Publications by authors named "Sun-Seog Kweon"

185 Publications

Association between Albumin, Total Bilirubin, and Uric Acid Serum Levels and the Risk of Cancer: A Prospective Study in a Korean Population.

Yonsei Med J 2021 Sep;62(9):792-798

Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea.

Purpose: In this prospective study, we evaluated the association between the serum levels of antioxidants uric acid (UA), albumin, and total bilirubin and the risk of cancer in a Korean population.

Materials And Methods: A total of 15882 subjects were followed up for cancer development and cancer-related death. During the follow-up period, 1619 cancer diagnoses and 617 cancer-related deaths were recorded. Cox proportional regression was performed to calculate the hazard ratio (HR) per standard deviation (SD) increment and 95% confidence interval (CI). The model was adjusted for covariates such as the age, sex, smoking, alcohol consumption, physical activity, education level, body mass index, and family history. Sensitivity analyses using the study subjects with physiological serum levels of each indicator were also performed.

Results: UA levels were positively correlated with cancer risk (HR per SD increment 1.04; 95% CI, 1.01-1.09), and albumin levels were inversely associated with the overall cancer risk (HR, 0.92; 95% CI, 0.88-0.96) and cancer-related death (HR, 0.86; 95% CI, 0.80-0.93). Total bilirubin levels were negatively correlated with the risk of cancer-related death (HR, 0.91; 95% CI, 0.83-0.99). By cancer type, UA was positively associated with prostate cancer, total bilirubin was positively associated with liver cancer, and albumin was inversely associated with lung cancer.

Conclusion: The findings of this study support the role of antioxidants in carcinogenesis. Future large-cohort studies are needed to confirm the predictive value of albumin, UA, and total bilirubin levels in each type of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3349/ymj.2021.62.9.792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382725PMC
September 2021

Successful control of COVID-19 outbreak through tracing, testing, and isolation: Lessons learned from the outbreak control efforts made in a metropolitan city of South Korea.

J Infect Public Health 2021 Sep 13;14(9):1151-1154. Epub 2021 Jul 13.

Department of Preventive Medicine, College of Medicine, Chosun University, Gwangju, Republic of Korea; Gwangju Center for Infectious Disease Control and Prevention, Gwangju, Republic of Korea. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jiph.2021.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276554PMC
September 2021

Association between Alcohol Consumption and Serum Cortisol Levels: a Mendelian Randomization Study.

J Korean Med Sci 2021 Aug 2;36(30):e195. Epub 2021 Aug 2.

Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea.

Background: Several studies have reported conflicting results regarding the relationship between alcohol consumption and cortisol levels. However, the causality between alcohol consumption and cortisol levels has not been evaluated.

Methods: This study examined 8,922 participants from the Dong-gu Study. The aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was used as an instrumental variable for alcohol consumption. The association between the genetically predicted alcohol consumption and cortisol level was evaluated with Mendelian randomization (MR) using two-stage least squares regression.

Results: Alcohol consumption was positively associated with the serum cortisol level in both sexes in the observational analysis. In the MR analysis, the genetically predicted alcohol consumption was positively related to the cortisol level in men, with cortisol levels increasing by 0.18 μg/dL per drink per day. However, there was no relationship in women in the MR analysis.

Conclusion: The predicted alcohol consumption according to the ALDH2 rs671 polymorphism was positively related to the cortisol levels, suggesting a causal relationship between alcohol consumption and cortisol levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3346/jkms.2021.36.e195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329388PMC
August 2021

Association between cancer stigma and job loss among cancer survivors.

Psychooncology 2021 Aug 15;30(8):1347-1355. Epub 2021 Apr 15.

Department of Digital Health, SAIHST, Sungkyunkwan University, Seoul, South Korea.

Objective: Previous qualitative studies found cancer stigma was associated with work discrimination and job loss among cancer patients. This study aims to quantify the association between cancer stigma and job loss among cancer survivors.

Methods: For this study, we used the data from a face-to-face cross sectional survey conducted at two cancer hospitals in Seoul and Hwasun in South Korea from October 2017 to March 2018. Cancer stigma was assessed using a validated questionnaire which consists of 12 items in three domains: (a) impossibility of recovery; (b) stereotypes; and (c) discrimination. Multivariable logistic regression was performed to evaluate the association between cancer stigma and job loss adjusting age, sex, marital status, education, job type, residence area, cancer site, stage, comorbidity, time since diagnosis, and self-efficacy.

Results: Among 433 cancer survivors, 24.0% lost their jobs after cancer, and 20.7% experienced discrimination at work. Of total, 21.7% of the survivors agreed that it was difficult to treat cancer regardless of highly developed medical science. Survivors with stigma on impossibility of recovery and stereotypes were 3.10 (95% confidence interval [CI]: [1.76, 5.44]) and 2.10 (95% CI: [1.20, 3.67]) times more likely to lose a job than survivors without cancer stigma. Survivors with discrimination experience at work had 1.98 (95% CI: [1.05, 3.74]) times higher risk of losing a job than survivors without it.

