Health-Related Behaviors and Perceived Health Status According to Water and Sugar-Sweetened Beverage Intake in Korean Adolescents.

The objective of this study was to determine the relationship between water and sugar-sweetened beverage (SSB) intake, health behaviors, and self-perceived health status using data from the 2019 Korea Youth Risk Behavior Web-based Survey (KYRBS). The subjects included in this analysis were 57,302 Korean adolescents from the 7th to 12th grades. The intake patterns of water and SSBs were categorized into four groups: Group I, adequate water intake (≥4 cups/day) and low frequency of SSB intake (≤1-2 times/week); Group II, adequate water intake and high frequency of SSB intake; Group III, inadequate water intake (<4 cups/day) and low frequency of SSB intake; Group IV, inadequate water intake and high frequency of SSB intake (≥3 times/week). Complex sample analyses were used for considering strata, clusters, and weights for samples. Significant differences were observed in the distribution of sociodemographic characteristics between the water and SSB intake groups. As grade levels increased or if students were female, there was a significant increase in the proportion of students characterized by low water intake and high consumption of SSB. Adolescents with healthier beverage habits, characterized by adequate water intake and low frequency of SSB consumption (Group I), generally abstained from smoking and alcohol, were more physically active, and maintained a desirable diet, reporting a better perceived health status. In contrast, those with higher SSB consumption and inadequate water intake (Group IV) were more likely to perceive their health as poor, with higher rates of smoking and alcohol use, lower physical activity levels, and poorer dietary habits compared to Group I. In conclusion, adolescents with desirable beverage consumption habits differed by sex and grade and they reported positive health behaviors and better overall health status. This suggests that there is a need for more active education and intervention in schools and families, as well as increased efforts by adolescents to promote healthy beverage habits.

Effects of RAD50 SNP, sodium intake, and H. pylori infection on gastric cancer survival in Korea.

BACKGROUND: Double-strand break repair protein (RAD50) gene plays important roles in genomic integrity, DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. The risk allele of RAD50 may negatively affect cancer by reducing the DNA repair capacity. Additionally, Sodium intake and Helicobacter pylori (H. pylori) infection are major risk factors for gastric cancer (GC). Our study investigated the association between polymorphisms in RAD50 gene and the risk of GC case-fatality. We evaluated whether the association differed with sodium intake or H. pylori infection. METHODS: We enrolled 490 patients from two hospitals between 2002 and 2006. Their survival or death was prospectively followed up until December 31, 2016, through a review of medical records and telephone surveys. The GC survival was assessed using the Cox proportional hazards regression analysis. RESULTS: In 319 GC cases, the total person-years were 1928.3, and the median survival years was 5.4 years. A total of 137 GC deaths were recorded. Our fully adjusted model showed that the GG type of RAD50 rs17772583 polymorphism is significantly associated with an increased risk of GC case-fatality (hazard ratio [HR] = 2.20, 95% confidence interval [CI] = 1.28-3.77) compared to that associated with the homozygous AA type. In the high sodium intake group, patients with the GG type of RAD50 rs17772583 showed a significantly higher GC case-fatality (HR = 8.61, 95% CI = 2.58-26.68) than that of patients with homozygous AA type. In the positive-H. pylori infection group, patients with GG-type RAD50 rs17772583 showed a significantly higher GC case-fatality (HR = 10.11, 95% CI = 2.81-36.35) than that of with AA homozygotes. CONCLUSIONS: Patients with GG-type RAD50 rs17772583, high sodium intake, or a positive-H. pylori infection are at a significantly increased risk of GC case-fatality compared to that associated with the absence of these risk factors.

Glycemic Index, Glycemic Load, and FAS rs6586161 Polymorphism in Relation to Gastric Cancer Risk: A Case-Control Study in Korea.

