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This study aimed to understand the biological process related to the prevention of cardiovascular & metabolic diseases (CMD), including diabetes, hypertension, and dyslipidemia via regular exercise. This study included 17,053 subjects aged 40–69 years in the Health Examinees Study from 2004 to 2012. Participation in regular exercise was investigated by questionnaires. Data on 42 biomarkers were collected from anthropometric measures and laboratory tests. We examined the associations between regular exercise and biomarkers using general linear models, between biomarkers and the risk of CMD using cox proportional hazard models, and the mediation effect of biomarkers using mediation analyses. Biomarker networks were constructed based on the significant differential correlations (p

Background Obesity is well known as a risk factor for cardiovascular disease. We aimed to determine the performance of and the optimal cutoff values for obesity indices to discriminate the presence of metabolic abnormalities as a primary risk factor for cardiovascular diseases in a Health Examinees study (HEXA). Methods The current study analyzed 134,195 participants with complete anthropometric and laboratory information in a Health Examinees study, consisting of the Korean population aged 40 to 69 years. The presence of metabolic abnormality was defined as having at least one of the following: hypertension, hyperglycemia, or dyslipidemia. The area under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CIs) were calculated for body mass index, waist to hip ratio, waist to height ratio, waist circumference, and conicity index. Results The AUC of metabolic abnormalities was the highest for waist-to-height ratio (AUC [95% CIs], 0.677 [0.672–0.683] among men; 0.691 [0.687–0.694] among women), and the lowest for the C index (0.616 [0.611–0.622] among men; 0.645 [0.641–0.649] among women) among both men and women. The optimal cutoff values were 24.3 kg/m2 for the body mass index, 0.887 for the waist-to-hip ratio, 0.499 for the waist-to-height ratio, 84.4 cm for waist circumference and 1.20 m3/2/kg1/2 for the conicity index among men, and 23.4 kg/m2 for the body mass index, 0.832 for the waist-to-hip ratio, 0.496 for the waist-to-height ratio, 77.0 cm for the waist circumference and 1.18 m3/2/kg1/2 for the conicity index among women. Conclusion The waist-to-height ratio is the best index to discriminate metabolic abnormalities among middle-aged Koreans. The optimal cutoff of obesity indices is lower than the international guidelines for obesity. It would be appropriate to use the indices for abdominal obesity rather than general obesity and to consider a lower level of body mass index and waist circumference than the current guidelines to determine obesity-related health problems in Koreans.

PurposeDietary calcium intake has been suggested to be protective against the development of colorectal cancer. The mean dietary calcium intake of Koreans is 490 mg/day, which is far below the recommended calcium intake of 700-800 mg/day. In this study, we explored the relationship between dietary calcium intake and colorectal cancer development in Koreans with relatively low calcium intake compared with individuals in Western countries. Materials and MethodsThe Health Examinees Study, a large-scale genomic community-based prospective cohort study, was designed to identify the general characteristics of major chronic diseases in Koreans. A total of 119,501 participants aged 40-69 years recruited between 2004 and 2013 were included in this analysis. The calcium intake level was categorized using the Dietary Reference Intakes for Koreans (KDRIs). The Cox proportional hazards regression model was used to estimate the hazard ratio (HR) and the corresponding 95% confidence intervals (CIs) for colorectal cancer risk, adjusting for potential confounders.ResultsIn the multivariable-adjusted model, compared with the group that consumed less than the recommended amount of calcium, the group that consumed more than the recommended intake of calcium showed a significant reduction in the risk of colorectal cancer in women. (HR, 0.54; 95% CI, 0.31 to 0.95). Among men, however, no significant association was observed between dietary calcium intake and colorectal cancer risk (HR, 0.89; 95% CI, 0.54 to 1.45).ConclusionKorean women who adhere to the recommended intake of calcium showed a reduced risk of colorectal cancer.

Background Smoking is a well‐known risk factor for colorectal cancer incidence; however, the effect of smoking before and after cancer diagnosis on mortality has not been addressed well. Thus, we aimed to evaluate the association of prediagnosis and postdiagnosis smoking status and mortality among colorectal cancer patients. Methods A retrospective cohort consisted of 37,079 male colorectal cancer patients. Smoking status was defined from information within 2 years of colorectal cancer diagnosis for prediagnosis and at least 1 year later for postdiagnosis. The prediagnostic and postdiagnostic smoking status were categorized into four groups (nonsmoker/nonsmoker, nonsmoker/smoker, smoker/nonsmoker, and smoker/smoker). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazard model. Results During a median of 6.3 years of follow‐up, a total of 3980 deaths and 2137 deaths from colorectal cancer occurred. The number of prediagnosis smokers were 11,100 and 62.4% of them quitted smoking after the diagnosis. Significantly elevated mortality rate in prediagnosis smokers was observed regardless of postdiagnosis smoking status (smoker/nonsmoker [HR, 1.30; 95% CI, 1.20–1.41] and smoker/smoker [HR, 1.21; 95% CI, 1.09–1.34]). Among patients treated with surgical operation only, those who quit smoking after diagnosis showed lower mortality rates compared to continual smokers (HR, 0.80; 95% CI, 0.67–0.96). Conclusions Smoking before cancer diagnosis rather than postdiagnosis has stronger impact on prognosis colorectal cancer patients, and quitting smoking may improve survival, especially among early stage colorectal cancer patients., This study found that both smoking before and after cancer diagnosis is associated with increased mortality rate among colorectal cancer patient. Quitting smoking after diagnosis was significantly related to diminished mortality among colorectal cancer patients receiving only operation, who is considered as early stage colorectal cancer patients, though smoking cessation after diagnosis among colorectal cancer patients who received radiotherapy or chemotherapy was not associated with significantly decreased mortality.

While obesity increases colorectal cancer incidence, there are inconsistent results in the prognostic role of obesity or body weight change on survival. This study investigated the prognostic impact of body weight and weight change in stage III or high risk stage II colon cancer patients. We used data from patients enrolled in the phase III AVANT trial. The AVANT trial investigated the efficacy of adding bevacizumab to standard adjuvant chemotherapy (FOFOX or XELOX). Weight change during the first 6 months of adjuvant chemotherapy was measured. Cox proportional hazard model was used to assess the prognostic influence of body weight and weight change. Among 3451 intention-to-treat population, body weight and weight change was measured in 3449 (99.9%) and 2455 (71.1%) patients, respectively. Among 2455 patients, 651 (26.5%) had weight gain over 5 kg and 179 (7.3%) had weight loss over 5 kg. Weight gain was more frequently observed in Asian and male. Neither baseline BMI nor weight change affected recurrence or survival in the Cox proportional hazard model.

Background/Aims: The incidence of peptic ulcer disease has decreased in past decades; however, the trends in peptic ulcer bleeding (PUB) are inconsistent among regions. This study aimed to investigate the trends in PUB incidence and the effect of risk factors on PUB in Korea. Methods: The records of patients hospitalized with PUB from 2006 to 2015 were retrieved from the Korean National Health Insurance Service Database. Standardized incidences of PUB were calculated, and the clinical characteristics such as age, sex, Helicobacter pylori infection, drug exposure, comorbidities, and mortality were obtained. Results: In total, 151,507 hospitalizations with PUB were identified. The overall annual hospitalization rate was 34.98 per 100,000 person-years. The incidence of PUB showed no significant change from 2006 to 2008 and decreased from 2008 to 2015, with an annual change of -2.7% (p

Objective Previous studies have reported on marital status and the prevalence of obesity; however, few studies have assessed the prevalence of underweight in relation to marital status. This study aimed to explore the association of obesity and abdominal obesity with marital status among Koreans aged 40–69 years. Methods We selected a total of 137,608 participants from the Health Examinees Gem Study for the final analysis. Multinomial logistic regression models were used to estimate odds ratios (OR) and their 95% confidence intervals (CI) for the association of obesity with marital status, with controlling for potential confounders. Results The prevalence of underweight was higher in unmarried men (OR: 1.82, 95% CI: 1.25–2.63) and women (OR: 2.16, 95% CI: 1.79–2.61) than in married individuals. Compared to married individuals, a lower prevalence of BMI ≥ 25 kg/m2 was observed for those who were unmarried (men: OR: 0.71, 95% CI: 0.62–0.81, women: OR: 0.65, 95% CI: 0.58–0.73) or divorced/separated (men: OR: 0.80, 95% CI: 0.69–0.93, women: OR: 0.90, 95% CI: 0.83–0.98). Interestingly, widowed women showed higher prevalence of BMI ≥ 25 kg/m2 (OR: 1.17, 95% CI: 1.10–1.25) and abdominal obesity (OR: 1.23, 95% CI: 1.16–1.30) compared to married women, and the association persisted only among women in their 50s and 60s. Conclusions Married participants showed a higher prevalence of obesity and abdominal obesity than those in other marriage categories except for widowed women.