Conclusions: Survivors with cancer stigma were more likely to lose their jobs than survivors without cancer stigma. Considering its social and economic impact on job loss, comprehensive interventions for working cancer survivors as well as public campaigns against cancer stigma would be necessary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pon.5690DOI Listing
August 2021

Association between ALDH2 polymorphism and esophageal cancer risk in South Koreans: a case-control study.

BMC Cancer 2021 Mar 9;21(1):254. Epub 2021 Mar 9.

Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Republic of Korea.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-07993-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941978PMC
March 2021

Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.

Am J Clin Nutr 2021 06;113(6):1490-1502

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.

Objectives: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).

Methods: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.

Results: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.

Conclusions: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqab003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168352PMC
June 2021

Incorporating European GWAS findings improve polygenic risk prediction accuracy of breast cancer among East Asians.

Genet Epidemiol 2021 Jul 19;45(5):471-484. Epub 2021 Mar 19.

Department of Molecular Physiology & Biophysics, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, Tennessee, USA.

Previous genome-wide association studies (GWASs) have been largely focused on European (EUR) populations. However, polygenic risk scores (PRSs) derived from EUR have been shown to perform worse in non-EURs compared with EURs. In this study, we aim to improve PRS prediction in East Asians (EASs). We introduce a rescaled meta-analysis framework to combine both EUR (N = 122,175) and EAS (N = 30,801) GWAS summary statistics. To improve PRS prediction in EASs, we use a scaling factor to up-weight the EAS data, such that the resulting effect size estimates are more relevant to EASs. We then derive PRSs for EAS from the rescaled meta-analysis results of EAS and EUR data. Evaluated in an independent EAS validation data set, this approach increases the prediction liability-adjusted Nagelkerke's pseudo R by 40%, 41%, and 5%, respectively, compared with PRSs derived from an EAS GWAS only, EUR GWAS only, and conventional fixed-effects meta-analysis of EAS and EUR data. The PRS derived from the rescaled meta-analysis approach achieved an area under the receiver operating characteristic curve (AUC) of 0.6059, higher than AUC = 0.5782, 0.5809, 0.6008 for EAS, EUR, and conventional meta-analysis of EAS and EUR. We further compare PRSs constructed by single-nucleotide polymorphisms that have different linkage disequilibrium (LD) scores and minor allele frequencies (MAFs) between EUR and EAS, and observe that lower LD scores or MAF in EAS correspond to poorer PRS performance (AUC = 0.5677, 0.5530, respectively) than higher LD scores or MAF (AUC = 0.589, 0.5993, respectively). We finally build a PRS stratified by LD score differences in EUR and EAS using rescaled meta-analysis, and obtain an AUC of 0.6096, with improvement over other strategies investigated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gepi.22382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372543PMC
July 2021

Squalene epoxidase expression is associated with breast tumor progression and with a poor prognosis in breast cancer.

Oncol Lett 2021 Apr 4;21(4):259. Epub 2021 Feb 4.

Department of Pathology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.

Differentially expressed genes (DEGs) have been previously identified using massive parallel RNA sequencing in matched normal, breast cancer (BC) and nodal metastatic tissues. Squalene epoxidase (SQLE), one of these DEGs, is a key enzyme in cholesterol synthesis. The aim of the present study was to investigate the potential involvement of SQLE in the tumorigenic process of BC and to determine its association with the clinical outcome of BC. SQLE mRNA expression was measured using reverse transcription-quantitative PCR in 10 pairs of ductal carcinoma (DCIS) and BC tissues and their adjacent normal tissues. Immunohistochemical staining of SQLE on tissue microarray was performed in 26 normal breast, 79 DCIS and 198 BC samples. The role of SQLE as a prognostic biomarker in patients with BC has been verified using BreastMark. SQLE mRNA expression was significantly increased in DCIS and BC tissues compared with that in their adjacent normal tissues. High SQLE expression was detected in 0, 48.1 and 40.4% of normal breast, DCIS and BC tissues, respectively. SQLE expression in DCIS and BC tissues was significantly higher than that in normal breast tissues. High SQLE expression was observed in DCIS with higher nuclear grade, comedo-type necrosis and HER2 positivity. High SQLE expression in BC was associated with larger tumor size, nodal metastases, higher stage, HER2 subtype and distant metastatic relapse. High SQLE expression was associated with poor disease-free and overall survival, and independently predicted poor disease-free survival in patients with BC. Following BreastMark analysis, high SQLE mRNA expression in BC was significantly associated with a poor prognosis in the 'all', lymph node negative, lymph node positive, luminal A subtype and luminal B subtype groups. Therefore, SQLE expression may be upregulated during the tumorigenic process of BC, and high SQLE expression may be a useful biomarker for predicting a poor prognosis in patients with BC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2021.12520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882892PMC
April 2021

Causal Effects of Lifetime Smoking on Breast and Colorectal Cancer Risk: Mendelian Randomization Study.

