INTRODUCTION:We examined the age- and sex-specific distributions of biomarkers of tobacco smoke exposure to determine the optimal cutoffs to distinguish smokers from non-smokers over the last 10 years in Korea, during which smoking prevalence and secondhand smoke (SHS) exposure declined due to changes in tobacco control policy. METHODS:We analyzed data from the Korea National Health and Nutrition Examination Survey on creatinine-adjusted urinary cotinine (2008-2018; 33 429 adults: 15 653 males and 17 776 females) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; 2016-2018; 6337 adults: 3091 males and 3246 females). We determined the optimal cutoffs and confidence intervals (CIs) to distinguish smokers from non-smokers using receiver operator characteristic curve analysis and bootstrapping (1000 resamples). RESULTS:The optimal cutoff values of creatinine-adjusted urine cotinine and NNAL concentration were 20.9 ng/mg (95% CI: 20.8-21.0, sensitivity: 96.6%, specificity: 93.8%) and 8.9 pg/mg (95% CI: 8.8-8.9, sensitivity: 94.0%, specificity: 94.7%), respectively, in 2016-2018. The optimal cutoffs of both biomarkers increased with age and were higher in females than in males for NNAL concentration. In both sexes, the optimal cutoff of urine cotinine continuously declined over the study period. CONCLUSIONS:The optimal cotinine cutoff declined along with smoking prevalence and levels of SHS exposure due to enforcement of tobacco control policies, including smoke-free ordinances and tax increases. Monitoring of biomarkers of tobacco exposure appears necessary for verification of smoking status and regulatory use. IMPLICATIONS:Our results based on nationally representative data suggest that a large decrease in the optimal cutoff value of urine cotinine to distinguish smokers from non-smokers was caused by decreases in smoking prevalence and SHS exposure following enforcement of tobacco control policies over the last 10 years. We determined the optimal cutoff values of urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which were not previously reported in representative population in Asia, to enable more accurate estimation of exposure to tobacco smoke and proper assessment of disease risks. Gender- and age-specific differences in the optimal cutoffs require further study. Monitoring of biomarkers of tobacco smoke exposure seems necessary for verification of smoking status and regulatory use.

The legal regulations and cultural environment for smoking bans in hotels and motels in South Korea differ depending on the type of accommodation. The aim of this study was to assess the thirdhand smoke exposure for hotel and motel guests staying at accommodations who are expected to be relatively vulnerable to thirdhand smoke. Biomarkers for 28 participants were assessed before and after lodging at a hotel or motel for approximately 14 h. Hotel participants had statistically decreased urinary cotinine concentrations after their stay, whereas motel participants experienced increased concentrations. The concentration of nicotine-derived nitrosamine ketone in dust in hotels was lower than that in motels, and the higher dust nicotine-derived nitrosamine ketone concentration in motels had more effect on an increase in urinary cotinine concentration. Both hotels and motels legally allowed smoking in guest rooms. However, the study participants in hotels were less exposed to thirdhand smoke than those in motels.

No published studies have prospectively evaluated the association between urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels and lung cancer risk in the general population. Here, we conducted a prospective community-based cohort study in the Republic of Korea to evaluate the relationship between urinary NNAL levels and lung cancer risk using prediagnostic urine samples. This prospective cohort study was based on the Korean National Cancer Center Community Cohort. During the follow-up period, 173 primary lung cancer cases were identified. Total urinary NNAL levels were measured by liquid chromatography-tandem mass spectrometry, and data were analyzed using multivariable Cox proportional hazards regression models. The risk of lung cancer was significantly increased per unit of natural log-transformed urinary NNAL (HR, 1.27; 95% CI, 1.09–1.48), after adjusting for age, region, entry year into the cohort, education achievement, alcohol consumption status, BMI, smoking status, and urinary cotinine levels. Cox proportional-hazards models with NNAL quartiles also showed positive dose-response relationships with risk of lung cancer. A significantly increased risk of lung cancer was found in the fourth quartile of urinary NNAL levels (HR, 3.27; 95% CI, 1.37–7.79, P for trend < 0.01). After stratification with sex, the significant association remained in only men. Urinary NNAL levels are associated with the risk of lung cancer in the general population, and this association is independent from the quantification of cigarette smoking and nicotine uptake.

