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Abstract Observational studies have shown controversial associations between alcohol intake and radiographic osteoarthritis (OA). This study investigated whether this association was causal using a Mendelian randomization (MR) study in a population-based cohort in Korean. The study enrolled 2429 subjects (1058 men, 1371 women) from the Dong-gu Study. X-rays of the hand and knee joints were scored using a semi-quantitative grading system to calculate the total score of the hand and knee joints. ALDH2 rs671 genotyping was performed by high-resolution melting analysis. MR instrumental variable analysis and observational multivariable regression analysis were used to estimate the association between genetically predicted alcohol intake and the radiographic severity of OA. Subjects with the G/G genotype had a higher current alcohol intake than those with the G/A and A/A genotypes in both men and women (all P

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 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 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

Summary: Background: Type 2 diabetes is associated with higher risk of several cancer types. However, the biological intermediates driving this relationship are not fully understood. As novel interventions for treating and managing type 2 diabetes become increasingly available, whether they also disrupt the pathways leading to increased cancer risk is currently unknown. We investigated the effect of a type 2 diabetes intervention, in the form of intentional weight loss, on circulating proteins associated with cancer risk to gain insight into potential mechanisms linking type 2 diabetes and adiposity with cancer development. Methods: Fasting serum samples from participants with diabetes enrolled in the Diabetes Remission Clinical Trial (DiRECT) receiving the Counterweight-Plus weight-loss programme (intervention, N = 117, mean weight-loss 10 kg, 46% diabetes remission) or best-practice care by guidelines (control, N = 143, mean weight-loss 1 kg, 4% diabetes remission) were subject to proteomic analysis using the Olink Oncology-II platform (48% of participants were female; 52% male). To identify proteins which may be altered by the weight-loss intervention, the difference in protein levels between groups at baseline and 1 year was examined using linear regression. Mendelian randomization (MR) was performed to extend these results to evaluate cancer risk and elucidate possible biological mechanisms linking type 2 diabetes and cancer development. MR analyses were conducted using independent datasets, including large cancer meta-analyses, UK Biobank, and FinnGen, to estimate potential causal relationships between proteins modified during intentional weight loss and the risk of colorectal, breast, endometrial, gallbladder, liver, and pancreatic cancers. Findings: Nine proteins were modified by the intervention: glycoprotein Nmb; furin; Wnt inhibitory factor 1; toll-like receptor 3; pancreatic prohormone; erb-b2 receptor tyrosine kinase 2; hepatocyte growth factor; endothelial cell specific molecule 1 and Ret proto-oncogene (Holm corrected P-value

Abstract Background Sedentary behaviours have been associated with increased risks of some common cancers in epidemiological studies; however, it is unclear if these associations are causal. Methods We used univariable and multivariable two‐sample Mendelian randomisation (MR) to examine potential causal relationships between sedentary behaviours and risks of breast, colorectal and prostate cancer. Genetic variants associated with self‐reported leisure television watching and computer use were identified from a recent genome‐wide association study (GWAS). Data related to cancer risk were obtained from cancer GWAS consortia. A series of sensitivity analyses were applied to examine the robustness of the results to the presence of confounding. Results A 1‐standard deviation (SD: 1.5 h/day) increment in hours of television watching increased risk of breast cancer (OR per 1‐SD: 1.15, 95% confidence interval [CI]: 1.05–1.26) and colorectal cancer (OR per 1‐SD: 1.32, 95% CI: 1.16–1.49) while there was little evidence of an association for prostate cancer risk (OR per 1‐SD: 0.94, 95% CI: 0.84–1.06). After adjusting for years of education, the effect estimates for television watching were attenuated (breast cancer, OR per 1‐SD: 1.08, 95% CI: 0.92–1.27; colorectal cancer, OR per 1‐SD: 1.08, 95% CI: 0.90–1.31). Post hoc analyses showed that years of education might have a possible confounding and mediating role in the association between television watching with breast and colorectal cancer. Consistent results were observed for each cancer site according to sex (colorectal cancer), anatomical subsites and cancer subtypes. There was little evidence of associations between genetically predicted computer use and cancer risk. Conclusions Our univariable analysis identified some positive associations between hours of television watching and risks of breast and colorectal cancer. However, further adjustment for additional lifestyle factors especially years of education attenuated these results. Future studies using objective measures of exposure can provide new insights into the possible role of sedentary behaviour in cancer development.

