Eo Rin Cho

Body mass index and cancer risk in Korean men and women

Obesity is associated with diverse health risks, but the role of body weight (BMI) as a risk factor for all and site‐specific cancers remains controversial and risks for cancer associated with obesity have not been well‐characterized in Asians. Body weight and risk for cancer were examined in a 14‐year prospective cohort study of 1,213,829 Koreans aged 30–95 years insured by the National Health Insurance Corporation who had a biennial medical evaluation in 1992–1995. Incidence rates for all cancers and site‐specific cancers were examined in relation to BMI. Age‐ and smoking‐status adjusted hazard ratios (HR) with 95% confidence intervals (CI) were examined using the Cox proportional hazards model. For both sexes, the average baseline BMI was 23.2 kg/m2, and the association of risk for all‐cancers with BMI was positive. Obese men (BMI ≥ 30 kg/m2) were at increased risk for developing the following cancers: stomach (1.31, 1.05–1.64), colon (1.42, 1.02–1.98), liver (1.63, 1.27–2.10) and gallbladder (1.65, 1.11–2.44). Obese women (BMI ≥ 30 kg/m2) were at increased risk for developing liver cancer (1.39, 1.00–1.94), pancreatic cancer (1.80, 1.14–2.86) and breast cancer among women aged ≥50 years old (1.38, 1.00–1.90). The HRs were comparable in never and ever smokers for all cancers and all specific sites except for lung cancer. For all cancers common to both sexes, the association was significantly weaker (p < 0.01) in females. Our study provides further confirmation of the excess cancer risk associated with obesity. Rising obesity in Asian populations raises concern that increasing numbers of avoidable cancer cases will occur among Asians.

The association between adiponectin and diabetes in the Korean population

As indicators of obesity, waist circumference (WC), body mass index (BMI), and adiponectin are well-known risk factors for diabetes mellitus. The objectives of this study were to measure the independent association between these obesity indicators and diabetes and to examine the combined effect of these indicators on diabetes in a Korean population. The WC, BMI, and serum adiponectin were measured in 4459 healthy Koreans and were classified into tertile groups for men and women. The independent and combined associations of the obesity indicators with diabetes were measured using logistic regression analyses. Diabetes was defined as fasting serum glucose greater than 126 mg/dL or taking medication. Levels of adiponectin were inversely associated with BMI and WC and directly associated with age and high-density lipoprotein (HDL) cholesterol (P < .001). After adjusting for age, BMI, WC, and other lifestyle factors, low levels of adiponectin were associated with an increased prevalence of diabetes. Further adjustment for HDL cholesterol and triglyceride attenuated this association in women but not men. The combined effects of WC and adiponectin on diabetes progressively increased; however, the interaction of these 2 variables was not statistically significant. The combined effect of BMI and adiponectin on diabetes showed similar results. These results suggest that adiponectin was associated with diabetes. The association was independent of BMI and WC and was partly modified by HDL and triglyceride. There were no effect modifications of adiponectin with WC and BMI on diabetes.

Helicobacter pylori blood biomarker for gastric cancer risk in East Asia

BACKGROUND Incidence and mortality rates for gastric cancer, the fifth most commonly diagnosed and third most deadly cancer worldwide, are highest in East Asia. We sought to identify gastric cancer risk biomarkers among eight prospective studies from China, Japan and Korea. METHODS This pooled nested case-control study included 1608 incident non-cardia gastric cancer cases and 1958 matched controls. Pre-diagnostic antibody levels to 15 Helicobacter pylori proteins were assessed using multiplex serology. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Sero-positivity to 10 H. pylori antigens (Omp, CagA, VacA, HcpC, HP 0305, GroEL, NapA, HyuA, Cad, HpaA) was associated with a 1.29- to 3.26-fold increase in odds of gastric cancer. Omp and HP 0305 consistently remained associated with gastric cancer risk after mutually adjusting for all other markers. Sero-positivity to both Omp and HP 0305 was associated with an over 4-fold increase in gastric cancer incidence (OR, 4.09; 95% CI 3.26-5.13). When limited to only those who are CagA+ H. pylori+, Omp/HP 0305 sero-positivity remained strongly associated with an over 3-fold increase in the odds of gastric cancer (OR, 3.34; 95% CI 2.27-4.91). The results were highly consistent among the cohorts. CONCLUSIONS We have confirmed new H. pylori biomarkers that are strongly associated with gastric cancer risk, even among those infected with the known H. pylori virulence factor CagA. These results may help to design cost-efficient prevention strategies to reduce gastric cancer incidence in East Asia.

