low high-density lioioritein, hypertension, and hyperglycemia) among Korean firefighters. A total of 965 firefighters of the Enhancement of Safety and Health cohort were analyzed in this study. MetS was defined according to the 2005 revised National Cholesterol Education Program-Adult Treatment Panel III criteria and the Korean Society for the Study of Obesity criteria for waist circumference. The collected data were analyzed using a logistic regression model. Of the 965 participants, 190 (19.7%) had MetS. After adjusting for age, body mass index, smoking, drinking, exercise, shift duty, and main duty position, the Cd level was significantly associated with an increased risk of MetS in the Korean firefighter population (odds ratio [OR] = 1.62, 95% confidence interval [CI] 1.07, 2.46). This association was significant among non-smokers and ex-smokers (OR = 1.58, 95% CI 1.03, 2.43), non-drinkers and ex-drinkers (OR = 1.77, 95% CI 1.06, 2.94), firefighters aged 40 year or older (OR = 1.77, 95% CI 1.10, 2.86), and office administrators (OR = 3.85, 95% CI 1.42, 10.39). This outcome suggests that exposure to Cd is likely to increase risk of MetS among firefighters.

Nypa fruticans Wurmb inhibits melanogenesis in isobutylmethylxanthine­treated melanoma via the PI3K/AKT/mTOR/CREB and MAPK signaling pathways.

Malignant melanoma is responsible for 3.0 and 1.7% of cases of tumor incidence and tumor-associated mortality, respectively, in the Caucasian population. Melanoma is a type of skin cancer that occurs when melanocytes mutate and divide uncontrollably. Nypa fruticans Wurmb (NF) is abundant in phytochemicals (polyphenols and flavonoids) and is traditionally used to treat diseases of the respiratory tract. The present study investigated the inhibitory effect of the ethyl acetate fraction of NF (ENF) on melanogenesis-related factors in isobutylmethylxanthine-treated B16F10 melanoma cells. Phenolics and flavonoids (caffeic acid, catechin, epicatechin and hirsutine) in ENF were analyzed via liquid chromatography-mass spectrometry. In addition, the main factors involved in melanogenesis were identified using immunoblotting, reverse transcription-polymerase chain reaction (RT-PCR), RT-quantitative PCR and immunofluorescence. ENF significantly suppressed the expression of tyrosinase (TYR) and TYR-related proteins 1 and 2 (TYRP-1/2), which are the main factors involved in melanogenesis. ENF also inhibited the expression of microphthalmia-associated transcription factor (MITF) by phosphorylating the related cell signaling proteins (protein kinase B, mammalian target of rapamycin, phosphoinositide 3-kinase and cAMP response element-binding protein). Furthermore, ENF inhibited the phosphorylation of extracellular signal-regulated kinase and thereby downregulated melanogenesis. In conclusion, ENF inhibited melanogenesis by suppressing MITF, which controls TYRP-1/2 and TYR. These results suggested that ENF may be a natural resource that can inhibit excessive melanin expression by regulating various melanogenesis pathways.

Impact of Wildfire Smoke Exposure on Health in Korea.

PURPOSE: The characteristic topography and climate often affect the occurrence of large-scale wildfires in the Eastern Gangwon-do region of Korea. However, there are no studies on the health effects of these wildfires in Korea. This study aimed to analyze the differences in medical use between a wildfire-affected area and an adjacent non-affected area before and after a wildfire in 2019 in Gangwon-do, Korea. MATERIALS AND METHODS: We used medical usage data from the Korean National Health Insurance Corporation. Rates of medical use were determined for citizens of a wildfire-affected area in the Eastern Yeongdong region and a non-affected area in the Western Yeongseo region. Logistic regression analysis was performed considering an increase in medical use per individual as a dependent variable; age, sex, income, smoking, drinking, and exercise were included as confounding variables. RESULTS: The odds ratio for medical use in Yeongdong region increased significantly after 3 days, 3 months, and 1 year after a fire occurred, compared with Yeongseo region. CONCLUSION: The results of this study confirmed that the use of medical care increased for residents of a wildfire-affected area, compared with those of an adjacent non-affected area. This is the first study on the relationship between wildfires and inpatient medical use in Korea.

The effect of polycyclic aromatic hydrocarbons on changes in the brain structure of firefighters: An analysis using data from the Firefighters Research on Enhancement of Safety & Health study.