Background: Recognizing the early signs of cancer risk is vital for informing prevention, early detection, and survival. Methods: To investigate whether changes in circulating metabolites characterize the early stages of colorectal cancer (CRC) development, we examined the associations between a genetic risk score (GRS) associated with CRC liability (72 single-nucleotide polymorphisms) and 231 circulating metabolites measured by nuclear magnetic resonance spectroscopy in the Avon Longitudinal Study of Parents and Children (N = 6221). Linear regression models were applied to examine the associations between genetic liability to CRC and circulating metabolites measured in the same individuals at age 8 y, 16 y, 18 y, and 25 y. Results: The GRS for CRC was associated with up to 28% of the circulating metabolites at FDR-P < 0.05 across all time points, particularly with higher fatty acids and very-low- and low-density lipoprotein subclass lipids. Two-sample reverse Mendelian randomization (MR) analyses investigating CRC liability (52,775 cases, 45,940 controls) and metabolites measured in a random subset of UK Biobank participants (N = 118,466, median age 58 y) revealed broadly consistent effect estimates with the GRS analysis. In conventional (forward) MR analyses, genetically predicted polyunsaturated fatty acid concentrations were most strongly associated with higher CRC risk. Conclusions: These analyses suggest that higher genetic liability to CRC can cause early alterations in systemic metabolism and suggest that fatty acids may play an important role in CRC development. Funding: This work was supported by the Elizabeth Blackwell Institute for Health Research, University of Bristol, the Wellcome Trust, the Medical Research Council, Diabetes UK, the University of Bristol NIHR Biomedical Research Centre, and Cancer Research UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work used the computational facilities of the Advanced Computing Research Centre, University of Bristol - http://www.bristol.ac.uk/acrc/.

Objectives This study aimed to evaluate the potential interaction between kidney function and the non-linear association between serum calcium levels and cardiovascular disease (CVD) mortality. Methods This study included 8927 participants enrolled in the Dong-gu Study. Albumin-corrected calcium levels were used and categorized into 6 percentile categories: 97.5th. Restricted cubic spline analysis was used to examine the non-linear association between calcium levels and CVD mortality. Cox proportional hazard regression was used to estimate hazard ratios (HRs) for CVD mortality according to serum calcium categories. All survival analyses were stratified by the estimated glomerular filtration rate. Results Over a follow-up period of 11.9±2.8 years, 1757 participants died, of whom 219 died from CVD. A U-shaped association between serum calcium and CVD mortality was found, and the association was more evident in the low kidney function group. Compared to the 25.0-50.0th percentile group for serum calcium levels, both low and high serum calcium tended to be associated with CVD mortality (97.5th: HR, 2.56; 95% CI, 0.76 to 8.66) in the low kidney function group. In the normal kidney function group, a similar association was found between serum calcium levels and CVD mortality (97.5th: HR, 1.65; 95% CI, 0.70 to 3.93). Conclusions We found a non-linear association between serum calcium levels and CVD mortality, suggesting that calcium dyshomeostasis may contribute to CVD mortality, and kidney function may modify the association.

Abstract Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

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.

Summary: Background: Arterial stiffening is central to the vascular ageing process and a powerful predictor and cause of diverse vascular pathologies and mortality. We investigated age and sex trajectories, regional differences, and global reference values of arterial stiffness as assessed by pulse wave velocity (PWV). Methods: Measurements of brachial-ankle or carotid-femoral PWV (baPWV or cfPWV) in generally healthy participants published in three electronic databases between database inception and August 24th, 2020 were included, either as individual participant-level or summary data received from collaborators (n = 248,196) or by extraction from published reports (n = 274,629). Quality was appraised using the Joanna Briggs Instrument. Variation in PWV was estimated using mixed-effects meta-regression and Generalized Additive Models for Location, Scale, and Shape. Findings: The search yielded 8920 studies, and 167 studies with 509,743 participants from 34 countries were included. PWV depended on age, sex, and country. Global age-standardised means were 12.5 m/s (95% confidence interval: 12.1–12.8 m/s) for baPWV and 7.45 m/s (95% CI: 7.11–7.79 m/s) for cfPWV. Males had higher global levels than females of 0.77 m/s for baPWV (95% CI: 0.75–0.78 m/s) and 0.35 m/s for cfPWV (95% CI: 0.33–0.37 m/s), but sex differences in baPWV diminished with advancing age. Compared to Europe, baPWV was substantially higher in the Asian region (+1.83 m/s, P = 0.0014), whereas cfPWV was higher in the African region (+0.41 m/s, P

Abstract Background While many studies investigated changes in working status in cancer survivors, most studies have been performed in survivors of breast cancer and few studies evaluated factors associated with changes in the working status of cancer survivors comprehensively. We aimed to evaluate the changes in the working status of cancer survivors after diagnosis and socio-demographic, clinical, work-related and psychological factors associated with it. Methods We conducted a cross-sectional survey of adult patients with cancer who were working at the time of diagnosis. A trained interviewer inquired about participants’ current working status, including leave of absence, discontinuing, continuing, and changing work. Sociodemographic, clinical, work-related and psychological factors were measured. Multinomial logistic regression was used to identify factors associated with changes in the working status. Results Among the 730 patients, 29%, 18% and 6% were currently on a discontinued working, leave of absence and had changed jobs, respectively. Patients who discontinued working after cancer diagnosis were more likely to be female, have ≥ $3,000 of monthly family income, not be the principal wage earners for their families and be blue-collar workers. In clinical characteristics, advanced-stage cancer and experienced cancer recurrence was associated with leave of absence and discontinued working. In work-related and psychological factors, stress due to insufficient job control (relative risk ratio [RRR] = 2.26), interpersonal conflict (RRR = 1.86), job insecurity (RRR = 2.63), organizational system (RRR = 3.49), and lack of reward (RRR = 11.76), and less meaning to work were more likely to discontinue working after a cancer diagnosis. Conclusion Occupational health care professionals and other stakeholders need to openly communicate with patients with cancer about potential barriers during the return-to-work trajectory.

