We evaluated the association between smoking status and thyroid cancer risk and whether this association is mediated by body mass index (BMI) and thyroid-stimulating hormone (TSH).
We performed a ...cohort study of 96,855 Korean adults who were followed annually or biennially for a median of 5.9 years.
During 511,052.9 person-years of follow-up, 1,250 participants developed thyroid cancer. In men, we observed a dose-dependent inverse association between current smoking, pack-years, and thyroid cancer. After adjustment for confounders, adjusted hazard ratios (95% confidence intervals) for thyroid cancer comparing current and former smokers to never smokers were 0.58 (0.45-0.75) and 0.93 (0.73-1.18), respectively. After further adjustment for BMI and TSH as potential mediators, this association was slightly attenuated, but remained significant. For women, current smokers tended to have a lower risk of thyroid cancer, but this association did not reach statistical significance.
In this cohort study, current smoking was associated with a decreased risk of incident thyroid cancer in men but not in women and this association was observed even after adjusting for TSH and BMI levels as potential mediators. Further mechanistic studies are needed to elucidate the possible effect of smoking on the pathogenesis of thyroid cancer development.
Objectives The purpose of this study was to compare the coronary artery calcium (CAC) scores of metabolically-healthy obese (MHO) and metabolically healthy normal-weight individuals in a large sample ...of apparently healthy men and women. Background The risk of cardiovascular disease among obese individuals without obesity-related metabolic abnormalities, referred to as MHO, is controversial. Methods We conducted a cross-sectional study of 14,828 metabolically-healthy adults with no known cardiovascular disease who underwent a health checkup examination that included estimation of CAC scores by cardiac tomography. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5. Results MHO individuals had a higher prevalence of coronary calcification than normal weight subjects. In multivariable-adjusted models, the CAC score ratio comparing MHO with normal-weight participants was 2.26 (95% confidence interval: 1.48 to 3.43). In mediation analyses, further adjustment for metabolic risk factors markedly attenuated this association, which was no longer statistically significant (CAC score ratio 1.24; 95% confidence interval: 0.79 to 1.96). These associations did not differ by clinically-relevant subgroups. Conclusions MHO participants had a higher prevalence of subclinical coronary atherosclerosis than metabolically-healthy normal-weight participants, which supports the idea that MHO is not a harmless condition. This association, however, was mediated by metabolic risk factors at levels below those considered abnormal, which suggests that the label of metabolically healthy for obese subjects may be an artifact of the cutoff levels used in the definition of metabolic health.
We examined the associations of smoking status and urinary cotinine levels, an objective measure of smoking, with the development of new-onset HL. This cohort study was performed in 293,991 Korean ...adults free of HL who underwent a comprehensive screening examination and were followed for up to 8.8 years. HL was defined as a pure-tone average of thresholds at 0.5, 1.0, and 2.0 kHz ≥ 25 dB in both ears. During a median follow-up of 4.9 years, 2286 participants developed new-onset bilateral HL. Self-reported smoking status was associated with an increased risk of new-onset bilateral HL. Multivariable-adjusted HRs (95% CIs) for incident HL comparing former smokers and current smokers to never-smokers were 1.14 (1.004-1.30) and 1.40 (1.21-1.61), respectively. Number of cigarettes, pack-years, and urinary cotinine levels were consistently associated with incident HL. These associations were similarly observed when introducing changes in smoking status, urinary cotinine, and other confounders during follow-up as time-varying covariates. In this large cohort of young and middle-aged men and women, smoking status based on both self-report and urinary cotinine level were independently associated with an increased incidence of bilateral HL. Our findings indicate smoking is an independent risk factor for HL.
The presence of an association between chronic hepatitis B virus (HBV) infection and fatty liver is controversial. We examined the association between HBV infection and the development of ...nonalcoholic fatty liver disease (NAFLD). We conducted a cohort study of 83,339 participants without NAFLD at baseline who underwent serologic testing for hepatitis B surface antigen (HBsAg) between 2002 and 2006 and were followed annually or biennially until December 2014. NAFLD was defined as the presence of ultrasonographic fatty liver in the absence of excessive alcohol use or other identifiable causes. We used a parametric Cox model to estimate adjusted hazard ratios with 95% confidence intervals of incident NAFLD. During 484,736.1 person‐years of follow‐up, 20,200 incident NAFLD cases were identified. In models adjusted for age, sex, year of visit, smoking status, alcohol intake, regular exercise, education level, and body mass index, the adjusted hazard ratio (95% confidence interval) for incident NAFLD comparing HBsAg‐positive to HBsAg‐negative participants was 0.83 (0.73‐0.94). After introducing HBV infection and confounders (including homeostasis model assessment of insulin resistance and metabolic factors) as time‐dependent exposures, the association between HBV infection and decreased risk of incident NAFLD was attenuated but persisted. These associations were consistently observed across clinically relevant, prespecified subgroups. Conclusion: In this large cohort of apparently healthy Korean adults, HBsAg seropositivity was associated with lower risk of developing NAFLD, indicating a possible effect of HBV infection on the pathogenesis of NAFLD development. (Hepatology 2017;65:828‐835).