Dietary patterns and their associations with health behaviours in Korea

OBJECTIVE Dietary habits, including dietary patterns, have been associated with the risk of chronic diseases, including cancer. The objective of the present study was to evaluate Korean dietary patterns as assessed by using an FFQ and associations of dietary patterns with lifestyle risk factors. DESIGN Dietary patterns were analysed by factor analysis using a sixteen-group FFQ. The associations between dietary patterns and lifestyle risk factors were investigated by logistic regression analysis. SETTING The National Cancer Center in South Korea. SUBJECTS The study population included 11 440 participants aged ≥ 30 years who were recruited between 2002 and 2007. RESULTS Compared with the lowest quartile intake of each dietary pattern, current smoking was positively associated with the Western pattern (OR = 1·55 for the highest quartile, 95 % CI 1·27, 1·88; P < 0·001) and the traditional pattern (OR = 1·34, 95 % CI 1·11, 1·62; P = 0·002) in men, but was inversely associated with the healthy pattern in both genders (P < 0·001) and the traditional pattern (OR = 0·52, 95 % CI 0·36, 0·75; P = 0·001) in women. Alcohol consumption was positively associated with all patterns in both genders, while no association was observed with the healthy pattern in women. Physical activity and dietary supplement use were positively associated with all patterns in both genders, with the exception of physical activity in women, which showed an inverse association with the traditional pattern. CONCLUSIONS Dietary patterns are strongly associated with health behaviours. The possible confounding effect of other risk behaviours should be appropriately considered when conducting nutritional epidemiological studies.

Factors associated with use of ultrasonography screening for hepatocellular carcinoma among hepatitis B or C carriers

OBJECTIVES Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important risk factors for hepatocellular carcinoma (HCC). Yet, there have been few studies on adherence to screening recommendations for groups at high risk for HCC. We assessed whether demographic factors or medical conditions affected screening participation among HBV/HCV carriers. METHODS The study population consisted of 15565 men and women who visited the National Cancer Center, Korea between August 2002 and July 2009. A self-administered questionnaire was used to collect information on demographic characteristics, medical history, including chronic HBV and HCV infection, and health check-up history. HBV surface antigen and HCV antibody levels were measured in serum. RESULTS Among 781 HBV carriers, 596 (76.3%) were aware of their infection and 451 (57.8%) had ever been tested by ultrasonography. Among HCV carriers, 49 of 127 (36.6%) were aware of their infection and 61 (48.0%) had ever been tested by ultrasonography. Among HBV carriers, male sex (OR, 1.68; 95% CI, 1.22-2.31), family history of liver disease (OR, 2.04; 95% CI, 1.43-2.90), medical history of hyperlipidemia (OR, 2.70; 95% CI, 1.36-5.33), and awareness of infection status (OR, 4.30; 95% CI, 2.99-6.17) were associated with being tested. Among HCV carriers, awareness of infection (OR, 3.77; 95% CI, 1.72-8.26) was significantly associated with being tested by ultrasonography. CONCLUSION Male sex, family history of liver disease, medical history of hyperlipidemia, and awareness of high risk status were associated with being tested by ultrasonography.

Fruit and Vegetable Consumption, Helicobacter pylori Antibodies, and Gastric Cancer Risk: A Pooled Analysis of Prospective Studies in China, Japan and Korea

Epidemiological findings on the association between fruit and vegetable consumption and gastric cancer risk remain inconsistent. The present analysis included 810 prospectively ascertained non‐cardia gastric cancer cases and 1,160 matched controls from the Helicobacter pylori Biomarker Cohort Consortium, which collected blood samples, demographic, lifestyle, and dietary data at baseline. Conditional logistic regression adjusting for total energy intake, smoking, and H. pylori status, was applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for gastric cancer risk across cohort‐ and sex‐specific quartiles of fruit and vegetable intake. Increasing fruit intake was associated with decreasing risk of non‐cardia gastric cancer (OR = 0.71, 95% CI: 0.52–0.95, p trend = 0.02). Compared to low‐fruit consumers infected with CagA‐positive H. pylori, high‐fruit consumers without evidence of H. pylori antibodies had the lowest odds for gastric cancer incidence (OR = 0.12, 95% CI: 0.06–0.25), whereby the inverse association with high‐fruit consumption was attenuated among individuals infected with CagA‐positive H. pylori (OR = 0.82, 95% CI: 0.66–1.03). To note, the small number of H. pylori negative individuals does influence this finding. We observed a weaker, nondose‐response suggestion of an inverse association of vegetable intake with non‐cardia gastric cancer risk. High fruit intake may play a role in decreasing risk of non‐cardia gastric cancer in Asia.

