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Abstract Background Effects of confounders on associations between diet and colorectal cancer (CRC) in observational studies can be minimized in Mendelian randomization (MR) approach. This study aimed to investigate observational and genetically predicted associations between dietary intake and CRC using one-sample MR. Methods Using genetic data of over 93 million variants, we performed a genome-wide association study to find genomic risk loci associated with dietary intake in participants from the UK Biobank. Then we calculated genetic risk scores of diet-related variants and used them as instrumental variables in the two-stage least square MR framework to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations. We also performed observational analyses using age as a time-scale in Cox proportional hazard models. Results Allele scores were calculated from 399 genetic variants associated with the consumption of of red meat, processed meat, poultry, fish, milk, cheese, fruits, vegetables, coffee, tea, and alcohol in participants from the UK Biobank. In MR analysis, genetically predicted fruit intake was significantly associated with a 21% decreased risk of CRC (HR = 0.79, 95% CI = 0.66–0.95), and there was a marginally inverse association between vegetable intake and CRC (HR = 0.85, 95% CI = 0.71–1.02). However, null findings were observed in multivariable analysis, with HRs (95% CIs) of 0.99 (0.98–1.01) and 0.99 (0.98–1.00) per increment of daily servings of fruits and vegetables, respectively. Conclusion Dietary habits were attributable to genetic variations, which can be used as instrumental variables in the MR framework. Our study supported a causal relationship between fruit intake and a decreased risk of CRC and suggested an effective strategy of consuming fruits in the primary prevention of CRC.

Abstract Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.

Abstract Dietary patterns may be a crucial modifiable factor in colorectal cancer (CRC) risk. This study aimed to examine the associations of dietary patterns derived from two methods with CRC risk in Korea. In a study of 1420 CRC patients and 2840 control participants, we obtained dietary patterns by principal component analysis (PCA) and reduced rank regression (RRR) using 33 predefined food groups. The associations between dietary patterns and CRC risk were assessed using unconditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). We identified two similar dietary patterns, derived from PCA 1 (prudent) and RRR (healthy), characterized by higher consumption of green/yellow vegetables, light-colored vegetables, fruits, eggs, and milk in both men and women. In women, higher prudent and healthy pattern scores were significantly associated with a lower risk of CRC (prudent, ORQ4 vs. Q1 = 0.59, 95% CI 0.40–0.86, P for trend = 0.005; healthy, ORQ4 vs. Q1 = 0.62, 95% CI 0.43–0.89, P for trend = 0.007). In men, a significant inverse association between dietary pattern and risk of rectal cancer was found only for the healthy dietary pattern (ORQ4 vs. Q1 = 0.66, 95% CI 0.45–0.97, P for trend = 0.036). Compared with the dietary pattern derived by PCA, the RRR dietary pattern had a slightly stronger association with a lower risk of distal colon cancer (ORQ4 vs. Q1 = 0.58, 95% CI 0.35–0.97, P for trend = 0.025) and rectal cancer (ORQ4 vs. Q1 = 0.29, 95% CI 0.15–0.57, P for trend

Abstract Background Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. Methods A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow‐up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random‐effects meta‐analyses. Results Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06–1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07–1.60 vs 1.12, 1.01–1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02–1.28 vs 1.17, 0.77–1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02–1.46 vs 1.00, 0.62–1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77–5.86), and decreased with time (nonlinear p

Abstract This study aimed to examine the impact of the COVID-19 pandemic on the emergency department (ED) visits of cardiovascular disease (CVD) patients. The customized data of the National Health Insurance Service (NHIS) from 2017 to 2020 were analyzed. CVD patients were defined by the code ‘V192’ based on the NHIS coverage benefit expansion policy. The number of ED visits of CVD patients, as well as executed procedures in 2020 (during the pandemic), were compared to the corresponding average numbers in 2018 and 2019 (prepandemic). Stratification by age group, residential area and hospital location was performed. The number of ED visits of newly diagnosed CVD patients decreased by 2.1% nationwide in 2020 (2018–2019: 97,041; 2020: 95,038) and decreased the most (by 14.1%) in March (2018–2019: 8539; 2020: 7334). However, the number of executed procedures increased by 1.1% nationwide in 2020 (2018–2019: 74,696; 2020: 75,520), while it decreased by 11.9% in April (2018–2019: 6603; 2020: 5819). The most notable decreases in the number of newly diagnosed CVD patients (31.7%) and procedures (29.2%) in March 2020 were observed in the Daegu·Gyeongbuk area. CVD patients living in the epicenter of the COVID-19 pandemic may experience difficulty accessing healthcare facilities and receiving proper treatment.

Abstract Background The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. Methods This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. Results Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66–1.13] compared to 0.60 [0.49–0.73], 0.46 [0.38–0.56] and 0.62 [0.51–0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14–1.84] compared to 1.25 [0.99–1.58], 1.06 [0.85–1.32] and 0.86 [0.69–1.08]) and alcohol consumption (1.22 [1.01–1.48] compared to 1.10 [0.90–1.33], 1.15 [0.96–1.38], and 1.07 [0.91–1.26]). Conclusion We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.