Background Although plasma free hemoglobin (fHb) test is important for assessing intravascular hemolysis, it is still dependent on the gold standard Harboe method using manual and labor-intensive spectrometric measurements at the wavelength of 380-415-450 nm. We established an automated fHb assay using a routine chemistry autoanalyzer that can be tuned to a wavelength of 380-416-450 nm. Methods The linearity, precision, accuracy, correlation, and sample carryover of fHb measurement using TBA200FRneo method and manual Harboe method were evaluated, respectively. fHb values measured by manual Harboe method were compared with those measured by our new automated TBA200FRneo method. Results fHb measurements were linear in the range of 0.05~38.75 mu mol/L by TBA200FRneo and 0.05~9.69 mu mol/L by manual Harboe method. Imprecision analysis (%CV) revealed 0.9~2.8% for TBA200FRneo method and 5.3~13.6% for the manual Harboe method. Comparison analysis showed 0.9986 of correlation coefficient (TBA200FRneo = 0.970 x Harboe + 0.12). In analytical accuracy analysis, the manual Harboe method revealed about 4 times higher average total error % (12.2%) than the TBA200FRneo automated method (2.8%). The sample carryover was -0.0016% in TBA200FRneo method and 0.0038% in Harboe method. Conclusions In the measurement of fHb, the automated TBA200FRneo method showed better performance than the conventional Harboe method. It is expected that the automated fHb assay using the routine chemistry analyzer can replace the gold standard Harboe method which is labor-intensive and need an independent spectrophotometry equipment.

Objectives: It is especially difficult for hospitality workers to avoid secondhand smoke (SHS), meaning that they are likely particularly vulnerable to the effects of SHS. The authors aimed to determine the degree to which smoke-free laws protect hospitality workers from SHS exposure, by examining biochemical markers of such exposure. Material and Methods: This was a cross-sectional study examining SHS exposure in non-smoking employees working in hospitality settings where smoking is prohibited or permitted. The following biomarkers were selected: cotinine and tobacco-specific nitrosamines, which are known to measure SHS exposure, and 2 representative carcinogens: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The authors compared these biomarkers between 3 hospitality settings. A descriptive analysis was performed. In addition, they conducted 1-way and 2-way analysis of covariance (ANCOVA) to compare the biochemical markers. Results: Smoking substances were identified by smoking ban levels. In the case of hair nicotine and urine cotinine. their concentrations were lower in areas with a complete smoking ban than in both areas with a separate smoking room and no smoking ban: however, there was no statistically significant difference between these. In the case of dust NNK, its level was the lowest in areas with a complete smoking ban. To confirm the smoking ban effect by hospitality settings, the authors checked the results of the 2-way ANCOVA. In karaoke and billiard halls, the dust NNK concentrations were significantly higher in areas with no smoking ban than in areas with a separate smoking room. Conclusions: Exposure to SHS is more prevalent in places that are more lenient when it comes to smoking (e.g., Internet cafes) than in places that are not (e.g., restaurants and cafes), even when smoking is similarly prohibited in both types of places.

AIMS:It is not known whether the machine-smoked nicotine yield of usual brand of cigarette smoked is associated with the chances of success of quit attempts. This study aimed to assess this association. DESIGN:Prospective study. SETTING:Republic of Korea. PARTICIPANTS:A total of 16 808 male smokers registered for the Quitline between 7 April 2006 and 31 December 2013. Of these, 13 176 participants who were > 19 years of age and provided data on their demographic characteristics, smoking-related behaviors, nicotine dependence, tobacco brands used and self-efficacy were included in this study. MEASUREMENTS:Machine-smoked nicotine yield was based on information provided by tobacco companies on cigarette packages that smokers reported as their usual brand. Ultra-low nicotine yield was defined as ≤ 0.1 mg machine-smoked nicotine yield per cigarette, whereas higher nicotine yield was defined as > 0.1 mg machine-smoked nicotine yield. Participant personal information and self-reported continuous abstinence at 1-month, 6-month and 1-year follow-up were recorded in electronic databases. FINDINGS:Continuous abstinence rates in the ultra-low nicotine yield versus higher nicotine yield groups were, respectively, 40.7 versus 34.6% at 1 month [odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.12-1.33], 22.7 versus 18.8% at 6 months (OR = 1.20, 95% CI = 1.08-1.32) and 19.5 versus 16.6% (OR = 1.19, 95% CI = 1.10-1.29) at 1 year. The association between ultra-low nicotine yield cigarette smoking and successful quitting was stronger among the smokers with higher cigarette dependence. CONCLUSIONS:Male smokers who use the Korean Quitline are more likely to quit successfully if they smoke ultra-low nicotine yield cigarettes than if they smoke higher nicotine yield cigarettes.