Polycyclic aromatic hydrocarbons (PAHs) are formed during incomplete combustion of organic matter, and firefighters are highly exposed to these toxic compounds at fire sites. Exposure to PAHs can cause cognitive decline and neurodegeneration; however, to date, few studies have examined the potential effects of PAH exposure on structural changes in the brain. We aimed to investigate the association between the four types of PAH metabolites and the corresponding changes in neuroimaging markers based on smoking status and hypertension in male firefighters. For this, we utilized the 2-year follow-up data of 301 Korean male firefighters aged over 40 years. The concentrations of four PAH metabolites in urine were measured. Subcortical volume and cortical thickness were estimated using 3 T magnetic resonance imaging of the brain. A generalized linear model was used to investigate the effects of PAHs on changes in the subcortical volume and cortical thickness. We found an association between 1-hydroxyphenathrene (1-OHPHE) and 2-hydroxyfluorene (2-OHF) and changes in several brain regions in all the study participants. Individuals who had never smoked showed significantly thinner frontal (p < 0.001), parietal (p < 0.001), temporal (p < 0.001), and cingulate lobes (p < 0.001) with 1% increase each in the urinary concentration of 1-OHPHE. Hypertension interacted with the concentration of 1-OHPHE to reduce the volume of gray matter and cause cortical thinning in the frontal, parietal, and temporal lobes. Exposure to PAHs may reduce cortical thickness and subcortical volume, which are definitive markers of neurodegeneration. Notably, hypertension can accelerate the degenerative effects of PAHs.

Association between exposure to polycyclic aromatic hydrocarbons and brain cortical thinning: The Environmental Pollution-Induced Neurological EFfects (EPINEF) study.

BACKGROUND: Although some studies have suggested that exposure to polycyclic aromatic hydrocarbons (PAHs) induces neurodevelopmental disturbances in children and neurodegeneration in animals, the neurotoxic effect of PAH exposure is unclear in adults. The aim was to examine the associations of PAH exposure with brain structure and neuropsychological function in adults without known neurological diseases. METHODS: This study included 421 men and 528 women dwelling in four cities in the Republic of Korea. Urinary concentrations of four PAH metabolites (1-hydroxypyrene, 2-naphthol, 1-hydroxyphenanthrene, and 2-hydroxyfluorene) were obtained. Participants underwent brain 3 T magnetic resonance imaging and neuropsychological tests. Cortical thickness and volume were estimated using the region-of-interest method. Separate generalized linear models were constructed for each sex, adjusting for age, years of education, cohabitation status, income, tobacco use, alcohol consumption, and vascular risk factors. RESULTS: The mean (standard deviation) age was 68.3 (6.6) years in men and 66.4 (6.1) years in women. In men, those in quartile 4 (versus quartile 1, the lowest) of urinary 2-naphthol concentration had cortical thinning in the global (ß = -0.03, P = .02), parietal (ß = -0.04, P = .01), temporal (ß = -0.06, P < .001), and insular lobes (ß = -0.05, P = .02). Higher quartiles of urinary 2-naphthol concentration were associated with cortical thinning in the global (P = .01), parietal (P = .004), temporal (P < .001), and insular lobes (P = .01). In women, those in quartile 4 (versus quartile 1) of urinary 1-hydroxypyrene concentration had cortical thinning in the frontal (ß = -0.03, P = .006) and parietal lobes (ß = -0.03, P = .003). Higher quartiles of urinary 1-hydroxypyrene concentration were associated with cortical thinning in the frontal (P = .006) and parietal lobes (P = .001). In both sexes, verbal learning and memory scores significantly declined with an increase in quartile of urinary 1-hydroxypyrene concentration. CONCLUSIONS: PAH exposure was associated with cortical thinning and decline in verbal learning and memory function in cognitively healthy adults. This suggests PAHs as an environmental risk factor for neurodegeneration.

Psychosocial factors affecting sleep quality of pre-employed firefighters: a cross-sectional study.

