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.

Association of food groups and dietary pattern with breast cancer risk: A systematic review and meta-analysis.

BACKGROUND & AIMS: We conducted a systematic review and meta-analysis of current evidence for the association between food groups, dietary patterns, and breast cancer risk among the Asian population. METHODS: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We performed a systematic literature search up to December 2022 in English in the PubMed, Web of Science, Embase, and Cochrane databases. Risk ratios (RRs) with 95% confidence intervals (CIs) were extracted as effect sizes. Publication bias was estimated by two different funnel plot methods. RESULTS: We collected the data from 15 cohort studies and 34 case-control studies meeting the search criteria. The meta-analysis found that the consumption of fruits and, likewise, vegetables were associated with a 29% lower risk of breast cancer, respectively [RR = 0.71 (0.55, 0.93); RR = 0.71 (0.53, 0.95)]. By contrast, no significance was found between meat, soy foods, and green tea consumption and breast cancer risk (P > 0.05). However, soy protein and isoflavone intake could lower breast cancer risk by 35% and 32%, respectively [RR = 0.65 (0.51, 0.83); RR = 0.68 (0.55, 0.82)]. As for the dietary pattern, high adherence to a healthy dietary pattern and, similarly, to a healthy eating index was associated with a 38% and 51% reduction in breast cancer risk, respectively [RR = 0.62 (0.44, 0.88; RR = 0.49 (0.27, 0.87)], while high adherence to an unhealthy dietary pattern was associated with a 44% increased risk [RR = 1.44 (1.06, 1.96)]. Considering alcohol consumption, a 75% increased risk of breast cancer was found [RR = 1.75 (1.33, 2.30)]. CONCLUSION: The present meta-analysis found that high intakes of fruits, vegetables, soy protein, and soy isoflavone significantly reduced the risk of breast cancer, while high intake of alcohol had a significantly increased risk. Meat, soy food, and green tea consumption were not significantly associated with breast cancer risk. Considering dietary patterns, high adherence to a healthy eating index and a healthy dietary pattern may reduce breast cancer risk. Conversely, adherence to unhealthy dietary patterns may increase breast cancer risk. However, further studies are needed to confirm the associations between dietary patterns and breast cancer in the Asian population.

Effects of Endocrine Therapy on Cardiovascular Diseases and Type 2 Diabetes Among Breast Cancer Survivors: The National Health Insurance Service Database of Korea.

Background Although endocrine therapy is an effective treatment for breast cancer, its antiestrogen effects are associated with increased risks of cardiovascular diseases and type 2 diabetes. This study aimed to investigate the association between endocrine therapy and the risk of cardiovascular diseases and type 2 diabetes among breast cancer survivors in Korea, in consideration of various age groups. Methods and Results In the National Health Insurance Service database of Korea, a total of 133 171 patients with breast cancer aged ≥20 years were included in the current study. Endocrine therapy was treated as time-varying exposure, and patients were categorized as nonusers, selective estrogen receptor modulator users, aromatase inhibitor users, and both users. Time-dependent Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs. Age at diagnosis, socioeconomic status, histological type, other treatments, and comorbidities were adjusted in the model. Compared with nonusers, selective estrogen receptor modulator users were associated with higher risks of stroke (HR, 1.20 [95% CI, 1.04-1.40]) and venous thromboembolism (HR, 1.47 [95% CI, 1.13-1.90]), whereas aromatase inhibitor users were associated with a higher risk of coronary heart disease (HR, 1.22 [95% CI, 1.06-1.41]). The risk of type 2 diabetes was associated with selective estrogen receptor modulator users (HR, 1.13 [95% CI, 1.05-1.21]), aromatase inhibitor users (HR, 1.14 [95% CI, 1.05-1.23]), and both users (HR, 1.24 [95% CI, 1.10-1.39]). In particular, the risk of a composite of cardiovascular diseases was higher in younger or premenopausal patients. Conclusions In breast cancer survivors in Korea, endocrine therapy is associated with a higher risk of cardiovascular diseases and type 2 diabetes. Monitoring of cancer comorbidities after endocrine therapy is needed in younger and older patients.

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.

Association of Coffee Consumption and Its Types According to Addition of Sugar and Creamer with Metabolic Syndrome Incidence in a Korean Population from the Health Examinees (HEXA) Study.

Coffee is widely consumed worldwide, and numerous studies indicate that coffee consumption may potentially affect the development of chronic diseases. Metabolic syndrome (MetS) may constitute a risk factor for chronic diseases. We aimed to prospectively evaluate the association between coffee consumption and MetS incidence. All participants were selected from the Health Examinees study. MetS was defined by the Adult Treatment Panel III criteria of the National Cholesterol Education Program. A multivariate Cox proportional hazards regression model was used to assess the relationship between coffee consumption and MetS incidence. In comparison with non-consumers, male moderate consumers (≤3 cups/day) showed a lower risk for low high-density lipoprotein cholesterol (HDL-C) (≤1 cup/day, hazard ratio (HR): 0.445, 95% confidence interval (CI): 0.254-0.780; 1-3 cups/day, HR: 0.507, 95% CI: 0.299-0.859) and high fasting blood glucose (FPG) (≤1 cup/day, HR: 0.694, 95% CI: 0.538-0.895; 1-3 cups/day, HR: 0.763, 95% CI: 0.598-0.972). Male 3-in-1 coffee (coffee with sugar and creamer) consumers also showed a lower risk for low HDL-C (HR: 0.423, 95% CI: 0.218-0.824) and high FPG (HR: 0.659, 95% CI: 0.497-0.874). These findings indicate a negative association between moderate coffee consumption and low HDL-C and high FPG among Korean male adults.