OBJECTIVES To investigate the efficacy of health coaching and a web-based program on survivor physical activity (PA), weight, and distress management among stomach, colon, lung and breast cancer patients. METHODS This randomised, controlled, 1-year trial conducted in five hospitals recruited cancer survivors within 2 months of completing primary cancer treatment who had not met ≥1 of these behavioural goals: (i) conducting moderate PA for at least 150 minutes/week or strenuous exercise for over 75 minutes per week or, in the case of lung cancer patients, low or moderate intensity exercise for over 12.5 MET per week, (ii) maintaining normal weight, and (iii) attaining a score >72 in the Post Traumatic Growth Inventory (PTGI). Participants were randomly assigned to one of three groups: the control group, a web-only group, or a health coaching + web group. The primary endpoint was based on a composite of PA, weight, and PTGI score at 12 months. RESULTS Patients in the health coaching + web group (difference = 6.6%, P = .010) and the web-only group (difference = 5.9%, P = .031) had greater overall improvements across the three-outcome composite than the control group. The health coaching + web group had greater overall improvement in PTGI (difference = 12.6%; P

The purpose of this study was to evaluate the nationwide benefit and cost of the national cancer screening program (NCSP) for gastric cancer treatment.For this nationwide, population-based study, the Korean National Health Insurance Big Data Base, which included gastric cancer-related treatment information and the costs for all patients with gastric cancer who were 40 years old or older between 2004 and 2013, was restructured. Patients with gastric cancer who participated in the NCSP at least once (the screening group) were compared with those who did not participate in the NCSP (the nonscreening group).The screening group (n = 116,775) spent significantly less on medical care expenses than the nonscreening group (n = 74,927) during the 5 years since the initial treatment (P .0001). The screening group presented a significantly better prognosis for 5 and 9 years than the nonscreening group (P .0001). The screening group revealed a 41% decreased hazard ratio (P .0001) for death in comparison with the nonscreening group; the prognostic benefit became more obvious when treatment was started within the first 4 months after screening. The age-standardized mortality rate ratio of the screening group versus the nonscreening group was 0.62 (P .0001). The NCSP for gastric cancer required an average of 22,169,769 Korean Republic won (US $20,309) for 1 life-year saved, which was less than the average gross domestic product (GDP) per capita in Korea.The screening group had significantly lower medical care expenses and showed a significantly better prognosis than the nonscreening group. On the basis of the GDP per capita, the NCSP for gastric cancer was cost-effective for treatment prognosis.

Background: Risk variants identified so far for colorectal cancer explain only a small proportion of familial risk of this cancer, particularly in Asians. Methods: We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, including 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 promising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls of European descent. To identify additional risk variants in known colorectal cancer loci, we performed conditional analyses in East Asians. Results: An indel variant, rs67052019 at 1p13.3, was found to be associated with colorectal cancer risk at P = 3.9 × 10–8 in Asians (OR per allele deletion = 1.13, 95% confidence interval = 1.08–1.18). This association was replicated in European descendants using a variant (rs2938616) in complete linkage disequilibrium with rs67052019 (P = 7.7 × 10–3). Of the remaining 59 variants, 12 showed an association at P < 0.05 in the European-ancestry study, including rs11108175 and rs9634162 at P < 5 × 10−8 and two variants with an association near the genome-wide significance level (rs60911071, P = 5.8 × 10−8; rs62558833, P = 7.5 × 10−8) in the combined analyses of Asian- and European-ancestry data. In addition, using data from East Asians, we identified 13 new risk variants at 11 loci reported from previous GWAS. Conclusions: In this large GWAS, we identified three novel risk loci and two highly suggestive loci for colorectal cancer risk and provided evidence for potential roles of multiple genes and pathways in the etiology of colorectal cancer. In addition, we showed that additional risk variants exist in many colorectal cancer risk loci identified previously. Impact: Our study provides novel data to improve the understanding of the genetic basis for colorectal cancer risk.

Objective Although menopausal hormone therapy (MHT) is the most effective treatment for menopausal symptoms, menopausal women hesitate to start MHT due to concerns about adverse events. Recently, however, it has been recommended to use it for appropriate patients who have been evaluated for baseline diseases, age, and timing of initiation. We aimed to investigate the association of MHT with cardiovascular diseases (CVDs) and type 2 diabetes among middle-aged postmenopausal women in Korea. Methods Data were collected from the National Health Insurance Service database in Korea from 2002 to 2016. A total of 58,060 postmenopausal women (including 8,013 [13.8%] MHT users and 50,047 [86.2%] nonusers) were included. The time-dependent Cox regression model with a 1-year latency period was used to evaluate the hazard ratio (HR) and 95% confidence interval (CI) of the associations of MHT with CVDs and type 2 diabetes outcomes. Subgroup analyses by regimen type and cumulative duration were conducted. Results In the multivariate-adjusted model, MHT was not significantly associated with CVDs (HR = 1.085, 95% CI: 0.899-1.310) or type 2 diabetes (HR = 1.104, 95% CI: 0.998-1.221). Differential effects were not observed by regimen type, cumulative duration, and years since menopause subgroups. Sensitivity analyses also did not show adverse events by MHT on CVDs and type 2 diabetes. Conclusions Although protective effects of MHT against CVDs or type 2 diabetes were not observed among postmenopausal women who had screened underlying diseases, our results may contribute to reducing the current concerns about the use of MHT for middle-aged postmenopausal women in Korea. Video Summary:http://links.lww.com/MENO/A807.

This study was performed to investigate the association between coffee consumption and risk of colorectal cancer in a Korean population and examine whether the association can be altered by adjustment for intake of coffee additives. We conducted a case-control study involving 923 colorectal cancer cases and 1846 controls matched by sex and age (within 5 years). A semi-quantitative food frequency questionnaire was used to assess coffee intakes. High coffee consumption was associated with lower odds of developing colorectal cancer (≥3 cups/day vs. no drinks, OR = 0.68, 95% CI: 0.49–0.96). When we additionally controlled for consumption of coffee additives including sugar and cream, the inverse association became stronger (≥3 cups/day vs. no drinks, OR = 0.22, 95% CI: 0.14–0.33), and a significant inverse linear trend was shown (Ptrend &lt, 0.0001). The inverse associations were observed for proximal (Ptrend = 0.0001) and distal (Ptrend = 0.0003) colon cancer, and rectal cancer (Ptrend &lt, 0.0001) in the stratified analysis by anatomical sub-sites. Regarding sex, inverse associations between coffee consumption and colorectal cancer were found for men (Ptrend &lt, 0.0001) and women (Ptrend = 0.0021). In the stratified analysis by obese status of subjects, inverse linear trends were observed in both non-obese and obese people (Ptrend &lt, 0.0001). High coffee consumption may be associated with a lower risk of colorectal cancer in the Korean population and the degree of decrease in the odds of developing colorectal cancer changes by adjustment for intake of coffee additives.

Objective Colorectal cancer (CRC) is the fourth most common site for cancer death in the Republic of Korea. The aim of this study was to describe the trends of colorectal cancer mortality by region. Methods CRC mortality trends in Republic of Korea were described by region using a Joinpoint regression model in both sexes. The annual percent changes (APCs) were calculated for each segment. Visualization of the changes in mortality rate of colorectal cancer death rates by 16 geographic areas in both sexes between 2000-2004 and 2009-2013 were also conducted. Results CRC mortality rates of men showed decreasing trend after increase in Daegu, Gyeongsangnam-do, and Chungcheongbuk-do between 2000 and 2013 based on the joinpoint model, while Gwangju, Jeollabuk-do, Jeollanam-do, and Gyeongsangbuk-do showed increase in CRC mortality during the same period. For women, CRC mortality of Seoul, Incheon, Daejeon, and Gyeongsangnam-do started to decrease in 2005, 2003, 2007, and 2006, respectively. The mortality rate for CRC in the eastern regions, which had relatively low rates of CRC among men in 2000 through 2004, reached a level similar to that in the northwestern regions of 2009 through 2013, while the highest CRC mortality rates in women was observed in Chungcheongbuk-do. Conclusions Reduction in CRC mortality varied across 16 metropolitan cities and provinces in men, and the visualization pattern showed that the east side of South Korea had the least progress in mortality reduction.