The objective of this study was to evaluate the validity of self-reported smoking prevalence in Korean adolescents by using an improved gold standard by a combined method. Using a stratified sampling method, we selected 13 schools from among 397 high schools that participated in the 2015 Korean Youth Health Risk Behavior Web-Based Survey (KYRBS). A second survey (repeated self-reporting questionnaire and urinary cotinine test) was conducted on 1058 students who completed the KYRBS. The gold standard of current smoker was defined as those either self-reporting as a smoker in the second survey or having a urinary cotinine concentration ≥50 ng/mL. The current smoking prevalence in the first survey (KYRBS) was 7.9% (boys 16.5% and girls 1.8%), which was lower than the results based on gold standard (11.3% total, boys 21.9% and girls 3.7%). The sensitivity and specificity of self-reported smoking status was 62.5% and 99.0%, respectively. In particular, the sensitivity of girls (43.5%) was lower than that of boys (67.0%). The self-reported smoking prevalence in Korean adolescents was underestimated, particularly among girls. Careful attention should be paid to interpreting adolescents’ smoking prevalence, and supplementary surveys or periodic validity tests need to be considered in Asian countries.

This pilot study sought to evaluate the feasibility of utilizing vaginal self-swabs and urine samples for HPV-based cervical cancer screening in 700 women who had undergone conventional Pap smear screening via the national cervical cancer program in Korea. The cobas 4800 HPV test was utilized to detect HPV in the self-samples. Pap smear results revealed three cases of atypical squamous cells of undetermined significance, 649 cases of negative for an intraepithelial lesion or malignancy, and 48 non-specific inflammatory findings. High-risk HPV was detected in 6.7% of urine samples and 9.6% of vaginal self-swab samples. The overall agreement for HPV 16/18 between urine and vaginal self-swab samples was 99.1% (95%CI 98.1% to 99.6%). Colposcopic biopsy revealed one cervical intraepithelial neoplasia (CIN) 3 lesion, 12 CIN1 lesions, and 23 normal or chronic cervicitis lesions. In conclusion, urine and vaginal self-swab sampling was feasible and deemed a potential alternative for HPV detection in women who hesitate to participate in cervical cancer screening programs. Meanwhile, due to overall lower rates of abnormal cytology and sexual risk behaviors in Korea, a larger sample size than expected is needed to assess the sensitivity of CIN2+ detection via self-samples.

INTRODUCTION To evaluate the level of tobacco smoke exposure in taxis in Korea using tobacco specific environmental markers. METHODS From June to September 2012, cross-sectional measurements of air nicotine levels and dust nicotine-derived nitrosamine ketone (NNK) concentrations were conducted in 17 taxis in Goyang, Korea. Field investigators completed an observational questionnaire on building characteristics, smoking policies and evidence of smoking. Descriptive statistics including geometric means (GMs) ± standard deviations were produced for air nicotine levels and dust NNK concentrations. RESULTS There was no evidence of active smoking in the 17 taxis monitored, despite the fact that 10 drivers were current smokers. The overall GMs of air nicotine and dust NNK concentration were 0.42 μg/m3 and 6.78 pg/mg, respectively. These levels were 3.4-fold and 2.6-fold higher in taxis whose drivers were current smokers compared to the taxis of nonsmokers (GM of air nicotine: 0.65 μg/m3 vs 0.19 μg/m3; GM of dust NNK: 10.07 pg/mg vs 3.85 pg/mg). CONCLUSIONS The present study shows that air nicotine and dust NNK were detected in all taxis regardless of whether the taxi driver was smoking or not, which indicates the potential for exposure to SHS or THS. It suggests that an appreciable level of SHS and TSH exposure might occur if the environment is not completely smoke-free and enforcement is lacking. ABBREVIATIONS THS: third-hand smoke, SHS: second-hand smoke, FCTC: Framework Convention Alliance for Tobacco Control, NNK: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, LOD: limit of detection, GM: geometric mean, GSD: geometric standard deviation.