Cancer Epidemiol Biomarkers Prev 2021 05 2;30(5):953-964. Epub 2021 Mar 2.

Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.

Background: Observational evidence has shown that smoking is a risk factor for breast and colorectal cancer. We used Mendelian randomization (MR) to examine causal associations between smoking and risks of breast and colorectal cancer.

Methods: Genome-Wide Association Study summary data were used to identify genetic variants associated with lifetime amount of smoking ( = 126 variants) and ever having smoked regularly ( = 112 variants). Using two-sample MR, we examined these variants in relation to incident breast (122,977 cases/105,974 controls) and colorectal cancer (52,775 cases/45,940 controls).

Results: In inverse-variance weighted models, a genetic predisposition to higher lifetime amount of smoking was positively associated with breast cancer risk [OR per 1-SD increment: 1.13; 95% confidence interval (CI): 1.00-1.26; = 0.04]; although heterogeneity was observed. Similar associations were found for estrogen receptor-positive and estrogen receptor-negative tumors. Higher lifetime amount of smoking was positively associated with colorectal cancer (OR per 1-SD increment, 1.21; 95% CI, 1.04-1.40; = 0.01), colon cancer (OR, 1.31; 95% CI, 1.11-1.55; < 0.01), and rectal cancer (OR, 1.36; 95% CI, 1.07-1.73; = 0.01). Ever having smoked regularly was not associated with risks of breast (OR, 1.01; 95% CI, 0.90-1.14; = 0.85) or colorectal cancer (OR, 0.97; 95% CI, 0.86-1.10; = 0.68).

Conclusions: These findings are consistent with prior observational evidence and support a causal role of higher lifetime smoking amount in the development of breast and colorectal cancer.

Impact: The results from this comprehensive MR analysis indicate that lifetime smoking is a causal risk factor for these common malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-1218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611442PMC
May 2021

Efficacy of an inpatient smoking cessation program at a single regional cancer center: A prospective observational study.

Medicine (Baltimore) 2021 Feb;100(6):e24745

Jeonnam Tobacco Control Center, Chonnam National University Hwasun Hospital, Jeonnam.

Abstract: Smoking is the leading cause of preventable death and a risk factor for cancer, but smoking cessation is difficult even in patients who need hospitalization. This study aimed to investigate the usefulness of an inpatient smoking cessation consultation program and to analyze the clinical factors associated with abstinence. In this observational study, patients received regular counseling for 6 months, and abstinence was objectively assessed via urine and exhaled carbon monoxide testing. Cessation rates were assessed at 4 weeks and 6 months, and clinical characteristics associated with cessation success were investigated. Of the 571 patients referred to participate in the program, 170 (29.8%) were enrolled, and only 2 (1.2%) used smoking cessation drugs in addition to counseling. The smoking cessation rate was 77.6% after 4 weeks and 59.1% after 6 months. The cessation rates were significantly higher in patients with cancer than in those without cancer at both timepoints (63.8% vs 21.9%, P < .001, 53.6% vs 12.5%, P < .001), and they were also higher in the first admission group than in the re-admission group (87.4% vs 74.7%, P = .033, 88.5% vs 76.1%, P = .037). In patients with lung cancer, progression-free survival and overall survival tended to be better in those enrolled in the program (P = .158, P = .183). In conclusion, the inpatient smoking cessation program was associated with a high abstinence rate. Most patients maintained cessation without medication, suggesting that initial admission, along with a cancer diagnosis, can provide enough motivation to abstain from smoking. In addition, the smoking cessation effort showed potential to improve survival during lung cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000024745DOI Listing
February 2021

Increased adiponectin levels are associated with higher radiographic scores in the knee joint, but not in the hand joint.

Sci Rep 2021 01 19;11(1):1842. Epub 2021 Jan 19.

Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School & Hospital, 42 Jebong-ro, Dong-gu, Gwangju, 61469, Republic of Korea.

