Genome-Wide Interaction Study of Dietary Intake and Colorectal Cancer Risk in the UK Biobank.

Importance: Candidate gene analysis approaches have shown that colorectal cancer (CRC) risk attributable to diet may differ according to genotype. A genome-wide approach further allows for the exploration of underlying pathways for associations between diet and CRC risk across the genome. Objectives: To identify genetic variants that modify diet-CRC associations and to further explore the underlying pathways in the cause of CRC. Design, Setting, and Participants: This nested case-control study used data on White British participants from the prospective cohort UK Biobank. Participants were recruited between March 13, 2006, and October 1, 2010, and data were censored June 25, 2021. Exposures: The average frequency intake of 11 dietary factors in the year preceding baseline was obtained via a touchscreen questionnaire. After quality control for more than 93 million variants of imputed genetic data, 4 122 345 variants remained. Main Outcomes and Measures: Colorectal cancer cases were identified according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Genome-wide interaction analysis was performed to test interactions between dietary factors and variants using a conditional logistic regression model. Summary statistics of interactions at the variant level were used to calculate empirical P values for interactions at gene and gene-set levels in gene-based and gene-set enrichment analyses. Results: A total of 4686 participants with CRC (mean [SD] age, 60.7 [6.6] years; 2707 men [57.8%]) received a new diagnosis during a median of 12.4 years (IQR, 11.6-13.1 years) of follow-up. Once a case was detected, 3 matched controls were identified, for a total of 14 058 controls (mean [SD] age, 60.4 [6.6] years; 8121 men [57.8%]). A total of 324 variants were identified that interacted with diet consumption at the suggestive threshold (P < 1 × 10-5). In gene-based analysis, aggregation of multiple EPDR1 gene variants was found to interact with fish intake regarding CRC risk. Furthermore, gene-set enrichment analysis found that several sets of protein-coding genes, which were overrepresented with particular functions and pathways, interacted with the consumption of milk (ART), cheese (OR), tea (KRT), and alcohol (PRM and TNP). Conclusions and Relevance: In this nested case-control study, the risk of CRC associated with fish intake was modified by multiple single-nucleotide polymorphisms of the EPDR1 gene. The findings further suggested possible functions and pathways that might link the consumption of milk, cheese, tea, and alcohol with CRC development.

Interaction between vitamin E intake and a COMT gene variant on colorectal cancer risk among Korean adults: a case-control study.

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

Coffee consumption and its interaction with the genetic variant AhR rs2066853 in colorectal cancer risk: a case-control study in Korea.

The bioactive compounds in coffee have several antioxidant properties that may beneficially impact colorectal cancer (CRC) development. The aryl hydrocarbon receptor (AhR) is an important transcription factor that regulates an enzyme related to the caffeine metabolism pathway. We investigated the modification effect on coffee of AhR gene polymorphism in the risk of CRC. A case-control study was conducted with 699 cases and 1393 controls to investigate the interaction between coffee intake and the AhR rs2066853 variant in CRC risk. The odds ratios (ORs) and 95% confidence intervals (CIs) were assessed using multiple logistic regression analyses. We observed a significant protective effect of coffee against CRC in the overall and male populations. Consuming three or more cups of coffee per day may significantly lower CRC risk in all subjects by 77% and in men by 83% (OR = 0.23, 95% CI: 0.14-0.39 and OR = 0.17, 95% CI: 0.09-0.34, respectively, P-trends < 0.001). No association between AhR rs2066853 and CRC risk was found. In the dominant model, the G/G genotype had a strongest synergistic effect with coffee on protection against CRC (OR = 0.12, 95% CI: 0.06-0.26, P-interaction = 0.014). The interaction remained significant in men and the distal colon cancer subgroup. In the additive model, the interaction was clearly shown strongest in G/G carriers (OR = 0.12, 95% CI: 0.06-0.27, P-interaction = 0.039), followed by A/A and G/A carriers. The interaction remained significant in men and the rectal cancer subgroup. In conclusion, the protective effect of coffee on CRC risk might interact with the genetic variant AhR rs2066853, and this joint effect was determined by sex and site-specific cancer.

Coffee and tea consumption and mortality from all causes, cardiovascular disease and cancer: a pooled analysis of prospective studies from the Asia Cohort Consortium.