Identifying preferences for stool collection devices may help increase uptake rates for colorectal cancer screening via fecal immunochemical test (FIT). This study surveyed satisfaction with different devices utilized to collect stool samples for FIT: a conventional container and a sampling bottle (Eiken OC-Sensor).

BackgroundUse of total laboratory automation (TLA) system has expanded to microbiology and hemostasis and upgraded to second and third generations. We herein report the first successful upgrades and fusion of different versions of the TLA system, thus improving laboratory turnaround time (TAT).MethodsA 21‐day schedule was planned from the time of pre‐meeting to installation and clinical sample application. We analyzed the monthly TAT in each menu, distribution of the “out of range for acceptable TAT” samples, and “prolonged time out of acceptable TAT,” before and after the upgrade and fusion.ResultsWe installed and customized hardware, middleware, and software. The one‐way CliniLog 2.0 version track, 50.0‐m long, was changed to a 23.2‐m long one‐way 2.0 version and an 18.7‐m long two‐way 4.0 version. The monthly TAT in the outpatient samples, before and after upgrading the TLA system, were uniformly satisfactory in the chemistry and viral marker menus. However, in the tumor marker menu, the target TAT (98.0% of samples ≤60 minutes) was not satisfied during the familiarization period. There was no significant difference in the proportion of “out of acceptable TAT” samples, before and after the TLA system upgrades (7.4‰ and 8.5‰). However, the mean “prolonged time out of acceptable TAT” in the chemistry samples was significantly shortened to 17.4 (±24.0) minutes after the fusion, from 34.5 (±43.4) minutes.ConclusionsDespite experimental challenges, a fusion of the TLA system shortened the “prolonged time out of acceptable TAT,” indicating a distribution change in overall TAT.

OBJECTIVES:This study aimed to evaluate the impact of seasonal variations in climate on the performance of the fecal immunochemical test (FIT) in screening for colorectal cancer in the National Cancer Screening Program in Korea.METHODS:Data were extracted from the National Cancer Screening Program databases for participants who underwent FIT between 2009 and 2010. We compared positivity rates, cancer detection rates, interval cancer rates, positive predictive value, sensitivity, and specificity for FIT during the spring, summer, fall, and winter seasons in Korea.RESULTS:In total, 4,788,104 FIT results were analyzed. FIT positivity rate was lowest during the summer months. In the summer, the positive predictive value of FIT was about 1.1 times (adjusted odds ratio (aOR) 1.08, 95% confidence interval (CI) 1.00-1.16) higher in the overall FIT group and about 1.3 times (aOR 1.29, 95% CI 1.10-1.50) higher in the quantitative FIT group, compared to those in the other seasons. Cancer detection rates, however, were similar regardless of season. Interval cancer risk was significantly higher in the summer for both the overall FIT group (aOR 1.16, 95% CI 1.07-1.27) and the quantitative FIT group (aOR 1.31, 95% CI 1.12-1.52). In addition, interval cancers in the rectum and distal colon were more frequently detected in the summer and autumn than in the winter.CONCLUSIONS:The positivity rate of FIT was lower in the summer, and the performance of the FIT screening program was influenced by seasonal variations in Korea. These results suggest that more efforts to reduce interval cancer during the summer are needed in population-based screening programs using FIT, particularly in countries with high ambient temperatures.