Association between the prevalence of metabolic syndrome and coffee consumption among Korean adults: results from the Health Examinees study.

The aim of this study was to evaluate the association between the frequency and quantity of coffee consumption and metabolic syndrome (MetS) in the Health Examinees study. A total of 130 420 participants (43 682 men and 86 738 women) were included in our study. Coffee consumption was categorized into 5 categories (0, <1, 1, 2-3, and ≥4 cups/day). We calculated odds ratios (ORs) and 95% confidence intervalS (CIs) using multivariate logistic regression. In this study population, the prevalence of MetS was 12 701 (29.1%) in men and 21 338 (24.6%) in women. High coffee consumption (≥4 cups/day) was associated with a lower prevalence of MetS compared with non-coffee consumers (OR = 0.79, 95% CI = 0.70-0.90, p for trend <0.0001 in men; OR = 0.70, 95% CI = 0.62-0.78, p for trend <0.0001 in women). The multivariable-adjusted ORs for high fasting glucose decreased with increasing levels of coffee consumption in men (OR = 0.60, 95% CI = 0.54-0.67, p for trend <0.0001) and women (OR = 0.70, 95% CI = 0.63-0.79, p for trend <0.0001). For women, the multivariable-adjusted ORs for hypertriglyceridemia (OR = 0.84, 95% CI = 0.75-0.93, p for trend = 0.0007) decreased with increasing levels of coffee consumption. We found that coffee consumption was inversely associated with the prevalence of metabolic syndrome among Korean men and women. Our study warrants further prospective cohort studies.

Oily Fish Consumption and the Risk of Dyslipidemia in Korean Adults: A Prospective Cohort Study Based on the Health Examinees Gem (HEXA-G) Study.

Despite the beneficial effects of omega-3 fatty acids from fish or fish oil on cardiovascular diseases, limited information is available regarding the effects of oily fish in the diet on the risk of dyslipidemia. This study aimed to investigate the association between oily fish consumption and the incidence of dyslipidemia among Korean adults included in the Health Examinees Gem (HEXA-G) cohort during 5 years of follow-up. In total, 20,670 participants (5710 men and 14,960 women) were included in this study. The average intake of oily fish including dark meat fish, such as mackerel, pacific saury, and Spanish mackerel, and eel, was estimated using food frequency questionnaires. Oily fish consumption was associated with a significantly lower risk of hypertriglyceridemia in both men (Relative risk (RR) comparing extreme quintiles = 0.75; 95% CI 0.60-0.95; P for trend = 0.0121) and women (RR comparing extreme quintiles = 0.81; 95% CI 0.69-0.96; P for trend = 0.0110) after adjusting for potential confounders. In conclusion, increased consumption of oily fish was significantly associated with a lower risk of hypertriglyceridemia in the general Korean population. Future randomized clinical trials or prospective studies are required to confirm these findings in the Korean or other Asian populations.

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.

Plasma phytoestrogens concentration and risk of colorectal cancer in two different Asian populations.

BACKGROUND & AIMS: To evaluate the relationship between phytoestrogen and colon cancer risk, we quantified plasma isoflavones (Genistein and Daidzein) and lignan (enterolactone) in a Korean nested case-control study and conducted replication study in a Vietnamese case-control study. METHODS: Study populations of 101 cases and 391 controls were selected from the Korean Multicenter Cancer Cohort which was constructed from 1993 to 2004. For replication study, Vietnamese hospital-based case-control subjects of 222 cases and 206 controls were selected from 2003 to 2007. The concentrations of plasma genistein, daidzein, and enterolactone were quantified by liquid chromatography-mass spectrometry. Logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs), and meta-analysis was conducted to estimate combined ORs (CORs) and 95% Cis of Korean and Vietnamese population in 2014. RESULTS: Genistein showed a continual decrease in colorectal cancer risk according to level up of the concentration categories in Korean and Vietnamese population (P for trend = 0.032, and 0.001, respectively) and a significantly decreased risk was found at the highest concentration of genistein and daidzein (for the highest category compared to the lowest: COR (95% CI) = 0.46 (0.30-0.69), and COR (95% CI) = 0.54 (0.36-0.82)). When the study population was stratified, the beneficial relationship of genistein with colorectal cancer was observed regardless of sex and anatomical subtype. However, enterolacton level was not associated with colorectal cancer risk. CONCLUSIONS: High plasma levels of isoflavones had relationship with a decreased risk of colorectal cancer, regardless of different ethnic background.

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.

The potential application of personalized preventive research.