BACKGROUND: Accumulating evidence suggests that consuming coffee may lower the risk of death, but evidence regarding tea consumption in Asians is limited. We examined the association between coffee and tea consumption and mortality in Asian populations. METHODS: We used data from 12 prospective cohort studies including 248 050 men and 280 454 women from the Asia Cohort Consortium conducted in China, Japan, Korea and Singapore. We estimated the study-specific association of coffee, green tea and black tea consumption with mortality using Cox proportional-hazards regression models and the pooled study-specific hazard ratios (HRs) using a random-effects model. RESULTS: In total, 94 744 deaths were identified during the follow-up, which ranged from an average of 6.5 to 22.7 years. Compared with coffee non-drinkers, men and women who drank at least five cups of coffee per day had a 24% [95% confidence interval (CI) 17%, 29%] and a 28% (95% CI 19%, 37%) lower risk of all-cause mortality, respectively. Similarly, we found inverse associations for coffee consumption with cardiovascular disease (CVD)-specific and cancer-specific mortality among both men and women. Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption. CONCLUSIONS: In Asian populations, coffee consumption is associated with a lower risk of death overall and with lower risks of death from CVD and cancer. Green tea consumption is associated with lower risks of death from all causes and CVD.

Effect of chemotherapy and radiotherapy on cognitive impairment in colorectal cancer: evidence from Korean National Health Insurance Database Cohort.

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

Effects of menopausal hormone therapy on cardiovascular diseases and type 2 diabetes in middle-aged postmenopausal women: analysis of the Korea National Health Insurance Service Database.

OBJECTIVE: Although menopausal hormone therapy (MHT) is the most effective treatment for menopausal symptoms, menopausal women hesitate to start MHT due to concerns about adverse events. Recently, however, it has been recommended to use it for appropriate patients who have been evaluated for baseline diseases, age, and timing of initiation. We aimed to investigate the association of MHT with cardiovascular diseases (CVDs) and type 2 diabetes among middle-aged postmenopausal women in Korea. METHODS: Data were collected from the National Health Insurance Service database in Korea from 2002 to 2016. A total of 58,060 postmenopausal women (including 8,013 [13.8%] MHT users and 50,047 [86.2%] nonusers) were included. The time-dependent Cox regression model with a 1-year latency period was used to evaluate the hazard ratio (HR) and 95% confidence interval (CI) of the associations of MHT with CVDs and type 2 diabetes outcomes. Subgroup analyses by regimen type and cumulative duration were conducted. RESULTS: In the multivariate-adjusted model, MHT was not significantly associated with CVDs (HR = 1.085, 95% CI: 0.899-1.310) or type 2 diabetes (HR = 1.104, 95% CI: 0.998-1.221). Differential effects were not observed by regimen type, cumulative duration, and years since menopause subgroups. Sensitivity analyses also did not show adverse events by MHT on CVDs and type 2 diabetes. CONCLUSIONS: Although protective effects of MHT against CVDs or type 2 diabetes were not observed among postmenopausal women who had screened underlying diseases, our results may contribute to reducing the current concerns about the use of MHT for middle-aged postmenopausal women in Korea.

Video Summary:http://links.lww.com/MENO/A807 .

The Association between Coffee Consumption and Risk of Colorectal Cancer in a Korean Population.

This study was performed to investigate the association between coffee consumption and risk of colorectal cancer in a Korean population and examine whether the association can be altered by adjustment for intake of coffee additives. We conducted a case-control study involving 923 colorectal cancer cases and 1846 controls matched by sex and age (within 5 years). A semi-quantitative food frequency questionnaire was used to assess coffee intakes. High coffee consumption was associated with lower odds of developing colorectal cancer (≥3 cups/day vs. no drinks, OR = 0.68; 95% CI: 0.49-0.96). When we additionally controlled for consumption of coffee additives including sugar and cream, the inverse association became stronger (≥3 cups/day vs. no drinks, OR = 0.22; 95% CI: 0.14-0.33), and a significant inverse linear trend was shown (Ptrend < 0.0001). The inverse associations were observed for proximal (Ptrend = 0.0001) and distal (Ptrend = 0.0003) colon cancer, and rectal cancer (Ptrend < 0.0001) in the stratified analysis by anatomical sub-sites. Regarding sex, inverse associations between coffee consumption and colorectal cancer were found for men (Ptrend < 0.0001) and women (Ptrend = 0.0021). In the stratified analysis by obese status of subjects, inverse linear trends were observed in both non-obese and obese people (Ptrend < 0.0001). High coffee consumption may be associated with a lower risk of colorectal cancer in the Korean population and the degree of decrease in the odds of developing colorectal cancer changes by adjustment for intake of coffee additives.