Abstract Background Clinical diabetic traits have been reported to be associated with increased colorectal cancer (CRC) risk in observational studies. Using the Mendelian randomization (MR) analysis method, we examined the causal association between glycemic traits, such as fasting glucose (FG), fasting insulin (FI), and glycosylated hemoglobin A1c (HbA1c), and survival in a cohort of CRC patients. Methods We conducted a two‐sample MR analysis among a cohort of patients with locally advanced CRC at Seoul National University Hospital. Single‐nucleotide polymorphisms robustly associated (p

Abstract Background This study aimed to explore the potential interaction between dietary intake and genetics on incident colorectal cancer (CRC) and whether adherence to healthy dietary habits could attenuate CRC risk in individuals at high genetic risk. Methods We analyzed prospective cohort data of 374,004 participants who were free of any cancers at enrollment in UK Biobank. Dietary scores were created based on three dietary recommendations of the World Cancer Research Fund (WCRF) and the overall effects of 11 foods on CRC risks using the inverse-variance (IV) method. Genetic risk was assessed using a polygenic risk score (PRS) capturing overall CRC risk. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs (confidence intervals) of associations. Interactions between dietary factors and the PRS were examined using a likelihood ratio test to compare models with and without the interaction term. Results During a median follow-up of 12.4 years, 4,686 CRC cases were newly diagnosed. Both low adherence to the WCRF recommendations (HR = 1.12, 95% CI = 1.05–1.19) and high IV-weighted dietary scores (HR = 1.27, 95% CI = 1.18–1.37) were associated with CRC risks. The PRS of 98 genetic variants was associated with an increased CRC risk (HRT3vsT1 = 2.12, 95% CI = 1.97–2.29). Participants with both unfavorable dietary habits and a high PRS had a more than twofold increased risk of developing CRC; however, the interaction was not significant. Adherence to an overall healthy diet might attenuate CRC risks in those with high genetic risks (HR = 1.21, 95% CI = 1.08–1.35 for high vs. low IV-weighted dietary scores), while adherence to WCRF dietary recommendations showed marginal effects only (HR = 1.09, 95% CI = 1.00–1.19 for low vs. high WCRF dietary scores). Conclusion Dietary habits and the PRS were independently associated with CRC risks. Adherence to healthy dietary habits may exert beneficial effects on CRC risk reduction in individuals at high genetic risk.

Abstract Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values

Objectives The association between long sleep duration and mortality is frequently attributed to the confounding influence of comorbidities. Nevertheless, past efforts to account for comorbidities have yielded inconsistent outcomes. The objective of this study was to evaluate this relationship using a large prospective cohort in Korea. Methods The study included 114 205 participants from the Health Examinees Study, who were followed for a median of 9.1 years. A composite comorbidity score was developed to summarize the effects of 21 diseases. Using Cox proportional hazards regression, hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cancer, and cardiovascular mortality associated with sleep duration were estimated. These estimates were adjusted for socio-demographic factors, lifestyle factors, body mass index, and comorbidity score. Additionally, a stratified analysis by subgroups with and without comorbidities was conducted. Results Throughout the follow-up period, 2675 deaths were recorded. After all adjustments, an association was observed between a sleep duration of 8 hours or more and all-cause mortality (HR, 1.10; 95% CI, 1.01 to 1.20). However, no such association was detected in the stratified analysis for the subgroups based on comorbidity status. Conclusions Long sleep duration was found to be associated with all-cause mortality among Koreans, even after adjusting for comorbidities. Additional studies are required to explore the mechanism underlying the association between sleep duration and major causes of mortality.

Abstract Background Physical activity (PA) is recommended to improve the survival of cancer patients. However, the prognostic impact of specific PAs is not well understood. Therefore, we investigated the associations of the duration, type, intensity, and number of PAs one participates in pre‐ and post‐diagnosis with mortality in Korean patients with cancer. Methods Among the participants aged 40–69 years recruited from the Health Examines study, those diagnosed with cancer after baseline (n = 7749) and within 10 years before baseline (n = 3008) were included in the analyses for pre‐ and post‐diagnosis PA, respectively. Duration, intensity, type, and number of leisure‐time physical activities participated in were assessed using questionnaires. The Cox proportional hazard model was used to characterize the association between PA and cancer‐specific mortality, adjusting for demographics, behaviors, comorbidities, and cancer stage based on the Surveillance, Epidemiology, and End Results program. Results Pre‐diagnosis, patients participating in vigorous‐intensity activities (hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.61–0.82), walking (HR: 0.85, 95% CI: 0.74–0.97), climbing (HR: 0.65, 95% CI: 0.55–0.77), sports (HR: 0.39, 95% CI: 0.25–0.61), and more than two activities (HR: 0.73, 95% CI: 0.63–0.86) had significantly lower all‐cause mortality. Importantly, these associations were only found in patients with colorectal cancer participating in vigorous‐intensity activities (HR: 0.40, 95% CI: 0.23–0.70). Post‐diagnosis, only patients who performed more than two activities (HR: 0.65, 95% CI: 0.44–0.95) had significantly lower all‐cause mortality. Similar associations were found for cancer mortality, both pre‐ and post‐diagnosis. Conclusion Specific characteristics of PA pre‐ and post‐diagnosis may influence the survival of cancer patients.

Abstract Background We aimed to examine the lymphohematopoietic cancer mortality in a cohort of workers at a semiconductor manufacturing company in South Korea according to their jobs. Methods A retrospective cohort was constructed using the personnel records of semiconductor manufacturing workers who were employed in a semiconductor company in South Korea in 1998–2012. Data on their vital status and causes of death were obtained from the National Statistical Office of South Korea. The standardized mortality ratios (SMRs) of lymphohematopoietic cancer were calculated. Results A total of 288 deaths were reported, of which 22 were caused by lymphohematopoietic cancer, among 65,782 workers in 878,325 person-years. The SMRs for lymphohematopoietic cancer were 0.78 (95% confidence interval [CI] = 0.39–1.40; the number of observed cases [Obs] = 11) among male workers and 1.71 (95% CI = 0.85–3.06; Obs = 11) among female workers. Among female operators, excess deaths due to lymphohematopoietic cancer (SMR = 2.59, 95% CI = 1.24–4.76) and leukemia (SMR = 2.92, 95% CI = 1.26–5.76) were observed. However, they were not observed among office workers, facility managers, utility managers, or process managers. Conclusion Female operators involved in the semiconductor wafer fabrication process had higher risk of mortality from lymphohematopoietic cancer.