OBJECTIVES Elevated C-reactive protein (CRP) levels are associated with an increased risk for colorectal cancer (CRC), as well as a poor prognosis, but it remains unclear whether these associations are causal. This study examined the potential causality between CRP levels and CRC survival using 2-sample Mendelian randomization (MR). METHODS From the Korean Genome and Epidemiology Study, a genome-wide association study (n=59,605), 7 single-nucleotide polymorphisms (SNPs) related to log2-transformed CRP levels were extracted as instrumental variables for CRP levels. The associations between the genetically predicted CRP and CRC-specific and overall mortality among CRC patients (n=6,460) were evaluated by Aalen’s additive hazard model. The sensitivity analysis excluded a SNP related to the blood lipid profile. RESULTS During a median of 8.5 years of follow-up, among 6,460 CRC patients, 2,676 (41.4%) CRC patients died from all causes and 1,622 (25.1%) died from CRC. Genetically predicted CRP levels were not significantly associated with overall or CRC-specific mortality in CRC patients. The hazard difference per 1,000 person-years for overall and CRC-specific mortality per 2-fold increase in CRP levels was -2.92 (95% confidence interval [CI], -14.05 to 8.21) and -0.76 (95% CI, -9.61 to 8.08), respectively. These associations were consistent in a subgroup analysis according to metastasis and a sensitivity analysis excluding possible pleiotropic SNPs. CONCLUSIONS Our findings do not support a causal role for genetically predisposed CRP levels in CRC survival.

Abstract Although the resting heart rate (RHR) predicts the clinical outcomes of cardiovascular disease, chronic obstructive lung disease, diabetes mellitus, and the risk of cancer, its role in patients with musculoskeletal diseases, such as osteoarthritis (OA), remains unclear. We explored the association of the RHR with the extents of radiographic changes in the knees and hands of 2369 subjects from the Dong-gu Study. The radiographic hand and knee joint findings were graded semi-quantitatively; we calculated total hand and knee joint scores. Multiple linear regression was performed to examine the associations between the RHR and the radiographic characteristics of these joints. For the knee joints, the RHR was associated positively with the total (p

The first surge of coronavirus disease 2019 (COVID-19) cases began on June 27, 2020 in Gwangju metropolitan city, located in the southwestern part of South Korea, with a population of 1,501,000. Local governments and the Korean Center for Disease Control and Prevention immediately started an epidemiologic investigation and traced the contacts of patients using a wide variety of data sources, including location data from mobile devices, credit card transaction, and closed-circuit television footage. Until July 16, 2020, 138 community transmission cases and 10 infection clusters were identified across the city. Through contact tracing, epidemiologic relatedness was found in 136 (98.6%) of 138 cases. Our investigation showed how the extensive and meticulous contact tracing suppressed COVID-19 outbreak in a populated city.

OBJECTIVES We evaluated whether the coronavirus disease 2019 (COVID-19) pandemic caused delays in the diagnosis and treatment of colorectal cancer (CRC) in Korea, where there have been no regional or hospital lockdowns during the pandemic period. METHODS Data on CRC patients (n=1,445) diagnosed in Gwangju Metropolitan City and Jeonnam Province between January 2019 and December 2021 were assessed. The stage at the time of CRC diagnosis, route to diagnosis, time to initial cancer treatment, and length of hospital admission were compared before and during the COVID-19 pandemic. Logistic regression was also performed to identify factors associated with the risk for diagnosis in an advanced stage. RESULTS No negative effects indicating a higher CRC stage at diagnosis or delayed treatment during the pandemic were observed. Instead, the risk for an advanced stage at diagnosis (TNM stage III/IV) decreased in CRC patients diagnosed during the pandemic (odds ratio, 0.768; 95% confidence interval, 0.647 to 0.911). No significant differences in the interval from diagnosis to operation or chemotherapy were observed. CONCLUSIONS No negative effects on CRC diagnosis and treatment were found until the end of 2021, which may be related to the small magnitude of the COVID-19 epidemic, the absence of a lockdown policy in Korea, and the rebound in the number of diagnostic colonoscopy procedures in 2021.