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 < 0.001), osteophyte (P = 0.003), and joint space narrowing (JSN) scores (P < 0.001) after adjustment for age, sex, BMI, smoking, alcohol consumption, education, and physical activity. In terms of hand joint scores, no association was found between serum adiponectin levels and the total, osteophyte, JSN, subchondral cyst, sclerosis, erosion, or malalignment score after the above-mentioned adjustments. Similarly, subjects with serum adiponectin levels above the median had higher total radiographic scores in the knee joints, but not in the hand joints, after adjustment. An increased serum adiponectin levels was associated with a higher radiographic score in the knee joint, but not in the hand joint, suggesting the involvement of different pathophysiologic mechanisms in the development of OA between those joints.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-81513-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815782PMC
January 2021

Association between ALDH2 and ADH1B Polymorphisms and the Risk for Colorectal Cancer in Koreans.

Cancer Res Treat 2021 Jul 24;53(3):754-762. Epub 2020 Dec 24.

Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea.

Purpose: Excessive alcohol consumption has been linked to an increased risk of colorectal cancer (CRC). We evaluated the association between alcohol-related genetic variants and CRC risk.

Materials And Methods: The study cohort consisted of 5,435 CRC cases and 3,553 population-based cancer-free controls. Genotype data were generated from germline DNA using the Infinium OncoArray-500K BeadChip in 2,535 cases and 2,287 controls and the Infinium Multi-Ethnic Global BeadChip in 2,900 cases and 1,266 controls. The associations between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol dehydrogenase 1B (ADH1B) rs1229984 polymorphisms and CRC risk were assessed using multivariate logistic regression analyses.

Results: Compared with the major homozygous ALDH2 genotype (GG), heterozygous or minor homozygous ALDH2 genotype (GA or AA, related to a low alcohol consumption) was significantly associated with a reduced risk for CRC in men (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.68 to 0.90), but not in women (OR, 0.70; 95% CI, 0.47 to 1.05). A stronger association was found among regular drinkers (OR, 0.58; 95% CI, 0.47 to 0.71 in men and OR, 0.33; 95% CI, 0.18 to 0.58 in women). No association of CRC risk with ADH1B rs1229984 genotype was found. The association between alcohol-related combined genotypes and risk of CRC was significant (p for linear=0.001). The combined genotype with the highest genetically predicted alcohol consumption (ALDH2 rs671 GG and ADH1B rs1229984 AG/GG) was associated with a high risk for CRC (OR, 1.35; 95% CI, 1.11 to 1.63).

Conclusion: Our study provides strong evidence for a possible causal association between alcohol consumption and CRC risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4143/crt.2020.478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291179PMC
July 2021

Low serum 25-hydroxyvitamin D levels, tooth loss, and the prevalence of severe periodontitis in Koreans aged 50 years and older.

J Periodontal Implant Sci 2020 Dec;50(6):368-378

Department of Periodontology, Dental Science Research Institute, Chonnam National University School of Dentistry, Gwangju, Korea.

Purpose: Vitamin D deficiency may cause bone loss and increased inflammation, which are well-known symptoms of periodontal disease. This study investigated whether serum 25-hydroxyvitamin D (25(OH)D) levels are associated with periodontal disease status and tooth loss.

Methods: Cross-sectional data from 5,405 individuals aged ≥50 years (2,253 males and 3,152 females) were obtained from the 2008-2010 Dong-gu study, a prospective cohort study of risk factors for chronic diseases. Periodontal examinations were conducted to evaluate the number of remaining teeth, the periodontal probing depth (PPD), the clinical attachment level (CAL), and bleeding on probing. The percentages of sites with PPD ≥4 mm and CAL ≥4 mm were recorded for each participant. The severity of periodontitis was classified using the Centers for Disease Control and Prevention and the American Academy of Periodontology case definitions. Serum 25(OH)D levels were classified as reflecting severe deficiency, deficiency, insufficiency, or sufficiency. Multivariate linear regression analysis was performed to assess the associations of serum 25(OH)D levels with periodontal parameters and the number of remaining teeth after adjusting for confounders including age, smoking status, alcohol consumption status, month of blood collection, and physical activity. Multivariate logistic regression was used to evaluate the association between serum vitamin D levels and severe periodontitis. An overall statistical analysis and a stratified analysis by sex were performed.

Results: Overall, the rates of severe deficiency, deficiency, insufficiency, and sufficiency were 6.5%, 67.9%, 22.4%, and 3.2%, respectively. After adjustment for confounders, vitamin D levels were directly associated with the number of remaining teeth, an association that was significant in males, but not in females. Sufficient serum 25(OH)D was associated with a low frequency of severe periodontitis.

Conclusions: This population-based cross-sectional study indicates that low serum 25(OH)D is significantly associated with tooth loss and severe periodontitis in Koreans aged 50 years and older.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5051/jpis.2002540127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758301PMC
December 2020

Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study.

BMC Med 2020 12 17;18(1):396. Epub 2020 Dec 17.

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

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/m) 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/m) 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12916-020-01855-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745469PMC
December 2020

A Combined Proteomics and Mendelian Randomization Approach to Investigate the Effects of Aspirin-Targeted Proteins on Colorectal Cancer.

