Associations of coffee and tea consumption with lung cancer risk.

Associations of coffee and tea consumption with lung cancer risk have been inconsistent, and most lung cancer cases investigated were smokers. Included in this study were over 1.1 million participants from 17 prospective cohorts. Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Potential effect modifications by sex, smoking, race, cancer subtype and coffee type were assessed. After a median 8.6 years of follow-up, 20 280 incident lung cancer cases were identified. Compared with noncoffee and nontea consumption, HRs (95% CIs) associated with exclusive coffee drinkers (≥2 cups/d) among current, former and never smokers were 1.30 (1.15-1.47), 1.49 (1.27-1.74) and 1.35 (1.15-1.58), respectively. Corresponding HRs for exclusive tea drinkers (≥2 cups/d) were 1.16 (1.02-1.32), 1.10 (0.92-1.32) and 1.37 (1.17-1.61). In general, the coffee and tea associations did not differ significantly by sex, race or histologic subtype. Our findings suggest that higher consumption of coffee or tea is associated with increased lung cancer risk. However, these findings should not be assumed to be causal because of the likelihood of residual confounding by smoking, including passive smoking, and change of coffee and tea consumption after study enrolment.

Quantifying the association of low-intensity and late initiation of tobacco smoking with total and cause-specific mortality in Asia.

BACKGROUND: Little is known about the health harms associated with low-intensity smoking in Asians who, on average, smoke fewer cigarettes and start smoking at a later age than their Western counterparts. METHODS: In this pooled analysis of 738 013 Asians from 16 prospective cohorts, we quantified the associations of low-intensity (<5 cigarettes/day) and late initiation (≥35 years) of smoking with mortality outcomes. HRs and 95% CIs were estimated for each cohort by Cox regression. Cohort-specific HRs were pooled using random-effects meta-analysis. FINDINGS: During a mean follow-up of 11.3 years, 92 068 deaths were ascertained. Compared with never smokers, current smokers who consumed <5 cigarettes/day or started smoking after age 35 years had a 16%-41% increased risk of all-cause, cardiovascular disease (CVD), respiratory disease mortality and a >twofold risk of lung cancer mortality. Furthermore, current smokers who started smoking after age 35 and smoked <5 cigarettes/day had significantly elevated risks of all-cause (HRs (95% CIs)=1.14 (1.05 to 1.23)), CVD (1.27 (1.08 to 1.49)) and respiratory disease (1.54 (1.17 to 2.01)) mortality. Even smokers who smoked <5 cigarettes/day but quit smoking before the age of 45 years had a 16% elevated risk of all-cause mortality; however, the risk declined further with increasing duration of abstinence. CONCLUSIONS: Our study showed that smokers who smoked a small number of cigarettes or started smoking later in life also experienced significantly elevated all-cause and major cause-specific mortality but benefited from cessation. There is no safe way to smoke-not smoking is always the best choice.

High-Risk Population Based on BC Risk Factors.

Breast cancer (BC) is the second leading cause of female cancers worldwide in 2018, followed by lung cancer, and the fifth fatal cancer, followed by lung, colorectal, gastric, and liver cancers. The incidence and mortality rates of breast cancer in Western women have been shown to decrease for a long period of time, while the incidence and mortality rates of Asian women are rapidly increasing. The incidence and mortality rates of BC in Western women have been changing to a recent decrease from a fluctuation in rates for a long time, while in Asian women, the incidence and mortality rates have increased rapidly. The secular changes in rates are mainly related to medical advancement in treatment or diagnosis for BC, and preventive management and policy in each country, but also to the change of risk factors in the population.In this chapter, we briefly review the epidemiologic characteristics of breast cancer reported so far and summarize the results for various risk factors of breast cancer. Moreover, we summarize the potential for risk modification in high-risk population of breast cancer with various risk factors.

The U-shaped association between body mass index and gastric cancer risk in the Helicobacter pylori Biomarker Cohort Consortium: A nested case-control study from eight East Asian cohort studies.