Persistent organic pollutants (POPs) can affect epigenetic mechanisms and obesity development. Polybrominated diphenyl ethers (PBDEs) — widely used to make flames — are one of the important POPs. Prenatal exposure to endocrine disrupting chemicals (EDCs), such as POPs, may affect global DNA methylation in long interspersed nuclear elements (LINE-1), increasing the risk of obesity later in life. Therefore, pregnant Sprague-Dawley (SD) rats were used to elucidate whether BDE-47 and BDE-209 transferred through placenta and breast milk cause epigenetic changes in LINE-1 and increase genetic susceptibility to obesity as obesogen during the developmental periods. Global DNA methylation in LINE-1 and gene expression related to obesity were measured in dams and offspring, using a methylation-sensitive high resolution melting analysis (MS-HRM) and direct bisulfite sequencing and quantitative real time polymerase chain reaction (qPCR), respectively. The results of MS-HRM showed global DNA hypomethylation patterns in LINE-1 of exposed offspring (2 of total 4) at PND 4, but bisulfite sequencing showed no difference in both the exposed and non-exposed groups. Gene expression in dams related to  -oxidation pathway and those related to adipokines showed different patterns between the two groups. On the contrary, gene expressions of offspring showed a similar pattern. Gene expressions related to  -oxidation pathway and obesity were significantly increased when compared with 'at birth', but not PPAR-  . In conclusion, this study demonstrated the possibility that co-exposure to BDE-47 and BDE-209 — via the placenta and breast milk — may affect epigenetic changes and modulate gene expression levels

Recently, because the quality of laboratory analyses has increased along with the need for quality improvement, several external quality control bodies have adapted performance specifications using the Desirable Biological Variation Database, termed "Ricos goals"; these criteria are more stringent than those presented in CLIA 88. In this study, we aimed to validate newly introduced serum separator tubes, Improvacutor, for routine clinical chemistry testing in accordance with Ricos goals and CLIA 88. Blood samples were collected from 100 volunteers into three types of serum vacuum tubes: Greiner Vacuette, Becton Dickinson (BD) Vacutainer, and Improve Improvacutor. The samples were subjected to 16 routine chemistry tests using a TBA-200fr NEO chemistry autoanalyzer. In the comparison analysis, all 16 test results were acceptable according to CLIA 88. However, in the comparison of Improve and BD tubes, creatinine showed 4.31% (+0.08 μmol/L) bias. This slightly exceeded the Desirable Specification for Inaccuracy Ricos limit of ±3.96%, but still satisfied the CLIS88 limit of ±26.52 μmol/L. The remaining 15 analytes performed acceptably according to the Desirable Specifications of Ricos. The correlation coefficient of 12 analytes was greater than 0.95 in Passing-Bablok regression analysis among the three tubes, but was lower for four analytes: calcium, sodium, potassium, and chloride. In the stability assay, only potassium tested in the Greiner tube revealed a larger positive bias (2.18%) than the Ricos Desirable Specification for Inaccuracy based on biologic variation (1.8%). The BD tube also showed a positive bias of 1.74%, whereas the new Improve tube showed the smallest positive bias of 1.17% in potassium level after 72 h storage. Thus, the results of this study demonstrate that recently introduced analytical performance specifications based on components of biological variation (Rico's goal) could be extended to criterion for performance evaluation and applied.

Background: Human papillomavirus (HPV) testing based on cervical samples is important for use in cervical cancer screening. However, cervical sampling is invasive. Therefore, non-invasive methods for detecting HPV, such as urine samples, are needed.Objectives: For HPV detection in urine samples, two real-time PCR (RQ-PCR) tests, Roche cobas 4800 test (Roche_HPV; Roche Molecular Diagnostics) and Abbott RealTime High Risk HPV test (Abbott.HPV; Abbott Laboratories) were compared to standard cervical samples.Study design: The performance of Roche_HPV and Abbott.HPV for HPV detection was evaluated at the National Cancer Center using 100 paired cervical and urine samples. The tests were also compared using urine samples stored at various temperatures and for a range of durations.Results: The overall agreement between the Roche_HPV and Abbott.HPV tests using urine samples for any hrHPV type was substantial (86.0% with a kappa value of 0.7173), and that for HPV 16/18 was nearly perfect (99.0% with a kappa value of 0.9668). The relative sensitivities (based on cervical samples) for HPV 16/18 detection using Roche_HPV and Abbott.HPV with urine samples were 79.2% (95% CI; 57.9-92.9%) and 81.8% (95% CI; 59.7-94.8%), respectively. When the cut-off C-T value for Abbott_HPV was extended to 40 for urine samples, the relative sensitivity of Abbott_HPV increased to 91.7% from 81.8% for HPV16/18 detection and to 87.0% from 68.5% for other hrHPV detection. The specificity was not affected by the change in the CT threshold.Conclusions: Roche_HPV and Abbott_HPV showed high concordance. However, HPV DNA detection using urine samples was inferior to HPV DNA detection using cervical samples. Interestingly, when the cutoff CT value was set to 40, Abbott_HPV using urine samples showed high sensitivity and specificity, comparable to those obtained using cervical samples. Fully automated DNA extraction and detection systems, such as Roche_HPV and Abbott_HPV, could reduce the variability in HPV detection and accelerate the standardization of HPV detection in urine. Thus, urine samples may be an effective alternative for HPV detection in women who hesitate to participate in cervical cancer screening programs. (C) 2017 Elsevier B.V. All rights reserved.