Objectives We aimed to investigate the association between the use of various sedative-hypnotics and the incidence of overall and individual cancers in a large, population-based, retrospective cohort study. Methods We selected a 5% random sample of individuals aged 50 years or older from data maintained by the Korean National Health Insurance Service for the years 2002–2015, excluding individuals with a prior diagnosis of cancer and with any sedative-hypnotic use in the initial two years of follow-up, leaving 236,759 participants for the final analysis. Exposure to sedative-hypnotics was defined by type of drug, standardized to a defined daily dose, and coded as a time-varying variable. Cox proportional hazard models were applied after adjusting for sex, socio-economic status, and comorbidities. Results We observed increased risk for overall cancer among men and women who used sedative-hypnotics (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.01–1.13 for men; HR = 1.21, 95% CI = 1.09–1.25 for women) compared with non-users after full adjustment. In the fully adjusted model, women with any sedative-hypnotic use had significantly increased risk for thyroid (HR = 1.53, 95% CI = 1.24–1.87), breast (HR = 1.29, 95% CI = 1.04–1.61), ovarian (HR = 1.65, 95% CI = 1.10–2.46), and lung cancer (HR = 1.40, 95% CI = 1.17–1.69) compared with non-users. Men with sedative-hypnotic use had increased risk for prostate (HR = 1.36, 95% CI = 1.16–1.58), brain (HR = 1.67, 95% CI = 1.04–2.69), and lung cancer (HR = 1.20, 95% CI = 1.07–1.35) compared with non-users. Conclusion We found a significant increase in overall cancer incidence among participants who used sedative-hypnotics, and both male and female sedative-hypnotic users had significantly increased risk for certain types of cancer.

The current case-control study comprehensively evaluated the status, quantity, and duration of smoking and alcohol drinking for both men and women, considering the subsites of colorectal cancer. A total of 925 colorectal cancer cases and 2775 controls were included in the analysis. Odds ratios (OR) and 95% confidence intervals (CI) were computed by logistic regression models adjusting for potential confounders. In men, the risk of colorectal cancer significantly increased for heavy smokers who smoked ≥40 pack-years (OR 1.74, 95% CI 1.22-2.50), ≥40 years (OR 1.50, 95% CI 1.05-2.16), or ≥40 cigarettes/day (OR 1.92, 95% CI 1.04-3.54). Men showed a significant increase in risk, especially for rectal cancer with an increasing amount or duration of smoking. In women, distal colon cancer risk increased in smokers who smoked ≥20 years (OR 3.21, 95% CI 1.27-8.14) or ≥20 cigarettes/day (OR 4.75, 95% CI 1.09-20.57). Additionally, female smokers who smoked ≥20 cigarettes/day had an increased risk of rectal cancer (OR 6.46, 95% CI 1.64-25.46). Regarding the association of cigarettes smoked per day and the risk of rectal cancer, there was no significant difference between men and women (gender interaction p value = 0.14). Compared with never-drinkers, those who consumed alcohol at ≥40 g/day in men and ≥20 g/day in women had an OR of 2.39 (95% CI 1.68-3.41) and 3.52 (95% CI 1.56-7.96), respectively. The effect of daily alcohol consumption (g of ethanol/day) on cancer risk was not significantly different among subsites. Association of alcohol consumption quantity (g of ethanol/day) and the risk of proximal and distal colon cancer were stronger in women than in men (gender interaction p value 0.01). There was no significant interaction in the multiplicative level when alcohol consumption and cigarette smoking were combined. The duration and amount of smoking as well as the amount of alcohol consumption were associated with an elevated risk of colorectal cancer in both men and women.

Background: We aimed to report the prevalence and correlates of high-risk alcohol consumption and types of alcoholic beverages. Methods: The baseline data of the Health Examinees-Gem (HEXA-G) study participants, including 43,927 men and 85,897 women enrolled from 2005 through 2013, were used for analysis. Joinpoint regression was performed to estimate trends in the age-standardized prevalence of alcohol consumption. Associations of demographic and behavioral factors, perceived health-related effects, social relationships, and the diagnostic history of diseases with alcohol consumption were assessed using multinomial logistic regression. Results: The prevalence of alcohol consumption remained higher in men during the study period and increased in women. The amount of alcohol consumed has increased in women, especially that from beer and makgeolli, a traditional Korean fermented rice wine. Older participants were less likely to be high-risk drinkers (men and women who drink more than 40 or 20 g/day of alcohol, respectively) and drink Soju, a distilled liquor, and beer, and more likely to drink makgeolli. Educational level was negatively associated with high-risk drinking. However, it was positively associated with the consumption of strong spirits and wine. Smoking was associated with high-risk drinking and the consumption of soju and strong spirits. Engaging in regular exercise and having stress were associated with drinking all types of beverages except for soju. Conclusions: Sex-specific trends in alcohol consumption were influenced by demographic, behavioral, and perceived health-related factors. The findings will help improve the understanding of alcohol-related problems and provide evidence for establishing country-specific policies and campaigns in Korea.

A lack of estrogen due to menopause changes metabolic homeostasis, which increases the risk of metabolic syndrome (MetS) in postmenopausal women. Hormone therapy (HT) has beneficial effects on chronic diseases as well as on menopause symptoms. The aim of this study was to investigate the association of HT use with MetS and its components by diabetes status in middle-aged postmenopausal Korean women. A cross-sectional analysis was undertaken of a total of 39,295 non-diabetic and 3,359 diabetic postmenopausal women aged 40 to 69 years from the Health Examinees-Gem (HEXA-G) study (2004–2013). The mean differences in the MetS components by HT use were assessed using a general linear model and Tukey’s multiple comparisons tests. The prevalence odds ratio (POR) and 95% confidence intervals (CIs) were estimated using the logistic regression model. HT use was associated with lower fasting glucose level, total cholesterol, systolic blood pressure, body mass index, waist circumference, and waist-to-hip ratio among both diabetic and non-diabetic women. In non-diabetic women, HT ‘ever’ use was negatively associated with the prevalence of MetS (POR = 0.80, 95% CI: 0.75-0.85), and current users had a lower prevalence of MetS (POR = 0.68, 95% CI: 0.60-0.76). A longer duration of HT use was associated with a decreasing prevalence of MetS. We did not find heterogeneity by age regarding MetS prevalence. Our results suggest that HT use is negatively associated with the prevalence of MetS among postmenopausal women. However, further longitudinal studies are required to investigate the effect of HT on MetS in Korean women.

Marital status has been shown to be associated with mortality, but evidence in Asian populations is limited.To examine the association of marital status with total and cause-specific mortality.This cohort study included individual participant data from 16 prospective studies in the Asia Cohort Consortium conducted between 1963 and 2015. Asian participants with complete information on marital and vital status were included. Study-specific hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards model and then pooled using a random-effects meta-analysis. The analysis began in February 2021 and ended in August 2021.Marital status.All-cause and cause-specific mortality.Of 623 140 participants (326 397 women [52.4%] and 296 743 men [47.6%]; mean [SD] age, 53.7 [10.2] years; mean [SD] follow-up time, 15.5 [6.1] years), 123 264 deaths were ascertained. Compared with married individuals, those who were unmarried had pooled HRs of 1.15 (95% CI, 1.07-1.24) for total mortality, 1.12 (95% CI, 1.03-1.22) for cerebrovascular disease mortality, 1.20 (95% CI, 1.09-1.31) for coronary heart disease mortality, 1.17 (95% CI, 1.07-1.28) for circulatory system diseases mortality, 1.06 (95% CI, 1.01-1.11) for cancer mortality, 1.14 (95% CI, 1.05-1.23) for respiratory diseases mortality, and 1.19 (95% CI, 1.05-1.34) for external causes of death. Positive associations with total mortality were also observed for those who were single (HR, 1.62; 95% CI, 1.41-1.86), separated (HR, 1.35; 95% CI, 1.13-1.61), divorced (HR, 1.38; 95% CI, 1.13-1.69), and widowed (HR, 1.09; 95% CI, 1.04-1.13). In subgroup analyses, the positive association persisted across baseline health conditions, and the risk of death was more pronounced among men or people younger than 65 years.This large pooled cohort study of individual participant data provides strong evidence that being unmarried, as well as belonging to the unmarried subcategories, was positively associated with total and cause-specific mortality. Investment of targeted social support services might need to be considered in light of the mortality differences between married and unmarried individuals.

