Evaluation of gene-environment interactions for colorectal cancer susceptibility loci using case-only and case-control designs

Background Genome-wide association studies (GWAS) have identified more than 40 colorectal cancer susceptibility loci, but only a small fraction of heritability was explained. To account for missing heritability, we investigated gene-environment interactions (G × Es) between GWAS-identified single-nucleotide polymorphisms (SNPs) and established risk or protective factors for colorectal cancer using both case-only and case-control study designs. Methods Data on 703 colorectal cancer cases and 1406 healthy controls from the National Cancer Center in Korea were used. We tested interactions between 31 GWAS-identified SNPs and 13 established risk or protective factors for colorectal cancer (family history, body mass index, history of colorectal polyps, inflammatory bowel disease, and diabetes mellitus, alcohol drinking, smoking, regular exercise, regular aspirin use, postmenopausal hormone replace therapy, red meat and processed meat intake, and dairy consumption). Logistic regression models were used to assess G × Es for colorectal cancer risk. Results The SNP rs4444235 at 14q22.2 interacted with regular exercise in colorectal cancer (pcase-only = 2.4 × 10− 3, pcase-control = 1.5 × 10− 3). The risk allele (C) of rs4444235 increased the risk of colorectal cancer in regularly exercising individuals (OR = 1.47, 95% CI = 1.02–2.10) but decreased the risk in non-exercising individuals (OR = 0.76, 95% CI = 0.62–0.94). Furthermore, the G × E between the SNP rs2423279 at 20p12.3 and regular aspirin use was statistically significant (pcase-only = 7.7 × 10− 3, pcase-control = 1.6 × 10− 3). The additive effect of the risk allele (T) of rs2423279 on colorectal cancer risk was increased among regular aspirin users (OR = 4.62, 95% CI = 1.97–10.80). Conclusion Our results suggest that SNP rs4444235 at 14q22.2 and SNP rs2423279 at 20p12.3 may interact with regular exercise and aspirin use in colorectal carcinogenesis.This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2009–0093820, 2010–0010276, 2016R1D1A1B04935872, 2017R1A2B4009233) and by National Cancer Center (NCC) in Korea (0910220, 1210141). The funding bodies have no role in study design, collection, analysis, interpretation of data or writing the manuscript

Population-attributable causes of cancer in Korea : obesity and physical inactivity

Changes in lifestyle including obesity epidemic and reduced physical activity influenced greatly to increase the cancer burden in Korea. The purpose of the current study was to perform a systematic assessment of cancers attributable to obesity and physical inactivity in Korea. Gender- and cancer site-specific population-attributable fractions (PAF) were estimated using the prevalence of overweight and obesity in 1992-1995 from a large-scale prospective cohort study, the prevalence of low physical activity in 1989 from a Korean National Health Examination Survey, and pooled relative risk estimates from Korean epidemiological studies. The overall PAF was then estimated using 2009 national cancer incidence data from the Korea Central Cancer Registry. Excess body weight was responsible for 1,444 (1.5%) and 2,004 (2.2%) cancer cases among men and women, respectively, in 2009 in Korea. Among men, 6.8% of colorectal, 2.9% of pancreatic, and 16.0% of kidney cancer was attributable to excess body weight. In women, 6.6% of colorectal, 3.9% of pancreatic, 18.7% of kidney, 8.2% of postmenopausal breast, and 32.7% of endometrial cancer was attributable to excess body weight. Low leisure-time physical activity accounted for 8.8% of breast cancer, whereas the PAF for overall cancer was low (0.1% in men, 1.4% in women). Projections suggest that cancers attributable to obesity will increase by 40% in men and 16% in women by 2020. With a significantly increasing overweight and physically inactive population, and increasing incidence of breast and colorectal cancers, Korea faces a large cancer burden attributable to these risk factors. Had the obese population of Korea remained stable, a large portion of obesity-related cancers could have been avoided. Efficient cancer prevention programs that aim to reduce obesity- and physical inactivity-related health problems are essential in Korea