BACKGROUND: There have been no health-related studies of pre-employed firefighters without firefighter-specific job-related factors (FSJRF). This study aimed to evaluate the sleep quality of pre-employed firefighters and to examine the relationship between sleep quality and psychosocial factors. METHODS: We conducted a self-report questionnaire survey for 602 pre-employed firefighters at 3 Fire Service Academies after brief lecture about sleep. Sleep quality and psychosocial variables such as depression, anxiety, stress and social support were evaluated. The independent 2 sample t-test, χ2 test and multiple logistic regression analysis were used to evaluate the effect of the variables on the sleep quality of pre-employed firefighters. RESULTS: Among a total of 602 people, 347 (57.6%) had good sleep quality and 255 (42.4%) had poor sleep quality. Pittsburgh Sleep Quality Index score of them was 3.29 ± 1.41) and 7.87 ± 2.20), respectively. 24 (4.0%) were evaluated to have insomnia by Insomnia Severity Index. Logistic regression analyses showed that the depression (adjusted odds ratio [aOR]: 5.940, 95% confidence interval [CI]: 3.124-11.292), anxiety (aOR: 4.233, 95% CI: 2.138-8.381), stress (aOR: 2.880, 95% CI: 1.915-4.330) and social support (aOR: 0.959, 95% CI: 0.939-0.980) have a significant effect on sleep quality after adjusted by sex, age, smoking status, drinking status, caffeine intake, past shift working and circadian rhythm type. CONCLUSIONS: Depression, anxiety, stress and social support were associated with sleep quality among pre-employed firefighters. Repeated follow-up studies of pre-employed firefighters are needed to further assess their change of sleep quality and identify the FSJRF that may affect the sleep quality of firefighters.

LOX family and ZFPM2 as novel diagnostic biomarkers for malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that develops in the pleural and outer layer of tissues surrounding the lungs. MPM is primarily caused by occupational exposure to asbestos and results in a poor prognosis. Effective therapeutics as well as early diagnostics for the MPM are still lacking. To identify potential diagnostic biomarkers for MPM, we performed bioinformatics analysis of public database. METHODS: Utilizing databases from Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO), we identified several potential candidates that could act as MPM biomarkers. We carried out additional molecular analyses of these potential markers using MPM patient tissue samples via quantitative polymerase chain reaction. RESULTS: We identified Lysyl oxidase (LOX), Lysyl oxidase homologs 1&2 (LOXL1& LOXL2) Zinc Finger Protein, FOG Family Member 2 (ZFPM2) as potential diagnostic biomarkers for MPM. In this study, we found that the LOX family and ZFPM2 showed comparable diagnostic ability to Fibulin-3 or mesothelin (MSLN) and would be better potential biomarkers than Sulfatase 1 (SULF1), Thrombospondin 2 (THBS2) and Cadherin 11 (CDH11). CONCLUSIONS: LOX family and ZPFM2 were identified as novel MPM diagnostic biomarkers which could strengthen MPM clinical diagnostic capabilities.

Exposure to pesticides and the prevalence of diabetes in a rural population in Korea.

BACKGROUND: Among the adverse health effects of exposure to pesticides, an association with diabetes has been reported. However, there is a lack of epidemiologic studies on the health effects of exposure to pesticides, particularly investigating the association between occupational pesticide exposure and diabetes prevalence. PURPOSE: The present study examined the association between pesticide exposure and prevalence of diabetes in a rural population in Korea. METHODS: This cross-sectional study used data from the Korea Farmers Cohort study, and included 2559 participants in the baseline survey between November 2005 and January 2008. We performed a clinical examination including blood sampling and assessed data on diabetes diagnosis, demographics, and pesticide exposure. Logistic regression was performed to evaluate the association between pesticide exposure and diabetes prevalence, adjusting for age, sex, monthly income, and marital status. In addition, a stratified analysis by body mass index (BMI) was conducted, with two categories: normal weight (<25 kg/m2) and overweight or obese (≥25 kg/m2). RESULTS: At baseline, the prevalence of diabetes was 9.30%. Pesticide exposure was associated with the risk of diabetes after adjustment for covariates. In the analysis stratified by BMI, all the variables related to pesticide exposure were associated with prevalence of diabetes in the overweight or obese group, whereas no significant association was found in the normal weight group. CONCLUSION: Exposure to pesticides was associated with diabetes, and this association was stronger in overweight or obese individuals than in normal weight individuals. Further longitudinal studies that consider information on BMI are necessary.

Gender-specific risk factors for androgenetic alopecia in the Korean general population: Associations with medical comorbidities and general health behaviors.