Abstract Background Alcohol consumption is a major risk factor for esophageal cancer; however, a high incidence of esophageal cancer is observed particularly among Eastern Asians, although they consume relatively less alcohol, presumably due to the high frequency of aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms. Nevertheless, the association between ALDH2 polymorphisms and esophageal cancer remains under debate. In the present study, we evaluated the association between ALDH2 rs671 polymorphisms and the risk of esophageal cancer in the South Korean population. Methods This study included 783 hospital based-cases and 8732 population-based controls. Information on smoking history and alcohol consumption was obtained from the medical records or interview questionnaires. Age-adjusted logistic regression analysis was performed to assess the association between ALDH2 rs671 polymorphisms and esophageal cancer. Results Odds ratios (ORs) for esophageal cancer in men with GA and AA genotypes were 2.75 (95% confidence interval [CI]: 2.34–3.23) and 0.08 (95% CI: 0.00–0.35), respectively; whereas, in women, these ratios were 2.99 (95% CI: 1.43–6.34) and 6.18 (95% CI: 1.40–19.62), respectively, taking subjects with the ALDH2 GG genotype as a reference. In men, the association between ALDH2 polymorphisms and esophageal cancer was modified by alcohol consumption. Conclusion In Eastern Asians, ALDH2 rs671 polymorphisms are associated with esophageal cancer, which may be linked to acetaldehyde accumulation.

Abstract Several studies have evaluated the association between serum adiponectin levels and knee and hand osteoarthritis (OA); mixed results have been reported. We investigated the relationship between OA and serum adiponectin levels according to the radiographic features of knee and hand OA. A total of 2402 subjects was recruited from the Dong-gu Study. Baseline characteristics were collected via a questionnaire, and X-rays of knee and hand joints were scored using a semi-quantitative grading system. The relationship between serum adiponectin levels and radiographic severity was evaluated by linear and logistic regression analysis. Subjects in the higher serum adiponectin levels tertiles were older and had a lower body mass index (BMI) than those in the lower tertiles. Regarding knee joint scores, serum adiponectin levels was positively associated with the total (P

Abstract Background Higher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adiposity on CRC are not fully understood. Methods We examined sex- and site-specific associations of adiposity with CRC risk and whether adiposity-associated metabolites explain the associations of adiposity with CRC. Genetic variants from genome-wide association studies of body mass index (BMI) and waist-to-hip ratio (WHR, unadjusted for BMI; N = 806,810), and 123 metabolites from targeted nuclear magnetic resonance metabolomics (N = 24,925), were used as instruments. Sex-combined and sex-specific Mendelian randomization (MR) was conducted for BMI and WHR with CRC risk (58,221 cases and 67,694 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry). Sex-combined MR was conducted for BMI and WHR with metabolites, for metabolites with CRC, and for BMI and WHR with CRC adjusted for metabolite classes in multivariable models. Results In sex-specific MR analyses, higher BMI (per 4.2 kg/m2) was associated with 1.23 (95% confidence interval (CI) = 1.08, 1.38) times higher CRC odds among men (inverse-variance-weighted (IVW) model); among women, higher BMI (per 5.2 kg/m2) was associated with 1.09 (95% CI = 0.97, 1.22) times higher CRC odds. WHR (per 0.07 higher) was more strongly associated with CRC risk among women (IVW OR = 1.25, 95% CI = 1.08, 1.43) than men (IVW OR = 1.05, 95% CI = 0.81, 1.36). BMI or WHR was associated with 104/123 metabolites at false discovery rate-corrected P ≤ 0.05; several metabolites were associated with CRC, but not in directions that were consistent with the mediation of positive adiposity-CRC relations. In multivariable MR analyses, associations of BMI and WHR with CRC were not attenuated following adjustment for representative metabolite classes, e.g., the univariable IVW OR for BMI with CRC was 1.12 (95% CI = 1.00, 1.26), and this became 1.11 (95% CI = 0.99, 1.26) when adjusting for cholesterol in low-density lipoprotein particles. Conclusions Our results suggest that higher BMI more greatly raises CRC risk among men, whereas higher WHR more greatly raises CRC risk among women. Adiposity was associated with numerous metabolic alterations, but none of these explained associations between adiposity and CRC. More detailed metabolomic measures are likely needed to clarify the mechanistic pathways.

International migrants could be considered a risk group susceptible to vaccine-preventable diseases. We conducted a measles seroprevalence study among 419 marriage migrant women living in Sinan-gun and Wando-gun, South Jeolla Province, located in the southwestern part of Korea. The overall seroimmunity was 92.8%. The seroimmunity varied considerably according to the country of origin and increased with age. Our current analysis could be valuable in the context of discussions concerning vaccination policies for immigrants in Korea.

In breast cancer, genome-wide associations studies (GWAS) have highlighted loci associated with disease risk. Here, the authors perform a meta-analysis of GWAS data from Asian populations, discovering 31 potential new risk loci, 10 of which are validated in an independent disease cohort.