Dysbiotic microbiome variation in colorectal cancer patients is linked to lifestyles and metabolic diseases

Abstract Background Differences in the composition and diversity of the gut microbial communities among individuals are influenced by environmental factors. However, there is limited research on factors affecting microbiome variation in colorectal cancer patients, who display lower inter-individual variations than that of healthy individuals. In this study, we examined the association between modifiable factors and the microbiome variation in colorectal cancer patients. Methods A total of 331 colorectal cancer patients who underwent resection surgery at the Department of Surgery, Seoul National University Hospital between October 2017 and August 2019 were included. Fecal samples from colorectal cancer patients were collected prior to the surgery. Variations in the gut microbiome among patients with different lifestyles and metabolic diseases were examined through the network analysis of inter-connected microbial abundance, the assessment of the Anna Karenina principle effect for microbial stochasticity, and the identification of the enriched bacteria using linear discrimination analysis effect size. Associations of dietary diversity with microbiome variation were investigated using the Procrustes analysis. Results We found stronger network connectivity of microbial communities in non-smokers, non-drinkers, obese individuals, hypertensive subjects, and individuals without diabetes than in their counterparts. The Anna Karenina principle effect was found for history of smoking, alcohol consumption, and diabetes (with significantly greater intra-sample similarity index), whereas obesity and hypertension showed the anti-Anna Karenina principle effect (with significantly lower intra-sample similarity index). We found certain bacterial taxa to be significantly enriched in patients of different categories of lifestyles and metabolic diseases using linear discrimination analysis. Diversity of food and nutrient intake did not shape the microbial diversity between individuals (pProcrustes>0.05). Conclusions Our findings suggested an immune dysregulation and a reduced ability of the host and its microbiome in regulating the community composition. History of smoking, alcohol consumption, and diabetes were shown to affect partial individuals in shifting new microbial communities, whereas obesity and history of hypertension appeared to affect majority of individuals and shifted to drastic reductions in microbial compositions. Understanding the contribution of modifiable factors to microbial stochasticity may provide insights into how the microbiome regulates effects of these factors on the health outcomes of colorectal cancer patients.This study was supported by grants from Seoul National University Hospital (No. 0420190530) and the National Research Foundation of Korea (NRF) grant funded by the Korea goverment (MSIT) (No. 2022R1A2C1004608). The funding bodies have no role in study design, collection, analysis, interpretation of data,or writing the manuscript. The authors declare no conficts of interest. Authors Minjung Kim and Aesun Shin had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis

Medicare Part D Plan Optimization: The Need for an Annual Check-Up

Background: Since its inception, Medicare Part D requires beneficiaries to choose from a myriad of insurance plans in order to receive prescription drug coverage. Moreover, each year beneficiaries are confronted with plan cancellations, new plan offerings, changes in existing plan formularies and cost-sharing structure. Objective: This study prospectively examined the relationship between stand-alone prescription drug plan (PDP) costs, subsidy status, and the number of plans offered in California from 2009-2012. Methods: Forty-one community outreach events were held throughout Central/Northern California during the Medicare Part D annual election periods from 2008-2011. In total, 1,578 beneficiaries were assisted, 983 (62.2%) of whom had a PDP. During each intervention, beneficiary subsidy status, cost data for the beneficiary\u27s current plan and lowest cost plan for the upcoming year were recorded from the Medicare website. The percent of beneficiaries that did not need to switch plans to reduce their out-of-pocket (OOP) drug costs was compared to the number of available plans in the subsequent year.Results: On average, 14.3-23.7% of beneficiaries would have been enrolled in the lowest cost plan in the upcoming year had they remained in their current plan. Subsidy recipients were significantly more likely to be in the lowest cost plan each year. The chance of being in the lowest cost plan was significantly negatively correlated to the number of drug plans offered in the subsequent year. Conclusion: Annual Part D plan reexamination is essential to ensure that beneficiaries optimize their prescription medication coverage and minimize their OOP costs