Many dietary and genetic factors have been confirmed to be associated with gastric cancer risk. This research investigated gastric cancer risk with regard to the glycemic index, glycemic load, and FAS rs6586161 polymorphism. A total of 232 matched pairs were included in this case-control study. Data collection was conducted at two hospitals in Korea from 2002 to 2006. Dietary information was obtained from a food frequency questionnaire, and genotypes of FAS rs6586161 polymorphism were TT, TA, and AA type. Gastric cancer risk was increased for the highest tertile of glycemic index (vs. lowest tertile, OR = 1.84, 95% CI = 1.07-3.18), the highest tertile of glycemic load (vs. lowest tertile, OR = 2.14, 95% CI = 1.23-3.75), and the AA type of FAS rs6586161 polymorphism (vs. TT types, OR = 1.95, 95% CI = 1.13-3.39). Furthermore, gastric cancer risk was significantly elevated for the participants with the highest glycemic load and AA type of FAS rs6586161 polymorphism (vs. the lowest glycemic load and TT type, OR = 5.53, 95% CI = 2.01-15.21). Both the high glycemic load and AA type of FAS rs6586161 polymorphism increased gastric cancer risk; however, the interactions between these two elevated the risk of gastric cancer even more.

Alleviating air pollutant-associated hypertension by potassium intake in Korean adults: a cross-sectional study from the 2012-2016 Korea National Health and Nutrition Examination Survey.

Air pollution may increase the risk of hypertension (HTN) by increasing oxidative stress and inflammation, and reducing sodium excretion. Potassium intake may reduce the risk of HTN through sodium excretion and reduce inflammation and oxidative stress. This study is aimed at investigating the association between air pollutants and HTN and whether these associations differ based on the potassium intake data of Korean adults from the 2012-2016 Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study used data from KNHANES (2012-2016) combined with annual air pollutant data from the Ministry of Environment using administrative units. We included 15,373 adults who responded to the semi-food frequency questionnaire. Associations between ambient PM10, SO2, NO2, CO, and O3 with HTN according to potassium intake were assessed using the survey logistic regression model for complex samples analysis. After adjusting for potential covariates such as, age, sex, education level, smoking status, family income, alcohol consumption, body mass index (BMI), exercise status, and survey year, as the air pollutant score considering the five air pollutants increased (severe air pollution), the prevalence of HTN increased in a dose-dependent manner (p for trend < 0.001). Meanwhile, in the adults with higher potassium intake and who were exposed to lowest levels of air pollutants score (score = 0), the ORs of HTN were significantly lower (OR = 0.56, 95% CI: 0.32-0.97). In conclusion, our study suggests that exposure to air pollutants may increase the prevalence of HTN among Korean adults. However, high potassium intake may help prevent HTN caused by air pollutants.

Association between soy products, fruits, vegetables, and dairy products and gastric cancer risk in Helicobacter pylori-infected subjects: a case-control study in Korea.

BACKGROUND/OBJECTIVES: Consumption of certain protective foods may help inhibit Helicobacter pylori (H. pylori) associated gastric pathologies. However, studies conducted to assess the efficacy of protective foods in H. pylori-infected subjects are either limited or inconsistent. This study evaluated the association of individual or a combination of protective foods on the incidence of gastric cancer (GC) in H. pylori-positive subjects through a case-control study. MATERIALS/METHODS: Subjects aged 20-79 years were selected from 2 hospitals between December 2002 and September 2006. In total, 134 patients and 212 controls tested positive for H. pylori infection. Among these, we included 82 pairs of cases and controls matched by sex, age (± 5 years), enrollment period (± 1 years), and hospital. RESULTS: A higher intake of soy products was associated with a significantly lower risk of GC than a lower intake of soy products (odds ratio [OR] = 0.37, 95% confidence interval [CI] = 0.14-0.96). Additionally, a higher fruit intake resulted in a significantly lower risk of GC than a lower fruit intake (OR = 0.35, 95% CI = 0.13-0.94). A combination of food groups was evaluated, and a lower risk of GC was observed with a high intake of both soy products and fruits (OR = 0.20, 95% CI = 0.06-0.67), high intake of soy and dairy products (OR = 0.28, 95% CI = 0.10-0.78) and high intake of fruits and dairy products (OR = 0.28, 95% CI = 0.09-0.83). CONCLUSIONS: A high intake of soy products or fruits was associated with a lower risk of GC. A combination of soy products or fruits with dairy products was associated with a lower risk of GC. A balanced intake of soy products, fruits, and dairy products may help reduce GC risk.

