Differential patterns of reproductive and lifestyle risk factors for breast cancer according to birth cohorts among women in China, Japan and Korea.

BACKGROUND: The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. METHODS: This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. RESULTS: Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66-1.13] compared to 0.60 [0.49-0.73], 0.46 [0.38-0.56] and 0.62 [0.51-0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14-1.84] compared to 1.25 [0.99-1.58], 1.06 [0.85-1.32] and 0.86 [0.69-1.08]) and alcohol consumption (1.22 [1.01-1.48] compared to 1.10 [0.90-1.33], 1.15 [0.96-1.38], and 1.07 [0.91-1.26]). CONCLUSION: We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.

Association between reproductive factors with lung cancer incidence and mortality: A pooled analysis of over 308,000 females in the Asia cohort consortium.

Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. In order to assess this association among Asian women, a total of 308,949 female participants from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). A total of 3,119 primary lung cancer cases and 2247 lung cancer deaths were identified with a mean follow-up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70-0.96) and 0.78 (95% CI = 0.65-0.94). The protective association of parity and lung cancer incidence was greater among ever-smokers (HR = 0.66, 95% CI = 0.49-0.87) than in never-smokers (HR = 0.90, 95% CI = 0.74-1.09) (P-interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (21-25, ≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Women who ever used hormone replacements had a higher likelihood of developing non-small cell lung cancer (HR = 1.31, 95% CI = 1.02-1.68), compared to those who never used hormone replacements. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time.

Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium.

The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone-related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16-1.70 for 17 years and older vs. 13-14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50-4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08-2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.

Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium.

Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2 ); normal (18.5-22.9 kg/m2 ); overweight (23-24.9 kg/m2 ); and obese (25+ kg/m2 ). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.

Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium.

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust.

Family history and gastric cancer incidence and mortality in Asia: a pooled analysis of more than half a million participants.

BACKGROUND: The family history of gastric cancer holds important implications for cancer surveillance and prevention, yet existing evidence predominantly comes from case-control studies. We aimed to investigate the association between family history of gastric cancer and gastric cancer risk overall and by various subtypes in Asians in a prospective study. METHODS: We included 12 prospective cohorts with 550,508 participants in the Asia Cohort Consortium. Cox proportional hazard regression was used to estimate study-specific adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between family history of gastric cancer and gastric cancer incidence and mortality, then pooled using random-effects meta-analyses. Stratified analyses were performed for the anatomical subsites and histological subtypes. RESULTS: During the mean follow-up of 15.6 years, 2258 incident gastric cancers and 5194 gastric cancer deaths occurred. The risk of incident gastric cancer was higher in individuals with a family history of gastric cancer (HR 1.44, 95% CI 1.32-1.58), similarly in males (1.44, 1.31-1.59) and females (1.45, 1.23-1.70). Family history of gastric cancer was associated with both cardia (HR 1.26, 95% CI 1.00-1.60) and non-cardia subsites (1.49, 1.35-1.65), and with intestinal- (1.48, 1.30-1.70) and diffuse-type (1.59, 1.35-1.87) gastric cancer incidence. Positive associations were also found for gastric cancer mortality (HR 1.30, 95% CI 1.19-1.41). CONCLUSIONS: In this largest prospective study to date on family history and gastric cancer, a familial background of gastric cancer increased the risk of gastric cancer in the Asian population. Targeted education, screening, and intervention in these high-risk groups may reduce the burden of gastric cancer.

Assessments of dietary intake and polygenic risk score in associations with colorectal cancer risk: evidence from the UK Biobank.