Association between serum persistent organic pollutants and DNA methylation in Korean adults

Background Exposure to persistent organic pollutants (POPs) has been associated with epigenetic changes such as DNA methylation, which can influence human health. However, the association between POPs and DNA methylation by sex was not shown in previous studies. Objectives We investigated the association between POPs and DNA methylation in men and women using a larger population. Methods A cross‐sectional study was conducted using the data of 444 Koreans (253 men and 191 women). Measurements for sixteen different POPs, including six organochlorine pesticides (OCPs) and ten polychlorinated biphenyls (PCBs) were taken in serum. DNA methylation via Alu and LINE‐1 in peripheral leukocytes was measured by pyrosequencing. To evaluate the association between POPs and DNA methylation, the Pearsons correlation and multiple linear regression analyses were performed. Results Except for PCB52 and PCB101, we found significant inverse associations between p,p’‐DDE, cis‐Heptachlor epoxide, and PCBs and Alu assay in men after adjusting for age, BMI, smoking status, and alcohol consumption (&bgr; = −0.67 for p,p′‐DDE; −0.28 for cis‐Heptachlor epoxide; in the range from −0.43 to −1.60 for PCBs). In women, PCB153 and PCB180 showed statistically significant inverse association with Alu assay (&bgr; = −0.22 for PCB153; −0.22 for PCB180). Except for PCB101, p,p′‐DDE and PCBs were positively associated with LINE‐1 assay in women (&bgr; = 0.48 for p,p′‐DDE; in the range from 0.40–0.89 for PCBs) while p,p′‐DDE, PCB153, and PCB180 showed positive associations with LINE‐1 assay in men (&bgr; = 0.55 for p,p′‐DDE; 0.65 for PCB153; 1.02 for PCB180). Conclusions We found that several POPs were associated with global DNA hypomethylation in the Alu assay for men and global DNA hypermethylation in the LINE‐1 assay for women. HighlightsExposure to POPs has been associated with epigenetic changes such as DNA methylation.We investigated the association between POPs level and DNA methylation.Measurements for 6 OCPs and 10 PCBs were taken in serum.The sum of POPs level was associated to DNA hypomethylation in men.The sum of POPs level was associated to DNA hypermethylation in women.

Effect of obesity on the association between MYL2 (rs3782889) and high-density lipoprotein cholesterol among Korean men.

High-density lipoprotein (HDL) cholesterol levels are associated with a decreased risk of coronary artery disease. Several genome-wide association studies that have examined HDL cholesterol levels have implicated myosin light chain 2 regulatory cardiac slow (MYL2) as a possible causal factor. Herein, the association between the rs3782889 single-nucleotide polymorphism (SNP) in the MYL2 gene and HDL cholesterol levels was tested in the Korean population. A total of 4294 individuals were included in a replication study with MYL2 SNP rs3782889. SNP rs3782889 in the MYL2 gene was associated with mean HDL cholesterol level (effect per allele, −1.055 mg dl−1, P=0.0005). Subjects with the CT/CC genotype had a 1.43-fold (range 1.19–1.73-fold) higher risk of an abnormal HDL cholesterol level (<40 mg dl−1) than subjects with the TT genotype. When analyzed by sex, the MYL2 association was stronger in men than that in women. When analyzed by body mass index (BMI), the MYL2 association was much stronger in male subjects with BMI ⩾26.44 kg m−2 (odds ratio (OR)=2.68; 95% confidence interval (CI)=1.87–3.84; P<0.0001) than that in male subjects with BMI <26.44 kg m−2. When compared with subjects having the TT genotype and BMI <26.44 kg m−2, ORs (95% CI) were 3.30 (2.41–4.50) in subjects having the CT/CC genotype and BMI ⩾26.44 kg m−2 (P for interaction <0.0001). Our results clearly demonstrate that genetic variants in MYL2 influence HDL cholesterol levels in Korean obese male subjects.