Background/Aims Gastric varices (GVs) are a major cause of upper gastrointestinal bleeding in patients with liver cirrhosis. The current treatments of choice are balloon-occluded retrograde transvenous obliteration (BRTO) and the placement of a transjugular intrahepatic portosystemic shunt (TIPS). We aimed to compare the efficacy and outcomes of these two methods for the management of GV bleeding. Methods This retrospective study included consecutive patients who received BRTO (n=157) or TIPS (n=19) to control GV bleeding from January 2005 to December 2014 at a single tertiary hospital in Korea. The overall survival (OS), immediate bleeding control rate, rebleeding rate and complication rate were compared between patients in the BRTO and TIPS groups. Results Patients in the BRTO group showed higher immediate bleeding control rates (p=0.059, odds ratio [OR]=4.72) and lower cumulative rebleeding rates (log-rank p=0.060) than those in the TIPS group, although the difference failed to reach statistical significance. There were no significant differences in the rates of complications, including pleural effusion, aggravation of esophageal varices, portal hypertensive gastropathy, and portosystemic encephalopathy, although the rate of the progression of ascites was significantly higher in the BRTO group (p=0.02, OR=7.93). After adjusting for several confounding factors using a multivariate Cox analysis, the BRTO group had a significantly longer OS (adjusted hazard ratio [aHR]=0.44, p=0.01) and a longer rebleeding-free survival (aHR=0.34, p=0.001) than the TIPS group. Conclusions BRTO provides better bleeding control, rebleeding-free survival, and OS than TIPS for patients with GV bleeding.

This study investigated prescriptions for sedative–hypnotics via data obtained from the Health Insurance Review and Assessment (HIRA) service. Data on sedative–hypnotic prescriptions from the HIRA service of the Republic of Korea were analyzed from 2011 to 2015. We included prescriptions for subjects > 18 years of age from hospitals and community healthcare centers. In addition, subgroup analyses with a subsample restricted to prescriptions from patients with diagnostic codes F510 (nonorganic insomnia) or G470 (insomnia) were performed. After analyzing the number of prescriptions by individual pharmacy items, the prescription codes were grouped as: (1) benzodiazepines; (2) non-benzodiazepines, including zolpidem; (3) antidepressants; and (4) antipsychotics. We calculated the monthly percent change in the number of prescriptions by drug group using Joinpoint regression. Among the sedative–hypnotic groups, benzodiazepines were the most commonly prescribed drugs in Korea during the study period. As a single sedative–hypnotic item, zolpidem was the most frequently prescribed medication for patients with insomnia. Prescriptions for all groups of sedative–hypnotics increased significantly during the study period. When stratified by age group, antipsychotic prescriptions increased significantly by 0.19–0.21% per month among men and women aged 50–59 years and > 70 years. Prescriptions for antidepressants in 30–39-year-old men increased significantly by 0.20%. Benzodiazepine prescriptions as well as those for antipsychotics and antidepressants to treat insomnia increased during 2011–2015 in Korea. Monitoring the use of sedative–hypnotics at the national level is necessary, especially in the elderly population.

Background We sought to investigate intentions to undergo primary screening with colonoscopy in an attempt to predict future colorectal cancer screening behaviors and the feasibility of implementing colonoscopy as the primary screening modality for colorectal cancer in the National Cancer Screening Program (NCSP) of Korea. Methods Data were obtained from a nationwide online survey conducted in 2018. The survey included a total of 800 eligible adults aged over 45 years. Study measures included the history of screening colonoscopy within the past 10 years and intentions to undergo primary screening with colonoscopy under the NCSP based on the five constructs of the Health Belief Model. Logistic regression analysis was conducted to examine factors associated with intentions to undergo primary screening with colonoscopy. Results Approximately 77% of the participants expressed strong willingness to undergo primary screening with colonoscopy under the NCSP. Higher perceived severity and perceived benefits were significantly associated with stronger intentions to undergo screening with colonoscopy (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.10–2.14 and aOR, 2.74; 95% CI, 1.76–4.28, respectively). Greater perceived barriers (aOR, 0.65; 95% CI, 0.45–0.93) were significantly associated with weaker intentions. Cues to action elicited the strongest screening intentions (aOR, 8.28; 95% CI, 5.23–13.12). Conclusion The current study findings highlight the need for increasing awareness of the severity of CRC and the benefits of colonoscopy screening. Family-orientated recommendation strategies and reducing complications may boost an individual’s intentions to undergo colonoscopy.

Although a number of studies explain the association between dietary patterns, which take into account that foods are eaten in combination, and breast cancer risk, the findings are inconsistent. We examined the association between dietary patterns and multi-grain rice intake, and the risk of breast cancer in a large-scale prospective cohort study in Korean women. A total of 93,306 women aged 40&ndash, 69 years from the Health Examinees-Gem (HEXA-G) study (2004 and 2013) were included. We obtained Information on cancer diagnosis via linkage to the Korea Central Cancer Registry. Factor analysis was conducted to obtain dietary patterns, and Cox proportional models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CI) for breast cancer risk. For 494,490 person-years, 359 new cases of breast cancer occurred. We identified three major dietary patterns, that explained 23.9% of the total variance based on daily total food intake (g/day) from 37 food groups: the meat dietary pattern (higher intake of bread and red meat), the white rice dietary pattern (higher intake of white rice and lower intake of multi-grain rice), and the other pattern. Women who had higher white rice dietary pattern scores had a 35% higher risk of breast cancer, than did women with lower white rice dietary pattern scores (multivariable HR 1.35, 95% CI 1.00&ndash, 1.84 for the highest vs. lowest quartile of the white rice dietary pattern scores, p for trend = 0.0384). We found that women who consumed three or more servings of multi-grain rice per day had 33% lower risk of breast cancer than did those who consumed one or less multi-grain rice serving per day among women under 50 years of age (multivariable HR 0.67, 95% CI 0.45&ndash, 0.99, p for trend = 0.0204). Our study suggests that a multi-grain rice diet may be associated with lower risk of breast cancer in Korean women.

Purpose We aimed to assess the association between the dietary intake of fish-derived omega-3 polyunsaturated fatty acids and the risk of colorectal cancer among Swedish women. Materials and Methods A total of 48,233 women with information on dietary intake were included in the analysis. Participants were followed for incident colorectal cancer until 31 December 2012. Cox proportional hazard models were used to assess the association between baseline fatty acid intake and colorectal cancer risk. All analyses were stratified by colon and rectal cancers. Results During a median of 21.3 years of follow-up, a total of 344 colorectal cancer cases were ascertained. Although there was no overall association between omega-3 fatty acid intake and colorectal cancer risk, high intake of fish-derived docosahexaenoic acid was associated with reduced risk of rectal cancer (hazard ratios for the third and the highest quartiles were 0.59 (95% confidence interval [CI], 0.37 to 0.96) and 0.62 (95% CI, 0.39 to 0.98), respectively). Conclusion In conclusion, we found only limited support for an association between omega-3 polyunsaturated fatty acids and colorectal cancer in a large Swedish cohort of middle-aged women. Funding Agencies|Korea Research FoundationKorea Research Foundation [2017-R1A2B4009233]

Genome-wide association studies (GWAS) have identified multiple single-nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. To evaluate the potential influence of colorectal cancer susceptibility SNPs on disease prognosis, we investigated whether GWAS-identified colorectal cancer risk SNPs and polygenic risk scores (PRSs) might be associated with survival among colorectal cancer patients. A total of 1374 colorectal cancer patients were recruited from the Korean National Cancer Center. For genotyping, 30 colorectal cancer-susceptibility SNPs previously identified by GWAS were selected. The Cox proportional hazard model was used to evaluate associations of these risk SNPs and PRSs with disease-free survival (DFS) and overall survival (OS). The prognostic values were compared between genetic and nongenetic models using Harrell's c index. During the follow-up period (median: 88, 91 months for DFS and OS), 570 DFS (41.5%) and 487 OS (35.4%) events were observed. We found that 5 SNPs were significantly associated with DFS or OS among colorectal cancer patients at P

STUDY OBJECTIVES: Researchers have previously reported a possible association between sedative-hypnotics and increased mortality. However, the relationship remains controversial. We investigated the association between sedative-hypnotics and mortality using a large population-based database from the Republic of Korea. METHODS: We used a National Health Insurance Service database. The study population was a 5% random sample of the database from the years 2002– 2015. Individuals who were age 40 years and older were included in the analysis. The sedative-hypnotic users were defined as individuals prescribed 30 or more defined daily doses of sedative-hypnotics per year since January 2004. Sedative-hypnotics were classified based on type and total amount. We estimated the risk of mortality (death from January 2004 to December 2015) using time-dependent Cox regression model adjusted for age, sex, Charlson Comorbidity Index, and psychiatric comorbidity. RESULTS: We identified 180,823 study participants who used sedative-hypnotics and 320,136 nonusers. In a multivariate model, study participants who used sedative-hypnotics had significantly higher mortality risk than nonusers (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.12–1.16). Specifically, study participants who used zolpidem had a higher mortality risk (HR 1.59, 95% CI 1.52–1.67) than nonusers. CONCLUSIONS: Based on the current study results, sedative-hypnotics were associated with an increased risk of mortality, especially in study participants who used zolpidem. CITATION: Choi JW, Lee J, Jung SJ, Shin A, Lee YJ. Use of sedative-hypnotics and mortality: a population-based retrospective cohort study. J Clin Sleep Med. 2018;14(10):1669–1677.