BACKGROUND: This study aimed to explore the potential interaction between dietary intake and genetics on incident colorectal cancer (CRC) and whether adherence to healthy dietary habits could attenuate CRC risk in individuals at high genetic risk. METHODS: We analyzed prospective cohort data of 374,004 participants who were free of any cancers at enrollment in UK Biobank. Dietary scores were created based on three dietary recommendations of the World Cancer Research Fund (WCRF) and the overall effects of 11 foods on CRC risks using the inverse-variance (IV) method. Genetic risk was assessed using a polygenic risk score (PRS) capturing overall CRC risk. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs (confidence intervals) of associations. Interactions between dietary factors and the PRS were examined using a likelihood ratio test to compare models with and without the interaction term. RESULTS: During a median follow-up of 12.4 years, 4,686 CRC cases were newly diagnosed. Both low adherence to the WCRF recommendations (HR = 1.12, 95% CI = 1.05-1.19) and high IV-weighted dietary scores (HR = 1.27, 95% CI = 1.18-1.37) were associated with CRC risks. The PRS of 98 genetic variants was associated with an increased CRC risk (HRT3vsT1 = 2.12, 95% CI = 1.97-2.29). Participants with both unfavorable dietary habits and a high PRS had a more than twofold increased risk of developing CRC; however, the interaction was not significant. Adherence to an overall healthy diet might attenuate CRC risks in those with high genetic risks (HR = 1.21, 95% CI = 1.08-1.35 for high vs. low IV-weighted dietary scores), while adherence to WCRF dietary recommendations showed marginal effects only (HR = 1.09, 95% CI = 1.00-1.19 for low vs. high WCRF dietary scores). CONCLUSION: Dietary habits and the PRS were independently associated with CRC risks. Adherence to healthy dietary habits may exert beneficial effects on CRC risk reduction in individuals at high genetic risk.

Association between metabolic syndrome and gastric cancer risk: results from the Health Examinees Study.

BACKGROUND: Previous studies suggested that metabolic syndrome (MetS) might create a pro-cancer environment and increase cancer incidence. However, evidence on the risk of gastric cancer (GC) was limited. This study aimed to evaluate the association between MetS and its components and GC in the Korean population. METHODS: Included were 108,397 individuals who participated in the large-scale prospective cohort study, the Health Examinees-Gem study during 2004-2017. The multivariable Cox proportional was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) on the association between MetS and its components with GC risk. Age was used as the time scale in the analyses. The stratified analysis was performed to determine the joint effect of lifestyle factors and MetS on GC risk in different groups. RESULTS: During the mean follow-up of 9.1 years, 759 cases of newly diagnosed cancer (408 men and 351 women) were identified. Overall, participants with MetS had a 26% increased risk of GC than those without MetS (HR 1.26; 95% CI 1.07-1.47); the risk increased with the number of MetS components (p for trend 0.01). Hypertriglyceridemia, low HDL-cholesterol, and hyperglycemia were independently associated with the risk of GC. The potential joint effect of MetS and current smokers (p for interaction 0.02) and obesity (BMI ≥ 25.0) (p for interaction 0.03) in GC. CONCLUSIONS: In this prospective cohort study, we found that MetS were associated with an increased risk of GC in the Korean population. Our findings suggest that MetS may be a potentially modifiable risk factor for GC risk.

Soybean product consumption decreases risk of gastric cancer: results from the Health Examinees Study.

BACKGROUND: Epidemiological findings on the association between soybean product consumption and gastric cancer risk remain inconsistent. We evaluated the relationship between soybean product consumption and the risk of gastric cancer in a prospective cohort study in Korea. METHODS: This prospective cohort study included a total of 139,267 participants aged 40-69 years from the Health Examinees-Gem (HEXA-G) study between 2004 and 2013. Information on cancer diagnosis was retrieved from the Korea Central Cancer Registry until 31 December 2018. Multivariate hazard ratios (HRs) and 95% of confidence intervals (CIs) for the risk of gastric cancer according to the consumption of soybean products were estimated using Cox proportional hazards models. RESULTS: A total of 767 incident cases of gastric cancer occurred over an average follow-up period of 9.21 years. We found that men who consumed two servings per week had 37% lower risk of gastric cancer compared with who consume those who almost never consumed (HR for tofu consumption of more than two servings/week vs. almost never consumed was 0.63 (95% CI 0.45, 0.89); p for trend = 0.04). Among men with a BMI of less than 25 kg/m2, increased consumption of soybean paste (p for trend = 0.02) and tofu (HR 0.51 (95% CI 0.32, 0.82 for more than two servings/week vs. almost never consumed); p for trend = 0.01) was associated with decreased risk of gastric cancer. CONCLUSION: Our results suggest that a high consumption of soybean products has a protective effect against gastric cancer.

Incorporating European GWAS findings improve polygenic risk prediction accuracy of breast cancer among East Asians.