Objectives We reviewed the operational definitions of colorectal cancer (CRC) from studies using the Korean National Health Insurance Service (NHIS) and compared CRC incidence derived from the commonly used operational definitions in the literature with the statistics reported by the Korea Central Cancer Registry (KCCR). Methods We searched the MEDLINE and KoreaMed databases to identify studies containing operational definitions of CRC, published until January 15, 2021. All pertinent data concerning the study period, the utilized database, and the outcome variable were extracted. Within the NHIS-National Sample Cohort, age-standardized incidence rates (ASRs) of CRC were calculated for each operational definition found in the literature between 2005 and 2019. These rates were then compared with ASRs from the KCCR. Results From the 62 eligible studies, 9 operational definitions for CRC were identified. The most commonly used operational definition was “C18–C20” (n=20), followed by “C18–C20 with claim code for treatment” (n=3) and “C18–C20 with V193 (code for registered cancer patients’ payment deduction)” (n=3). The ASRs reported using these operational definitions were lower than the ASRs from KCCR, except for “C18–C20 used as the main diagnosis.” The smallest difference in ASRs was observed for “C18–C20,” followed by “C18–C20 with V193,” and “C18–C20 with claim code for hospitalization or code for treatment.” Conclusions In defining CRC patients utilizing the NHIS database, the ASR derived through the operational definition of “C18–C20 as the main diagnosis” was comparable to the ASR from the KCCR. Depending on the study hypothesis, operational definitions using treatment codes may be utilized.

Abstract Background With the availability of health insurance claim data, pharmacovigilance for various drugs has been suggested; however, it is necessary to establish an appropriate analysis method. To detect unintended drug effects and to generate new hypotheses, we conducted a hypothesis-free study to systematically examine the relationship between all prescription nonanticancer drugs and the mortality of colorectal cancer patients. Methods We used the Korean National Health Insurance Service-National Sample Cohort database. A total of 2,618 colorectal cancer patients diagnosed between 2004 and 2015 were divided into drug discovery and drug validation sets (1:1) through random sampling. Drugs were classified using the Anatomical Therapeutic Chemical (ATC) classification system: 76 drugs classified as ATC level 2 and 332 drugs classified as ATC level 4 were included in the analysis. We used a Cox proportional hazard model adjusted for sex, age, colorectal cancer treatment, and comorbidities. The relationship between all prescription nonanticancer drugs and the mortality of colorectal cancer patients was analyzed, controlling for multiple comparisons with the false discovery rate. Results We found that one ATC level-2 drug (drugs that act on the nervous system, including parasympathomimetics, addictive disorder drugs, and antivertigo drugs) showed a protective effect related to colorectal cancer prognosis. At the ATC level 4 classification, 4 drugs were significant: two had a protective effect (anticholinesterases and opioid anesthetics), and the other two had a detrimental effect (magnesium compounds and Pregnen [4] derivatives). Conclusions In this hypothesis-free study, we identified four drugs linked to colorectal cancer prognosis. The MWAS method can be useful in real-world data analysis.

Abstract This study aimed to examine whether the ISX rs5755368 genotypes are associated with the effect of dietary retinol consumption on CRC risk. We recruited 923 CRC patients and 1846 controls to identify the association between dietary retinol and CRC risk. Dietary retinol intake was assessed using a semiquantitative food frequency questionnaire. Genotype data were available for 1419 patients (600 cases and 819 controls) of the total study population. Genotyping was performed using an Illumina MEGA Expanded Array. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression models. Retinol intake was inversely associated with CRC (OR = 0.49; 95% CI = 0.37–0.63). Participants with AA genotype showed lower CRC risk than subjects carrying the G allele (AG + GG) (OR = 0.76; 95% CI = 0.58–0.99). A 68% reduced risk of CRC was related to subjects who had the highest retinol intake and carrying AA genotype compared to the risk of participants consumed the lowest retinol intake and carrying the G allele (OR = 0.32; 95% CI = 0.20–0.53; P interaction = 0.026). Retinol intake could be a protective factor for CRC risk while this association could be strengthened among individuals carrying the homozygous AA genotype.

OBJECTIVES Previous human trials have not supported the anticarcinogenic effect of vitamin E despite biological plausibility and considerable epidemiological evidence. A possible explanation for this inconsistency is the interactive effect of the catechol-O-methyltransferase (COMT) gene and supplemental vitamin E on cancer. We examined whether a COMT gene variant modulates the effect of dietary vitamin E intake on colorectal cancer (CRC) risk. METHODS In this case-control study of Korean adults (975 cases and 975 age- and sex-matched controls), dietary vitamin E density (mg/1,000 kcal) was measured using a semiquantitative food frequency questionnaire, COMT single nucleotide polymorphism (SNP) rs740603 (A>G) was genotyped, and CRC was verified histologically. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models with adjustments for potential confounders. RESULTS Higher vitamin E density was associated with a lower risk of CRC (highest vs. lowest quartiles: OR, 0.72; 95% CI, 0.55 to 0.96; p-for-trend=0.002). When stratified by COMT SNP rs740603 genotype, the inverse association between vitamin E density and CRC risk was confined to those with at least 1 A allele (≥median vs.