The association between body mass index (BMI) and noncardia gastric cancer (NCGC) risk remains controversial. The purpose of our study was to examine the association of BMI with NCGC risk with consideration of Helicobacter pylori (HP) biomarkers. This international nested case-control study, composed of 1,591 incident NCGC cases and 1,953 matched controls, was established from eight cohorts in China, Japan and Korea, where the majority of NCGCs are diagnosed worldwide. HP antibody biomarkers were measured in blood collected at cohort enrollment by multiplex serology. The NCGC risk according to baseline BMI was estimated using logistic regression to produce odds ratios (ORs) and 95% confidence intervals (CIs). We found a U-shaped association between BMI category and NCGC risk. Compared to those with reference BMI (22.6-25.0 kg/m2 ), those with lower and higher BMI had an increased NCGC risk (BMI <18.5 kg/m2 , OR = 1.56, 95% CI = 1.04-2.34; BMI >27.5 kg/m2 , OR = 1.48, 95% CI = 1.15-1.91; adjusted for age, sex and smoking). The U-shaped association was persistent among subjects with HP infection and high-risk biomarkers (HP+ CagA+: BMI <18.5 kg/m2 , OR = 1.60, 95% CI = 1.00-2.55; BMI >27.5 kg/m2 , OR = 1.59, 95% CI = 1.21-2.11; and Omp+ HP0305+: BMI <18.5 kg/m2 , OR = 1.88, 95% CI = 1.04-3.42; BMI >27.5 kg/m2 , OR = 1.70, 95% CI = 1.20-2.42, respectively). Our study provides evidence of significantly increased NCGC risk among individuals with low or high BMI, including in subjects with high-risk HP biomarkers (HP+ CagA+, Omp+ HP0305+) in the high-risk area of East Asia.

Altered Hypothalamus-Pituitary-Adrenal Axis Function: A Potential Underlying Biological Pathway for Multiple Concurrent Symptoms in Patients With Advanced Lung Cancer.

OBJECTIVE: Patients with advanced cancer commonly experience multiple symptoms that present as groups or clusters. The present study aimed to examine whether hypothalamus-pituitary-adrenal (HPA) axis dysfunction underlies the concurrent multiple symptoms in patients with advanced cancer. METHODS: Patients' cortisol levels were determined in saliva samples collected after awakening (0, 30, and 60 minutes after awakening) and at nighttime (21:00-22:00 PM) from 46 patients with lung cancer (15.2% women), with a mean (standard deviation) age of 64.3 (9.2) years and 47 healthy participants (53.2% women; age = 62.0 [4.6] years). Cancer-related symptoms were measured using the M.D. Anderson Symptom Inventory (MDASI). RESULTS: Compared with healthy participants, patients showed a significantly reduced cortisol awakening response (F(1,364) = 46.2, p < .001) and had flatter diurnal slope of cortisol (larger ß values) (mean [standard error of the mean] = -0.64 [0.06] versus -0.18 [0.05], p < .001). Altered HPA axis function was significantly and adversely associated with performance status and burden of symptoms (all p values < .01). However, each MDASI item varied widely in the degree of association with the HPA axis function. Hierarchical clustering analysis based on Spearman's rank correlation with complete linkage identified that nausea was clustered with vomiting, numbness, and dry mouth, whereas the other nine MDASI core symptoms associated with altered HPA axis function were clustered together. CONCLUSIONS: Altered HPA axis function may be a possible biological pathway that can explain the concurrence of core symptoms in patients with advanced lung cancer.

Associations between genetic polymorphisms of membrane transporter genes and prognosis after chemotherapy: meta-analysis and finding from Seoul Breast Cancer Study (SEBCS).

Membrane transporters can be major determinants of the pharmacokinetic profiles of anticancer drugs. The associations between genetic variations of ATP-binding cassette (ABC) and solute carrier (SLC) genes and cancer survival were investigated through a meta-analysis and an association study in the Seoul Breast Cancer Study (SEBCS). Including the SEBCS, the meta-analysis was conducted among 38 studies of genetic variations of transporters on various cancer survivors. The population of SEBCS consisted of 1338 breast cancer patients who had been treated with adjuvant chemotherapy. A total of 7750 SNPs were selected from 453 ABC and/or SLC genes typed by an Affymetrix 6.0 chip. ABCB1 rs1045642 was associated with poor progression-free survival in a meta-analysis (HR = 1.33, 95% CI: 1.07-1.64). ABCB1, SLC8A1, and SLC12A8 were associated with breast cancer survival in SEBCS (Pgene < 0.05). ABCB1 rs1202172 was differentially associated with survival depending on the chemotherapy (Pinteraction = 0.035). Our finding provides suggestive associations of membrane transporters on cancer survival.