Omega-3 and -6 Fatty Acid Intake and Colorectal Cancer Risk in Swedish Women's Lifestyle and Health Cohort.

PURPOSE: We aimed to assess the association between the dietary intake of fish-derived omega-3 polyunsaturated fatty acids and the risk of colorectal cancer among Swedish women. MATERIALS AND METHODS: A total of 48,233 women with information on dietary intake were included in the analysis. Participants were followed for incident colorectal cancer until 31 December 2012. Cox proportional hazard models were used to assess the association between baseline fatty acid intake and colorectal cancer risk. All analyses were stratified by colon and rectal cancers. RESULTS: During a median of 21.3 years of follow-up, a total of 344 colorectal cancer cases were ascertained. Although there was no overall association between omega-3 fatty acid intake and colorectal cancer risk, high intake of fish-derived docosahexaenoic acid was associated with reduced risk of rectal cancer (hazard ratios for the third and the highest quartiles were 0.59 (95% confidence interval [CI], 0.37 to 0.96) and 0.62 (95% CI, 0.39 to 0.98), respectively). CONCLUSION: In conclusion, we found only limited support for an association between omega-3 polyunsaturated fatty acids and colorectal cancer in a large Swedish cohort of middle-aged women.

Protective Effect of Green Tea Consumption on Colorectal Cancer Varies by Lifestyle Factors.

The inconsistent findings regarding green tea intake and colorectal cancer (CRC) risk in several epidemiological studies might result from variations in lifestyle factors. Therefore, we examined whether increased green tea intake was associated with a decreased risk of CRC and how the risk of CRC was altered by the protective effect of green tea consumption and five health-related factors. A case-control study including 2742 participants (922 cases and 1820 controls) was conducted in Korea. Green tea consumption was assessed using a semiquantitative food frequency questionnaire. The risk of CRC was approximately 40% less in the participants in the highest green tea intake tertile than in participants in the lowest green tea intake tertile. Of the five lifestyle factors examined, high body mass index and physical inactivity were independent risk factors for CRC. Regarding the interactions between tea consumption and lifestyle factors, high green tea consumption was associated with a decreased risk of CRC, with or without considering lifestyle factors. However, moderate green tea consumption increased the risk of CRC among ever-smokers, ever-drinkers and the high-inflammatory diet group. Increased consumption of green tea might be helpful to reduce the risk of CRC in those with an unhealthy lifestyle.

Association between sedative-hypnotic medication use and incidence of cancer in Korean Nation Health Insurance Service data.

OBJECTIVES: We aimed to investigate the association between the use of various sedative-hypnotics and the incidence of overall and individual cancers in a large, population-based, retrospective cohort study. METHODS: We selected a 5% random sample of individuals aged 50 years or older from data maintained by the Korean National Health Insurance Service for the years 2002-2015, excluding individuals with a prior diagnosis of cancer and with any sedative-hypnotic use in the initial two years of follow-up, leaving 236,759 participants for the final analysis. Exposure to sedative-hypnotics was defined by type of drug, standardized to a defined daily dose, and coded as a time-varying variable. Cox proportional hazard models were applied after adjusting for sex, socio-economic status, and comorbidities. RESULTS: We observed increased risk for overall cancer among men and women who used sedative-hypnotics (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.01-1.13 for men; HR = 1.21, 95% CI = 1.09-1.25 for women) compared with non-users after full adjustment. In the fully adjusted model, women with any sedative-hypnotic use had significantly increased risk for thyroid (HR = 1.53, 95% CI = 1.24-1.87), breast (HR = 1.29, 95% CI = 1.04-1.61), ovarian (HR = 1.65, 95% CI = 1.10-2.46), and lung cancer (HR = 1.40, 95% CI = 1.17-1.69) compared with non-users. Men with sedative-hypnotic use had increased risk for prostate (HR = 1.36, 95% CI = 1.16-1.58), brain (HR = 1.67, 95% CI = 1.04-2.69), and lung cancer (HR = 1.20, 95% CI = 1.07-1.35) compared with non-users. CONCLUSION: We found a significant increase in overall cancer incidence among participants who used sedative-hypnotics, and both male and female sedative-hypnotic users had significantly increased risk for certain types of cancer.