BACKGROUND: The relationships between androgenetic alopecia (AGA) and various factors related to metabolic syndrome have been demonstrated in previous studies. However, it remains unclear because of inconsistent results. We investigated the associations between AGA and various risk factors related to metabolic syndrome according to gender. METHODS: We conducted a population-based cross-sectional survey of 2028 Koreans (1050 men, 978 women). The basic and specific (BASP) classification was used for diagnosis of AGA. We collected information on risk factors though questionnaires and medical records. RESULTS: AGA was significantly associated with age, family history of AGA, hypertension, diabetes mellitus, and waist circumference in both genders. Female subjects with AGA were more likely to have cerebrovascular disease, dyslipidemia, and obesity; however, these associations were not observed in the male subjects. When multiple regression analysis was applied, there was a significant relationship between hypertension and AGA in male subjects. However, there was no statistically significant association in female subjects. CONCLUSION: The different results according to gender might arise from different mechanisms of AGA. There was a significant relationship between hypertension and AGA in male subjects. Evaluation of blood pressure in male patients with AGA might facilitate interventions for hypertension.

Pesticide metabolite and oxidative stress in male farmers exposed to pesticide.

BACKGROUND: The objective of this study was to measure malondialdehyde (MDA) and isoprostane which has been used as an index of lipid injury, 8-hydroxy-2'-deoxyguanosine (8-OHdG), which has been used as an index of DNA damage, and dialkyl-phosphate (DAP), which has been used to quantify pesticide exposure, and to investigate the relationship between pesticide exposure and oxidative stress. METHODS: This study was a cross-sectional study that evaluated 84 male farmers exposure to pesticide. In this study, 8-OHdG, isoprostane, and MDA were measured as oxidative stress indices, and dialkyl-phosphate (dimethylphosphate(DMP), diethylphosphate(DEP), dimethylthiophosphate(DMTP), and diethylthiophosphate (DETP)) excreted in the urine was also measured to evaluate pesticide exposure. A linear regression analysis was performed to investigate the relationship between pesticide metabolites, and oxidative stress biomarkers. RESULTS: A Correlation analysis was performed for pesticide exposure month (PEI), cumulative exposure index (CEI), and DAP as well as the concentration of the oxidative stress biomarkers. The PEM significantly and positively correlated to the levels of 8-OHdG, isoprostane, CEI, and DMP. CEI showed a correlation to 8-OHdG and PEM. DMP, DEP, and DETP showed a positive correlation to 8-OHdG, isoprostane, and MDA. A correlation analysis was adjusted some demographic characteristics, such as age, smoking, drinking, and exercise to determine the relationship between pesticide exposure and oxidative stress. The 8-OHdG, isoprostane, and MDA levels were significantly related to the DMP (ß = 0.320), DEP (ß = 0.390), and DETP (ß = 0.082); DMP (ß = 0.396), DEP (ß = 0.508), and DETP (ß = 0.504); and DMP (ß = 0.432), DEP (ß = 0.508), and DETP (ß = 0.329) levels, respectively. CONCLUSIONS: The concentration between oxidative stress biomarkers and the pesticide metabolite were a positive correlation. Indicators of oxidative stress was associated with a pesticide metabolite DMP, DEP, and DETP. Therefore, Pesticide exposure and oxidative stress were relevant.

Orai1 Expression Is Closely Related with Favorable Prognostic Factors in Clear Cell Renal Cell Carcinoma.

Store-operated calcium (Ca(2+)) entry (SOCE) is the principal Ca(2+) entry route in non-excitable cells, including cancer cells. We previously demonstrated that Orai1 and STIM1, the molecular components of SOCE, are involved in tumorigenesis of clear cell renal cell carcinoma (CCRCC). However, a clinical relevance of Orai1 and STIM1 expression in CCRCC has been ill-defined. Here, we investigated the expression of Orai1 and STIM1 in CCRCC, and compared their expression with clinico-pathological parameters of CCRCC and the patients' outcome. Immunohistochemical staining for Orai1 and STIM1 was performed on 126 formalin fixed paraffin embedded tissue of CCRCC and western blot analysis for Orai1 was performed on the available fresh tissue. The results were compared with generally well-established clinicopathologic prognostic factors in CCRCC and patient survival. Membrane protein Orai1 is expressed in the nuclei in CCRCC, whereas STIM1 shows the cytosolic expression pattern in immunohistochemical staining. Orai1 expression level is inversely correlated with CCRCC tumor grade, whereas STIM1 expression level is not associated with tumor grade. The higher Orai1 expression is significantly associated with lower Fuhrman nuclear grade, pathologic T stage, and TNM stage and with favorable prognosis. The expression level of STIM1 is not correlated with CCRCC grade and clinical outcomes. Orai1 expression in CCRCC is associated with tumor progression and with favorable prognostic factors. These results suggest that Orai1 is an attractive prognostic marker and therapeutic target for CCRCC.