Background: This study aimed to estimate the prevalence and trends of participation in physical activity (PA) in Korean adults. Methods: The Korea National Health and Nutrition Examination Survey (KNHANES; 2009–2013) and the Korea Community Health Survey (KCHS; 2009–2013) were used to estimate the prevalence of PA. Age standardization was performed using population projections for Korea in 2005 as a standard population. Trends of the prevalence from 2009 to 2013 were assessed by joinpoint regression analysis. Results: The age-standardized prevalence for achieving the recommended level of PA was 63.0% in KNHANES and 64.5% in KCHS for men, and 53.7% in KNHANES and 56.3% in KCHS for women. Decreasing trends were observed for the prevalence of achieving the recommended level of PA in the KNHANES and KCHS; however, only the trend for women in KNHANES was statistically significant. Conclusions: Approximately, 60% of adults participate in the recommended level of PA in Korea. The survey design and characteristics should be considered when interpreting the prevalence of PA from different databases.

Objectives We investigated the association between cholecystectomy or appendectomy and the subsequent risk of colorectal cancer (CRC) in the Korean population. Methods A retrospective cohort study was conducted with the National Health Insurance Service-National Sample Cohort of Korea; this sample was followed up from January 1, 2002, until the date of CRC incidence, loss to follow-up, or December 31, 2015. The exposure status of cholecystectomy and appendectomy was treated as a time-varying covariate. The calculated risk of CRC was stratified by follow-up period, and the association between these surgical procedures and CRC was investigated by a Cox regression model applying appropriate lag periods. Results A total of 707 663 individuals were identified for analysis. The study population was followed up for an average of 13.66 years, and 4324 CRC cases were identified. The hazard ratio (HR) of CRC was elevated in the first year after cholecystectomy (HR, 1.71; 95% confidence interval [CI], 1.01 to 2.89) and in the first year and 2-3 years after appendectomy (HR, 4.22; 95% CI, 2.87 to 6.20; HR, 2.34; 95% CI, 1.36 to 4.03, respectively). The HRs of CRC after applying 1 year of lag after cholecystectomy and 3 years of lag after appendectomy were 0.80 (95% CI, 0.57 to 1.13) and 0.77 (95% CI, 0.51 to 1.16), respectively. Conclusions The risk of CRC increased in the first year after cholecystectomy and appendectomy, implying the possibility of bias. When appropriate lag periods after surgery were applied, no association was found between cholecystectomy or appendectomy and CRC.

Background Genome-wide association studies (GWAS) have identified more than 40 colorectal cancer susceptibility loci, but only a small fraction of heritability was explained. To account for missing heritability, we investigated gene-environment interactions (G × Es) between GWAS-identified single-nucleotide polymorphisms (SNPs) and established risk or protective factors for colorectal cancer using both case-only and case-control study designs. Methods Data on 703 colorectal cancer cases and 1406 healthy controls from the National Cancer Center in Korea were used. We tested interactions between 31 GWAS-identified SNPs and 13 established risk or protective factors for colorectal cancer (family history, body mass index, history of colorectal polyps, inflammatory bowel disease, and diabetes mellitus, alcohol drinking, smoking, regular exercise, regular aspirin use, postmenopausal hormone replace therapy, red meat and processed meat intake, and dairy consumption). Logistic regression models were used to assess G × Es for colorectal cancer risk. Results The SNP rs4444235 at 14q22.2 interacted with regular exercise in colorectal cancer (pcase-only = 2.4 × 10− 3, pcase-control = 1.5 × 10− 3). The risk allele (C) of rs4444235 increased the risk of colorectal cancer in regularly exercising individuals (OR = 1.47, 95% CI = 1.02–2.10) but decreased the risk in non-exercising individuals (OR = 0.76, 95% CI = 0.62–0.94). Furthermore, the G × E between the SNP rs2423279 at 20p12.3 and regular aspirin use was statistically significant (pcase-only = 7.7 × 10− 3, pcase-control = 1.6 × 10− 3). The additive effect of the risk allele (T) of rs2423279 on colorectal cancer risk was increased among regular aspirin users (OR = 4.62, 95% CI = 1.97–10.80). Conclusion Our results suggest that SNP rs4444235 at 14q22.2 and SNP rs2423279 at 20p12.3 may interact with regular exercise and aspirin use in colorectal carcinogenesis.

Background and Aim The diagnostic and therapeutic modalities of esophageal cancer have recently improved in Asia, and its prognosis is expected to change. This study provides a population‐based report on the epidemiology of esophageal cancer in Korea. Methods Cancer incidence data from 1999 to 2013 were obtained from the Korea Central Cancer Registry, covering the entire population. Age‐standardized incidence rates and annual percent changes were calculated according to subsites and histological types. Five‐year relative survival rates were estimated for cases diagnosed between 1993 and 2013. Relative excess rates were compared between patients diagnosed from 2009 to 2013 and 2006 to 2008. Results The age‐standardized incidence rates decreased from 8.8 per 100 000 populations in 1999 to 5.9 in 2013 with an annual percent change of −2.6% in men and −2.2% in women. The most common histological type was squamous cell carcinoma, accounting for 90.2% of all esophageal cancers in 2013, followed by adenocarcinomas (3.1%), and their incidences decreased. The proportion of localized and regional cancer tended to increase compared with that of distant cancer. Five‐year relative survival of squamous cell carcinoma improved from 12.1% (1993–1995) to 34.6% (2009–2013). Relative excess rate was 0.72 (95% confidence interval 0.65–0.80) in localized stage and 0.88 (95% confidence interval, 0.82–0.95) in regional stage comparing patients diagnosed from 2009 to 2013 and 2006 to 2008. Conclusions The incidence of esophageal cancer has decreased in Korea for the past 15 years, and 5‐year survival rates have improved significantly. These increases may be attributable to more effective detection of early‐stage disease.

PURPOSE To determine the prevalence and clinical characteristics of pseudoexfoliation syndrome (PXS) within Korean population living in Woodo Island. METHODS Among the 625 residents aged 50 years or older, 305 residents (197 women and 108 men) participated in the study; a response rate of 48.8%. Participants filled out questionnaires on life style. Intraocular pressure and corneal endothelial cell function was measured. Both pupils were dilated. Fundus photographs and stereo disc photographs were taken. Vertical cup-to-disc ratio was determined. Pure tone audiometry threshold was measured at 0.5, 1, 2, 4, and 6 kHz of frequencies for each ear. RESULTS The prevalence rate of PXS among Woodo Island residents older than 50 years significantly increased with age, from 1.0% [95% confidence interval (CI), 0%-2.8%] in participants aged 50 to 59 years to 23.3% (95% CI, 8.2%-38.5%) in those aged over 80 years (P

