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Hepatitis B virus (HBV) infection is common throughout Asia and Africa. Whether chronic HBV infection increases risk of non-Hodgkin lymphoma (NHL) is unclear. We aimed to assess the association between chronic HBV infection and subsequent development of NHL in a South Korean cohort. The Korean Cancer Prevention Study is a cohort study of South Korean workers and their dependants enrolled during 1992–95. From this cohort, we excluded individuals who died before Jan 1, 1993, who had cancer at or before the initial visit, who had missing information about weight, height, alanine aminotransferase or aspartate aminotransferase concentrations, or alcohol use, or who had evidence of HIV or HCV infection. Of 1 284 586 eligible participants, 603 585 had baseline data for serum hepatitis B surface antigen (HBsAg) status and were included in our study. We regarded HBsAg positivity at baseline as evidence of chronic HBV infection. Participants were followed up from baseline until Dec 31, 2006. We used national databases of inpatient and outpatient diagnoses and mortality records to ascertain occurrence of haematological malignancies. We assessed incidence of NHL overall and of NHL subtypes, malignant immunoproliferation, Hodgkin's lymphoma, multiple myeloma, and various leukaemias. We used Cox regression to evaluate associations with HBsAg status, adjusting for sex, age, and enrolment year. 53 045 (9%) of 603 585 participants tested positive for HBsAg at baseline. Subsequently, 133 HBsAg-positive and 905 HBsAg-negative individuals developed NHL. HBsAg-positive participants had an increased risk of NHL overall compared with those who were HBsAg-negative (incidence 19·4 vs 12·3 per 100 000 person-years; hazard ratio [HR] 1·74, 95% CI 1·45–2·09, adjusted for sex, age at baseline, and enrolment year). Among NHL subtypes, HBsAg positivity was associated with increased risk of diffuse large B-cell lymphoma (n=325, incidence 6·86 vs 3·79 per 100 000 person-years; adjusted HR 2·01, 1·48–2·75) and other or unknown subtypes (n=591, incidence 10·5 vs 7·07 per 100 000 person-years; adjusted HR 1·65, 1·29–2·11), compared with HBsAg negativity. Increased risk was also recorded for malignant immunoproliferation (n=14, incidence 0·44 vs 0·15 per 100 000 person-years; adjusted HR 3·79, 1·05–13·7). Risk of these malignancies was consistently raised in HBsAg-positive participants throughout 14 years of follow-up. HBsAg positivity was not associated with follicular or T-cell NHL, Hodgkin's lymphoma, multiple myeloma, or various leukaemias. During extended follow-up, HBsAg-positive individuals had an increased risk of NHL, suggesting that chronic HBV infection promotes lymphomagenesis. Korean Seoul City Research and the National Research and Development Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea; US National Cancer Institute.

This 12-year prospective Korean cohort study from the National Health Insurance Corporation indicates that the relationship between the risk of death from any cause and body-mass index is J-shaped — higher in underweight, overweight, and obese men and women than in those of normal weight. The association between body-mass index and mortality varies according to the cause of death and is modified by age, sex, and smoking history. This 12-year prospective study indicates that the relationship between the risk of death from any cause and body-mass index is J-shaped — higher in underweight, overweight, and obese men and women than in those of normal weight. Although obesity is widely accepted as an important health risk, the optimal body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) and the effects of being either underweight or overweight on the risk of death are controversial. In the Cancer Prevention Study (CPS) II, 1 sponsored by the American Cancer Society, the rate of death was lowest among men with a BMI of 23.5 to 24.9 and among women with a BMI of 22.0 to 23.4; above and below these levels, the risk of death increased. However, being overweight was not associated with an . . .