Association of Dietary Antioxidant Vitamin Intake and Gastric Cancer Risk According to Smoking Status and Histological Subtypes of Gastric Cancer: A Case-Control Study in Korea.

Smoking is a risk factor for gastric cancer (GC) and causes oxidative stress. Antioxidant vitamins may protect against oxidative stress. This study aimed to determine the association between dietary antioxidant vitamin intake and GC risk according to smoking status and the histological subtype. This case-control study included 286 pairs of patients with GC and controls aged 20-79 years enrolled at two hospitals from 2002 to 2006, matched by age (± 2 years), sex, hospital, and participation period (± 1 years). Dietary information was collected using a quantitative food frequency questionnaire (FFQ). When stratified by smoking status, increased intake of vitamin C (OR = 0.38; 95% CI = 0.17-0.84 for highest vs. lowest; P for trend = 0.033) and folate (OR = 0.28; 95% CI = 0.12-0.64 for highest vs. lowest; P for trend = 0.003) decreased GC risk in nonsmokers. Vitamin C (P for interaction = 0.043) and folate (P for interaction =0.015) levels were significantly associated with smoking status. Similar results were observed in nonsmokers with diffuse and mixed types of GC, but not in those with intestinal type of GC. Therefore, we found an inverse association between higher intake of dietary vitamin C and folate with the risk of GC among nonsmokers. These protective associations were strong in nonsmokers with diffuse and mixed types of GC.

Sex-dependent associations between MAP3K1 gene polymorphisms and soy products with the gastric cancer risk in Korea: a case-control study.

BACKGROUND/OBJECTIVES: The hormone-dependent effect of MAP3K1 gene polymorphisms may explain sex-specific differences in gastric cancer (GC) risk. Phytoestrogens have been shown to interact with this genetic factor. Here, we investigated the association between MAP3K1 gene polymorphisms and GC risk by sex and whether these associations differ depending on soy products intake. METHODS: Participants aged 20-79 years were recruited from two hospitals between December 2002 and September 2006. In all, 440 cases and 485 controls were recruited, among, 246 pairs of cases and controls, matched by sex, age (± 5 years), study admission period (± 1 years), and hospital, were included for the analysis. RESULTS: In dominant model, men with the A allele of rs252902 showed significantly increased GC risk (odd ratio; OR=2.19, 95% confidence interval; CI=1.31-3.64) compared to GG homozygotes. When stratified by intake of soy products, men with the A allele of rs252902 and low intake of soy products showed significantly higher GC risk (OR=3.29, 95% CI=1.55-6.78) than that in GG homozygotes. CONCLUSIONS: Men with the risk allele of MAP3K1 had a significantly increased GC risk compared to GG homozygotes; this trend was more pronounced in those with low intake of soy products.

Dietary zinc intake and mortality in patients with intestinal-type gastric cancer: A prospective cohort study in Korea.

Purpose: Current evidence regarding the association between zinc intake and gastric cancer (GC)-specific survival in patients with intestinal-type GC is lacking. Therefore, this cohort study investigated the association between zinc intake and GC mortality through follow-up on GC death among patients with intestinal-type GC and whether these effects differ according to the source of zinc intake. Methods: A total of 185 patients with intestinal-type GC were enrolled from two hospitals between 2002 and 2006. Their survival or death was prospectively followed up until December 31, 2016, through a review of medical records and telephone surveys. Results: A total of 178 patients were included and analyzed. The median follow-up period was 7.3 years. In the fully adjusted models, the highest tertile of total zinc intake showed a significantly lower GC mortality than the lowest tertile (hazard ratio, 0.22; 95% confidence interval: 0.08-0.64). In addition, the tertile of total zinc intake showed a dose-response association with GC mortality (p=0.015). Analysis of the source of zinc intake revealed that when zinc intake from staples (rice and noodles), animal, and plant food sources were combined, the results were similar to those of total zinc intake and GC mortality. Conclusion: Zinc intake through various foods may be effective in reducing GC mortality by achieving balance with other nutrients. Our results suggest that zinc improves the survival of patients with intestinal-type GC in Korea.