// Jeong-Hwa Choi 1 , Jeonghee Lee 1 , Jae Hwan Oh 2 , Hee Jin Chang 2 , Dae Kyung Sohn 2 , Aesun Shin 3 , Jeongseon Kim 1 1 Molecular Epidemiology Branch, Division of Cancer Epidemiology and Prevention, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408, Korea 2 Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408, Korea 3 Department of Preventive Medicine, Seoul National University College of Medicine, Jongno-gu, Seoul, 03080, Korea Correspondence to: Jeongseon Kim, email: jskim@ncc.re.kr Aesun Shin, email: shinaesun@snu.ac.kr Keywords: bitterness perception, CA6, colorectal cancer, dietary intake, TAS2R38 Received: November 08, 2016 Accepted: February 07, 2017 Published: February 19, 2017 ABSTRACT Bitterness perception is known to be an important factor in individuals’ dietary behaviors and is also associated with the sensing of nutritious/noxious molecules for subsequent metabolic responses in multiple organs. Therefore, the genetic variation in bitterness sensing may be associated with diet-related diseases, including colorectal cancer (CRC). We investigated the influence of variations in the bitterness-sensing genes taste receptor type 2 member 38 ( TAS2R38 ) and carbonic anhydrase 6 ( CA6 ) on the consumption of food, tobacco and alcohol and the risk of CRC in Koreans. The study population consisted of 681 cases and 1361 controls, and their intake of vegetables, fruits, fiber, fat-food and sweets was analyzed. The genotypes for TAS2R38 A49P, V262A and I296V and CA6 rs2274333 A/G were assessed using the MassArray technique. Our findings suggested that the TAS2R38 diplotype, CA6 rs2274333 and their combined genotype had a negligible influence on dietary and alcohol intake. The combined TAS2R38-CA6 AVI/AVI-AA genotype was associated with higher tobacco consumption than the other genotypes in CRC cases only. However, the genetic variations were a significant risk factor for CRC. The TAS2R38 AVI/AVI diplotype and CA6 G allele were associated with a reduced risk of CRC. Moreover, when the combined genotypes of the subjects were analyzed, possessing both the variant diplotype/variant allele (AVI/AVI+G*) was associated with a greater reduction in the risk of CRC (adjusted OR = 0.49; 95%CI: 0.34–0.74). In summary, variations in the bitterness perception genes TAS2R38 and CA6 did not influence the examined food intake in Koreans. However, those genetic variants were a decisive modifying factor of CRC susceptibility.

Objective The use of information communication technology (ICT)–based tailored health management program can have significant health impacts for cancer patients. Information provision, health-related quality of life (HRQOL), and decision conflicts were analyzed for their relationship with need for an ICT-based personalized health management program in Korean cancer survivors. Methods The health program needs of 625 cancer survivors from two Korean hospitals were analyzed in this cross-sectional study. Multivariate logistic regression was used to identify factors related to the need for an ICT-based tailored health management system. Association of the highest such need with medical information experience, HRQOL, and decision conflicts was determined. Furthermore, patient intentions and expectations for a web- or smartphone-based tailored health management program were investigated. Results Cancer survivors indicated high personalized health management program needs. Patients reporting the highest need included those with higher income (adjusted odds ratio [aOR], 1.70; 95% [confidence interval] CI, 1.10-2.63), those who had received enough information regarding helping themselves (aOR, 1.71; 95% CI, 1.09-2.66), and those who wished to receive more information (aOR, 1.59; 95% CI, 0.97-2.61). Participants with cognitive functioning problems (aOR, 2.87; 95%CI, 1.34-6.17) or appetite loss (aOR, 1.77; 95% CI, 1.07-2.93) indicated need for a tailored health care program. Patients who perceived greater support from the decision-making process also showed the highest need for an ICT-based program (aOR, 0.49; 95% CI, 0.30-0.82). Conclusions We found that higher income, information provision experience, problematic HRQOL, and decisional conflicts are significantly associated with the need for an ICT-based tailored self-management program.

// Young Ae Cho 1 , Jeonghee Lee 1 , Jae Hwan Oh 2 , Hee Jin Chang 2 , Dae Kyung Sohn 2 , Aesun Shin 1, 3 , Jeongseon Kim 1 1 Molecular Epidemiology Branch, National Cancer Center, Goyang, South Korea 2 Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, South Korea 3 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea Correspondence to: Jeongseon Kim, email: jskim@ncc.re.kr Aesun Shin, email: shinaesun@snu.ac.kr Keywords: diet, inflammation, polymorphism, PPARGC1A, interaction Received: September 02, 2016 Accepted: December 07, 2016 Published: December 29, 2016 ABSTRACT The role of inflammation in colorectal carcinogenesis may differ according to individuals’ genetic variations. Therefore, we investigated whether genetic susceptibility alters the association between inflammatory potential of diet and the risk of colorectal cancer within the Korean population. We genotyped four polymorphisms in four genes ( IL1B , TNF , PPARG , and PPARGC1A ) and calculated the dietary inflammatory index (DII) in a case-control study with 701 colorectal cancer patients and 1,402 controls. Among the investigated polymorphisms, heterozygous carriers of rs3774921 in PPARGC1A showed a higher risk of colorectal cancer (OR [95% CI] = 1.26 [1.02–1.55] for TC vs. TT). When the data were stratified by rs3774921 genetic variant, the association of a pro-inflammatory diet with colorectal cancer risk was more prominent among homozygous variant allele carriers (OR [95% CI] = 5.15 [2.35–11.29] for high vs. low DII) ( P for interaction = 0.009). When stratified by anatomic site, this association was much stronger for rectal cancer patients (OR [95% CI] = 8.06 [2.67–24.16] for high vs. low DII) ( P for interaction = 0.006). Additionally, this interaction was stronger among those older than 50 years and not exercising regularly. Conversely, no association or interaction was found for the other investigated polymorphisms. In conclusion, the results of this study suggest that a pro-inflammatory diet may have a differential effect on colorectal cancer risk based on PPARGC1A genetic variation. This interaction may differ by anatomic location and other risk factors.

Chronic inflammation is a leading cause of colorectal cancer (CRC). Inflammatory biomarkers are considered indicators of occult malignancy. To contribute to the investigation of CRC prevention strategies, we aimed to identify associations between inflammatory biomarkers (insulin-like growth factor-1 (IGF-1), soluble tumor necrosis factor receptor 2 (sTNFR-2), and interleukin-8 (IL-8)) and modifiable lifestyle factors including body mass index (BMI), prior BMI, smoking status, alcohol consumption status, physical activity, and dietary inflammatory index (DII) score in terms of CRC risk.In a hospital-based case-control study, we explored the associations of plasma IGF-1, sTNFR-2, and IL-8 levels with CRC risk in 697 cases and 1845 controls. Unconditional logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for CRC with the inflammatory biomarkers adjusted for confounders.CRC patients had significantly higher levels of sTNFR-2 and IL-8 than the controls (P 0.001). In multivariate models, the levels of IGF-1, sTNFR-2, and IL-8 were significantly associated with CRC risk after adjusting for confounders (IGF-1 OR (95% CI) = 1.39 (1.02-1.89), P for trend = 0.018; sTNFR-2 = 2.14 (1.59-2.90), P for trend 0.001; IL-8 = 1.95 (1.43-2.66), P for trend 0.001, highest vs. lowest quartiles). The biomarkers showed either positive or negative trends when modifiable lifestyle factors were stratified. In particular, the inverse associations of CRC risk with the biomarkers were significant among subjects who engaged in regular physical activity and had an anti-inflammatory diet pattern.Elevated levels of inflammatory biomarkers were associated with CRC risk and could be modified by risk and protective lifestyle factors. Our findings may provide a strategy to identify CRC risk based on the associations between inflammatory biomarkers and lifestyle factors.

ObjectivesThis study evaluated whether individuals with affected family member adhered to healthy behaviours.Design and settingThis was a cross-sectional study of participants selected from health examinees who underwent the national health check-up programme of Korea in 39 centres between 2004 and 2013.ParticipantsThe baseline data of 128 520 participants enrolled in the Health Examinees-Gem study were used for analysis.Main outcomes and measuresAssociations of family history of diabetes with adherence to regular exercise, healthy diet and body composition, and clusters of healthy behaviours were evaluated while adjusting for potential confounders selected by a directed acyclic graph.ResultsParticipants with a family history of diabetes were more likely to adhere to a regular exercise regimen (OR=1.12, 95% CI 1.06 to 1.18 for men and OR=1.10, 95% CI 1.07 to 1.14 for women) and healthy diet (OR=1.06, 95% CI 1.01 to 1.12 for men and OR=1.06, 95% CI 1.01 to 1.12 for women) but were less likely to have a normal body composition (OR=0.83, 95% CI 0.78 to 0.87 for men and OR=0.83, 95% CI 0.80 to 0.86 for women). These associations were strengthened when the affected family members were siblings, the number of affected members was increased or the age at diagnosis of the affected member was younger than 50 years. In men and women, having a normal body composition is important in determining the cluster of behaviours, and those with a family history of diabetes were less likely to adhere to the normal body composition cluster.ConclusionsThe group with high risk of diabetes showed healthy behaviors, but they did not have a normal body composition. Policies and campaigns targeting integrated health behaviors will be needed to reduce the burden of diseases and improve public health.