OBJECTIVES The purpose of this study was to explore the association between adherence to 2 cancer prevention recommendations and cancer risk. METHODS In total, 104,386 individuals aged 40-69 years old who were recruited between 2004 and 2013 in the Health Examinees-Gem study were included. Adherence scores were constructed based on 8 items from the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations, including body weight, physical activity, diet, alcohol consumption and breastfeeding, and on 6 items from the Korean cancer prevention guidelines (smoking status, eating vegetables and fruits, salty foods, alcohol intake, physical activity, and body weight). A Cox proportional hazards model was used to estimate the associations between adherence scores and the risk of total and 5 major cancers. RESULTS The multivariable hazard ratio (HR) for total cancer with the high adherence score versus the lowest score (4.25-7.00 vs. 0.00-3.25) for the WCRF/AICR guidelines was 0.91 (95% confidence interval [CI], 0.82 to 1.00) in men. A reduced breast cancer risk was observed among women with the highest score. Men within the highest category of the Korean cancer prevention guideline score (3.25-6.00) had an HR of 0.80 (95% CI, 0.73 to 0.88) for developing total cancer compared to men within the lowest score (0.00-2.50). The higher adherence group among men showed lower risks of developing stomach, colorectal, and lung cancers. CONCLUSIONS Adhering to guidelines for cancer prevention can help to reduce the risk of developing cancer in Korean men. The association might differ by cancer type and gender.

Abstract Background Differences in the composition and diversity of the gut microbial communities among individuals are influenced by environmental factors. However, there is limited research on factors affecting microbiome variation in colorectal cancer patients, who display lower inter-individual variations than that of healthy individuals. In this study, we examined the association between modifiable factors and the microbiome variation in colorectal cancer patients. Methods A total of 331 colorectal cancer patients who underwent resection surgery at the Department of Surgery, Seoul National University Hospital between October 2017 and August 2019 were included. Fecal samples from colorectal cancer patients were collected prior to the surgery. Variations in the gut microbiome among patients with different lifestyles and metabolic diseases were examined through the network analysis of inter-connected microbial abundance, the assessment of the Anna Karenina principle effect for microbial stochasticity, and the identification of the enriched bacteria using linear discrimination analysis effect size. Associations of dietary diversity with microbiome variation were investigated using the Procrustes analysis. Results We found stronger network connectivity of microbial communities in non-smokers, non-drinkers, obese individuals, hypertensive subjects, and individuals without diabetes than in their counterparts. The Anna Karenina principle effect was found for history of smoking, alcohol consumption, and diabetes (with significantly greater intra-sample similarity index), whereas obesity and hypertension showed the anti-Anna Karenina principle effect (with significantly lower intra-sample similarity index). We found certain bacterial taxa to be significantly enriched in patients of different categories of lifestyles and metabolic diseases using linear discrimination analysis. Diversity of food and nutrient intake did not shape the microbial diversity between individuals (pProcrustes>0.05). Conclusions Our findings suggested an immune dysregulation and a reduced ability of the host and its microbiome in regulating the community composition. History of smoking, alcohol consumption, and diabetes were shown to affect partial individuals in shifting new microbial communities, whereas obesity and history of hypertension appeared to affect majority of individuals and shifted to drastic reductions in microbial compositions. Understanding the contribution of modifiable factors to microbial stochasticity may provide insights into how the microbiome regulates effects of these factors on the health outcomes of colorectal cancer patients.

Objectives We introduced the cohort studies included in the Korean Cohort Consortium (KCC), focusing on large-scale cohort studies established in Korea with a prolonged follow-up period. Moreover, we also provided projections of the follow-up and estimates of the sample size that would be necessary for big-data analyses based on pooling established cohort studies, including population-based genomic studies. Methods We mainly focused on the characteristics of individual cohort studies from the KCC. We developed “PROFAN”, a Shiny application for projecting the follow-up period to achieve a certain number of cases when pooling established cohort studies. As examples, we projected the follow-up periods for 5000 cases of gastric cancer, 2500 cases of prostate and breast cancer, and 500 cases of non-Hodgkin lymphoma. The sample sizes for sequencing-based analyses based on a 1:1 case-control study were also calculated. Results The KCC consisted of 8 individual cohort studies, of which 3 were community-based and 5 were health screening-based cohorts. The population-based cohort studies were mainly organized by Korean government agencies and research institutes. The projected follow-up period was at least 10 years to achieve 5000 cases based on a cohort of 0.5 million participants. The mean of the minimum to maximum sample sizes for performing sequencing analyses was 5917–72 102. Conclusions We propose an approach to establish a large-scale consortium based on the standardization and harmonization of existing cohort studies to obtain adequate statistical power with a sufficient sample size to analyze high-risk groups or rare cancer subtypes.

Abstract Epidemiological evidence suggests that hypertension is associated with breast cancer risk. However, previous studies disregard blood pressure components in the healthy population. We aimed to examine the relationship between systolic and diastolic blood pressure and breast cancer risk in a Korean population-based prospective cohort. A total of 73,031 women from the Health Examinees Gem Study were followed from baseline (2004 to 2013) through 2018. Systolic and diastolic blood pressure were measured by trainee physicians at baseline recruitment and then categorized based on the international guidelines for clinical hypertension. Associations between systolic and diastolic blood pressure with overall breast cancer and stratified by premenopausal and postmenopausal status were evaluated using adjusted multivariable Cox proportional hazard regression. A total of 858 breast cancer cases were recorded for a median follow-up period of 9 years. Compared with the normal DBP category (