A high glycemic index and glycemic load increased the risk of gastric cancer: A case-control study in Korea.

Diet is a critical risk factor for gastric cancer, and Koreans consume significantly high amounts of carbohydrates. This study examined the association between carbohydrate intake, glycemic index, and glycemic load and the risk of gastric cancer and whether the association varied based on the general risk factors for gastric cancer. We hypothesized that carbohydrate intake, glycemic index, and glycemic load elevated gastric cancer risk and the relationship differed by the gastric cancer risk factors. This was a case-control study with a total of 307 matched pairs aged 20 to 79 years. Data collection was completed at two hospitals from December 2002 to September 2006. A food frequency questionnaire was applied for dietary assessment. Carbohydrate intake was not related to gastric cancer risk. However, a high glycemic index (odds ratio [OR], 1.88; 95% confidence interval (95% CI), 1.18-2.97) and glycemic load (OR, 2.51; 95% CI, 1.53-4.12) were significantly associated with the elevated risk of gastric cancer. When the relationship between glycemic load and gastric cancer risk was stratified by risk factors for gastric cancer, the gastric cancer risk especially increased among men, ≥65 years, smokers, drinkers, and people with Helicobacter pylori infection. Although there was no association between carbohydrate consumption and gastric cancer, high glycemic index and glycemic load were associated with the increased gastric cancer risk.

Gastric Cancer Risk Was Associated with Dietary Factors Irritating the Stomach Wall: A Case-Control Study in Korea.

The incidence of gastric cancer is high in Korea, and dietary factors are important risk factors for gastric cancer. This study examined whether gastric cancer risk was related to dietary factors that directly irritate the stomach wall. This case−control study consisted of 308 matched pairs of gastric cancer cases and controls recruited from 2002 to 2006 at two hospitals in Korea. Dietary assessments were completed using a food frequency questionnaire and a dietary habit questionnaire. Gastric cancer risk was increased for high meal frequency of >3 vs. low meal frequency of ≤3 times per day, overeating vs. not overeating, and preferred vs. not preferred spicy or salty foods. Furthermore, participants with dietary factors of high meal frequency, overeating, and preference for spicy or salty foods elevated the risk of gastric cancer compared to those with low meal frequency, not overeating, and not preferring spicy or salty foods, simultaneously. In conclusion, gastric cancer risk was significantly increased in people with dietary factors that irritate the stomach wall, such as high meal frequency, overeating, and preference for spicy or salty foods.

The Associations of Dietary Intake of High Sodium and Low Zinc with Gastric Cancer Mortality: A Prospective Cohort Study in Korea.

Sodium and zinc display opposite effects on immune cells, such as regulatory T cells (Tregs) and T helper 17 cells (Th17), resulting in an altered immune response. Immune cells have a pivotal role in regulating tumor progression, which may affect gastric cancer (GC) mortality. Thus, this cohort study investigated the associations between the combination of sodium and zinc intake and GC mortality and whether these associations differ by histological type by following up deaths of GC cases in Korea. A total of 490 patients with GC were enrolled between 2002 and 2006. Survival or death was prospectively followed up until December 31, 2016. Finally, 300 patients with the two main histological types of GC were included; 99 GC deaths occurred during a median follow-up period of 7.1 years. Patients with high sodium and low zinc intake had a significantly higher GC mortality than those with low sodium and high zinc intake (hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.09-3.93). However, no significant association was found between the histological types of GC. In conclusion, we found that high sodium and low zinc intake may worsen the survival rate of patients with GC.