OBJECTIVE:Sodium bicarbonate has been reported to maximize the efficacy of intravesical instillation of mitomycin-C (IVI-MMC) therapy by urine alkalinization in non-muscle-invasive bladder cancer (NMIBC). This study aimed to analyze the changes in MMC concentration according to urinary pH and evaluate the efficacy of sodium bicarbonate to maintain the concentration of active form of MMC during IVI-MMC.METHODS:We prospectively enrolled 26 patients with NMIBC after transurethral resection of bladder tumor. Patients with very high-risk and low-risk NMIBC were excluded. Urinary creatinine, volume, pH, and concentrations of MMC and its degraded form were measured immediately before and after IVI-MMC. The patients were administered 1.5 g of oral sodium bicarbonate during the preceding evening, in the morning, and immediately before the fourth cycle of the six-cycle IVI-MMC. The correlation between MMC concentration and urinary pH changes was explored with or without oral bicarbonate therapy.RESULTS:Recurrence without progression to muscle-invasive disease was noted in 4 of 26 patients in a 23.7-month follow-up. The mean urinary pH before and after the therapy increased from 6.03 to 6.50, and 6.46 to 7.24, without or with oral SB therapy, respectively. Despite this increase, the concentration of active form of MMC did not change significantly. No correlation was found between urinary pH and MMC concentration. Urine alkalinization by SB administration did not maintain the high concentration of urinary MMC.CONCLUSIONS:Urine alkalinization by sodium bicarbonate administration for IVI-MMC did not maintain the high concentration of active urinary MMC in NMIBC.

Persistent organic pollutants (POPs) can affect epigenetic mechanisms and obesity development. Polybrominated diphenyl ethers (PBDEs)—widely used to make flames—are one of the important POPs. Prenatal exposure to endocrine disrupting chemicals (EDCs), such as POPs, may affect global DNA methylation in long interspersed nuclear elements (LINE-1), increasing the risk of obesity later in life. Therefore, pregnant Sprague-Dawley (SD) rats were used to elucidate whether BDE-47 and BDE-209 transferred through placenta and breast milk cause epigenetic changes in LINE-1 and increase genetic susceptibility to obesity as obesogen during the developmental periods. Global DNA methylation in LINE-1 and gene expression related to obesity were measured in dams and offspring, using a methylation-sensitive high resolution melting analysis (MS-HRM) and direct bisulfite sequencing and quantitative real time polymerase chain reaction (qPCR), respectively. The results of MS-HRM showed global DNA hypomethylation patterns in LINE-1 of exposed offspring (2 of total 4) at PND 4, but bisulfite sequencing showed no difference in both the exposed and non-exposed groups. Gene expression in dams related to β-oxidation pathway and those related to adipokines showed different patterns between the two groups. On the contrary, gene expressions of offspring showed a similar pattern. Gene expressions related to β-oxidation pathway and obesity were significantly increased when compared with ’at birth’, but not PPAR-α. In conclusion, this study demonstrated the possibility that co-exposure to BDE-47 and BDE-209—via the placenta and breast milk—may affect epigenetic changes and modulate gene expression levels related to obesity.