Association between family history of diabetes and clusters of adherence to healthy behaviors: cross-sectional results from the Health Examinees-Gem (HEXA-G) study.

OBJECTIVES: This study evaluated whether individuals with affected family member adhered to healthy behaviours. DESIGN AND SETTING: This was a cross-sectional study of participants selected from health examinees who underwent the national health check-up programme of Korea in 39 centres between 2004 and 2013. PARTICIPANTS: The baseline data of 128 520 participants enrolled in the Health Examinees-Gem study were used for analysis. MAIN OUTCOMES AND MEASURES: Associations of family history of diabetes with adherence to regular exercise, healthy diet and body composition, and clusters of healthy behaviours were evaluated while adjusting for potential confounders selected by a directed acyclic graph. RESULTS: Participants with a family history of diabetes were more likely to adhere to a regular exercise regimen (OR=1.12, 95% CI 1.06 to 1.18 for men and OR=1.10, 95% CI 1.07 to 1.14 for women) and healthy diet (OR=1.06, 95% CI 1.01 to 1.12 for men and OR=1.06, 95% CI 1.01 to 1.12 for women) but were less likely to have a normal body composition (OR=0.83, 95% CI 0.78 to 0.87 for men and OR=0.83, 95% CI 0.80 to 0.86 for women). These associations were strengthened when the affected family members were siblings, the number of affected members was increased or the age at diagnosis of the affected member was younger than 50 years. In men and women, having a normal body composition is important in determining the cluster of behaviours, and those with a family history of diabetes were less likely to adhere to the normal body composition cluster. CONCLUSIONS: The group with high risk of diabetes showed healthy behaviors, but they did not have a normal body composition. Policies and campaigns targeting integrated health behaviors will be needed to reduce the burden of diseases and improve public health.

Association of atopic dermatitis with depressive symptoms and suicidal behaviors among adolescents in Korea: the 2013 Korean Youth Risk Behavior Survey.

BACKGROUND: Atopic dermatitis (AD) is a chronic skin disease which has been known to negatively influence the mental health of patients. However, only a few studies have explored the prevalence of psychiatric problems among AD patients, particularly among adolescents. In this study, we aimed to assess the association of AD with depressive symptoms and suicidal behaviors among adolescents by analyzing data from the 2013 Korean Youth Risk Behavior Survey, a nationwide web-based survey. METHODS: Data from 72,435 adolescent middle and high school students in Korea were analyzed. Students self-reported AD diagnosed by a doctor and yes-or-no answers to questions about depressive symptoms and suicide ideation, suicide planning, and suicide attempts were analyzed. Relationships between AD and depressive symptoms or suicidal behaviors were tested by logistic regression models after controlling for potential confounding factors. RESULTS: The proportion of adolescents who had AD was 6.8%. The proportion of adolescents reporting depressive feelings was 31.0%, suicide ideation was 16.3%, suicide planning was 5.8%, and suicide attempts was 4.2%. Compared to adolescents without AD, adolescents with AD were significantly more likely to experience depressive feelings (odds ratio [OR]: 1.27, 95% confidence interval [Cl]: 1.19-1.36), suicide ideation (OR: 1.34, 95% Cl: 1.24-1.45), suicide planning (OR: 1.46, 95% Cl: 1.32-1.65), and suicide attempts (OR: 1.51, 95% Cl: 1.33-1.72). In the multivariate model, the relationships between AD and suicide ideation (OR: 1.26, 95% Cl:1.16-1.36), suicide planning (OR: 1.28, 95% Cl:1.14-1.44), and suicide attempt (OR: 1.29, 95% Cl:1.13-1.49) were statistically significant. CONCLUSION: Adolescents who have AD are associated with a higher prevalence of depression symptoms and suicidal behaviors. Adolescent AD patients may need interventions from clinicians and caregivers that use a holistic approach to prevent psychological comorbidities, although further research is needed to clarify this relationship.