Erratum: Dietary Intake of Soy Products, Vegetables, and Dairy Products and Gastric Cancer Survival according to Histological Subtype: a Long-term Prospective Cohort Study.

[This corrects the article on p. 403 in vol. 21, PMID: 35079442.].

Gastric Cancer and the Daily Intake of the Major Dish Groups Contributing to Sodium Intake: A Case-Control Study in Korea.

Studies on the association between gastric cancer (GC) and the intake of soup-based dish groups (noodles and dumplings, soups, and stews), which are sodium-contributing foods, in Korea are insufficient, and the results of studies on the intake of pickled vegetables such as kimchi are inconsistent. This study aimed to determine the association between the incidence of GC and the daily intake of high-sodium dish groups (noodles and dumplings, soups, stews, and pickled vegetables) and whether these associations differ depending on behavioral risk factors for GC. In this case-control study, subjects aged 20-79 years were recruited from two hospitals between December 2002 and September 2006. A total of 440 cases and 485 controls were recruited, of which 307 pairs were matched and included for the analysis. In our results, a higher intake of noodles and dumplings was associated with a significantly increased incidence of GC. In the participants who consumed past or current alcohol, a higher intake of noodles and dumplings was associated with a significantly increased incidence of GC. Our results suggest that efforts to reduce the daily sodium intake from noodles and dumplings are needed to prevent and reduce the incidence of GC.

Dietary Intake of Soy Products, Vegetables, and Dairy Products and Gastric Cancer Survival according to Histological Subtype: a Long-term Prospective Cohort Study.

PURPOSE: Owing to differences in the general characteristics of gastric cancer (GC) according to histological type, the association of GC risk factors, such as diet, may also differ depending on the histological type. We investigated the associations between individual and combined intake of soy products, vegetables, and dairy products and GC mortality by following up cases of death among Korean GC cases and whether these associations differ according to the histological type. MATERIALS AND METHODS: A total of 508 GC cases were enrolled from two hospitals between 2002 and 2006. Their survival or death was prospectively followed up until December 31, 2016, through a review of medical records and telephonic surveys. Finally, 300 GC cases classified as intestinal- or diffuse-type GC cases were included. The median follow-up period was 7.1 years. RESULTS: In the fully adjusted model, a high intake of soy products (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.19-0.96) and the combination of soy products and vegetables (HR, 0.34; 95% CI, 0.12-0.96) or soy products and dairy products (HR, 0.37; 95% CI, 0.14-0.98) decreased the mortality from intestinal-type GC. In particular, patients consuming various potentially protective foods (HR, 0.23; 95% CI, 0.06-0.83) showed a highly significant association with a lower mortality from intestinal-type GC. However, no significant association was found with diffuse-type GC. CONCLUSIONS: High intake of potentially protective foods, including soy products, vegetables, and dairy products, may help increase survival in intestinal-type GC.

Do Where The Elderly Live Matter? Factors Associated with Diet Quality among Korean Elderly Population Living in Urban Versus Rural Areas.

This study aimed to examine whether there is an area difference on diet quality among the Korean elderly population. The effect of personal factors on diet quality is also estimated and compared between rural and urban areas. A cross-sectional data from the 2013-2015 Korea National Health and Nutrition Examination Survey (KNHANES) was used for this study. The participants were older adults aged ≥ 65 years (n = 3207) who participated in the KNHANES. Urban and rural areas classified the region and the Korean Healthy Eating Index (KHEI) assessed the diet quality. Personal factors that were related to diet quality included socio-demographic factors, health behaviors, and health conditions. This study found that the diet quality was different between urban and rural areas in the Korean elderly population, showing a higher mean of KHEI scores in urban areas than rural areas (67.3 for urban seniors, 63.6 for rural seniors, p < 0.001), and the regional difference was still significant, even after adjusting for the personal factors (p < 0.001). Different sets of personal factors were found to be significant that explain the diet quality of participants between areas, such as economic resources, walking exercise, and perceived oral health status in urban areas, and age and food insecurity in rural areas. In conclusions, this study found that there was a regional disparity in diet quality and some personal factors affecting diet quality were dependent on areas, which implied that regional environment with diverse contexts could influence diet quality. These findings emphasize the need to provide targeted intervention programs that take into account both the characteristics of individuals and local food environments in order to improve the overall diet quality in older adults.