Dietary calcium intake and the risk of colorectal cancer: a case control study

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background High intake of dietary calcium has been thought to be a protective factor against colorectal cancer. To explore the dose-response relationship in the associations between dietary calcium intake and colorectal cancer risk by cancer location, we conducted a case-control study among Korean population, whose dietary calcium intake levels are relatively low. Methods The colorectal cancer cases and controls were recruited from the National Cancer Center in Korea between August 2010 and August 2013. Information on dietary calcium intake was assessed using a semi-quantitative food frequency questionnaire and locations of the colorectal cancers were classified as proximal colon cancer, distal colon cancer, and rectal cancer. Binary and polytomous logistic regression models were used to evaluate the association between dietary calcium intake and risk of colorectal cancer. Results A total of 922 colorectal cancer cases and 2766 controls were included in the final analysis. Compared with the lowest calcium intake quartile, the highest quartile group showed a significantly reduced risk of colorectal cancer in both men and women. (Odds ratio (OR): 0.16, 95 % confidence interval (CI): 0.11–0.24 for men; OR: 0.16, 95 % CI: 0.09–0.29 for women). Among the highest calcium intake groups, decrease in cancer risk was observed across all sub-sites of colorectum in both men and women. Conclusion In conclusion, calcium consumption was inversely related to colorectal cancer risk in Korean population where national average calcium intake level is relatively lower than Western countries. A decreased risk of colorectal cancer by calcium intake was observed in all sub-sites in men and women

Association between sleep duration and metabolic syndrome: a cross-sectional study

Background Both short and long sleep duration have been consistently studied as a risk factor for obesity, hyperglycemia and hypertension. In this cross-sectional study, we provide an updated analysis of the Health Examinees (HEXA) study on the association between sleep duration and metabolic syndrome (MetS) occurrence among Koreans age 40–69 year olds. Methods A total of 133,608 subjects (44,930 men, 88,678 women) were enrolled in the HEXA study 2004–2013. Sleep duration was categorized into 4 sleep categories (< 6 h, 6 to < 8 h, 8 to < 10 h, ≥10 h). MetS criterion was based on the National Cholesterol Education Program, Adult Treatment Panel III. Logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results Compared with individuals sleeping 6 to < 8 h per day, less than 6 h of sleep was associated with MetS (multivariable adjusted OR: 1.12, 95% CI: 1.05–1.19) and elevated waist circumference (1.15, 1.08–1.23) among men; with elevated waist circumference (1.09, 1.04–1.14) among women. Greater than 10 h of sleep was associated with MetS (1.28, 1.08–1.50) and elevated triglycerides (1.33, 1.14–1.56) among men; with MetS (1.40, 1.24–1.58), elevated waist circumference (1.14, 1.02–1.27), elevated triglycerides (1.41, 1.25–1.58), reduced high-density lipoprotein cholesterol (HDL-C) (1.24, 1.12–1.38), and elevated fasting glucose (1.39, 1.23–1.57) among women. Conclusions Less than 6 h of sleep is associated with elevated waist circumference among both men and women and with MetS among men only. Greater than 10 h of sleep is associated with MetS and elevated triglycerides among both men and women and with elevated waist circumference, reduced HDL-C, and elevated fasting glucose among women only.This work was supported by the Research Program funded by the Korea Centers for Disease Control and Prevention [grant number 2004-E71004–00; 2005-E71011–00; 2005-E71009–00; 2006-E71001–00; 2006-E71004–00; 2006-E71010–00; 2006- E71003–00; 2007-E71004–00; 2007-E71006–00; 2008-E71006–00; 2008-E71008–00; 2009-E71009–00; 2010-E71006–00; 2011-E71006–00; 2012-E71001–00; 2013-E71009–00]. This funding source had roles in study design and data collection