Objective: Epidemiological studies indicate that alcohol increases gastric cancer (GC) risk, yet most studies have focused on heavy alcohol intake, leaving other factors understudied. A comprehensive investigation of the effects of the frequency and amount of alcohol intake may help elucidate the GC risk associated with drinking behavior. Methods: The Health Examinees-Gem (HEXA-G) study, a community-based large-scale prospective cohort study, enrolled Korean adults 40–69 years of age between the years 2004 and 2013. Incident GC cases were identified through linkage to Korea Central Cancer Registry data until December 31, 2017. Self-reported questionnaires were used to survey alcohol consumption-related factors (duration, frequency, amount, and type of alcoholic beverages). The frequency and amount of alcohol consumption were combined to explore GC risk according to 4 drinking patterns: “infrequent-light”, “frequent-light”, “infrequent-heavy”, and “frequent-heavy”. We used Cox proportional hazard models to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs), and investigate the relationship between alcohol intake and GC incidence. Results: A total of 128,218 participants were included in the analysis. During an average follow-up period of 8.6 years, 462 men and 385 women were diagnosed with GC. In men, current drinkers showed a 31% greater risk of GC than non-drinkers (HR 1.31, 95% CI 1.03–1.66), whereas no significant association was observed in women. In men, GC risk was associated with a higher frequency (P trend 0.02) and dose of ethanol intake in grams (P trend 0.03). In men, the “frequent-light” (≥5 times/week and

Abstract Background The effects of diet on the interaction between microbes and host health have been widely studied. However, its effects on the gut microbiota of patients with colorectal cancer (CRC) have not been elucidated. This study aimed to investigate the association between diet and the overall diversity and different taxa levels of the gut microbiota in CRC patients via the nutrition-wide association approach. Methods This hospital-based study utilized data of 115 CRC patients who underwent CRC surgery in Department of Surgery, Seoul National University Hospital. Spearman correlation analyses were conducted for 216 dietary features and three alpha-diversity indices, Firmicutes/Bacteroidetes ratio, and relative abundance of 439 gut microbial taxonomy. To identify main enterotypes of the gut microbiota, we performed the principal coordinate analysis based on the β-diversity index. Finally, we performed linear regression to examine the association between dietary intake and main microbiome features, and linear discriminant analysis effect size (LEfSe) to identify bacterial taxa phylogenetically enriched in the low and high diet consumption groups. Results Several bacteria were enriched in patients with higher consumption of mature pumpkin/pumpkin juice (ρ, 0.31 to 0.41) but lower intake of eggs (ρ, -0.32 to -0.26). We observed negative correlations between Bacteroides fragilis abundance and intake of pork (belly), beef soup with vegetables, animal fat, and fatty acids (ρ, -0.34 to -0.27); an inverse correlation was also observed between Clostridium symbiosum abundance and intake of some fatty acids, amines, and amino acids (ρ, -0.30 to -0.24). Furthermore, high intake of seaweed was associated with a 6% (95% CI, 2% to 11%) and 7% (95% CI, 2% to 11%) lower abundance of Rikenellaceae and Alistipes, respectively, whereas overall beverage consumption was associated with an 10% (95% CI, 2% to 18%) higher abundance of Bacteroidetes, Bacteroidia, and Bacteroidales, compared to that in the low intake group. LEfSe analysis identified phylogenetically enriched taxa associated with the intake of sugars and sweets, legumes, mushrooms, eggs, oils and fats, plant fat, carbohydrates, and monounsaturated fatty acids. Conclusions Our data elucidates the diet-microbe interactions in CRC patients. Additional research is needed to understand the significance of these results in CRC prognosis.

Abstract We aimed to compare the short- and long-term outcomes of simultaneous laparoscopic, hybrid, and open resection for colorectal cancer and synchronous liver metastases. We retrospectively analyzed the data of 647 patients with simultaneous resection of colorectal cancer and liver metastases between January 2006 and December 2018 at three tertiary referral hospitals. Patient’s baseline characteristics, perioperative outcomes, pathological examination results, liver-specific recurrence rate and survivals were compared between the propensity score-matched groups. Forty-two and 81 patients were selected for the laparoscopic vs. hybrid groups, and 48 and 136 patients for laparoscopic vs. open groups, respectively. The laparoscopic group had fewer wound complications (2.1 vs. 13.2%; p = 0.028) than the open group, and a shorter postoperative hospital stay than the hybrid and open groups (8 vs. 11 days, p

OBJECTIVES Dietary and lifestyle exposures may affect the risk of colorectal cancer (CRC) by promoting chronic inflammation. Therefore, we assessed the separate and joint associations of dietary and lifestyle inflammation scores (DIS and LIS, respectively) with CRC. METHODS Data from 919 pathologically confirmed CRC cases and 1,846 age- and sex-matched controls recruited at the National Cancer Center Korea were analyzed. We calculated the DIS and LIS, which characterize the collective contributions of 19 dietary and 4 lifestyle factors, respectively, to systemic inflammation by applying weights based on high-sensitivity C-reactive protein. A higher score represented a higher balance of pro- to anti-inflammatory exposures. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for CRC risk compared across the DIS and LIS tertile categories, with the lowest tertile as the reference group. RESULTS The highest DIS tertile had significantly increased odds of having CRC (OR, 2.65; 95% CI, 2.10 to 3.36), and the odds increased with increasing DIS. The highest LIS tertile group had 1.28-fold higher odds of having CRC (95% CI, 1.03 to 1.58). In the cross-classification analysis, the odds of having CRC increased as the DIS and LIS jointly increased until the DIS reached the highest tertile, where the risk was very high (3-fold or more) regardless of the LIS. CONCLUSIONS In conclusion, a higher balance of pro-inflammatory relative to anti-inflammatory dietary and lifestyle factors, especially dietary factors, was associated with higher CRC risk among Korean adults.