This study evaluated the associations of liver fibrosis biomarkers [non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 (FIB-4), aspartate aminotransferase/platelet ratio index (APRI), and BARD score] with mortality in Korean adults aged ≥50 years. We analyzed 7,702 subjects who participated in Dong-gu Study. The associations of liber fibrosis biomarkers with mortality were investigated using Cox proportional hazards models. Overall mortality increased with increasing NFS level [adjusted hazard ratio (aHR) 4.3, 95% confidence interval (CI) 3.3–5.5 for high risk vs. low risk], increasing FIB-4 level (aHR 3.5, 95% CI 2.9–4.4 for high risk vs. low risk), and increasing APRI level (aHR 3.5, 95% CI 2.1–5.8 for high risk vs. low risk) but not with BARD score. The Harrell’s concordance index for overall mortality for the NFS and FIB-4 was greater than that for the APRI and BARD score. In conclusion, NFS, FIB-4, and APRI showed a significant relationship with the overall mortality, and NFS and FIB-4 showed a significant relationship with the CVD mortality after adjustment for covariates. In addition, the NFS and FIB-4 were more predictive of overall mortality than the APRI and BARD score in Korean adults aged ≥50 years.

Background: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets. Methods: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets. Findings: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P

Objectives: The purpose of this study was to evaluate the association between body mass index (BMI) and severe lower urinary tract symptoms (LUTS) in Korean males. Methods: This study was conducted on males aged ≥50 years who participated in the 2011 Korean Community Health Survey. LUTS severity was assessed using the Korean version of the International Prostate Symptom Score (IPSS) questionnaire, and was dichotomized as severe (IPSS >19) and non-severe (IPSS ≤19). BMI was divided into 6 categories:

Summary: Homozygotes for the higher penetrance hemochromatosis risk allele, HFE c.845G>A (p.Cys282Tyr, or C282Y), have been reported to be at a 2- to 3-fold increased risk for colorectal cancer (CRC). These results have been reported for small sample size studies with no information about age at diagnosis for CRC. An association with age at diagnosis might alter CRC screening recommendations. We analyzed two large European ancestry datasets to assess the association of HFE genotype with CRC risk and age at CRC diagnosis. The first dataset included 59,733 CRC or advanced adenoma cases and 72,351 controls from a CRC epidemiological study consortium. The second dataset included 13,564 self-reported CRC cases and 2,880,218 controls from the personal genetics company, 23andMe. No association of the common hereditary hemochromatosis (HH) risk genotype and CRC was found in either dataset. The odds ratios (ORs) for the association of CRC and HFE C282Y homozygosity were 1.08 (95% confidence interval [CI], 0.91–1.29; p = 0.4) and 1.01 (95% CI, 0.78–1.31, p = 0.9) in the two cohorts, respectively. Age at CRC diagnosis also did not differ by HFE C282Y/C282Y genotype in either dataset. These results indicate no increased CRC risk in individuals with HH genotypes and suggest that persons with HH risk genotypes can follow population screening recommendations for CRC.

Purpose: This study describes the protocol for the design and evaluation of a self-assessment based educational program supporting cancer patients’ return-to-work (RTW), prior to its complete and ongoing implementation. Methods: We designed a multi-center, randomized controlled trial with three follow-up points. The study population (N = 239) includes recently diagnosed cancer patients who plan to receive active treatment at two university hospitals in Korea. A pre-test is conducted at the point of enrollment for both groups. The intervention group receives a leaflet clarifying misconceptions about RTW and is shown a video clip of patient interviews concerning RTW. The control group receives a booklet about cancer and nutrition, and is not provided with further intervention. After active treatment, the intervention group receives a one-time, face-to-face education session with an oncology nurse. Following the education session, both groups receive three follow-up phone calls. The first follow-up call occurs at the end of intervention and at the end of active treatment for intervention and control groups, respectively. The next two follow-up calls will be conducted one month and a year following the post-test. The primary outcome is whether the patient has RTW or has plans to RTW, and the secondary outcome is knowledge of RTW. Results: As of April 2020, 239 patients have been enrolled in the trial. Statistical analyses will be conducted upon trial completion in December 2020. Discussion: We hypothesize that the provision of RTW education near diagnosis will not only enhance patients’ intentions to RTW, but also effectively encourage them to RTW.

Salicylic acid (SA) has observationally been shown to decrease colorectal cancer (CRC) risk. Aspirin (acetylsalicylic acid, that rapidly deacetylates to SA) is an effective primary and secondary chemopreventive agent. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, stratifying by aspirin use. A two-sample MR analysis was performed using GWAS summary statistics of SA (INTERVAL and EPIC-Norfolk, N = 14,149) and CRC (CCFR, CORECT, GECCO and UK Biobank, 55,168 cases and 65,160 controls). The DACHS study (4410 cases and 3441 controls) was used for replication and stratification of aspirin-use. SNPs proxying SA were selected via three methods: (1) functional SNPs that influence the activity of aspirin-metabolising enzymes; (2) pathway SNPs present in enzymes’ coding regions; and (3) genome-wide significant SNPs. We found no association between functional SNPs and SA levels. The pathway and genome-wide SNPs showed no association between SA and CRC risk (OR: 1.03, 95% CI: 0.84–1.27 and OR: 1.08, 95% CI: 0.86–1.34, respectively). Results remained unchanged upon aspirin use stratification. We found little evidence to suggest that an SD increase in genetically predicted SA protects against CRC risk in the general population and upon stratification by aspirin use.