Environmental contributions to gastrointestinal and liver cancer in the Asia-Pacific region.

In the Asia-Pacific region, gastric, colorectal, and hepatocellular (liver) cancer show substantial regional variation in incidence consistent with the presence of important environmental factors. For gastric cancer, global incidence is concentrated in Asia with substantially higher rates in East Asia than in South-East Asia and Australia. The differences in incidence rates for gastric cancer in the Asia-Pacific region may be due, in part, to differences in the prevalence of Helicobacter pylori infection and the prevalence of H. pylori virulence factors. Smoking is also correlated with gastric cancer risk and is responsible for the highest population attributable fraction among men in East Asia. Colorectal cancer has increased rapidly in incidence to become the third most common digestive cancer in Asia. According to cohort studies in Asia, smoking, alcohol use, obesity, and physical inactivity increase the risk of colorectal cancer. Unlike West Asia, East Asia and Australia have high incidence rates for colorectal cancer that correlates to a high Human Development Index and a high prevalence of alcohol consumption and obesity. Liver cancer is the second most common digestive cancer in Asia. The high incidence of liver cancer in East Asia and South-East Asia is concordant with the high prevalence of hepatitis B virus and hepatitis C virus infection. Other important risk factors include alcohol use, smoking, and diabetes. The identification of the earlier and other environmental factors (currently under investigation) is central to the development and implementation of effective cancer control programs for the region.

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

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

The association between somatic and psychological discomfort and health-related quality of life according to the elderly and non-elderly.

PURPOSE: Symptoms and discomfort are common complaints in primary care settings. It has been postulated that the physical symptoms are informative index in estimating Health-related quality of life (HRQOL). Thus, we conducted a community-based cross-sectional study to assess the relationship between somatic and psychological discomfort and HRQOL in elderly and non-elderly people. METHODS: A total of 2467 participants were recruited in 2013 from a population of 17,066 rural residents aged 20 or older. Information on demographic characteristics, somatic and psychological discomfort symptoms, and HRQOL was collected. Two months after the baseline survey, we conducted a repeated survey to assess changes in the discomfort symptoms and HRQOL. We evaluated associations of the discomfort symptoms with HRQOL using multiple linear regression and mixed model. RESULTS: EuroQol-Visual Analogue Scale (EQ-VAS), index of HRQOL, was correlated with fatigue, pain, sleep disturbances, indigestion, and anxiety/depression, after adjusting for covariates. However, the factors most significantly associated with EQ-VAS differed between the elderly and non-elderly. Pain was the most important factor contributing to EQ-VAS in the elderly, whereas depression and anxiety were the predominant factors in the non-elderly. These relationships were replicated in the repeated measurements to assess the change of symptoms and change of EQ-VAS. CONCLUSION: Our study suggests that somatic and psychological discomfort symptoms are associated with HRQOL. The main factors related to HRQOL vary according to age and large prospective studies and clinical trials are needed to clarify the association between specific symptoms and HRQOL according to the age.

Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium.