Summary Background & aims The main source of mercury exposure is food such as fish and shellfish. Mercury is a growing concern due to its associations with a number of harmful health effects, including cancer. The objectives of this study were to examine the association between dietary mercury intake and colorectal cancer (CRC) risk and to determine whether this association differs by anatomical site and menopausal status. Methods A case-control study was conducted with 2769 participants (923 cases and 1846 controls) in Korea. Dietary mercury intake and fish and shellfish consumption were assessed using a semiquantitative food frequency questionnaire. Results A high intake of dietary mercury was associated with an increased risk of CRC (in the group with lower fish and shellfish consumption; odds ratio (OR): 3.13; 95% confidence interval (95% CI): 2.33, 4.71, in the group with higher fish and shellfish intake; OR: 3.84, 95% CI: 2.20, 7.30) after adjusting for all potential confounders by anatomic site in men. Among women, the results differed by fish and shellfish consumption and menopausal status. Regarding the amount of fish and shellfish intake, a positive association was found only in the group with lower intake (CRC; OR: 2.24, 95% CI: 1.36, 3.72, colon cancer; OR: 2.25, 95% CI: 1.22, 4.16, rectal cancer; OR: 2.28, 95% CI: 1.13, 4.57). In the stratified analysis by menopausal status, the elevated risk of CRC was still observed among both pre- and postmenopausal women depending on anatomical site, except for the colon cancer patients with premenopausal status. Conclusions A high intake of mercury was associated with an elevated risk of overall CRC. Future large-scale prospective cohort studies are recommended to investigate the causal effects of dietary mercury intake by fish and shellfish consumption on CRC risk depending on anatomical site and menopausal status.

// Sung Yong Oh 1 , Aesun Shin 2 , Seong-Geun Kim 3 , Jung-Ah Hwang 4 , Seung Hyun Hong 4 , Yeon-Su Lee 4 , Hyuk-Chan Kwon 5 1 Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea 2 Department of Preventive Medicine, Seoul National University, Korea 3 Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea 4 Cancer Genomics Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi-do, Korea 5 Sillajen Inc., Busan, Korea Correspondence to: Yeon-Su Lee, email: yslee2@ncc.re.kr Hyuk-Chan Kwon, email: hckwon@sillajen.com Keywords: insulin-like growth factor, polymorphism, gastric cancer Received: January 08, 2016 Accepted: April 11, 2016 Published: April 29, 2016 ABSTRACT The insulin-like growth factor (IGF) axis plays a crucial role in proliferation, differentiation, migration, angiogenesis, and apoptosis. The present study evaluated the associations between IGF axis single-nucleotide polymorphisms (SNPs) and clinical outcomes in advanced gastric cancer (AGC) patients treated with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX). A total of 190 patients undergoing FOLFOX chemotherapy for AGC were considered eligible for this study. Forty-four SNPs of 10 IGF axis genes were genotyped. Levels of serum IGF1 were measured using enzyme-linked immunoassays. SNPs of the IGF1R (rs12423791), and IGF1 (rs2162679, rs5742612, rs35767) genes were significantly associated with tumor response to FOLFOX. SNPs of rs4619 and rs17847203 were significantly associated with PFS (hazard ratio [HR] 0.575, 95% CI 0.385–0.858, P = 0.007; and HR 2.530, 95% CI 1.289–4.966, P = 0.007; respectively). SNPs of rs2872060 were significantly associated with OS—OS was shorter in patients carrying the TT variant than in those with the GG/GT genotypes (HR, 1.708, 95% CI 1.024–2.850, P = 0.040). The GT genotype of rs12847203 was also identified as an independent prognostic factor (HR 2.087, 95% CI 1.070–4.069, P = 0.031). These results suggest that IGF axis-pathway SNPs could be used as prognostic biomarkers of the outcome of FOLFOX chemotherapy in AGC patients. This information may facilitate identification of population subgroups that could benefit from IGF1R-targeted agents.

BackgroundAlthough many studies have focused on leisure time physical activity (LTPA), household physical activity (HPA) can contribute to health benefits. This study aimed to compare LTPA and HPA patterns and to examine the association of these types of activities with the risk of mortality in Korea.MethodsA total of 125,299 participants 40 to 69 years old and enrolled in the Health Examinees (HEXA) study from 2004 to 2012 were included in this study. The sex-specific LTPA and HPA categories were defined based on a questionnaire. A multinomial logistic regression was used to examine the LTPA and HPA correlates. Hazard ratios (HR) with 95% confidence intervals (95% CIs) of all-cause mortality were estimated using the Cox proportional hazard model.ResultsOverall, the LTPA and HPA patterns differed by age, income, and history of chronic diseases. LTPA reduced the risk of death, and lower risks were observed in more time spent engaged in or a vigorous LTPA intensity. The subjects who participated only in HPA and were not involved in LTPA also had lower risks of mortality (HR = 0.72, 95% CIs: 0.60-0.85 for men, and HR = 0.84, 95% CIs: 0.69-1.02 for women) than those who did not participate in both LTPA and HPA.ConclusionsHPA reduced the risks of mortality in middle-aged Korean adults and could even decrease the risk of death in those who did not participate in LTPA.

Epidemiologic studies regarding breast cancer risk related to milk consumption remain controversial. The aim of this study was to evaluate the association between milk consumption and the risk for breast cancer. A total of 93,306 participants, aged 40&ndash, 69 years, were included in the prospective cohort study in the Health Examinees-Gem (HEXA-G) study between 2004 and 2013. Dietary intake was assessed using a validated food frequency questionnaire. Information on cancer diagnosis in the eligible cohort was retrieved from the Korea Central Cancer Registry through 31 December 2014. The Cox proportional hazards model was used to estimate multivariate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 359 breast cancer cases were observed over a median follow-up period of 6.3 years. Milk consumption was not associated with decreased risk for breast cancer in the total population (p for trend = 0.0687). In women under 50 years of age, however, milk consumption was inversely associated with breast cancer risk. In the comparison between highest (&ge, 1 serving/day) and lowest (&lt, 1 serving/week) intake categories of milk, the multivariate HR (95% CI) was 0.58 (0.35&ndash, 0.97, p for trend = 0.0195)) among women under 50 years of age. In conclusion, our findings show that milk consumption in Korean women aged 50 or younger is associated with a decreased risk for breast cancer, when compared to those who never or rarely consumed milk. Further studies need to be conducted to assess this relationship and confirm these results.

Based on an inverse association between vitamin D levels and the risks of colorectal diseases, a functional start codon polymorphism in the vitamin D receptor (VDR) gene is speculated to affect the risks for these diseases. To validate this hypothesis, we first conducted a case-control study of 695 colorectal cancer patients and 1,397 controls. The association of VDR FokI polymorphism with colorectal cancer risk was analyzed using a logistic regression model. In the present case-control study, compared to the F allele, the f allele seemed to be associated with lower risks of colon cancer and advanced colorectal cancer. Additionally, a meta-analysis of 27 studies was conducted to combine findings from previous studies investigating the association of FokI polymorphism with colorectal disease using a random effects model. In the present meta-analysis, the f allele was positively associated with the risk of inflammatory bowel disease, including Crohn’s disease and ulcerative colitis. However, this allele was inversely associated with colon cancer and was not associated with the risk of rectal cancer or colorectal adenoma. In conclusion, the findings from this study imply that the role of VDR FokI polymorphism may differ based on the type and severity of colorectal disease.

We aimed to examine the effect of weight change attributable to cessation of cigarette smoking on newly diagnosed metabolic syndrome (MetS). We prospectively followed 5,809 men aged between 40 to 69 years without MetS at baseline in the Health Examinees-Gem (HEXA-G) study up to 4 years. The participants were grouped into continual smokers, quitters with weight gain, quitters without weight change, quitters with weight loss, and never smokers. We constructed multivariable logistic regression models adjusted for sociodemographic factors, health status, and health conditions to estimate the odds of newly diagnosed MetS. During the follow-up, there were 609 cases of newly diagnosed MetS in 5,809 men of the HEXA-G study. After adjustment for potential confounders, the odd ratios (OR) and 95% confidence intervals (95% CI) for MetS were 1.90 (95% CI: 1.43–2.52) in quitters with weight gain, 0.77 (95% CI: 0.60–1.00) in quitters without weight change, and 0.40 (95% CI: 0.28–0.57) in quitters with weight loss compared with continual smokers. Never smokers also had lower odds of MetS (OR = 0.54; 95% CI: 0.42–0.71) compared to continual smokers. Weight management program following smoking cessation may be necessary in clinical practice to reduce worsening of cardiometabolic risk factors related to post-cessation weight gain.