Previous genome-wide association studies (GWASs) have been largely focused on European (EUR) populations. However, polygenic risk scores (PRSs) derived from EUR have been shown to perform worse in non-EURs compared with EURs. In this study, we aim to improve PRS prediction in East Asians (EASs). We introduce a rescaled meta-analysis framework to combine both EUR (N = 122,175) and EAS (N = 30,801) GWAS summary statistics. To improve PRS prediction in EASs, we use a scaling factor to up-weight the EAS data, such that the resulting effect size estimates are more relevant to EASs. We then derive PRSs for EAS from the rescaled meta-analysis results of EAS and EUR data. Evaluated in an independent EAS validation data set, this approach increases the prediction liability-adjusted Nagelkerke's pseudo R2 by 40%, 41%, and 5%, respectively, compared with PRSs derived from an EAS GWAS only, EUR GWAS only, and conventional fixed-effects meta-analysis of EAS and EUR data. The PRS derived from the rescaled meta-analysis approach achieved an area under the receiver operating characteristic curve (AUC) of 0.6059, higher than AUC = 0.5782, 0.5809, 0.6008 for EAS, EUR, and conventional meta-analysis of EAS and EUR. We further compare PRSs constructed by single-nucleotide polymorphisms that have different linkage disequilibrium (LD) scores and minor allele frequencies (MAFs) between EUR and EAS, and observe that lower LD scores or MAF in EAS correspond to poorer PRS performance (AUC = 0.5677, 0.5530, respectively) than higher LD scores or MAF (AUC = 0.589, 0.5993, respectively). We finally build a PRS stratified by LD score differences in EUR and EAS using rescaled meta-analysis, and obtain an AUC of 0.6096, with improvement over other strategies investigated.

The Association of Serum High-Sensitivity C-Reactive Protein Level With the Risk of Site-Specific Cancer Mortality: The Health Examinees (HEXA) Study Cohort.

Few studies have investigated the association between high-sensitivity C-reactive protein (hsCRP) level and site-specific cancer mortality. In this study, we aimed to examine the associations of hsCRP with overall and site-specific cancer mortality among South Koreans using data on the Health Examinees (HEXA) Study cohort (41,070 men and 81,011 women aged ≥40 years). We obtained mortality information from the National Statistical Office of Korea, which provided the dates and causes of all deaths occurring through December 31, 2015, by linking mortality data with each participant's unique national identifier. Cox proportional hazards and restricted cubic spline models were used to assess the association between hsCRP and cancer mortality with adjustment for covariates. An analysis of site-specific cancer mortality was focused on 5 major cancers (lung, liver, gastric, colorectal, and breast/prostate). Median hsCRP levels were 0.77 mg/L and 0.59 mg/L for men and women, respectively. A dose-response association between hsCRP and overall cancer mortality was observed in men but disappeared in women after exclusion of deaths occurring in the first 1 or 2 years of follow-up. Elevated hsCRP levels increased the risks of lung, liver, and gastric cancer mortality in men, but the risks of colorectal and breast cancer mortality were not increased. The dose-response association between hsCRP and cancer mortality was observed differently depending on site-specific cancer mortality by sex.

Polygenic risk scores for prediction of breast cancer risk in Asian populations.

PURPOSE: Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups. METHODS: The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases). RESULTS: The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk. CONCLUSION: PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry.

Socioecological approach for identifying the determinants of objectively measured physical activity: A prospective study of the UK Biobank.

The socioecological approach emphasises that health promotion should focus on a variety of factors that surround individuals simultaneously, yet there is little evidence on how these factors relatively affect physical activity (PA). The main objective was to identify relevant determinants of PA by examining the associations between factors within multilayered socioecological categories and PA. A prospective analysis was conducted with 84,052 participants participating in the accelerometer measurement from the UK Biobank. Time spent in moderate-to-vigorous PA (MVPA) was calculated from participants who wore a wrist-worn accelerometer for seven days; a questionnaire-based self-reported leisure-time physical activity was also assessed. A categorical principal component analysis was conducted to reduce the dimensions of 184 variables. The associations between principal components (PCs) and PA were evaluated using general linear models. A network of PCs was constructed to assess the comprehensive association with PA. PCs related to body composition and chronic diseases were suggested as key determinants of objectively measured MVPA and found to be clustered in the network. PCs related to body composition and socio-economic status were proposed as the key regulatory hubs in the network because they exhibited the highest level of indirect linkages with other components. In the environmental category, PCs related to greenness and air pollution were revealed to be key factors in the self-reported walking for pleasure. Using a socioecological approach, it was discovered that obesity and disease-related factors were the most important determinants, and they had an integrative influence with other factors in different categories.

Comparison of the Prevalence of Cardiometabolic Disorders and Comorbidities in Korea and the United States: Analysis of the National Health and Nutrition Examination Survey.