Background: The aim of this study was to evaluate whether stage at cancer diagnosis differed according to patient economic status. Methods: A total of 10,528 patients with cancer of the stomach, colorectum, breast, or cervix, which are target organs of the Korean National Cancer Screening Program (NCSP; fully implemented in 2005) were extracted from population-based cancer registries. The patients were classified into four groups based on socioeconomic status (SES), as determined using their National Health Insurance (NHI) monthly premium at the time of cancer diagnosis. Cancer stage at diagnosis was defined as early (in situ/local) or late stage (regional/distant) based on the Surveillance, Epidemiology, and End Results (SEER) summary stage. Multivariable logistic regression analysis was performed to estimate the risk of non-local stage using age, residential area, and community deprivation index as covariates. Results: The lowest SES subjects showed significantly higher risks of being diagnosed at a later stage for stomach, colorectal, and female breast cancer, but not for cervical cancer, compared with the highest SES subjects. The estimated ORs were 1.28 (95% CI, 1.10–1.49), 1.29 (95% CI, 1.03–1.61), and 1.35 (95% CI, 1.02–1.81) in the lowest SES subjects with stomach, colorectal, and breast cancer, respectively. Conclusions: In conclusion, later stage diagnoses of stomach, colon, and female breast cancer are still associated with SES in Korea in the era of the NCSP for the lower SES population.

This study aimed to identify clinical or microbiological factors affecting the clinical relevance of Corynebacterium striatum isolated from blood cultures. A total of 64 isolates from 51 patients identified as C. striatum by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing were assessed. More than two blood cultures were positive in 25 (48.1%) patients. Diabetes, solid tumor, and a history of previous exposure to antibiotics were more common in patients with multiple positive blood cultures. Charlson comorbidity scores were also higher, and more isolates were recovered after 48 hours of hospital stay in patients with multiple positive blood cultures. Strains recovered from patients with multiple positive blood cultures produced significantly more biofilm. Based on multilocus sequence typing (MLST), sequence type (ST) 20 (31.3%) was the most dominant, followed by ST2 (20.3%) and ST23 (10.9%). There was no relationship between the number of positive blood culture sets and sequence typing. In multivariate analyses, Carlson comorbidity score (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.09-3.36; P = 0.03) and biofilm formation were associated with multiple positive blood cultures (OR, 17.43; 95% CI, 3.71-81.91; P = 0.03). This study provides evidence that the biofilm phenotype could contribute to determining the clinical significance of C. striatum in patients with severe underlying conditions. The predominance of certain STs suggests the relatedness of C. striatum infection and the nosocomial environment.

We assessed whether grip strength was related to various types of radiographic damage in Korean adults with osteoarthritis (OA).Data from 2,251 subjects enrolled in the Dong-gu study, who had no hand joint pain, were analyzed to investigate the relationship between grip strength and OA. Hand grip strength was measured using a hand-held dynamometer, and radiographs of the hand and knee were scored according to a semi-quantitative grading system. Multiple linear regressions were used to explore associations between grip strength and radiographic features of OA.Grip strength in men and women was negatively related to hand (both p < 0.001) and knee (men, p < 0.001; women, p = 0.010) OA after adjusting for confounders. Hand (men, p < 0.001; women, p = 0.001) and knee (both p < 0.001) joint space narrowing (JSN) showed the strongest associations with low grip strength, regardless of gender. Moreover, the severity of hand osteophytes in women (p = 0.001), and subchondral cysts (men, p < 0.001) was correlated with low grip strength in both genders.Among subjects without hand joint pain, low grip strength was associated significantly with hand and knee radiographic OA, regardless of gender. Among all types of OA radiographic damage, low grip strength showed the strongest association with JSN.

Laterally spreading colorectal tumors (LSTs) are divided into four subtypes, including homogenous (HG), nodular mixed (NM), flat elevated (FE), and pseudo-depressed (PD), based on their different endoscopic morphologies. The aim of this study was to investigate the clinicopathological significance of LST subtypes and their association with advanced histology.We investigated the medical records of consecutive patients with LST who initially underwent endoscopic resection at five university hospitals in Honam province of South Korea between January 2012 and December 2013. A total of 566LST lesions removed via endoscopic procedures were collected retrospectively for data analysis.The PD, FE, and NM subtypes were more common in the distal colon and the HG subtype in the proximal colon. The PD subtype had the biggest tumor size, followed by the NM subtype. The frequency of adenomatous pit pattern was significantly higher in the HG, NM, and FE subtypes than in the PD subtype. In contrast, the frequency of cancerous pit pattern was significantly higher in the PD subtype than in the other three subtypes. The rate of advanced histology (high-grade dysplasia or carcinoma) among the LSTs was 36.0%. The risk of advanced histology increased in the distal colon compared with the proximal colon. The PD subtype had the highest incidence of villous component, advanced histology,submucosal invasion, and postprocedure perforation among the four subtypes. The distal colon as tumor site, larger tumor size, PD subtype, and villous component were associated with a statistically significant increased risk of advanced histology.Our results indicate that the location, size, endoscopic subtype, and histologic component of the LSTs are associated with an increased risk of advanced histology. Therefore, these clinicopathological parameters may be useful in selecting therapeutic strategies in the clinical setting.