Epstein-Barr Virus Antibody Titers Are Not Associated with Gastric Cancer Risk in East Asia.

BackgroundEpstein–Barr virus (EBV)-positive gastric cancers represent a distinct subtype of gastric cancers and account for nearly 10% of the gastric cancer burden, yet risk detection strategies for this cancer subtype are lacking.MethodsWe conducted a nested case–control study where we assayed 4 EBV antigens [viral capsid antigen (VCA), early antigen (EA), Epstein–Barr nuclear antigen (EBNA), and BZLF1-encoded replication activator protein (ZEBRA)] in either sera or plasma from 1447 gastric cancer cases and 1797 controls obtained from seven prospective cohorts representing individuals from the high gastric cancer-risk countries of China, Japan, and Korea.ResultsThe prevalence of EBV sero-positivity was universal with the exception of one sero-negative individual, and the highest titers of the EBV antigens VCA (OR 0.95, 95% CI 0.78–1.17), EBNA (OR 0.88, 95% CI 0.72–1.08), EA (OR 0.97, 95% CI 0.79–1.19), and ZEBRA (OR 0.87, 95% CI 0.71–1.07) were not associated with risk of incident gastric cancer. When we stratified these data by H. pylori status, there was no change in the association.ConclusionsMultiplex serology of the aforementioned EBV antigens in serum may not be a suitable biomarker for predicting gastric cancer risk in East Asian populations.

Abstract 1735: Fruit and vegetable consumption and risk of gastric cancer: a prospective nested case-control study in China, Japan and Korea

Introduction: Epidemiological findings on the association between fruit and vegetable consumption and gastric cancer risk remain inconsistent, resulting in the designation of fruits and vegetables as “probable” and “possible” respectively, but not “convincing”, protective factors. However, intervention studies provide support for the effect of micronutrient supplementation in the prevention of gastric cancer and its precursor lesions, though the effects remain less substantial than for Helicobacter pylori (H. pylori) eradication. Objective: To ascertain the association between fruit and vegetable intake and non-cardia gastric cancer incidence with adjustment for H. pylori within East Asian cohort studies. Methods: The present analysis includes 1970 participants (810 prospectively ascertained non-cardia gastric cancer cases with 1160 matched controls) from 5 cohort studies in the Helicobacter pylori Biomarker Cohort Consortium. These cohorts collected blood samples as well as demographic, lifestyle, and dietary data at baseline. Pre-diagnostic antibody levels to 15 H. pylori proteins were assessed using multiplex serology. Conditional logistic regression, adjusting for total energy intake, smoking, and H. pylori status, was applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for gastric cancer risk across cohort- and sex-specific quartiles of fruit and vegetable intake. Results: Increasing fruit intake was significantly associated with decreasing risk of non-cardia gastric cancer, so that individuals in the highest quartile of fruit consumption had a 29% reduced odds of gastric cancer, compared to individuals in the lowest quartile (OR = 0.71, 95% CI, 0.52-0.95, P for trend = 0.02). Compared to CagA-positive H. pylori low fruit consumers, the strongest inverse association of gastric cancer risk was amongst those high fruit consumers without evidence of H. pylori antibodies (OR = 0.12, 95% CI: 0.06-0.25), whereby the inverse association by increasing fruit consumption was attenuated among individuals infected with CagA-positive H. pylori (OR = 0.82, 95% CI: 0.66-1.03). We observed a weaker, non-dose-response suggestion of an inverse association of vegetable intake with non-cardia gastric cancer risk. Conclusions: To our knowledge, this is the largest prospective study in the high-risk region of East Asia to examine the association of fruit and vegetable consumption with non-cardia gastric cancer risk adjusted for H. pylori. We have found that high fruit intake may play a role in decreasing risk of non-cardia gastric cancer, even after adjustment for H. pylori subtype-specific infection. Funding: R01 CA174853 Citation Format: Tianyi Wang, Hui Cai, Shizuka Sasazuki, Shoichiro Tsugane, Wei Zheng, Eo Rin Cho, Sun Ha Jee, Angelika Michel, Michael Pawlita, Yong-Bing Xiang, Yu-Tang Gao, Xiao-Ou Shu, Weicheng You, Meira Epplein. Fruit and vegetable consumption and risk of gastric cancer: a prospective nested case-control study in China, Japan and Korea. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1735.