AIMS/HYPOTHESIS: The aims of the study were to evaluate the association between type 2 diabetes and the risk of death from any cancer and specific cancers in East and South Asians. METHODS: Pooled analyses were conducted of 19 prospective population-based cohorts included in the Asia Cohort Consortium, comprising data from 658,611 East Asians and 112,686 South Asians. HRs were used to compare individuals with diabetes at baseline with those without diabetes for the risk of death from any cancer and from site-specific cancers, including cancers of the oesophagus, stomach, colorectum, colon, rectum, liver, bile duct, pancreas, lung, breast, endometrium, cervix, ovary, prostate, bladder, kidney and thyroid, as well as lymphoma and leukaemia. RESULTS: During a mean follow-up of 12.7 years, 37,343 cancer deaths (36,667 in East Asians and 676 in South Asians) were identified. Baseline diabetes status was statistically significantly associated with an increased risk of death from any cancer (HR 1.26; 95% CI 1.21, 1.31). Significant positive associations with diabetes were observed for cancers of the colorectum (HR 1.41; 95% CI 1.26, 1.57), liver (HR 2.05; 95% CI 1.77, 2.38), bile duct (HR 1.41; 95% CI 1.04, 1.92), gallbladder (HR 1.33; 95% CI 1.10, 1.61), pancreas (HR 1.53; 95% CI 1.32, 1.77), breast (HR 1.72; 95% CI 1.34, 2.19), endometrium (HR 2.73; 95% CI 1.53, 4.85), ovary (HR 1.60; 95% CI 1.06, 2.42), prostate (HR 1.41; 95% CI 1.09, 1.82), kidney (HR 1.84; 95% CI 1.28, 2.64) and thyroid (HR 1.99; 95% CI 1.03, 3.86), as well as lymphoma (HR 1.39; 95% CI 1.04, 1.86). Diabetes was not statistically significantly associated with the risk of death from leukaemia and cancers of the bladder, cervix, oesophagus, stomach and lung. CONCLUSIONS/INTERPRETATION: Diabetes was associated with a 26% increased risk of death from any cancer in Asians. The pattern of associations with specific cancers suggests the need for better control (prevention, detection, management) of the growing epidemic of diabetes (as well as obesity), in order to reduce cancer mortality.

Population attributable risks of modifiable reproductive factors for breast and ovarian cancers in Korea.

BACKGROUND: Breast and ovarian cancers are predominant female cancers with increasing prevalence. The purpose of this study was to estimate the population attributable risks (PARs) of breast and ovarian cancer occurrence based on the relative risks (RRs) of modifiable reproductive factors and population-specific exposure prevalence. METHODS: The PAR was calculated by using the 1990 standardized prevalence rates, the 2010 national cancer incidence with a 20 year lag period, the meta-analyzed RRs from studies conducted in the Korean population for breast cancer, and the meta-analyzed RRs from a Korean epithelial ovarian cancer study and a prior meta-analysis, and ovarian cancer cohort results up to 2012. For oral contraceptive and hormone replacement therapy use, we did not consider lag period. RESULTS: The summary PARs for modifiable reproductive factors were 16.7% (95% CI 15.8-17.6) for breast cancer (2404 cases) and 81.9% (95% CI 55.0-100.0) for ovarian cancer (1579 cases). The modifiable reproductive factors included pregnancy/age at first birth (8.0%), total period of breastfeeding (3.1%), oral contraceptive use (5.3%), and hormone replacement therapy use (0.3%) for breast cancer and included breastfeeding experience (2.9%), pregnancy (1.2%), tubal ligation (24.5%), and oral contraceptive use (53.3%) for ovarian cancer. CONCLUSIONS: Despite inherent uncertainties in the risk factors for breast and ovarian cancers, we suggest that appropriate long-term control of modifiable reproductive factors could reduce breast and ovarian cancer incidences and their related burdens by 16.7% and 81.9%, respectively.

Plasma isoflavone concentration is associated with decreased risk of type 2 diabetes in Korean women but not men: results from the Korean Genome and Epidemiology Study.

AIMS/HYPOTHESIS: To examine the association between soybean products and risk of type 2 diabetes, we measured four isoflavone biological markers--genistein, daidzein, glycitein and equol--in a nested case-control study. METHODS: The study population was composed of 693 cases (316 women and 377 men) and 698 matched controls (317 women and 381 men) within the Korean Genome and Epidemiology Study. The concentrations of isoflavone biomarkers were measured using HPLC-MS/MS on plasma samples that were collected at baseline. A stratified analysis was undertaken to examine the association between plasma isoflavone concentrations and risk of type 2 diabetes according to sex and equol production. Logistic regression models were used to compute ORs and 95% CIs adjusted for confounders. RESULTS: In women, compared with the lowest quartile of plasma concentration of genistein, the highest quartile exhibited a significantly decreased risk of diabetes (OR 0.58, 95% CI 0.35, 0.95). When stratified by equol-producing status in women, the OR for diabetes in the highest vs the lowest quartile of genistein concentration was 0.31 (95% CI 0.16, 0.60) in equol producers, but genistein concentration was not associated with risk of diabetes in equol non-producers (p for interaction = 0.013). In men, isoflavone concentrations were not associated with risk of diabetes, regardless of equol-producing status. CONCLUSIONS/INTERPRETATION: High plasma concentrations of genistein were associated with a decreased risk of type 2 diabetes in women. This inverse association was prominent in equol-producing participants. These results suggest a beneficial effect of a high intake of soybean products on risk of type 2 diabetes in women.