BackgroundThe virtual reality (VR) experience of an operation room (OR) prior to anesthesia and surgery has been known to reduce the anxiety and distress of pediatric patients. However, the proper timing needed for this is unknown. This randomized clinical study aimed to evaluate the proper timing of a VR tour of an OR (a few days before vs. immediately before anesthesia) to reduce the anxiety in a pediatric patient undergoing elective surgery.MethodsThe children from the ages of 4–10 years old were randomly divided into three groups. The control group received standard verbal information about the process of anesthesia and surgery 10 min before anesthesia. The VR A group experienced a VR tour at the outpatient clinic a few days before anesthesia, whereas the VR B group experienced the tour 10 min before anesthesia at the reception area of the OR. The 4-min VR video used in this study showed the experience of Pororo, an animation character, entering the OR and undergoing anesthesia. We evaluated the anxiety of children using the modified Yale preoperative anxiety scale (m-YPAS), the anxiety of caregivers using Beck anxiety inventory (BAI), and caregivers’ satisfaction.ResultsThe m-YPAS of the VR B group was significantly lower than that of the control and VR A groups (p = 0.001), whereas there was no statistically significant difference in BAI (p = 0.605) among the 3 groups. The score of caregivers’ satisfaction with the overall process of anesthesia and surgery was higher in VR A group than in the control and VR B groups (p = 0.054).ConclusionThe VR experience of an OR immediately before anesthesia was more effective than standard verbal information or a VR tour at the outpatient clinic a few days before anesthesia in reducing the anxiety and distress of children prior to surgery.Clinical trial registration[https://cris.nih.go.kr/cris/search/detailSearch.do/20773], identifier [KCT0006845].

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

Abstract 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: The complete contact tracing of coronavirus disease-19 (COVID-19) cases in South Korea allows a unique opportunity to investigate cluster characteristics. This study aimed to investigate all reported COVID-19 clusters in the Seoul metropolitan area from January 23 to September 24, 2020. Methods: Publicly available COVID-19 data was collected from the Seoul Metropolitan City and Gyeonggi Province. Community clusters with ≥5 cases were characterized by size and duration, categorized using K-means clustering, and the correlation between the types of clusters and the level of social distancing investigated. Results: A total of 134 clusters comprised of 4033 cases were identified. The clusters were categorized into small (type I and II), medium (type III), and large (type IV) clusters. A comparable number of daily reported cases in different time periods were composed of different types of clusters. Increased social distancing was related to a shift from large to small-sized clusters. Conclusions: Classification of clusters may provide opportunities to understand the pattern of COVID-19 outbreaks better and implement more effective suppression strategies. Social distancing administered by the government may effectively suppress large clusters but may not effectively control small and sporadic clusters.

OBJECTIVES The coronavirus disease 2019 (COVID-19) pandemic has affected the utilization of healthcare services, including participation in cancer screening programs. We compared cancer screening participation rates for colorectal, gastric, breast, and cervical cancers among participants in the National Cancer Screening Program (NCSP) in 2019 and 2020 to address the potential distraction effect of COVID-19 on cancer screening. METHODS Data from the NCSP for 4 cancer types (stomach, colorectal, breast, and cervical) in 2019 and 2020 were used to calculate cancer screening participation rates by calendar month, gender, age group, and geographical region. Monthly participation rates were analyzed per 1,000 eligible individuals. RESULTS The screening participation rate decreased in 2020 compared to 2019 for all 4 cancers: colorectal (40.5 vs. 35.3%), gastric (61.9 vs. 54.6%), breast (63.8 vs. 55.8%), and cervical (57.8 vs. 52.2%) cancers. Following 2 major COVID-19 waves in March and December 2020, the participation rates in the 4 types of cancer screening dropped compared with those in 2019. The highest decline was observed in the elderly population aged 80 years and older (percentage change: -21% for colorectal cancer; -20% for gastric cancer; -26% for breast cancer; -20% for cervical cancer). CONCLUSIONS After the 2 major COVID-19 waves, the screening participation rate for 4 types of cancer declined compared with 2019. Further studies are needed to identify the indirect effects of the COVID-19 pandemic on cancer patients, such as delayed diagnoses of cancer or excess cancer deaths.

OBJECTIVES We investigated the impact of the COVID-19 pandemic on cancer care in a tertiary hospital in Korea without specific lockdown measures. METHODS A retrospective cohort of cancer patients from one of the largest tertiary hospitals in Korea was used to compare healthcare utilization in different settings (outpatient cancer clinic, the emergency department [ED], and admissions to the hematology/oncology ward) between January 1 and December 31, 2020 and the same time period in 2019. The percent changes in healthcare utilization between the 2 periods were calculated. RESULTS A total of 448,833 cases from the outpatient cohort, 26,781 cases from the ED cohort, and 14,513 cases from the admission cohort were reviewed for 2019 and 2020. The total number of ED visit cases significantly decreased from 2019 to 2020 by 18.04%, whereas the proportion of cancer patients remained stable. The reduction in ED visits was more prominent in patients with symptoms suspicious for COVID-19, high-acuity cases, and those who lived in non-capital city areas. There were no significant changes in the number of total visits, new cases in the outpatient clinic, or the total number of hospitalizations between the 2 periods. CONCLUSIONS During the pandemic, the number of ED visits significantly decreased, while the use of the outpatient clinic and hospitalizations were not affected. Cancer patients’ ED visits decreased after the COVID-19 outbreak, suggesting the potential for collateral damage outside the hospital if patients cannot reach the ED in a timely manner.

Abstract 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.

Men and women are different, but this difference has not been well reflected in clinical trials and preclinical studies of biomedical science. Gender medicine, which systematically analyzes research results according to sex and gender, has been emphasized to overcome this problem. On the other hand, researchers still have difficulty in applying gender medicine to their research. To perform rigorous gender medicine, using correct terms, a thorough literature review during research planning, appropriate statistical analysis and reporting, and cautious interpretation of the results are necessary. Applying gender medicine will increase the reproducibility of studies, promote discoveries, expand the study relevance, and ultimately improve patient care in both men and women. Here, this study reviewed the practical issues on applying gender medicine to both preclinical and clinical studies in the field of biomedical science.