Alcohol consumption and gastric cancer risk in Korea: a case-control study.

BACKGROUND/OBJECTIVES: The International Agency for Research on Cancer defined alcohol beverages and acetaldehyde derived from alcoholic beverages as a Group 1 carcinogen to humans. However, the association between alcohol consumption and gastric cancer risk has been controversial in Korean. We assessed the relationship between alcohol consumption and gastric cancer risk in Korea through a case-control study. SUBJECTS/METHODS: From 2 hospitals, a total of 316 cases with gastric cancer (208 men, 108 women) were selected and matched to 316 controls by sex and age (± 5 years) during the same duration. The current status, frequency, and amount of alcohol consumption for a year three years ago were assessed by trained interviewers. RESULTS: Alcohol consumption status and frequency did not show any significant association with gastric cancer risk. However, high alcohol consumption (≥ 20 g/day for women or ≥ 40 g/day for men) significantly increased the risk of gastric cancer (odds ratio (OR) 1.73; 95% confidence interval (CI) 1.05-2.85). Gastric cancer risk was strongly positively associated with alcohol consumption of ≥ 20 g/day, especially in women (OR 5.62; 95% CI 1.32-23.81). CONCLUSION: The results from this study suggest that excessive alcohol consumption rather than the current status or frequency of alcohol consumption contributes to the increased risk of gastric cancer, especially in women.

Impact of age on stage-specific mortality in patients with gastric cancer: A long-term prospective cohort study.

Controversies exist regarding the impact of age on gastric cancer-related mortality according to cancer stage. In our prospective cohort study, we evaluated the impact of age on stage-specific mortality in patients with gastric cancer. Between 2002 and 2006, patients with newly diagnosed gastric cancer were recruited from two university-affiliated hospitals in Korea. Follow-up data were updated regularly based on medical records and telephone surveys. Patients were classified into four subgroups according to age: <50, 50-59, 60-69, and 70-79 years. A total of 448 patients were followed up for 81.6 months (interquartile range, 25.0-139.3 months). The number of patients with stage I, II, III, and IV disease was 247, 74, 88, and 39, respectively. Overall, age was an independent risk factor for gastric cancer-specific mortality (hazard ratio [HR], [95% confidence interval (CI)]: 1.53 [0.91-2.57], 1.88 [1.21-2.91], and 2.64 [1.69-4.14] in the 50-59, 60-69, and 70-79 years groups, respectively, with the <50 years group as reference). In patients with stage I and II gastric cancer, the 70-79 years group was associated with a significantly higher rate of cancer-specific mortality than the <50 years group (stage I: HR [95% CI], 9.55 [2.11-43.12]; stage II: HR [95% CI], 7.17 [2.32-22.18]). However, age was not an independently associated factor for cancer-specific mortality in patients with stage III and IV gastric cancer. Although age was an independent risk factor for gastric cancer-related mortality in patients with gastric cancer, its impact may differ depending on the stage of cancer.

Prediagnostic Smoking and Alcohol Drinking and Gastric Cancer Survival: A Korean Prospective Cohort Study.