Associations of body mass index, smoking, and alcohol consumption with prostate cancer mortality in the Asia Cohort Consortium.

Many potentially modifiable risk factors for prostate cancer are also associated with prostate cancer screening, which may induce a bias in epidemiologic studies. We investigated the associations of body mass index (weight (kg)/height (m)(2)), smoking, and alcohol consumption with risk of fatal prostate cancer in Asian countries where prostate cancer screening is not widely utilized. Analysis included 18 prospective cohort studies conducted during 1963-2006 across 6 countries in southern and eastern Asia that are part of the Asia Cohort Consortium. Body mass index, smoking, and alcohol intake were determined by questionnaire at baseline, and cause of death was ascertained through death certificates. Analysis included 522,736 men aged 54 years, on average, at baseline. During 4.8 million person-years of follow-up, there were 634 prostate cancer deaths (367 prostate cancer deaths across the 11 cohorts with alcohol data). In Cox proportional hazards analyses of all cohorts in the Asia Cohort Consortium, prostate cancer mortality was not significantly associated with obesity (body mass index >25: hazard ratio (HR) = 1.08, 95% confidence interval (CI): 0.85, 1.36), ever smoking (HR = 1.00, 95% CI: 0.84, 1.21), or heavy alcohol intake (HR = 1.00, 95% CI: 0.74, 1.35). Differences in prostate cancer screening and detection probably contribute to differences in the association of obesity, smoking, or alcohol intake with prostate cancer risk and mortality between Asian and Western populations and thus require further investigation.

Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls.

In a consortium including 23 637 breast cancer patients and 25 579 controls of East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in 67 independent breast cancer susceptibility loci recently identified by genome-wide association studies (GWASs) conducted primarily in European-ancestry populations. SNPs in 31 loci showed an association with breast cancer risk at P < 0.05 in a direction consistent with that reported previously. Twenty-one of them remained statistically significant after adjusting for multiple comparisons with the Bonferroni-corrected significance level of <0.0015. Eight of the 70 SNPs showed a significantly different association with breast cancer risk by estrogen receptor (ER) status at P < 0.05. With the exception of rs2046210 at 6q25.1, the seven other SNPs showed a stronger association with ER-positive than ER-negative cancer. This study replicated all five genetic risk variants initially identified in Asians and provided evidence for associations of breast cancer risk in the East Asian population with nearly half of the genetic risk variants initially reported in GWASs conducted in European descendants. Taken together, these common genetic risk variants explain ~10% of excess familial risk of breast cancer in Asian populations.

Impact of alcohol drinking on gastric cancer development according to Helicobacter pylori infection status.

BACKGROUND: Helicobacter pylori are major carcinogen of gastric cancer, but the associations among gastric cancer, H. pylori infection status, and alcohol consumption are not fully described. This study aimed to clarify how H. pylori infection status affects the association between alcohol consumption and gastric cancer risk. METHODS: We selected 949 case-cohort participants from the 18,863 Korean Multi-center Cancer Cohort (KMCC) populations. Gastric cancer incidence inside and outside of the subcohort were 12 and 254 cases, respectively. Seropositivities for CagA, VacA, and H. pylori infection were determined by performing immunoblot assays. Weighted Cox regression models were used to calculate hazard ratios and 95% confidence intervals (CIs). RESULTS: Relative to non-drinking, heavy drinking (⩾7 times a week), and binge drinking (⩾55 g alcohol intake per occasion) showed a 3.48-fold (95% CI, 1.13-10.73) and 3.27-fold (95% CI, 1.01-10.56) higher risk in subjects not previously infected by H. pylori. There was no significant association between drinking pattern and gastric cancer risk in H. pylori IgG seropositive subjects. An increased risk for gastric cancer in heavy- and binge-drinking subjects were also present in subjects not infected by CagA- or VacA-secreting H. pylori. CONCLUSIONS: Heavy and binge alcohol consumption is an important risk factor related to an increasing incidence of gastric cancer in a population not infected by H. pylori.