ObjectivesThis study aimed to examine the risk of cardiovascular disease (CVD) death according to blood pressure levels and systolic and/or diastolic hypertension.MethodsFrom 20,636 cohort participants, 14,375 patients were enrolled after patients with prior hypertension on antihypertensive drugs were excluded. For the combination analysis, participants were divided into four groups (systolic/diastolic hypertension, systolic hypertension only, diastolic hypertension only, and non-hypertension). The risk of CV death was calculated using the hazard ratio (HR) and 95% confidence intervals (95% CI) in a Cox regression model.ResultsThe risk of CVD death increased in systolic hypertension (HR = 1.59, 95% CI 1.26-2.00) and systolic/diastolic hypertension (HR = 1.84, 95% CI 1.51-2.25). The highest risks of hemorrhagic and ischemic stroke were observed in the diastolic hypertension (HR = 4.11, 95% CI 1.40-12.06) and systolic/diastolic hypertension groups (HR = 2.59, 95% CI 1.92-3.50), respectively. The risk of CVD death was drastically increased in those with SBP≥120 mmHg/DBP≥80 mmHg. The highest risk was observed in those with SBP of 130-131 mmHg and 134-137 mmHg.ConclusionThe combined analysis of systolic and/or diastolic hypertension appears to be a good predictor of CVD death. The risk of CVD death in the prehypertensive group could be carefully monitored as well as in the hypertensive group, presumably due to less attention and the lack of antihypertensive treatment.

Emerging evidence has indicated a possible link between obesity in early life with subsequent cancer risks, but its association with gastric cancer remains unknown. This study aimed to investigate the association of obesity at ages 18-20 and 35 with the later risk of gastric cancer among the Korean population. Included were 122,724 individuals who participated in the large-scale prospective cohort study, the Health Examinees-Gem (HEXA-G) study, during 2004-2017. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for gastric cancer risk associated with body mass index (BMI) at ages 18-20 and 35 years. During a mean follow-up period of 8.6±2.1 years, a total 927 gastric cancer cases (531 men and 396 women) were identified. When compared to normal BMI (18.5-23.0 kg/m2), obesity (BMI ≥30 kg/m2) at age 35 was significantly associated with increased risk of gastric cancer later in life among total participants (HR 1.94, 95% CI 1.26-2.97, p 0.01). When analyzed separately by sex, obesity at 35 years of age was significantly associated with increased risk of gastric cancer among both men (HR 1.79, 95% CI 1.02-3.13, p 0.05) and women (HR 2.35, 95% CI 1.21-4.60, p 0.02). No significant associations were found for obesity at late adolescence in both men and women. Our findings suggest that obesity in early adulthood may be associated with an increased risk of gastric cancer. The results may aid in understanding the etiology of GC in a population with a divergent trend of gastric cancer.

Abstract 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 (p case-only = 2.4 × 10− 3, p case-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 (p case-only = 7.7 × 10− 3, p case-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: Agricultural work can expose workers to potentially hazardous agents including known and suspected carcinogens. This study aimed to evaluate cancer incidence in male and female agricultural workers in an international consortium, AGRICOH, relative to their respective general populations. Methods: The analysis included eight cohorts that were linked to their respective cancer registries: France (AGRICAN: n = 128,101), the US (AHS: n = 51,165, MESA: n = 2,177), Norway (CNAP: n = 43,834), Australia (2 cohorts combined, Australian Pesticide Exposed Workers: n = 12,215 and Victorian Grain Farmers: n = 919), Republic of Korea (KMCC: n = 8,432), and Denmark (SUS: n = 1,899). For various cancer sites and all cancers combined, standardized incidence ratios (SIR) and 95% confidence intervals (CIs) were calculated for each cohort using national or regional rates as reference rates and were combined by random-effects meta-analysis. Results: During nearly 2,800,000 person-years, a total of 23,188 cancers were observed. Elevated risks were observed for melanoma of the skin (number of cohorts = 3, meta-SIR = 1.18, CI: 1.01–1.38) and multiple myeloma (n = 4, meta-SIR = 1.27, CI: 1.04–1.54) in women and prostate cancer (n = 6, meta-SIR = 1.06, CI: 1.01–1.12), compared to the general population. In contrast, a deficit was observed for the incidence of several cancers, including cancers of the bladder, breast (female), colorectum, esophagus, larynx, lung, and pancreas and all cancers combined (n = 7, meta-SIR for all cancers combined = 0.83, 95% CI: 0.77–0.90). The direction of risk was largely consistent across cohorts although we observed large between-cohort variations in SIR for cancers of the liver and lung in men and women, and stomach, colorectum, and skin in men. Conclusion: The results suggest that agricultural workers have a lower risk of various cancers and an elevated risk of prostate cancer, multiple myeloma (female), and melanoma of skin (female) compared to the general population. Those differences and the between-cohort variations may be due to underlying differences in risk factors and warrant further investigation of agricultural exposures.