Previous studies of urinary bisphenol A (BPA), phthalate metabolites, and obesity risk have shown inconsistent results. Menopausal status is one of the main factors that affect hormone secretion change in women. In this study, we examined whether urinary BPA and phthalate metabolite levels are associated with obesity and whether the associations differ by sex and menopausal status in a sample of Korean adult populations. We recruited participants at three branches (Yeouido, Gangnam, and Gwanghwamun) of the Korea Medical Institute, a nationwide health check-up center, from 2015 to 2016. Urinary BPA level was measured by high-performance liquid chromatography–tandem mass spectrometry (Agilent 6490 Triple Quad LC-MS/MS; Agilent Technologies, CA, USA). Urinary six phthalate metabolites were analyzed with ultra-high-performance liquid chromatography–tandem mass spectrometry (TSQ Quantum Access Mass; Thermo Fisher Scientific, MA, USA). Participants with body mass index ≥ 25 kg/m 2 were defined as general obesity group. Men with waist circumference (WC) ≥ 90 cm and women with WC ≥ 85 cm were defined as abdominal obesity group. Age, sex, alcohol intake, smoking, and exercise were considered in multivariate logistic regression models. Among the total of 702 participants, 211 participants were classified into the general obesity group, and 131 participants were classified into the abdominal obesity group. Urinary phthalate metabolite levels were not associated with general and abdominal obesity in men and women. However, in women, urinary BPA concentration was positively associated with abdominal obesity (OR = 1.50, 95% CI 1.00–2.26). Also, the association was stronger in postmenopausal women (OR = 2.23, 1.01–4.92), while it was weak in premenopausal women (OR = 1.31, 0.78–2.20). In this study, urinary BPA concentration was associated with abdominal obesity in women, especially postmenopausal women. Future studies should consider sex and menopausal status when investigating associations between urinary BPA, phthalate metabolites levels, and obesity.

Better information on lung cancer occurrence in lifelong nonsmokers is needed to understand gender and racial disparities and to examine how factors other than active smoking influence risk in different time periods and geographic regions. We pooled information on lung cancer incidence and/or death rates among self-reported never-smokers from 13 large cohort studies, representing over 630,000 and 1.8 million persons for incidence and mortality, respectively. We also abstracted population-based data for women from 22 cancer registries and ten countries in time periods and geographic regions where few women smoked. Our main findings were: (1) Men had higher death rates from lung cancer than women in all age and racial groups studied; (2) male and female incidence rates were similar when standardized across all ages 40+ y, albeit with some variation by age; (3) African Americans and Asians living in Korea and Japan (but not in the US) had higher death rates from lung cancer than individuals of European descent; (4) no temporal trends were seen when comparing incidence and death rates among US women age 40-69 y during the 1930s to contemporary populations where few women smoke, or in temporal comparisons of never-smokers in two large American Cancer Society cohorts from 1959 to 2004; and (5) lung cancer incidence rates were higher and more variable among women in East Asia than in other geographic areas with low female smoking. These comprehensive analyses support claims that the death rate from lung cancer among never-smokers is higher in men than in women, and in African Americans and Asians residing in Asia than in individuals of European descent, but contradict assertions that risk is increasing or that women have a higher incidence rate than men. Further research is needed on the high and variable lung cancer rates among women in Pacific Rim countries.

We tested the hypothesis that the cumulative effects of common genetic variants related to elevated fasting glucose are collectively associated with oxidative stress. Using 25 single nucleotide polymorphisms (SNPs), a weighted genetic risk score (wGRS) was constructed by summing nine risk alleles based on nominal significance and a consistent effect direction in 1,395 controls and 718 patients with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes. All the participants were divided into the following three groups: low-wGRS, middle-wGRS, and high-wGRS groups. Among the nine SNPs, five SNPs were significantly associated with IFG and type 2 diabetes in this Korean population. wGRS was significantly associated with increased IFG and newly diagnosed type 2 diabetes ( p  = 6.83 × 10 −14 , odds ratio = 1.839) after adjusting for confounding factors. Among the IFG and type 2 diabetes patients, the fasting serum glucose and HbA 1c levels were significantly higher in the high-wGRS group than in the other groups. The urinary 8-epi-PGF 2α and malondialdehyde concentrations were significantly higher in the high-wGRS group than in the other groups. Moreover, general population-level instrumental variable estimation (using wGRS as an instrument) strengthened the causal effect regarding the largely adverse influence of high levels of fasting serum glucose on markers of oxidative stress in the Korean population. Thus, the combination of common genetic variants with small effects on IFG and newly diagnosed type 2 diabetes are significantly associated with oxidative stress.