Determinants of gastric cancer screening attendance in Korea: a multi-level analysis.

BACKGROUND: We aimed to assess individual and area-level determinants of gastric cancer screening participation. METHOD: Data on gastric cancer screening and individual-level characteristics were obtained from the 2007-2009 Fourth Korea National Health and Nutrition Examination Survey. The area-level variables were collected from the 2005 National Population Census, 2008 Korea Medical Association, and 2010 National Health Insurance Corporation. The data were analyzed using multilevel logistic regression models. RESULTS: The estimated participation rate in gastric cancer screening adhered to the Korea National Cancer Screening Program guidelines was 44.0% among 10,658 individuals aged over 40 years who were included in the analysis. Among the individual-level variables, the highest income quartile, a college or higher education level, living with spouse, having a private health insurance, limited general activity, previous history of gastric or duodenal ulcer, and not currently smoking were associated with a higher participation rate in gastric cancer screening. Urbanization showed a significant negative association with gastric cancer screening attendance among the area-level factors (odds ratio (OR) = 0.73; 95% confidence interval (CI) = 0.57-0.93 for the most urbanized quartile vs. least urbanized quartile). CONCLUSION: There are differences in gastric cancer screening attendance according to both individual and regional area characteristics.

SLC15A2 genomic variation is associated with the extraordinary response of sorafenib treatment: whole-genome analysis in patients with hepatocellular carcinoma.

Reliable biomarkers are required to predict the response to sorafenib. We investigated genomic variations associated with responsiveness to sorafenib for patients with unresectable hepatocellular carcinoma (HCC). Blood samples from 2 extreme, 2 strong and 3 poor responders to sorafenib were subjected to whole-genome analysis. Then, we validated candidate genomic variations with another 174 HCC patients, and performed in vitro functional analysis and in silico analyses. Genomic data of >96 gigabases/sample was generated at average of ~34X sequencing depth. In total, 1813 genomic variations were matched to sorafenib responses in clinical data; 708 were located within regions for sorafenib-target genes or drug absorption, distribution, metabolism, and excretion (ADME)-related genes. From them, 36 variants were within the coding regions and 6 identified as non-synonymous single-nucleotide variants from 4 ADME-related genes (ABCB1, FMO3, MUSK, and SLC15A2). Validation genotyping confirmed sequencing results and revealed patients genotype for rs2257212 in SLC15A2 showed longer progression-free survival (HR = 2.18). In vitro study displayed different response to sorafenib depending on the genotype of SLC15A2. Structural prediction analysis revealed changes of the phosphorylation levels in protein, potentially affecting sorafenib-associated enzymatic activity. Our finding using extreme responder seems to generate robust biomarker to predict the response of sorafenib treatment for HCC.

Gene polymorphisms in the ornithine decarboxylase-polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations.

BACKGROUND: The study aimed to examine the association between genes encoding molecules in the ornithine decarboxylase (ODC)-polyamine pathway (ODC1, AMD1, NQO1, NOS2A, and OAZ2) and gastric cancer risk and whether the gene-phytoestrogen interaction modifies gastric cancer risk. METHODS: Among 76 gastric cancer cases and their 1:4 matched controls within the Korean Multi-center Cancer Cohort, a total of 30 SNPs in five genes involved in the ODC pathway were primarily analyzed. The second-stage genotyping in 388 matched case-control sets was conducted to reevaluate the significant SNPs interacting with phytoestrogens during the primary analysis. The summary odds ratios (ORs) [95 % confidence intervals (CIs)] for gastric cancer were estimated. Interaction effects between the SNPs and plasma concentrations of phytoestrogens (genistein, daidzein, equol, and enterolactone) were evaluated. RESULTS: In the pooled analysis, NQO1 rs1800566 showed significant genetic effects on gastric cancer without heterogeneity [OR 0.83 (95 % CI 0.70-0.995)] and a greater decreased risk at high genistein/daidzein levels [OR 0.36 (95 % CI 0.15-0.90) and OR 0.26 (95 % CI 0.10-0.64), respectively; p interaction < 0.05]. Risk alleles of AMD1 rs1279599, AMD1 rs7768897, and OAZ2 rs7403751 had a significant gene-phytoestrogen (genistein and daidzein) interaction effect to modify the development of gastric cancer. They had an increased gastric cancer risk at low isoflavone levels, but a decreased risk at high isoflavone levels (p interaction < 0.01). CONCLUSIONS: Our findings suggest that common variants in the genes involved in the ODC pathway may contribute to the risk of gastric cancer possibly by modulating ODC polyamine biosynthesis or by interaction between isoflavones and NQO1, OAZ2, and AMD1.