Cancer Epidemiol Biomarkers Prev 2021 03 14;30(3):564-575. Epub 2020 Dec 14.

Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France.

Background: Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk.

Methods: Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL ( = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium ( = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls).

Results: Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03-1.13; OR: 3.33, 95% CI, 2.46-4.50; and OR: 1.15, 95% CI, 1.02-1.29, respectively).

Conclusions: MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin's reduction of metastasis.

Impact: Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-1176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086774PMC
March 2021

Cystatin C-based estimated GFR and albuminuria are independently associated with all-cause and CVD mortality in Korean population: The Dong-gu Study.

Maturitas 2021 Jan 2;143:178-183. Epub 2020 Nov 2.

Department of Preventive Medicine, Chosun University Medical School, 309, Pilmun-daero, Dong-gu, Gwangju, 61452, Republic of Korea. Electronic address:

Objective: To assess the associations among the estimated glomerular filtration rate (eGFR), albumin to creatinine ratio (ACR), and all-cause and CVD mortality rate and to compare the performances of eGFR, eGFR, and eGFR using receiver operating characteristic (ROC) analysis in Korean adults aged ≥ 50 years.

Methods: Of the 9,260 subjects who participated in the baseline survey of a prospective longitudinal study conducted in Korea, 9,009 (men: 3,574 (39.7%); women: 5,435 (60.3%)) were included in this analysis after the exclusion of 217 subjects with missing eGFR and 34 subjects with missing ACR data.

Main Outcome Measure: The associations of eGFR and ACR with all-cause and CVD mortality were investigated using Cox proportional hazards models that included sex, age, waist circumference, smoking, alcohol intake, degree of physical activity, hypertension, diabetes, systolic blood pressure, log-HbA, total cholesterol, log-triglyceride, log-HDL and log-ACR or eGFR.

Results: After adjustment for covariates, independent associations were found between all-cause mortality and the eGFR (mL/min per 1.73 m) [HR 1.23, 95% confidence interval (CI) 1.05-1.43 for 60-89 vs. ≥ 90; HR 1.87, 95% CI 1.49-2.34 for 45-59 vs. ≥ 90; HR 2.38, 95% CI 1.77-3.20 for 30-44 vs. ≥ 90; HR 2.82, 95% CI 1.89-4.23 for <30 vs. ≥ 90] and ACR (μg/mg creatinine) [HR 1.09, 95% CI 0.88-1.34 for Q2 vs. Q1; HR 1.34, 95% CI 1.10-1.63 for Q3 vs. Q1; HR 1.49, 95% CI 1.22-1.81 for Q4 vs. Q1]. In addition, independent associations of CVD mortality with the eGFR and ACR were significant. In the comparison of eGFR performance, the ROC-plot AUC for all-cause mortality was significantly greater for the eGFR than for the eGFR and eGFR.

Conclusion: The eGFR and ACR were associated independently with all-cause and CVD mortality after adjustment for covariates, including the eGFR and ACR. In addition, the ROC-plot AUC for all-cause mortality was greater for the eGFR than for the eGFR and eGFR in Korean adults aged ≥ 50 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.maturitas.2020.10.016DOI Listing
January 2021

A return-to-work intervention protocol directed at cancer patients (self-assessment, tailored information & lifestyle management for returning to work among cancer patients, START): A multi-center, randomized controlled trial.

Contemp Clin Trials Commun 2020 Sep 12;19:100633. Epub 2020 Aug 12.

Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.conctc.2020.100633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451719PMC
September 2020

Association between Polymorphism and Gastric Cancer Risk in a Korean Population.

J Korean Med Sci 2020 May 4;35(17):e148. Epub 2020 May 4.

Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea.

The association between alcohol and gastric cancer is stronger in East Asians than in other ethnic groups, presumably due to an aldehyde dehydrogenase 2 () polymorphism. Therefore, we investigated the relationship between the rs671 polymorphism and gastric cancer in a Korean population. This case-control study included 3,245 hospital patients newly diagnosed with gastric cancer and 8,732 population controls. The rs671 genotype was classified as inactive (GG) or active (GA/AA). The risk of gastric cancer was higher in men with the inactive than in those with active (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.09-1.39), whereas no significant association was found between genotype and gastric cancer in women (OR, 1.00; 95% CI, 0.99-1.02). In men, the association between genotype and gastric cancer was stronger in current drinkers. Our findings support the previously reported association between inactive and high risk of gastric cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3346/jkms.2020.35.e148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200175PMC
May 2020

Effect Modification of Acetaldehyde Dehydrogenase 2 rs671 Polymorphism on the Association between Alcohol Intake and Blood Pressure: the Dong-gu Study.