Studies on the associations between persistent organic pollutants (POPs) and smoking according to gender and smoking amount (cigarettes/day) are limited, and the results regarding the relationship between POPs and smoking are not completely consistent across studies. The smoking rate in Korea is one of the highest among the Organization for Economic Cooperation and Development (OECD) countries. We investigated the association between serum concentrations of POPs and cigarette smoking in Koreans by smoking status (never-smoker/ever-smoker) and smoking amount (cigarettes/day) according to gender. Serum concentrations of 32 polychlorinated biphenyls (PCBs) and 19 organochlorine pesticides (OCPs) were measured in 401 participants (232 men and 169 women) who received health examinations during the Korean Cancer Prevention Study-II. We compared POP levels in ever-smokers and never-smokers and conducted multivariate logistic regression analyses to identify associations between POPs and smoking. Among women, the concentrations of PCB 156, PCB 167, and PCB 180 were significantly higher in ever-smokers than in never-smokers. After adjustments for age, body mass index, gamma-glutamyl transpeptidase, and alcohol intake, serum PCB 157 concentration was positively associated with male ever-smokers (OR 2.26; 95% CI, 1.01–5.04). In addition, trans-nonachlordane in OCPs as well as PCBs was significantly positively related with female ever-smokers (OR 3.21; 95% CI, 1.04–9.86). We found that subjects who smoked fewer than 15 cigarettes/day had a higher risk of having high POP concentrations than never-smokers. These results indicate that smoking may be associated with human serum POPs levels. •For women, serum PCB levels were higher in ever-smokers than in never-smokers.•The risk of high level of POPs was higher in ever-smokers than in never-smokers.•Subjects who smoked <15 cigarettes/day had a high risk of having high POP levels.

Bisphenol A (BPA) and phthalates are endocrine disruptors that can induce oxidative stress. Serum bilirubin has antioxidant properties and may serve as a biomarker of oxidative stress. The objective of this study was to explore the relationship of BPA and phthalates with serum bilirubin levels in a Korean population. Urinary concentrations of BPA and six phthalate [mono- n -butyl phthalate (MnBP), mono-iso-butyl phthalate (MiBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5- hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono-benzyl phthalate (MBzP)] were measured in 709 participants. Serum concentrations of BPA and three phthalate metabolites [MnBP, MiBP, and mono-(2-ethylhexyl) phthalate (MEHP)] were measured in 752 participants. After excluding missing variables, associations between above chemicals and serum bilirubin levels were analyzed using multivariate linear regression with age, sex, BMI, GGT, GOT, GPT, and alcohol intake adjustment. Participants were further stratified by sex. Among the urinary chemicals, BPA and four phthalate metabolites (MnBP, MEOHP, MEHHP and MECPP) were inversely associated with serum bilirubin levels (BPA: β  = − 0.071, P  < 0.0001; MnBP: β  = − 0.055, P  = 0.025; MEOHP: β  = − 0.101, P  < 0.0001; MEHHP: β  = − 0.106, P  < 0.0001; MECPP: β  = − 0.052, P  = 0.003). In a case of serum chemicals, only MiBP showed significantly positive association ( β  = 0.036, P  = 0.016). After stratification by sex, the associations of urinary BPA remained both in male and female, of which urinary phthalates disappeared in female. The association of serum MiBP was disappeared after stratification. Urinary BPA and phthalate metabolites were inversely associated with serum bilirubin levels, whereas serum MiBP showed positive association with bilirubin. These results could provide clues for understanding the mechanisms of endocrine disruptor from oxidative stress to excretion from our body.