Interaction effects between genes involved in the AKT signaling pathway and phytoestrogens in gastric carcinogenesis: a nested case-control study from the Korean Multi-Center Cancer Cohort.

SCOPE: To investigate whether genes involved in AKT/nuclear factor kappa B signaling and/or gene-environment interactions between the genes and phytoestrogens may be susceptible factors for gastric cancer. METHODS AND RESULTS: The representative single nucleotide polymorphisms (SNPs) identified during the primary analysis (screening a total of 622 SNPs within ± 5 kbp of the 51 target gene locations) were further investigated in 317 matched case-control sets. The summary odds ratios (ORs) and 95% confidence intervals (CIs) for gastric cancer were calculated. Interaction effects between the SNPs and phytoestrogen biomarkers (genistein, daidzein, equol, and enterolactone) were computed. CDK1 rs4145643, FAS rs6586161, and FAS rs1468063 in the AKT signaling pathway presented significant genetic effects on gastric cancer (OR = 0.81 (95% CI: 0.66-0.99) for CDK1 rs4145643; OR = 1.27 (95% CI: 1.03-1.58) for FAS rs6586161; OR = 1.29 (95% CI: 1.03-1.56) for FAS rs1468063; Cochran Q statistics > 0.10). Risk alleles of FAS rs6586161, FAS rs1468063, MAP3K1 rs16886448, and MAP3K1 rs252902 showed significant interaction effects with enterolactone (p(interaction) < 0.05). CONCLUSION: CDK1 and FAS genes involved in AKT signaling and influenced by anti-carcinogenic property of phytoestrogens can play a role as susceptible genetic factors in gastric carcinogenesis. FAS and MAP3K1 genes significantly interact with enterolactone, thereby modifying the individual's risk for gastric cancer.

Genetic susceptibility on CagA-interacting molecules and gene-environment interaction with phytoestrogens: a putative risk factor for gastric cancer.

OBJECTIVES: To evaluate whether genes that encode CagA-interacting molecules (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2) are associated with gastric cancer risk and whether an interaction between these genes and phytoestrogens modify gastric cancer risk. METHODS: In the discovery phase, 137 candidate SNPs in seven genes were analyzed in 76 incident gastric cancer cases and 322 matched controls from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes (SRC, c-MET and CRK) were re-evaluated in 386 cases and 348 controls in the extension phase. Odds ratios (ORs) for gastric cancer risk were estimated adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity. Summarized ORs in the total study population (462 cases and 670 controls) were presented using pooled- and meta-analysis. Plasma concentrations of phytoestrogens (genistein, daidzein, equol and enterolactone) were measured using the time-resolved fluoroimmunoassay. RESULTS: SRC rs6122566, rs6124914, c-MET rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95% CI 2.05-7.65], 1.24 [95% CI = 1.01-1.53], 1.19 [95% CI = 1.01-1.41], and 1.37 [95% CI = 1.15-1.62], respectively; meta OR = 4.59 [95% CI 2.74-7.70], 1.36 [95% CI = 1.09-1.70], 1.20 [95% CI = 1.00-1.44], and 1.32 [95% CI = 1.10-1.57], respectively). Risk allele of CRK rs7208768 had a significantly increased risk for gastric cancer at low phytoestrogen levels (p interaction<0.05). CONCLUSIONS: Our findings suggest that SRC, c-MET and CRK play a key role in gastric carcinogenesis by modulating CagA signal transductions and interaction between CRK gene and phytoestrogens modify gastric cancer risk.

Adherence to follow-up after a positive fecal occult blood test in an organized colorectal cancer screening program in Korea, 2004-2008.