BACKGROUND: Comparison of the prevalence of cardiometabolic disorders (CMDs) and comorbidities in Korea and the United States (US) can be an important indicator for forecasting future risk of cardiovascular events in Korea. This study aimed to estimate and compare the prevalence of hypertension, diabetes mellitus (DM), dyslipidemia, obesity, and metabolic syndrome (MetS) in Korea and the US. METHODS: A total of 15,872 individuals from the US National Health and Nutrition Examination Survey (NHANES) 2003-2014 and 26,492 from the Korea NHANES (KNHANES) 2007-2014 were included. Additionally, 164,339 (139,345 from the Health Examinees-Gem Study and 24,994 from the Cardiovascular Disease Association Study) participants enrolled in the Korea Genome and Epidemiology Study were included to investigate the differences of CMDs between urban and rural regions. To estimate the age-standardized prevalence of CMDs in individuals aged 40-69 years, direct standardization using the World Health Organization standard population was performed. RESULTS: The prevalence of CMDs was lower in Korea than the US (hypertension 49.9% vs. 56.8%; DM 13.4% vs. 14.3%; hypercholesterolemia 16.8% vs. 17.8%; obesity 36.2% vs. 38.6%; and MetS 29.4% vs. 36.5%). According to the median survey years, dyslipidemia has become more prevalent in Korea than in the US since 2010. The prevalence of CMDs was greater in rural than that in urban areas in Korea. CONCLUSION: The prevalence of dyslipidemia in Korea exceeded that of the US after 2010, which was associated with increasing burden of cardiovascular events. The present study suggests that further preventive strategies are needed to mitigate the prevalence of CMDs in Korea.

Relative Effects of Demographic, Psychological, Behavioral, and Social Factors on the Initiation and Maintenance of Leisure-time Physical Activity: Results From a Confirmatory Path Analysis in a Longitudinal Study.

BACKGROUND: There is a lack of evidence of the complicated pathways of underlying determinants in the phases of physical activity. The purpose of this study was to evaluate simultaneously a set of potential determinants on the initiation and maintenance phases of leisure-time physical activity (LTPA). METHODS: The longitudinal data of 54,359 Korean adults aged 40-69 years from the Health Examinees study were used. The median follow-up duration was 4.2 years. The self-reported durations per week of LTPA was repeatedly assessed. Based on previous longitudinal studies, the potential determinants were selected, and hypothetical models were constructed that consider the complex associations between the determinants. The standardized coefficients for direct and indirect effects were estimated using path analysis to differentiate contributions of mediation from the total effects. RESULTS: In the total population, age, education, chronic diseases, smoking, depression symptoms, and self-rated health were significantly associated with both initiation and maintenance phases. Income (B = 0.025) and social supports (B = 0.019) were associated only with the initiation phase. Waist-to-hip ratio (B = -0.042) and stress (B = -0.035) were associated only with the maintenance phase. After stratifying by sex, the significant effects of education, chronic diseases, and smoking were found only in men. The initiation phase-specific effects of income and social supports and the maintenance phase-specific effects of stress were found only in women. It was estimated that indirect effects contributed approximately 15% of the total effect. CONCLUSION: The findings suggested that there were initiation- or maintenance-specific determinants of leisure-time physical activity according to sex.

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.

Optimal cutoff values for anthropometric indices of obesity as discriminators of metabolic abnormalities in Korea: results from a Health Examinees study.

BACKGROUND: Obesity is well known as a risk factor for cardiovascular disease. We aimed to determine the performance of and the optimal cutoff values for obesity indices to discriminate the presence of metabolic abnormalities as a primary risk factor for cardiovascular diseases in a Health Examinees study (HEXA). METHODS: The current study analyzed 134,195 participants with complete anthropometric and laboratory information in a Health Examinees study, consisting of the Korean population aged 40 to 69 years. The presence of metabolic abnormality was defined as having at least one of the following: hypertension, hyperglycemia, or dyslipidemia. The area under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CIs) were calculated for body mass index, waist to hip ratio, waist to height ratio, waist circumference, and conicity index. RESULTS: The AUC of metabolic abnormalities was the highest for waist-to-height ratio (AUC [95% CIs], 0.677 [0.672-0.683] among men; 0.691 [0.687-0.694] among women), and the lowest for the C index (0.616 [0.611-0.622] among men; 0.645 [0.641-0.649] among women) among both men and women. The optimal cutoff values were 24.3 kg/m2 for the body mass index, 0.887 for the waist-to-hip ratio, 0.499 for the waist-to-height ratio, 84.4 cm for waist circumference and 1.20 m3/2/kg1/2 for the conicity index among men, and 23.4 kg/m2 for the body mass index, 0.832 for the waist-to-hip ratio, 0.496 for the waist-to-height ratio, 77.0 cm for the waist circumference and 1.18 m3/2/kg1/2 for the conicity index among women. CONCLUSION: The waist-to-height ratio is the best index to discriminate metabolic abnormalities among middle-aged Koreans. The optimal cutoff of obesity indices is lower than the international guidelines for obesity. It would be appropriate to use the indices for abdominal obesity rather than general obesity and to consider a lower level of body mass index and waist circumference than the current guidelines to determine obesity-related health problems in Koreans.