J Korean Med Sci 2020 Mar 9;35(9):e14. Epub 2020 Mar 9.

Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea.

Background: Elevated blood pressure is a major preventable cause of cardiovascular diseases. Alcohol consumption is a well-known risk factor of elevated blood pressure. The aldehyde dehydrogenase 2 () polymorphism is common in Eastern Asians, and inactive genotypes are associated with both avoiding alcohol consumption and aldehyde accumulation. Therefore, this study assessed the associations between alcohol consumption and hypertension and blood pressure according to the genotypes.

Methods: This study consists of 8,526 participants in the Dong-gu Study. Multivariate logistic regression was used to calculate the odds ratio (OR) according to alcohol consumption after stratifying by gender and genotypes. Multivariate linear regression was performed to estimate the systolic blood pressure (SBP) and diastolic blood pressure (DBP) according to the amount of alcohol consumed.

Results: In men, alcohol consumption was positively associated with both SBP and DBP in active carriers, but not in inactive carriers. In active carriers, compared to non-drinkers, the OR of hypertension was 1.16 (95% confidence interval [CI], 0.91-1.49) for < 1 drink/day, and 1.44 (95% CI, 1.15-1.80) for ≥ 1 drink/day in men. With each 1 drink/day increase, SBP and DBP increased by 3 and 1 mmHg in men, respectively. There was no significant association between genotypes and hypertension and blood pressure in women.

Conclusion: genotype modified the association between alcohol consumption and blood pressure in men. There was a positive relationship between alcohol consumption and blood pressure in active carriers, but no significant relationship in inactive carriers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3346/jkms.2020.35.e14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061145PMC
March 2020

Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants.

Nat Commun 2020 03 5;11(1):1217. Epub 2020 Mar 5.

Departments of Health Research and Policy, School of Medicine, Stanford University, California, CA, USA.

Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-15046-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057957PMC
March 2020

B7-H3 and B7-H4 Expression in Breast Cancer and Their Association with Clinicopathological Variables and T Cell Infiltration.

Pathobiology 2020 21;87(3):179-192. Epub 2020 Feb 21.

Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea,

Objectives: B7-H3 and B7-H4 proteins are expressed in breast cancer tissues, but their relationships with respect to tumor immune surveillance and outcomes in breast cancer are not conclusive.

Methods: We first examined B7-H3 and B7-H4 mRNA expression in the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. Next, mRNA and protein expression were assessed by RNAscope in situ hybridization (ISH) and immunohistochemistry in 10 pairs of breast cancer and matched normal tissues. Immunohistochemical staining of B7-H3, B7-H4, CD3, and CD8 was performed in tissue microarray slides containing 198 breast cancer samples. Association of B7-H3 and B7-H4 expression with survival was verified using the publicly accessible BreastMark tool.

Results: B7-H3 and B7-H4 mRNA expression were significantly higher in breast cancer samples in the TCGA dataset than in normal breast tissues in the GTEx dataset. RNAscope ISH and immunohistochemistry showed that B7-H3 and B7-H4 mRNA and protein appeared to be mainly expressed in cancer cells. Expression of B7-H3 and B7-H4 tended to be associated with low-density scores of stromal tumor-infiltrating lymphocytes (TILs) as well as molecular subtypes. Expressions of B7-H3 and B7-H4 were negatively correlated with stromal CD3+ and CD8+ T cell infiltration density. B7-H3 and B7-H4 expression was not associated with survival, which was verified by BreastMark analysis.

Conclusion: Expression levels of B7-H3 and B7-H4 were independent of clinical outcomes of breast cancer. There was an inverse relationship between the expression of B7-H3 and B7-H4 in breast cancer and the density of stromal TILs and CD8+ T lymphocytes. This inverse relationship may represent a promising target in the field of breast cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000505756DOI Listing
March 2021

Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses.

Gastroenterology 2020 04 27;158(5):1300-1312.e20. Epub 2019 Dec 27.

Department of Cancer Biology and Genetics and the Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.

Background & Aims: Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development.

Methods: Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) RESULTS: After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05-1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03-1.12; P = 3.3 × 10). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06-1.18; P = 4.2 × 10). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2.

Conclusions: In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2019.12.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152801PMC
April 2020

Identification of Novel Loci and New Risk Variant in Known Loci for Colorectal Cancer Risk in East Asians.

Cancer Epidemiol Biomarkers Prev 2020 02 11;29(2):477-486. Epub 2019 Dec 11.

Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.

Background: Risk variants identified so far for colorectal cancer explain only a small proportion of familial risk of this cancer, particularly in Asians.

Methods: We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, including 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 promising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls of European descent. To identify additional risk variants in known colorectal cancer loci, we performed conditional analyses in East Asians.