There is a growing body of evidence demonstrating an association between smoking and DNA methylation. Accordingly, DNA methylation is now considered a promising biomarker of smoking exposure. We evaluated the relationship between methylation markers (AHRR and F2RL3) and urine cotinine as well as self-reported smoking status. DNA methylation levels of AHRR and F2RL3 in blood as well as urine cotinine were measured in 330 adults (46 to 87 years of age). Pyrosequencing was performed to measure DNA methylation of AHRR and F2RL3 associated with smoking exposure. The lung cancer risk associated with DNA methylation and urine cotinine was analyzed using logistic regression analysis. The AHRR and F2RL3 genes were significantly hypomethylated in current smokers compared to in individuals who have never smoked. An inverse relationship was observed between urine cotinine and methylation levels. Methylation of AHRR and F2RL3 distinguished current smokers from never-smokers with high accuracy. Logistic multivariate analysis showed that AHRR methylation is significantly associated with the risk of lung cancer (OR = 0.96, P = 0.011). Our study validated the smoking-associated DNA methylation markers reported in a Korean population-based cohort. In conclusion, DNA methylation of AHRR and F2RL3 provided accurate measures for smoking exposure. Methylation markers reflecting the long-term effect of smoking on the risk of lung cancer showed better performance in distinguishing former smokers from never-smokers.

Background/AimsWe are in the process of conducting a randomized trial to determine whether compliance with the fecal immunochemical test (FIT) for colorectal cancer screening differs according to the stool-collection method. This study was an interim analysis of the performance of two stool-collection devices (sampling bottle vs conventional container).Methods : In total, 1,701 individuals (age range, 50 to 74 years) were randomized into the sampling bottle group (intervention arm) or the conventional container group (control arm). In both groups, we evaluated the FIT positivity rate, the positive predictive value for advanced neoplasia, and the detection rate for advanced neoplasia.Results : The FIT positivity rates were 4.1% for the sampling bottles and 2.0% for the conventional containers; these values were significantly different. The positive predictive values for advanced neoplasia in the sampling bottles and conventional containers were 11.1% (95% confidence interval [CI], −3.4 to 25.6) and 12.0% (95% CI, −0.7 to 24.7), respectively. The detection rates for advanced neoplasia in the sampling bottles and conventional containers were 4.5 per 1,000 persons (95% CI, 2.0 to 11.0) and 2.4 per 1,000 persons (95% CI, 0.0 to 5.0), respectively.Conclusion : sThe impact of these findings on FIT screening performance was unclear in this interim analysis. This impact should therefore be evaluated in the final analysis following the final enrollment period.

Aim of this study was to evaluate HRQoL of patients affected by NMIBC underwent intravesical instillations of Bacillus Calmette-Gu erin (BCG) or Mytomicin C (MMC) with a short-term follow-up.METHODS: From December 2011 to December 2014 we recruited 108 consecutive patients in a single academic center with a first-time diagnosis of NMIBC at intermediate or high risk.The median age was 73 years (38-94) and 55.3% (N 57) patients underwent BCG and 44.7% (N 46) patients underwent MMC after TURBT respectively.The assessment of HRQoL was performed using two questionnaires from EORTC: QLQ-C30 and QLQ-BLS24 specific for NMIBC.Patients self-completed the questionnaires in three different times: T0 (before intravesical instillation), T1 (after intravesical instillation), T2 (at three months after last instillation).The above analysis was stratified by gender, age (?70 years and >70 years), tumour degree risk (intermediate and high risk) and type of intravesical therapy (MMC and BCG).Wilcoxon two sample test was used to verify differences.Statistical significance was achieved if pvalue was ¼0.05 (two-sides).RESULTS: Treatment was well tolerated in both groups of patients underwent intravesical instillations of BCG and MMC respectively.Grade I and II side effects, as CTCAE classification, were reported by 46.6% of patients at T1 and 47.5% at T2. 5 patients dropped out of the study (3 lost in follow-up and 2 developed side effects of BCG).At T1 we founded a drop in QoL, with reference to Physical, Role, Emotional and Social functioning domains and a worsening of urinary bladder symptoms with a generally decrease of Global Quality of Life Score.The sexual sphere was affected by adjuvant therapy with persistence or worsening of sexual disorders.At T2 patients showed a progressive return to baseline QoL, in particular in the Social and clinical symptoms domains.Male gender, age >70 years, high-risk tumours and BCG seem to be the factors that worsening HRQoL of these patients.CONCLUSIONS: Intravesical instillations seem to modify the HRQoL of these patients with a return at 3 months to baseline conditions.