OBJECTIVES We investigated the risk of chemotherapy-related and radiotherapy-related cognitive impairment in colorectal cancer patients. METHODS Medical use data of colorectal cancer patients were obtained from the Korean National Health Insurance Database from 2004 to 2018. We randomly selected 40% of all colorectal cancer patients (n=148,848). Cognitive impairment was defined as having 1 or more International Classification of Diseases, 10th revision diagnostic codes for dementia or mild cognitive impairment. Patients aged 18 years or younger, patients diagnosed with cognitive impairment before colorectal cancer diagnosis (n=8,225), and patients who did not receive primary resection (n=45,320) were excluded. The effects of individual chemotherapy regimens on cognitive impairment were estimated. We additionally estimated the effect of radiotherapy in rectal cancer patients. Time-dependent competing risk Cox regression was conducted to estimate the overall and age-specific hazard ratios (HR) separately for colon and rectal cancer. Landmark analyses with different lag times were conducted as sensitivity analyses. RESULTS Chemotherapy did not increase the risk of cognitive impairment in colorectal cancer patients (colon cancer: HR, 0.92; 95% confidence interval [CI], 0.83 to 1.03; rectal cancer: HR, 0.88; 95% CI, 0.75 to 1.04), while radiotherapy was negatively associated with cognitive impairment in rectal cancer patients (HR, 0.01; 95% CI, 0.84 to 0.99). Varying directions of the associations between regimens and cognitive impairment were detected. The adverse effect of certain chemotherapy regimens on cognition was more prominent in older adults. CONCLUSIONS Chemotherapy and radiotherapy did not increase the risk of cognitive impairment. Older patients with low cognitive reserve could be affected by the adverse cognitive effects of chemotherapy.

OBJECTIVES During the coronavirus disease 2019 (COVID-19) pandemic, crude incidence and mortality rates have been widely reported; however, age-standardized rates are more suitable for comparisons. In this study, we estimated and compared the age-standardized incidence, mortality, and case fatality rates (CFRs) among countries and investigated the relationship between these rates and factors associated with healthcare resources: gross domestic product per capita, number of hospital beds per population, and number of doctors per population. METHODS The incidence, mortality, and CFRs of 79 countries were age-standardized using the World Health Organization standard population. The rates for persons 60 years or older were also calculated. The relationships among the rates were analysed using trend lines and coefficients of determination (R2). Pearson correlation coefficients between the rates and the healthcare resource-related factors were calculated. RESULTS The countries with the highest age-standardized incidence, mortality, and CFRs were Czechia (14,253 cases/100,000), Mexico (182 deaths/100,000), and Mexico (6.7%), respectively. The R2 between the incidence and mortality rates was 0.852 for all ages and 0.945 for those 60 years or older. The healthcare resources-related factors were associated positively with incidence rates and negatively with CFRs, with weaker correlations among the elderly. CONCLUSIONS Compared to age-standardized rates, crude rates showed greater variation among countries. Medical resources may be important in preventing COVID-19-related deaths; however, considering the small variation in fatality among the elderly, preventive measures such as vaccination are more important, especially for the elderly population, to minimize the mortality rates.

OBJECTIVES This study aimed to validate a simple risk assessment tool for estimating the advanced colorectal neoplasia (ACN) risk at colonoscopy screenings and potential factors relevant for implementing this tool in the Korean population. METHODS Our study analyzed data from the Cancer Screenee Cohort Study conducted by the National Cancer Center in Korea. The risk level was assessed using the Asia Pacific Colorectal Screening (APCS) score developed by the Asia-Pacific Working Group on Colorectal Cancer. Logistic regression models were used to examine the associations between colorectal-related outcomes and the risk level by APCS score. The discriminatory performance of the APCS score for various colorectal-related outcomes was assessed using C-statistics. RESULTS In 12,520 individuals, 317 ACN cases and 4,528 adenoma cases were found. The APCS tool successfully classified the study population into different risk groups, and significant differences in the ACN rate and other outcomes were observed. The APCS score demonstrated acceptable discrimination capability with area under the curve values ranging from 0.62 to 0.65 for various outcomes. The results of the multivariate logistic regression model revealed that the high-risk group had a 3.1-fold higher risk of ACN (95% confidence interval, 2.08 to 4.67) than the average-risk group. Body mass index (BMI) was identified as a significant predictor of ACN in both multivariate and subgroup analyses. CONCLUSIONS Our study highlighted significant differences in colorectal-related screening outcomes by colorectal risk level measured using the APCS score, and BMI could be used to improve the discriminatory capability of the APCS score.

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.

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.

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. Conclusion : s BRTO provides better bleeding control, rebleeding-free survival, and OS than TIPS for patients with GV bleeding.

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.

OBJECTIVES Biliary tract cancers (BTCs) are rare but highly fatal. Although the etiology of BTC is poorly understood, gallstones are proposed to be a major risk factor. We conducted a systematic review and meta-analysis to examine the associations between gallstone characteristics and BTC risk. METHODS We searched the MEDLINE, Embase, and Cochrane Central databases and systematically reviewed cohort and case-control studies published before April 9, 2018. All the included studies reported appropriate risk estimates and confidence intervals (CIs) for associations between the presence, size, number, or duration of gallstones and the risk of BTC, including gallbladder cancer (GBC), extrahepatic bile duct cancer (EBDC), and ampulla of Vater cancer (AOVC). Summary odds ratios (ORs) and their 95% CIs were calculated using a random-effects model in the meta-analysis. Subgroup analyses were conducted to inspect sources of potential heterogeneity, and the Egger test was performed to assess publication bias. RESULTS Seven cohort studies and 23 case-control studies in Asian, European, and American populations were included. The presence of gallstones was associated with an increased risk of BTC (OR, 4.38; 95% CI, 3.23 to 5.93; I2=91.2%), GBC (OR, 7.26; 95% CI, 4.33 to 12.18), EBDC (OR, 3.17; 95% CI, 2.24 to 4.50), and AOVC (OR, 3.28; 95% CI, 1.33 to 8.11). Gallstone size (>1 vs.

BackgroundWe 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.MethodsData 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.ResultsApproximately 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).ConclusionThe 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.

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.

Abstract 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.

Abstract 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 (