BACKGROUND AND AIM: To investigate the participation rates, positivity rates, and follow-up rates from 2004 to 2008 in an organized colorectal cancer (CRC) screening program using a fecal occult blood test (FOBT) in Korea. METHODS: The study population was men and women aged 50 years or older who were invited to participate in the National Cancer Screening Program for CRC between 1 January 2004 and 31 December 2008. We collected the FOBT results and follow-up information for the FOBT positives. RESULTS: Participation rates increased steadily each year from 10.5% in 2004 to 21.1% in 2008. Between 2004 and 2008, FOBT positivity rates declined from 8.0% to 6.8%. Among the FOBT-positives, 61.3% of participants underwent either colonoscopy or double contrast barium enema (DCBE) in 2004, and this rate decreased to 38.6% in 2008. Age, health insurance type, and screening history were associated with adherence to follow-up test after a positive FOBT. With regard to follow-up tests, colonoscopy rates increased from 17.9% in 2004 to 27.6% in 2008, while DCBE decreased from 43.4% in 2004 to 11.0% in 2008. Colonoscopy was significantly more likely to be chosen as a follow-up test by men, participants aged 50-59 years, and National Health Insurance beneficiaries. CONCLUSION: These findings suggest that targeting participants for follow-up, based on age and previous screening history, could be a good way to improve the follow-up rate.

Isoflavones from phytoestrogens and gastric cancer risk: a nested case-control study within the Korean Multicenter Cancer Cohort.

BACKGROUND: The role of soybean products in gastric cancer risk is not clear in epidemiologic studies due to measurement error from dietary intake questionnaires and due to different degrees of bias according to study design. To examine the association between soybean products and gastric cancer risk, we measured phytoestrogen biological markers in a nested case-control study. METHODS: The study population was composed of 131 cases and 393 matched controls within the Korean Multicenter Cancer Cohort. The concentrations of the four biomarkers in the plasma samples were measured using time-resolved fluoroimmunoassay. Conditional and unconditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence intervals (CI). RESULTS: Median plasma concentrations of genistein (229 nmol/L for controls, 181.8 nmol/L for cases; P=0.07) and daidzein (131.2 nmol/L for controls, 80.5 nmol/L for cases; P=0.04) in cases were lower than in controls, whereas equol concentrations were similar. Compared with the reference group, gastric cancer risk decreased in the highest groups for genistein (OR, 0.54; 95% CI, 0.31-0.93) and daidzein (OR, 0.21; 95% CI, 0.08-0.58). Higher equol concentrations were associated with a decreased risk for gastric cancer (OR, 0.50; 95% CI, 0.27-0.90). The combination of the highest concentrations for each isoflavone category was associated with a 0.09-fold decreased risk for gastric cancer compared with the combination of the lowest concentrations for each category. There was no association between plasma lignan concentrations and gastric cancer. CONCLUSIONS: High serum concentrations of isoflavones were associated with a decreased risk for gastric cancer. IMPACT: These results suggest a beneficial effect of high soybean product intake for gastric cancer risk.

Sociodemographic and lifestyle factors are associated with the use of dietary supplements in a Korean population.

OBJECTIVE: The use of dietary supplements has been increasing rapidly in Korea over the last decade. The aim of this study was to investigate associations between the pattern of dietary supplement use and the sociodemographic/lifestyle characteristics of Korean consumers. METHODS: Participants were asked to complete a self-administered questionnaire on their sociodemographic and lifestyle characteristics, perceived health status, and regular dietary supplement use. RESULTS: A total of 697 men and 832 women completed the questionnaire. Of the respondents, 44.3% of the men and 53.2% of the women used some kind of dietary supplement regularly. Dietary supplement users were more likely to be women (P < 0.001), to be older than 50 years (P < 0.001), to have a higher household income (P = 0.003), to engage in moderate or vigorous physical activity (P < 0.032), to perceive themselves as healthy (P = 0.026), and to have received a diagnosis of a chronic disease (P < 0.001). In addition, the type of dietary supplements used varied with respect to sociodemographic and lifestyle factors. Among dietary supplement users, men preferred ginseng, and older respondents were more likely to use carbohydrate supplements and less likely to use lipid supplements. Those who had a lower BMI, were ex-smokers, or were nondrinkers preferred either vitamins or minerals. Those who were highly physical active or were nondrinkers tended to prefer either vitamin/mineral complexes or carbohydrate supplements. CONCLUSIONS: The use of dietary supplements was related to sociodemographic and lifestyle factors in a Korean population.