Although previous studies reported an association between serum vitamin D and parathyroid hormone (PTH) with carotid atherosclerosis or arterial stiffness, these were inconsistent. We examined the independent association between serum vitamin D and PTH with multiple subclinical markers of atherosclerosis.A total of 8,217 subjects who participated in the Dong-gu Study in Korea were included in the final analysis. The carotid artery structure, including intima-media thickness (IMT), plaques, and luminal diameter, was evaluated using a high-resolution B-mode ultrasound. The brachial-ankle pulse wave velocity (baPWV) was determined using an automatic waveform analysis device, and the mean of the left and right baPWV was used.The PTH concentration was positively associated with carotid luminal diameter and baPWV, but not with carotid IMT and plaques. The mean carotid luminal diameter of individuals with PTH levels in the second, third, and fourth quartiles was significantly larger compared with those in the first quartile (P-trend < 0.01). The mean baPWV of individuals with PTH levels in the fourth quartile was significantly greater than those with PTH levels in the first quartile (P-trend = 0.01). However, there was no significant association between vitamin D and any atherosclerotic phenotypes, including carotid IMT, plaques, luminal diameter, and baPWV.This suggests that PTH might affect the development of atherosclerosis by altering vascular compliance.

Background: Kidney dysfunction and albuminuria may be associated with BMD. However, little evidence has been reported on relationships between BMD and eGFR and albuminuria. Methods: A total of 8,992 subjects aged 50 years or older participated in a survey conducted. Participants had their lumbar spine and femoral neck BMD measured by a Lunar Prodigy bone densitometer (GE, Madison, WI). Kidney function was assessed using MDRD eGFR and diagnosis of albuminuria was based on albumin-creatinine ratio. Results: ACR was negatively associated with lumbar spine and femur neck BMD in females (lumbar spine: 1.001, 0.988, 0.974 and 0.979 g/cm2, p 2, p = 0.002), but not in males, after adjusting for covariates. Additionally, eGFR was shown to be negatively associated with lumbar spine BMD after adjusting for covariates (male: 1.181, 1.166, 1.152 and 1.149 g/cm2, p = 0.001; female: 0.997, 0.980, 0.979 and 0.982 g/cm2, p = 0.005), but demonstrated no association with femur BMD. Conclusions: ACR in females was negatively associated with lumbar spine and femur neck BMD, but not in males. eGFR was negatively associated with lumbar spine BMD in both males and females.

In type 2 diabetic patients, the relationships between 25-hydroxyvitamin D and parathyroid hormone levels, and glycemic control, remain unclear. We evaluated associations between 25-hydroxyvitamin D, parathyroid hormone, and hemoglobin A1c levels after adjusting for other covariates, including log transformed 25-hydroxyvitamin D levels and log transformed parathyroid hormone levels, in Korean patients with type 2 diabetes. In total, 1,175 patients with type 2 diabetes were selected from 8,857 individuals who completed the baseline survey of the Dong-gu study, conducted in Korea from 2007 to 2010. After adjusting for other covariates, we found that the mean hemoglobin A1c level was inversely associated with the 25-hydroxyvitamin D level (Q1: 7.47% [7.30-7.63], Q2: 7.25% [7.09-7.40], Q3: 7.17% [7.02-7.32], Q4: 7.19% [7.02-7.35]; p for trend = 0.021, p for between groups = 0.050) and the parathyroid hormone level (Q1: 7.35% [7.19-7.51], Q2: 7.34% [7.19-7.50], Q3: 7.28% [7.13-7.43], Q4: 7.09% [6.94-7.24]; p for trend = 0.022, p for between groups = 0.048). However, the mean fasting glucose level was not associated with either the 25-hydroxyvitamin D or parathyroid hormone level. In conclusion, inverse associations were evident between hemoglobin A1c, 25-hydroxyvitamin D and parathyroid hormone levels in Korean patients with type 2 diabetes. The associations remained significant after adjusting for other covariates, including the log transformed 25-hydroxyvitamin D levels and log transformed parathyroid hormone levels.