Relationship between androgenetic alopecia and cardiovascular risk factors according to BASP classification in Koreans.

There have been many studies on the relationship between androgenetic alopecia (AGA) and cardiovascular risk factors, but the study results were inconsistent and research on AGA in Asians remains insufficient. This study investigated the relationship between Korean AGA and various cardiovascular risk factors, considering life habits, type of hair loss and sex. We investigated subjects who visited a hospital for public or industrial health medical examinations between October 2012 and December 2014. A questionnaire as well as anthropometric measurements and a blood test were performed. Among the 1884 total subjects, 52.6% had AGA. AGA patients displayed a significantly higher prevalence rate of cardiovascular diseases, smoking rate, fasting glucose and triglyceride, and a significantly lower high-density lipoprotein cholesterol level than did the non-AGA group. The results of the subgroup analysis showed higher prevalence rates of hypertension, stroke, metabolic syndrome and smoking in male AGA patients. The more severe the AGA, the higher the incidences of hypertension, diabetes and smoking were observed. According to the analysis results by BASP classification, the F-type AGA patients displayed a higher body mass index, waist circumference and diastolic blood pressure, and had a significantly higher prevalence rate of hypertension. As a result of the large population-based study, modifications in lifestyle and early screening for cardiovascular disease, as well as hypertension and diabetes, are suggested.

Radon exposure and lung cancer: risk in nonsmokers among cohort studies.

Eleven cohorts of miners occupationally exposed to relatively high concentrations of radon showed a statistically significantly high risk of lung cancer, while three cohorts from the general population showed a relatively low concentration, but the results were not statistically significant. However, the risk of lung cancer tended to increase with increased radon exposure. The risk is likely to have been underestimated due to low statistical power. Therefore, additional well-designed studies on the risk of lung cancer in nonsmokers in the general population with relatively low concentrations of radon exposure are needed in the future. In addition, country-specific preventive policies are needed in order to actively reduce radon exposure and lung cancer incidence in nonsmokers.

Erratum to: Trends in research on indoor radon exposure and lung cancer in South Korea.

[This corrects the article DOI: 10.1186/s40557-016-0100-9.].

Association of active and passive smoking with occupational injury in manual workers: a cross-sectional study of the 2011 Korean working conditions survey.

This study was conducted to investigate the relationship of active and passive smoking with occupational injury among manual workers. Data from the 2011 Korean Working Conditions Survey were analyzed for 12,507 manual workers aged ≥15 yr. Overall, 60.4% of men and 5.8% of women were current smokers. The prevalence of injury was higher among never smokers who were exposed to secondhand smoke (SHS) (7.7% in men and 8.1% in women) than current smokers (4.2% in men and 4.1% in women). After controlling for potential confounders, in men, compared to those who never smoked and were not exposed to SHS, people who never smoked and were exposed to SHS (adjusted odds ratio (aOR)=3.7, 2.2-6.4) and current smokers (aOR=2.5, 1.6-3.8) were more likely to experience injury. Among women, the aORs of occupational injury were 8.4 (4.2-16.7) for never smoking women with occasional exposure to SHS and 3.5 (95% CI: 1.4-8.7) for current smokers, in comparison to never smoking women who were never exposed to SHS at work (reference group). The present study suggests that exposure to SHS is a possible risk factor of occupational injury for never smoking men and women.

Insulin receptor expression in clear cell renal cell carcinoma and its relation to prognosis.

PURPOSE: Both insulin and insulin-like growth factor (IGF)-1 signaling are key regulators of energy metabolism, cellular growth, proliferation, and survival. The IGF-1 receptor (IGF-1R) is overexpressed in most types of human cancers including renal cell carcinoma (RCC) with poor prognosis. Insulin receptor (IR) shares downstream effectors with IGF-1R; however, the expression and function of IR in the tumorigenesis of renal cancer remains elusive. Therefore, we examined the expression of IR and its prognostic significance in clear cell RCC (CCRCC). MATERIALS AND METHODS: Immunohistochemical staining for IR was performed on 126 formalin-fixed paraffin-embedded CCRCC tissue samples. Eight of these cases were utilized for western blot analysis. The results were compared with various clinico-pathologic parameters of CCRCC and patient survival. RESULTS: IR was expressed in the nuclei of CCRCC tumor cells in 109 cases (87.9%). Higher IR expression was significantly correlated with the presence of cystic change, lower Fuhrman nuclear grade, lower pathologic T stage, and lower TNM stage, although it wasn't significantly related to diabetes status and patient survival. Western blot analyses supported the results of the immunohistochemistry studies. CONCLUSION: IR expression in CCRCC may be associated with favorable prognostic factors.