Background Nut consumption is known to reduce the risk of obesity, diabetes mellitus, and cardiovascular disease. However, in previous studies, portion sizes and categories of nut consumption have varied, and few studies have assessed the association between colorectal cancer risk and nut consumption. In this study, we investigated the relationship between nut consumption and colorectal cancer risk. Methods A case-control study was conducted among 923 colorectal cancer patients and 1846 controls recruited from the National Cancer Center in Korea. Information on dietary intake was collected using a semi-quantitative food frequency questionnaire with 106 items, including peanuts, pine nuts, and almonds (as 1 food item). Nut consumption was categorized as none

Background Although genome-wide association studies (GWAS) have identified variants in approximately 40 susceptibility loci for colorectal cancer (CRC), there are few studies on the interactions between identified single-nucleotide polymorphisms (SNPs) and lifestyle risk factors. We evaluated whether smoking could modify associations between these genetic variants and CRC risk. Methods A total of 703 CRC patients and 1406 healthy controls were included in this case-control study from the National Cancer Center in Korea. Thirty CRC susceptibility SNPs identified in previous GWAS were genotyped. A logistic regression model was used to examine associations between the SNPs and smoking behaviors by sex. The interaction was estimated by including an additional interaction term in the model. Results In men, an increased CRC risk was observed for longer durations (OR>28 vs. ≤28years = 1.49 (95% CI = 1.11–1.98)), greater quantities (OR≥20 vs.

Previous cohort studies have demonstrated a positive association between diabetes mellitus (DM) and colorectal cancer (CRC). However, there are few comparisons between DM groups categorized by fasting glucose level. This study examined associations between diabetes as defined by fasting glucose level and self-reported history of DM and CRC risk among Korean adults. Data from the Korean Multi-center Cancer Cohort between 1993 and 2005 were analyzed. The study population comprised 14,570 participants aged 20 years or older. Participants were followed until December 31, 2012 (median follow-up: 11.9 years). Among participants with high fasting glucose (≥126mg/dL), the risk of developing CRC was significantly higher (HR: 1.51 [1.02-2.25]) than among participants with low fasting glucose (

Background In this study, we aimed to identify demographic and clinical variables that correlate with perceived information provision among cancer patients and determine the association of information provision with decisional conflict (DC). Patients and methods We enrolled a total of 625 patients with cancer from two Korean hospitals in 2012. We used the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire (QLQ-INFO26) to assess patients' perception of the information received from their doctors and the Decisional Conflict Scale (DCS) to assess DC. To identify predictive sociodemographic and clinical variables for adequate information provision, backward selective logistic regression analyses were conducted. In addition, adjusted multivariate logistic regression analyses were carried out to identify clinically meaningful differences of perceived level of information subscales associated with high DC. Results More than half of patients with cancer showed insufficient satisfaction with medical information about disease (56%), treatment (73%), other services (83%), and global score (80%). In multiple logistic regression analyses, lower income and education, female, unmarried status, type of cancer with good prognosis, and early stage of treatment process were associated with patients' perception of inadequate information provision. In addition, Information about the medical tests with high DCS values clarity [adjusted odds ratio (aOR), 0.54; 95% confidence interval (CI) 0.30–0.97] and support (aOR, 0.53; 95% CI 0.33–0.85) showed negative significance. For inadequate information perception about treatments and other services, all 5 DCS scales (uncertainty, informed, values clarity, support, and effective decision) were negatively related. Global score of inadequate information provision also showed negative association with high DCS effective decision (aOR, 0.43; 95% CI 0.26–0.71) and DCS uncertainty (aOR, 0.46; 95% CI 0.27–0.77). Conclusion This study found that inadequate levels of perceived information correlated with several demographic and clinical characteristics. In addition, sufficient perceived information levels may be related to low levels of DC.

We aimed to investigate the differences in health screening, including medical checkups and cancer screening, between HBV carriers and non-carriers in the Republic of Korea. In the fifth Korean National Health and Nutrition Examination Survey (KNHANES V), conducted between 2010 and 2012, 17,865 persons who answered regarding their HBV-infection status, medical checkup history, liver cancer screening and general cancer screening within the past years were included in the final analysis. In total, 295 persons were HBV carriers. Logistic regression models were used to compare the health check-up rate between the HBV carriers and non- HBV carriers. The HBV carriers were more likely to have been screened for liver cancer [adjusted odds ratio (OR): 2.83, 95% confidence interval (95%CI): 1.90-4.21] or cancer [OR: 1.44, 95%CI: 1.04-1.99]. The HBV carriers showed a probability of receiving medical checkups that was identical to that of the non-carriers [OR: 0.99, 95%CI: 0.72-1.35]. The HBV carriers, who were at higher risk of developing chronic liver disease, were more likely to be screened for cancer, including liver cancer, than the non-HBV carriers; no difference in the rate of medical checkups was observed between the HBV carriers and non-HBV carriers.

A growing body of evidence suggests that the peroxisome proliferator-activated receptor-gamma (PPARγ) gene may harbor targets for the chemoprevention of breast cancer. However, it is unclear whether polymorphisms in the PPARγ gene are associated with the susceptibility of breast cancer. We performed a candidate gene association study between PPARγ polymorphisms and breast cancer and a meta-analysis on the association of breast cancer with selected PPARγ variants. Six single nucleotide polymorphisms (SNPs) in the PPARγ gene were analyzed among 456 breast cancer patients and 461 controls from the National Cancer Center in Korea. Association between the polymorphisms and breast cancer risk were assessed using the Cochrane-Armitage test for trend and a multivariate logistic regression model. Two SNPs, rs3856806 and rs1801282, had been previously analyzed, thus enabling us to perform pooled analyses on their associations with breast cancer susceptibility. Our findings from the candidate gene association study showed no association between the PPARγ gene polymorphisms and breast cancer risk. A meta-analysis combining existing studies and our current study also refuted an association of the PPARγ gene with breast cancer. Our findings suggest that the PPARγ gene may not harbor variants that alter breast cancer susceptibility, although a moderate sample size might have precluded a decisive conclusion.

Background Both short and long sleep duration have been consistently studied as a risk factor for obesity, hyperglycemia and hypertension. In this cross-sectional study, we provide an updated analysis of the Health Examinees (HEXA) study on the association between sleep duration and metabolic syndrome (MetS) occurrence among Koreans age 40–69 year olds. Methods A total of 133,608 subjects (44,930 men, 88,678 women) were enrolled in the HEXA study 2004–2013. Sleep duration was categorized into 4 sleep categories (

Purpose To assess the validity of the cohort study participants’ self-reported cancer history via data linkage to a cancer registry database. Methods We included 143,965 participants from the Health Examinees (HEXA) study recruited between 2004 and 2013 who gave informed consent for record linkage to the Korean Central Cancer Registry (KCCR). The sensitivity and the positive predictive value of self-reported histories of cancer were calculated and 95% confidence intervals were estimated. Results A total of 4,860 participants who had at least one record in the KCCR were included in the calculation of sensitivity. In addition, 3,671 participants who reported a cancer history at enrollment were included in the calculation of positive predictive value. The overall sensitivity of self-reported cancer history was 72.0%. Breast cancer history among women showed the highest sensitivity (81.2%), whereas the lowest sensitivity was observed for liver cancer (53.7%) and cervical cancer (52.1%). The overall positive predictive value was 81.9%. The highest positive predictive value was observed for thyroid cancer (96.1%) and prostate cancer (96.1%), and the lowest was observed for cervical cancer (43.7%). Conclusion The accuracy of self-reported cancer history varied by cancer site and may not be sufficient to ascertain cancer incidence, especially for cervical and bladder cancers.

Common genetic risk variants for colorectal cancer (CRC) have been identified at approximately 40 loci by genome-wide association studies (GWAS). We investigated the association of these risk variants by age at onset of CRC using case-only and case-control analysis. A total of 1,962 CRC cases and 2,668 controls from two independent case-control studies conducted by Korea’s National Cancer Center were included in this study. We genotyped 33 GWAS-identified single-nucleotide polymorphisms (SNPs) associated with CRC risk. The risk allele in SNP rs704017, located at 10q22.3 in the ZMIZ1-AS1 gene, was consistently less frequent among CRC patients aged P = 2.7 × 10−3, in an additive model), although this did not surpass the threshold for multiple testing. The direction of associations between rs704017 and CRC risk differed by age group in the combined case-control analysis (P = 0.03 and ≥50 years: OR = 1.13, 95% CI = 0.98–1.29, P = 0.09, in a dominant model); the p-values for heterogeneity (Pheterogeneity = 7.5 × 10−3) and for interaction were statistically significant (Pinteraction = 7.8 × 10−3, in the dominant model). Our results suggest that the CRC susceptibility SNP rs704017 has a hereditary effect on onset age of CRC.