Acute kidney injury (AKI) is common after gastric surgery for gastric cancer and associated with adverse outcomes. However, the impact of transient or persistent AKI on clinical outcomes after gastric surgery for gastric cancer has not been described. We performed a retrospective study of 4,886 patients with normal renal function who underwent partial or total gastrectomy for gastric cancer between June 2002 and December 2012. AKI patients were classified as transient and persistent AKI based on the return of serum creatinine to the level indicating no AKI within 7 days. Our outcomes included occurrence of new-onset chronic kidney disease (CKD) and mortality 1 year after gastric surgery. AKI occurred in 638 (13.1%) after gastric surgery. Transient AKI was documented in 574 (90%). Use of diuretics and contrast agents was a common risk factor for persistent and transient AKI. Length of intensive care unit (ICU) and hospital stay, and ICU admission rate were higher in patients with transient AKI than in those without AKI. Although patients with persistent AKI had a higher new-onset CKD 1 year after gastric surgery after adjusting for multiple covariates, transient AKI was not associated with new-onset CKD. The 1-year mortality rates were significantly higher in patients with transient and persistent AKI. Not only persistent AKI but transient AKI is associated with increased risk of hospital complications and a significantly higher risk of long-term mortality than patients without AKI after gastric surgery. Moreover, persistent AKI, but not transient AKI, is associated with CKD progression at 1 year.

BACKGROUND: Postoperative acute kidney injury (AKI), a serious surgical complication, is common after cardiac surgery; however, reports on AKI after noncardiac surgery are limited. We sought to determine the incidence and predictive factors of AKI after gastric surgery for gastric cancer and its effects on the clinical outcomes. METHODS: We conducted a retrospective study of 4718 patients with normal renal function who underwent partial or total gastrectomy for gastric cancer between June 2002 and December 2011. Postoperative AKI was defined by serum creatinine change, as per the Kidney Disease Improving Global Outcomes guideline. RESULTS: Of the 4718 patients, 679 (14.4%) developed AKI. Length of hospital stay, intensive care unit admission rates, and in-hospital mortality rate (3.5% versus 0.2%) were significantly higher in patients with AKI than in those without. AKI was also associated with requirement of renal replacement therapy. Multivariate analysis revealed that male gender; hypertension; chronic obstructive pulmonary disease; hypoalbuminemia (

This study assessed the impact of distancing measures during the COVID-19 pandemic on cancer diagnostic activities, including gastrointestinal endoscopy (GIE). It analyzed GIE volumes from 2020 to 2022 in comparison to 2018-2019, considering variations in resilience linked to socioeconomic status (SES). The analysis utilized data from the Korean Health Insurance Review and Assessment Services database, covering the entire population and medical facilities. Diagnostic GIE rates (2018-2022) in Gwangju Metropolitan City and Jeonnam province were examined, comparing age-standardized rates (ASRs) by area, gender, and SES. The results indicated a decline in ASRs for colonoscopy and endoscopic gastroduodenoscopy (EGD) in 2020 compared to 2018-2019, followed by an increase in 2021-2022, except for EGD in the medical aid population. SES based and rural-urban disparities were evident in the recovery of GIE rates. The findings suggest that equity-focused strategies are needed to ensure equitable healthcare access among different socioeconomic groups after pandemic. [ABSTRACT FROM AUTHOR]

Background: Sedentary behaviours have been associated with increased risks of some common cancers in epidemiological studies; however, it is unclear if these associations are causal. Methods: We used univariable and multivariable two-sample Mendelian randomisation (MR) to examine potential causal relationships between sedentary behaviours and risks of breast, colorectal and prostate cancer. Genetic variants associated with self-reported leisure television watching and computer use were identified from a recent genome-wide association study (GWAS). Data related to cancer risk were obtained from cancer GWAS consortia. A series of sensitivity analyses were applied to examine the robustness of the results to the presence of confounding. Results: A 1-standard deviation (SD: 1.5h/day) increment in hours of television watching increased risk of breast cancer (OR per 1-SD: 1.15, 95% confidence interval [CI]: 1.05–1.26) and colorectal cancer (OR per 1-SD: 1.32, 95% CI: 1.16– 1.49) while there was little evidence of an association for prostate cancer risk (OR per 1-SD: 0.94, 95% CI: 0.84–1.06). After adjusting for years of education, the effect estimates for television watching were attenuated (breast cancer, OR per 1-SD: 1.08, 95% CI: 0.92–1.27; colorectal cancer, OR per 1-SD: 1.08, 95% CI: 0.90–1.31). Post hoc analyses showed that years of education might have a possible confounding and mediating role in the association between television watching with breast and colorectal cancer. Consistent results were observed for each cancer site according to sex (colorectal cancer), anatomical subsites and cancer subtypes. There was little evidence of associations between genetically predicted computer use and cancer risk. Conclusions: Our univariable analysis identified some positive associations between hours of television watching and risks of breast and colorectal cancer. However, further adjustment for additional lifestyle factors especially years of education attenuated these results. Future studies using objective measures of exposure can provide new insights into the possible role of sedentary behaviour in cancer development. [ABSTRACT FROM AUTHOR]