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.

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.

Body mass index at age 18-20 and later risk of spontaneous abortion in the Health Examinees Study (HEXA).

BACKGROUND: Spontaneous abortion (SA) affects 11.2% of recognized pregnancies in Korea. Many studies have focused on the increased risk of SA in obese populations, but there are few studies that have focused on underweight (Body mass index (BMI) <18.5 kg/m2) women, especially in relation to pre-pregnancy BMI. The aim of this study was to examine the role of pre-pregnancy BMI at age 18-20 in later SA. METHODS: Among the women who were ever pregnant in the Health Examinees Study (HEXA), which was one of the cohorts studied in the KoGES (Korean Genome and Epidemiology Study) from 2004 to 2012 (N = 80,447), the likelihood of SA based on pre-pregnancy BMI, classified by the criteria for Asians (Underweight: <18.5 kg/m2; Normal range: 18.5-22.9 kg/m2; Overweight at risk: 23-24.9 kg/m2; Obese I: 25-29.9 kg/m2; Obese II: ≥30 kg/m2), was presented as odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression models. RESULTS: Being underweight or obese relative to the normal weight range was associated with a higher likelihood of SA (OR = 1.10 [95% CI = 1.05-1.15] in underweight women and OR = 1.06 [95% CI = 0.96-1.16] in obese women), and this effect was much greater in women who experienced recurrent SAs (for three or more SAs: OR = 1.29 [95% CI 1.14-1.46] in underweight women and OR = 1.39 [95% CI 1.09-1.78] in obese women). Obesity was associated with an increased likelihood of SA at a younger age (≤25 years), whereas underweight was associated with an increased OR of SA at an older age (≥26 years). DISCUSSION: As this study was conducted with baseline data of original cohort which focused on other chronic diseases, recall for previous pregnancy-related information might be less accurate. However, this study shows strength in its large size and prospective potential. CONCLUSIONS: Pre-pregnancy BMI at ages 18-20 years revealed a U-shaped association with SA, and underweight and obese women showed increased likelihood for SA during different age periods.

Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer.

Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-ß activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8×10(-12) in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85-0.94) and 0.80 (0.75-0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9×10(-6) from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6×10(-7)), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively.

Computational Discrimination of Breast Cancer for Korean Women Based on Epidemiologic Data Only.

Breast cancer is the second leading cancer for Korean women and its incidence rate has been increasing annually. If early diagnosis were implemented with epidemiologic data, the women could easily assess breast cancer risk using internet. National Cancer Institute in the United States has released a Web-based Breast Cancer Risk Assessment Tool based on Gail model. However, it is inapplicable directly to Korean women since breast cancer risk is dependent on race. Also, it shows low accuracy (58%-59%). In this study, breast cancer discrimination models for Korean women are developed using only epidemiological case-control data (n = 4,574). The models are configured by different classification techniques: support vector machine, artificial neural network, and Bayesian network. A 1,000-time repeated random sub-sampling validation is performed for diverse parameter conditions, respectively. The performance is evaluated and compared as an area under the receiver operating characteristic curve (AUC). According to age group and classification techniques, AUC, accuracy, sensitivity, specificity, and calculation time of all models were calculated and compared. Although the support vector machine took the longest calculation time, the highest classification performance has been achieved in the case of women older than 50 yr (AUC = 64%). The proposed model is dependent on demographic characteristics, reproductive factors, and lifestyle habits without using any clinical or genetic test. It is expected that the model could be implemented as a web-based discrimination tool for breast cancer. This tool can encourage potential breast cancer prone women to go the hospital for diagnostic tests.