Background/Aims: Behavioral factors, such as smoking and heavy alcohol consumption, increase the risk of gastric cancer (GC), but their effects on survival are not clear. We examined associations between prediagnostic smoking and alcohol drinking behavior and GC death by long-term follow-up. Methods: The participants were 508 GC patients enrolled at Chungnam University Hospital and Hanyang University Guri Hospital from 2001 to 2006. Information on clinicopathologic and behavioral risk factors was collected, and patient survival was prospectively followed until 2016 by medical chart review and telephone survey. Results: During above 10 years follow-up period, overall death was 46.2% (n=226) and GC deaths was 38.2% (n=187) among the 489 GC patients included in the analysis. No significant association was found between smoking habits and overall or GC survival. However, after stratification by histological type, the hazard ratio (HR) of GC death for current smokers tended to be higher for the diffuse type (HR 1.61, 95% CI 0.57-4.59 for current vs. never) rather than for the intestinal type (HR 0.78, 95% CI 0.28-2.19 for current vs. never). Light alcohol consumption was found to be associated with a significantly lower risk of GC death (HR 0.52, 95% CI 0.36-0.75 for <20 g/day for women or <40 g/day for men vs. never and past), and the effects of alcohol drinking habits had similar effects on GC death for the intestinal and diffuse types. Conclusions: These results suggest smoking and alcohol drinking behaviors before a diagnosis of GC are weakly associated with GC survival. Nevertheless, the effect of smoking behavior on prognosis appears to depend on the histological type of GC.

Alcohol Consumption and Breast Cancer Risk in Younger Women According to Family History of Breast Cancer and Folate Intake.

To evaluate the association between alcohol consumption and breast cancer risk in younger women, overall and by family history of breast cancer and folate intake, we prospectively followed 93,835 US women aged 27-44 years in Nurses' Health Study II who had alcohol consumption data in 1991. Alcohol consumption and folate intake were measured by food frequency questionnaire every 4 years. We documented 2,866 incident cases of invasive breast cancer between 1991 and 2011. Alcohol consumption was not associated with breast cancer risk overall (for intake of ≥10 g/day vs. nondrinking, multivariate hazard ratio = 1.07, 95% confidence interval: 0.94, 1.22). When the association was stratified by family history and folate intake, a positive association between alcohol consumption and breast cancer was found among women with a family history and folate intake less than 400 µg/day (multivariate hazard ratio = 1.82, 95% confidence interval: 1.06, 3.12; P-trend = 0.08). Alcohol consumption was not associated with breast cancer in other categories of family history and folate intake (P-interaction = 0.55). In conclusion, in this population of younger women, higher alcohol consumption was associated with increased risk of breast cancer among those with both a family history of breast cancer and lower folate intake.

Decrease of 5hmC in gastric cancers is associated with TET1 silencing due to with DNA methylation and bivalent histone marks at TET1 CpG island 3'-shore.

Recent evidence has shown that the level of 5-hydroxymethylcytosine (5 hmC) in chromosomal DNA is aberrantly decreased in a variety of cancers, but whether this decrease is a cause or a consequence of tumorigenesis is unclear. Here we show that, in gastric cancers, the 5 hmC decrease correlates with a decrease in ten-eleven translocation 1 (TET1) expression, which is strongly associated with metastasis and poor survival in patients with gastric cancer. In gastric cancer cells, TET1-targeted siRNA induced a decrease in 5 hmC, whereas TET1 overexpression induced an increase in 5 hmC and reduced cell proliferation, thus correlating decreased 5 hmC with gastric carcinogenesis. We also report the epigenetic signatures responsible for regulating TET1 transcription. Methyl-CpG Binding Domain Sequencing and Reduced Representation Bisulfite Sequencing identified unique CpG methylation signatures at the CpG island 3'-shore region located 1.3 kb from the transcription start site of TET1 in gastric tumor cells but not in normal mucosa. The luciferase activity of constructs with a methylated 3'-shore sequence was greatly decreased compared with that of an unmethylated sequence in transformed gastric cancer cells. In gastric cancer cells, dense CpG methylation in the 3'-shore was strongly associated with TET1 silencing and bivalent histone marks. Thus, a decrease in 5 hmC may be a cause of gastric tumorigenesis owing to a decrease in TET1 expression through DNA methylation coupled with bivalent marks in the 3'-shore of TET1.