Background: This study evaluated the association between bilirubin subtypes (total, indirect, and direct bilirubin) and thyroid cancer risk, with a particular focus on stratified analyses using the ALBI (Albumin-Bilirubin) and PALBI (Platelet-Albumin-Bilirubin) indices by sex, smoking and drinking status, and age under 50 years. Methods: Data were obtained from 133,596 participants in the Korean Cancer Prevention Study-II (KCPS-II) cohort. During a mean follow-up period of 13.55 years, 2314 cases of thyroid cancer (ICD-10: C73) were identified. Serum bilirubin levels and ALBI and PALBI indices were analyzed using Cox proportional hazards regression models stratified by age, sex, smoking, and alcohol consumption status to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In women, indirect bilirubin showed the strongest inverse association with thyroid cancer risk. ALBI and PALBI indices based on indirect bilirubin also demonstrated significant associations. A 1 standard deviation (SD) increase in indirect bilirubin was associated with a decreased risk of thyroid cancer (HR: 0.92, 95% CI: 0.84–0.99), and the ALBI index similarly showed an inverse association (HR: 0.92, 95% CI: 0.87–0.99). In contrast, the PALBI index was positively associated with thyroid cancer risk (HR: 1.11, 95% CI: 1.03–1.20). Among women who had never smoked, significant associations were observed for indirect bilirubin (HR: 0.91, 95% CI: 0.83–1.00), ALBI (HR: 0.93, 95% CI: 0.86–1.00), and PALBI (HR: 1.14, 95% CI: 1.05–1.23). In analyses stratified by alcohol consumption, the PALBI index was associated with increased thyroid cancer risk in non-drinkers, former drinkers, and ever drinkers, with respective risk increases of 15%, 18%, and 9%. Conclusions: In women, indirect bilirubin was significantly and inversely associated with thyroid cancer risk, and the ALBI and PALBI indices incorporating indirect bilirubin showed consistent results. These findings suggest that indirect bilirubin may play a critical role in the metabolic pathways underlying thyroid cancer in women.

A prolonged PR interval predicts atrial fibrillation (AF) recurrence after catheter ablation. We investigated the causal association between the PR interval and AF clinical recurrence by a Mendelian randomization. We prospectively included 1722 patients with AF (73.2% male, 58.6 ± 10.8 years old, 71.3% paroxysmal AF) who underwent catheter ablation into a genome-wide association study (GWAS). We searched for the genetic associations between the PR interval and AF recurrence by analyzing 44 single nucleotide polymorphisms (SNPs) already known to be associated with the PR interval, and investigated the Mendelian randomization. Based on the quartile analysis, the highest quartile of the PR interval was associated with an increased risk of AF recurrence compared with the lowest quartile (Hazard ratio (HR) = 1.91, 95% CI = 1.51–2.42, P = 8.41 × 10−8) during 35.7 ± 28.5 months of follow-up. Among 44 SNPs known to be associated with the PR interval, two SNPs had significant associations with the PR interval (P < 0.001 for each SNP). CAV1 (HR = 1.15, 95% CI = 1.02–1.31, P = 0.024) was associated with clinical recurrence of AF. A Mendelian randomization analysis demonstrated a significant association with CAV1 (HR = 1.04, 95% CI = 1.01–1.07, P = 0.006). A prolonged PR interval was a risk factor for an AF recurrence, and the PR interval had a potentially causal association with an AF clinical recurrence after catheter ablation at the genetic level.

This study aimed to investigate the association between domain-specific physical activity (PA) and diabetes in Korean adults. We analyzed 26,653 men and women (aged > 18 years) from the Korea National Health and Nutrition Examination Survey (2014–2018). PA was measured using a validated Global PA Questionnaire. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for various confounders. Transport PA accounted for the majority of total PA (46%, men; 58%, women), followed by leisure-time PA (30%; 22%) and work PA (24%; 20%). In men, ORs (95% CI) of diabetes comparing ≥ 600 metabolic task of equivalent (MET)-min/week vs. no activity were 0.82 (0.71–0.95) for leisure-time PA, 0.85 (0.75–0.96) for transport PA, and 0.88 (0.78–0.99) for leisure-time + transport PA. In women, ORs (95% CI) of diabetes comparing the same groups were 0.73 (0.60–0.89) for leisure-time PA, 0.97 (0.85–1.10) for transport PA, and 0.88 (0.78–1.00) for leisure-time + transport PA. However, work PA showed no association with diabetes. In conclusion, leisure-time PA was inversely associated with diabetes in both men and women, while transport PA was inversely associated only in men. But work PA was not associated with diabetes in Korean adults.