With increases in life expectancy, the focus has shifted to living a healthier, longer life. By concentrating on preventing diseases before occurrence, researchers aim to diminish the increasing gap in medical costs and health inequalities prevalent across many nations. Although we have entered an era of post-genomics, we are still in infancy in terms of personalized preventive research. Personalized preventive research has and will continue to improve with advancements in the use of biomarkers and risk assessment. More evidence based on well-designed epidemiologic studies is required to provide comprehensive preventive medical care based on genetic and non-genetic profile data. The realization of personalized preventive research requires building of evidence through appropriate methodology, verification of results through translational studies as well as development and application of prediction models.

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.

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.

Soybean product intake modifies the association between interleukin-10 genetic polymorphisms and gastric cancer risk.

In this study, our aim was to investigate the association of inflammation-related genetic polymorphisms and gastric cancer risk and to examine whether the combined effect of soybean product intake modified cancer risk. Eighty-four incident gastric cancer cases and 336 matched controls were selected from the Korean Multi-Center Cancer Cohort. We selected 14 single nucleotide polymorphisms (SNP) from 5 genes [interleukin (IL)-1beta, IL-2, IL-4, IL-8, and IL-10] and used unconditional logistic regression model to calculate the odds ratios (OR) and 95% CI adjusting for H. pylori seropositivity, smoking, age, sex, enrollment year, and residential area. The risk for gastric cancer in relation to genetic polymorphisms and haplotypes were assessed according to soybean product intake levels. Although no single SNP effect was found, the combined effect between IL-10 gene variants of -592 GG/GA, -819 TC/CC, or -1082 AG/GG and low intake of soybean products had an increased risk for gastric cancer compared with the group with no risk gene variants and a high intake of soybean products (OR [95% CI] = 2.82 [1.04-7.62], 2.75 [1.02-7.44], and 4.34 [1.51-12.5], respectively). Among the low-soybean product intake group, IL-10 CCG haplotype had an increased risk of gastric cancer (OR = 3.38 [1.40-8.13]) relative to the ATA haplotype. Our results suggest that the association between IL-10 genetic polymorphisms and gastric cancer risk was modified by soybean product intake.

Functional variant of manganese superoxide dismutase (SOD2 V16A) polymorphism is associated with prostate cancer risk in the prostate, lung, colorectal, and ovarian cancer study.

Superoxide dismutase (SOD) plays a key role in the detoxification of superoxide free radicals. We evaluated the association of prostate cancer with genetic polymorphisms in SOD1 (CuZn-SOD; IVS3-251A>G), SOD2 [MnSOD; Ex2+24T>C (V16A)], and SOD3 (EC-SOD; IVS1+186C>T, Ex3-631C>G, Ex3-516C>T, and Ex3-489C>T), the three main isoforms of SOD. Prostate cancer cases (n = 1,320) from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were frequency matched to nondiseased controls (n = 1,842) by age, race, time since initial screening, and year of blood draw. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI); stratified analysis by the level of antioxidative vitamins was also conducted. The higher activity Ala variant at SOD2 Ex2+24T>C (V16A), which has been hypothesized to suppress prostate carcinogenesis, was associated with elevation of prostate cancer risk in Caucasians (Val/Ala versus Val/Val: OR, 1.17; 95% CI, 0.97-1.42; Ala/Ala versus Val/Val: OR, 1.28; 95% CI, 1.03-1.60; P(trend) = 0.03). Stratification by quartiles of dietary and supplemental vitamin E intake (IU/d) showed risks of prostate cancer tended to be increased among SOD2 Ala allele carriers, except at the highest quartile of vitamin E intake (>222; P(interaction) = 0.06, Q1-Q3 versus Q4). The association between Ala allele and prostate cancer risk among those with lower intake of vitamin E (

Design issues in cross-sectional biomarkers studies: urinary biomarkers of PAH exposure and oxidative stress.

Cross-sectional biomarker studies can provide a snapshot of the frequency and characteristics of exposure/disease in a population at a particular point in time and, as a result, valuable insights for delineating the multi-step association between exposure and disease occurrence. Three major issues should be considered when designing biomarker studies: selection of appropriate biomarkers, the assay (laboratory validity), and the population validity of the selected biomarkers. Factors related to biomarker selection include biological relevance, specificity, sensitivity, biological half-life, stability, and so on. The assay attributes include limit of detection, reproducibility/reliability, inter-laboratory variation, specificity, time, and cost. Factors related to the population validity include the frequency or prevalence of markers, greater inter-individual variation than intra-individual variation, intra-class correlation coefficients (ICC), association with potential confounders, invasiveness of specimen collection, and subject selection. Three studies are selected to demonstrate different features of cross-sectional biomarker studies: (1) characterizing the determinants of the biomarkers (study I: urinary PAH metabolites and environmental particulate exposure), (2) relationship of multiple biomarkers of exposure and effect (study II: relationship between urinary PAH metabolites and oxidative stress), and (3) evaluating gene-environmental interaction (study III: effect of genetic polymorphisms of GSTM1 on the association of green tea consumption and urinary 1-OHPG levels in shipbuilding workers).