Breast Cancer-Related Low Penetrance Genes.

Susceptibility genes involved in disease etiology and prognosis are categorized into two groups: high penetrance genes (i.e., BRCA1, CHEK2, ATM, etc.) and low penetrance genes (i.e., NATs, GSTs, CYPs, etc., and variants identified by genome-wide association studies). Since low penetrance genes have high population attributable risk, the usefulness of those genes to research on breast cancer prevention is not small. In this chapter, the previous studies on low-penetrance genetic susceptibility through a candidate gene approach and genome-wide association of breast cancer were summarized. The contribution of low-penetrance susceptibility genes to the breast cancer risk prediction models will also be discussed on the utility in clinical or public health application.

Effect of 'rice' pattern on high blood pressure by gender and obesity: using the community-based KoGES cohort.

OBJECTIVE: The present study aimed to examine the association between dietary pattern and the risk of high blood pressure (BP) and to estimate the attenuated effect by gender and obesity on the association using data from a prospective cohort study in Korea. DESIGN: Prospective study. Diet was assessed using a validated 103-item FFQ and was input into factor analysis after adjustment for total energy intake. SETTING: Community-based Korean Genome Epidemiology Study (KoGES) cohort. PARTICIPANTS: Healthy individuals (n 5151) without high BP at recruitment from the community-based cohort study. RESULTS: Dietary pattern was not associated with the risk of high BP regardless of the type of covariates, with the exception of the 'rice' pattern. The effect of the 'rice' pattern was observed in both men (Ptrend = 0·013) and women (Ptrend < 0·001), but the statistical significance remained only in women after adjustment for confounders (Ptrend = 0·004). The positive association of the 'rice' pattern with high BP risk was attenuated by obesity. After stratification by gender and obese status, in particular, the harmful effect of the 'rice' pattern was predominantly observed in obese women (Ptrend < 0·001) only. CONCLUSIONS: This longitudinal study in Korean adults found a positive association of the 'rice' pattern with long-term development of incident high BP, predominantly in women. The association is likely to be attenuated by gender and obese status.

Trends and Correlates of High-Risk Alcohol Consumption and Types of Alcoholic Beverages in Middle-Aged Korean Adults: Results From the HEXA-G Study.

BACKGROUND: We aimed to report the prevalence and correlates of high-risk alcohol consumption and types of alcoholic beverages. METHODS: The baseline data of the Health Examinees-Gem (HEXA-G) study participants, including 43,927 men and 85,897 women enrolled from 2005 through 2013, were used for analysis. Joinpoint regression was performed to estimate trends in the age-standardized prevalence of alcohol consumption. Associations of demographic and behavioral factors, perceived health-related effects, social relationships, and the diagnostic history of diseases with alcohol consumption were assessed using multinomial logistic regression. RESULTS: The prevalence of alcohol consumption remained higher in men during the study period and increased in women. The amount of alcohol consumed has increased in women, especially that from beer and makgeolli, a traditional Korean fermented rice wine. Older participants were less likely to be high-risk drinkers (men and women who drink more than 40 or 20 g/day of alcohol, respectively) and drink Soju, a distilled liquor, and beer, and more likely to drink makgeolli. Educational level was negatively associated with high-risk drinking. However, it was positively associated with the consumption of strong spirits and wine. Smoking was associated with high-risk drinking and the consumption of soju and strong spirits. Engaging in regular exercise and having stress were associated with drinking all types of beverages except for soju. CONCLUSIONS: Sex-specific trends in alcohol consumption were influenced by demographic, behavioral, and perceived health-related factors. The findings will help improve the understanding of alcohol-related problems and provide evidence for establishing country-specific policies and campaigns in Korea.