Results: An indel variant, rs67052019 at 1p13.3, was found to be associated with colorectal cancer risk at × 10 in Asians ( per allele deletion = 1.13, 95% confidence interval = 1.08-1.18). This association was replicated in European descendants using a variant (rs2938616) in complete linkage disequilibrium with rs67052019 ( = 7.7 × 10). Of the remaining 59 variants, 12 showed an association at < 0.05 in the European-ancestry study, including rs11108175 and rs9634162 at < 5 × 10 and two variants with an association near the genome-wide significance level (rs60911071, = 5.8 × 10; rs62558833, = 7.5 × 10) in the combined analyses of Asian- and European-ancestry data. In addition, using data from East Asians, we identified 13 new risk variants at 11 loci reported from previous GWAS.

Conclusions: In this large GWAS, we identified three novel risk loci and two highly suggestive loci for colorectal cancer risk and provided evidence for potential roles of multiple genes and pathways in the etiology of colorectal cancer. In addition, we showed that additional risk variants exist in many colorectal cancer risk loci identified previously.

Impact: Our study provides novel data to improve the understanding of the genetic basis for colorectal cancer risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-19-0755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571256PMC
February 2020

Causes of Death among Persons Affected by Leprosy in Korea, 2010-2013.

Am J Trop Med Hyg 2020 01;102(1):42-47

Department of Preventive Medicine, Chonnam National University, Hwasun-gun, Korea.

In addition to the complications of leprosy, people affected by leprosy (PALs) can suffer from chronic diseases. We evaluated the recent pattern of deaths among Korean PALs and compared it with that in the general population. We analyzed the death certificate data of 1,359 PALs from 2010 through 2013. The all-cause and cause-specific standardized mortality ratio (SMR) and standardized mortality with 95% CI were calculated. Malignancy had the highest standardized mortality, with 130.9 deaths per 100,000 persons, followed by cardiovascular diseases (CVDs; 85.5 deaths) and respiratory diseases (38.2 deaths). Of malignancies, liver cancer caused the greatest number of cancer deaths (40.0 deaths). The all-cause mortality of PALs was significantly lower than that in the general population, corresponding to an SMR of 0.84 (95% CI 0.79-0.88). Deaths from malignancy and CVDs were significantly lower, corresponding to SMRs (95% CIs) of 0.88 (0.79-0.98) and 0.75 (0.67-0.84), respectively. The death rates for lung and stomach cancers were lower, whereas mortality due to liver cancer was higher, with an SMR of 1.79 (95% CI 1.43-2.22). Except for liver cancer and infection, the causes of mortality of PALs tend to be lower than that in the general population. The most common underlying cause of death in PALs was stroke, followed by ischemic heart disease, liver cancer, and pneumonia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4269/ajtmh.19-0401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947775PMC
January 2020

Re-evaluating genetic variants identified in candidate gene studies of breast cancer risk using data from nearly 280,000 women of Asian and European ancestry.

EBioMedicine 2019 Oct 16;48:203-211. Epub 2019 Oct 16.

Department of Epidemiology, Cancer Prevention Institute of California, Fremont, CA, USA; Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.

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 < 2·19 × 10. The associations for four variants reached P < 5 × 10 and have been reported by previous GWAS, including rs6435074 and rs6723097 (CASP8), rs17879961 (CHEK2) and rs2853669 (TERT). The remaining eight variants were rs676387 (HSD17B1), rs762551 (CYP1A2), rs1045485 (CASP8), rs9340799 (ESR1), rs7931342 (CHR11), rs1050450 (GPX1), rs13010627 (CASP10) and rs9344 (CCND1). Further investigating these 10 genes identified associations for two additional variants at P < 5 × 10, including rs4793090 (near HSD17B1), and rs9210 (near CYP1A2), which have not been identified by previous GWAS.

Interpretation: Though most candidate gene variants were not associated with breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants. FUND: National Institutes of Health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2019.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838373PMC
October 2019

The Association between the Apolipoprotein E Gene Polymorphism and All-cause Mortality in the Korean Population.

J Korean Med Sci 2019 Oct 21;34(40):e269. Epub 2019 Oct 21.

Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea.

Background: Apolipoprotein E (APOE) gene polymorphism is associated with neurodegenerative and cardiovascular diseases. Although the effects of the gene differ by ethnic group, few studies have examined Asians. Therefore, the association between APOE polymorphism and mortality in Koreans was evaluated in this study.

Methods: This study population included participants from the Dong-gu and Namwon Studies. genotypes were categorized as E2 (E2/E2 and E2/E3), E3 (E3/E3), and E4 (E3/E4 and E4/E4). Multivariate Cox proportional hazard models were constructed using the E3 allele as a reference.