VEGFR-1 Expression Relates to Fuhrman Nuclear Grade of Clear Cell Renal Cell Carcinoma.

BACKGROUND: Increasing evidence suggests that vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) 1 signaling may play an important role in the progression of pathological angiogenesis that occurs in many tumors, including renal cell carcinoma (RCC). Therapeutic targeting directed against VEGF and VEGFR-2 has been proven to be successful for metastatic clear cell RCC (CCRCC). However, the expression of VEGFR-1 and its association with prognostic parameters of CCRCC in the tumorigenesis of renal cancer remains unclear. Therefore, we examined the expression of VEGFR-1 and its prognostic significance in CCRCC. METHODS: Immunohistochemical staining for VEGFR-1 was performed on 126 formalin-fixed paraffin-embedded CCRCC tissue samples. Six of these cases were available for Western blot analyses. The results were compared with various clinicopathologic parameters of CCRCC and patients' survival. RESULTS: VEGFR-1 expression was detected in 59 cases (46.8%) of CCRCC. Higher VEGFR-1 expression was significantly correlated with a lower Fuhrman nuclear grade and the absence of renal pelvis invasion, although it was not related to patients' survival. Western blot analyses showed higher VEGFR-1 expression in low grade tumors. CONCLUSION: VEGFR-1 expression may be associated with favorable prognostic factors, particularly a lower Fuhrman nuclear grade in CCRCC.

ROS1 expression in invasive ductal carcinoma of the breast related to proliferation activity.

PURPOSE: ROS1 is an oncogene, expressed primarily in glioblastomas of the brain that has been hypothesized to mediate the effects of early stage tumor progression. In addition, it was reported that ROS1 expression was observed in diverse cancer tissue or cell lines and ROS1 is associated with the development of several tumors. However, ROS1 expression has not been studied in breast cancer to date. Therefore, we investigated ROS1 expression at the protein and gene level to compare expression patterns and to verify the association with prognostic factors in invasive ductal carcinoma (IDC) of the breast. MATERIALS AND METHODS: Tissue samples from 203 patients were used. Forty-six cases were available for fresh tissue. We performed immunohistochemical staining and real-time polymerase chain reaction (PCR). RESULTS: ROS1 expression was significantly lower in proportion to higher histologic grade, higher mitotic counts, lower estrogen receptor expression, and a higher Ki-67 proliferation index, although ROS1 expression was not significantly associated with the survival rate. The result of real-time PCR revealed similar trends, however not statistically significant. CONCLUSION: Higher ROS1 expression may be associated with favorable prognostic factors of IDC and its expression in IDC is related to the proliferation of tumor cells.

CD133 expression is not an independent prognostic factor in stage II and III colorectal cancer but may predict the better outcome in patients with adjuvant therapy.

BACKGROUND: Cancer stem cells (CSCs) are notorious for their capacity of tumor progression, metastasis or resistance to chemo-radiotherapy. However, the undisputed role of cancer stem marker, CD133, in colorectal cancers (CRCs) is not clear yet. METHODS: We assessed 271 surgically-resected stage II and III primary CRCs with (171) and without (100) adjuvant therapy after surgery. CD133 expression was analyzed by immunohistochemical (IHC) staining and real-time RT-PCR. CD133 promoter methylation was quantified by pyrosequencing. RESULTS: The CD133 IHC expression was significantly correlated with mRNA expression (p=0.0257) and inversely correlated with the promoter methylation (p=0.0001). CD133 was expressed more frequently in rectal cancer (p=0.0035), and in moderately differentiated tumors (p=0.0378). In survival analysis, CD133 expression was not significantly correlated with overall survival (OS) (p=0.9689) as well as disease-free survival (DFS) (p=0.2103). However, CD133+ tumors were significantly associated with better OS in patients with adjuvant therapy compared to those without adjuvant therapy (p<0.0001, HR 0.125, 95% CI 0.052-0.299). But the patients with CD133- tumors did not show any significant difference of survival according to adjuvant therapy (p=0.055, HR 0.500, 95% CI 0.247-1.015). CONCLUSIONS: In stage II and III CRCs, CD133 IHC expression may signify the benefit for adjuvant therapy although it is not an independent prognostic factor.