Results: In the model adjusting for study site, age, gender, and lifestyle, the hazard ratio (HR) of mortality for those with the E4 allele was 1.08 (95% confidence interval [CI], 0.97-1.20), while that for those with the E2 allele was 0.84 (95% CI, 0.74-0.96). After adjusting for blood lipids to evaluate their mediating effects, the HRs of mortality for those with E4 and E2 alleles were 1.08 (95% CI, 0.97-1.20) and 0.80 (95% CI, 0.70-0.92), respectively. These associations were more evident in younger groups, with HRs of 0.70 (95% CI, 0.52-0.92) for the E2 allele and 1.25 (95% CI, 1.03-1.53) for the E4 allele.

Conclusion: In two large population-based cohort studies, the E2 allele was associated with a lower risk of mortality compared with the E3 allele, whereas the E4 genotype was not associated with mortality in Koreans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3346/jkms.2019.34.e269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801224PMC
October 2019

Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women.

Genomics 2020 03 12;112(2):1223-1232. Epub 2019 Jul 12.

Guangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygeno.2019.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954985PMC
March 2020

Non-linear Relationship Between Body Mass Index and Lower Urinary Tract Symptoms in Korean Males.

J Prev Med Public Health 2019 May 29;52(3):147-153. Epub 2019 Mar 29.

Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea.

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: <18.5, 18.5-22.9, 23.0-24.9, 25.0-27.4, 27.5-29.9, and ≥30.0 kg/m2. To evaluate the relationship between BMI and LUTS, a survey-weighted multivariate Poisson regression analysis was performed to estimate prevalence rate ratios (PRRs). Age, smoking status, alcohol intake, physical activity, educational level, household income, and comorbidities were adjusted for in the multivariate model.

Results: A U-shaped relationship was detected between BMI and severe LUTS. Compared with a BMI of 23.0-24.9 kg/m2, the PRR for a BMI <18.5 kg/m2 was 1.65 (95% confidence interval [CI], 1.35 to 2.02), that for a BMI of 18.5-22.9 kg/m2 was 1.25 (95% CI, 1.09 to 1.44), that for a BMI of 25.0-27.4 kg/m2 was 1.20 (95% CI, 1.00 to 1.45), that for a BMI of 27.5-29.9 kg/m2 was 1.11 (95% CI, 0.83 to 1.47), and that for a BMI ≥30.0 kg/m2 was 1.85 (95% CI, 1.18 to 2.88).

Conclusions: This study showed that both high and low BMI were associated with severe LUTS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3961/jpmph.18.259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549014PMC
May 2019

Association of Falls and Fear of Falling with Mortality in Korean Adults: The Dong-gu Study.

Chonnam Med J 2019 May 23;55(2):104-108. Epub 2019 May 23.

Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea.

This study evaluated the association between falls and the fear of falling (FOF) with the risk of all-cause mortality in Korean adults. The study enrolled 4,386 subjects aged 50 years and over who participated in the Dong-gu Study. Falls in the past year were categorized as yes or no. Injurious falls were defined as falls that resulted in fractures, head injuries, sprains or strains, bruising or bleeding, or other unspecified injuries. FOF was classified as low or high. The associations of falls and fall-related characteristics with mortality were assessed using Cox proportional hazards models. The average follow-up was 7.8 years. During this period, 255 men and 146 women died. In a fully adjusted model, falls in the past year were not associated with an increased risk of all-cause mortality (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.85-1.58), but a history of injurious falls was associated with an increased risk of mortality (HR 1.36, 95% CI 1.04-1.79). Compared with subjects without a FOF, subjects who were moderately or very afraid of falling had a higher mortality rate (HR 1.26, 95% CI 0.97-1.63). In conclusion, injurious falls and a high FOF increased the risk of all-cause mortality in Koreans. This study suggests that injurious falls and FOF can predict mortality in the general population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4068/cmj.2019.55.2.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536433PMC
May 2019

Novel Germline Mutations of and in Korean Familial Breast Cancer Patients.

Chonnam Med J 2019 May 23;55(2):99-103. Epub 2019 May 23.

Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea.

Breast cancer is the second most common cancer in Korean women. Germline mutations in the and genes cause hereditary breast cancer and are detected in 15-20% of hereditary breast cancer. We investigated the and mutations in 114 familial breast cancer patients using next-generation sequencing. We confirmed 20 different mutations of and in 25 subjects (21.9%). Two such mutations in eight patients were novel (not reported in any variant database or previous study). Six mutations have been reported as disease-causing mutations in public databases. Seven mutations were found only in a single nucleotide polymorphism database and one mutation has been reported in Korea. The mutation frequency was similar to that of other studies on familial breast cancer patients in the Korean population. Further studies should examine more cases and mutations of whole exons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4068/cmj.2019.55.2.99DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536435PMC
May 2019
-->