Background:A high level of apolipoprotein B (apoB) is associated with incident coronary artery disease (CAD) when low-density lipoprotein cholesterol (LDL-C) level is discordantly low or concordantly ...high. However, data on the relationship of apoB with subclinical measure of CAD are limited.Methods and Results:A total of 14,205 men (mean age 41.0 years) who were free of cardiovascular disease at baseline and who underwent a health checkup exam, including measurement of coronary artery calcium (CAC), were studied. Of the study group, 2,773 participants (19.5%) had CAC at baseline, and CAC progression was observed in 2,550 (18.0%). The multivariate-adjusted CAC score ratios (95% confidence interval) comparing discordantly high apoB/low LDL-C and concordantly high apoB/high LDL-C with concordantly low apoB/low LDL-C were 1.51 (0.98–2.32) and 2.70 (2.19–3.33), respectively. The corresponding relative risks for CAC progression were 1.26 (1.02–1.56) and 1.49 (1.34–1.66), respectively. These associations did not change appreciably after adjustment for insulin resistance and subclinical inflammation.Conclusions:Discordant analysis showed that a high apoB level was strongly associated with prevalence and progression of CAC independent of LDL-C in a large cohort of healthy adults. The present study results highlighted the importance of an apoB measure as a potential target for primary prevention of coronary atherosclerosis in healthy adults.
Whether isolated hepatitis B core antibody (anti-HBc) positivity is a risk factor for long-term liver-related outcomes in hepatitis B virus (HBV)-endemic areas remains unclear. We aimed to ...investigate liver-related and liver cancer mortality of isolated anti-HBc positivity in Korean adults.
A cohort study comprised 609,299 Korean adults who underwent hepatitis B serologic markers, as a part of health examination. Liver-related and liver cancer mortality were determined using the National Death Records.
During a median follow-up of 9.0 years (interquartile range, 5.5-13.7 years), 554 liver-related deaths were identified (liver-related mortality, 9.6 cases per 10 5 person-years). The prevalence of isolated anti-HBc positivity was 3.8% (n = 23,399) and was age-dependent. After adjustment for age, sex, and other confounders, hazard ratios (95% confidence interval) for liver-related mortality in isolated anti-HBc-positive and hepatitis B surface antigen-positive subjects compared with HBV-unexposed subjects were 1.69 (1.22-2.33) and 27.02 (21.45-34.04), respectively. These associations were pronounced in the analyses using liver cancer mortality as an outcome. Among isolated anti-HBc-positive patients, the risks of liver-related and liver cancer mortality were significantly higher in those with high fibrosis-4 scores compared with patients unexposed to HBV with the multivariable-adjusted hazard ratios (95% confidence interval) of 15.59 (9.21-26.37) and 72.66 (36.96-142.86), respectively.
In this cohort of Korean adults, isolated anti-HBc positivity was associated with an increased risk of liver-related and liver cancer mortality, especially when accompanied by a high fibrosis score. Isolated anti-HBc positivity may be an independent risk factor for liver-related outcomes, especially in high-endemic areas.
Purpose
Research on the role of insulin resistance (IR) in breast cancer risk in premenopausal women is scarce. We aimed to investigate the relationship between IR and the development of breast ...cancer in premenopausal women.
Methods
We analyzed the prospective association of IR and incident breast cancer in premenopausal women without breast cancer at baseline using a subsample of the Kangbuk Samsung Health Study.
Results
Among 134,488 Korean premenopausal women, 696 women developed incident breast cancers during a median follow-up of 4.34 years. After adjustment for dense breast and other potential confounders, HR (95% CI) for incident breast cancer comparing HOMA-IR quintiles 2, 3, 4, and 5 to the first quintile was 0.91 (0.71–1.17), 0.89 (0.69–1.15), 0.75 (0.57–0.98), and 0.87 (0.65–1.16), respectively (
P
for trend = 0.117), while HR (95% CI) comparing insulin quintiles 2, 3, 4, and 5 to the first quintile was 1.02 (0.80–1.30), 0.90 (0.69–1.16), 0.72 (0.54–0.96), and 0.96 (0.72–1.28), respectively (
P
for trend = 0.151). This pattern did not significantly differ by obesity. These results were attenuated and no longer significant in time-dependent analyses where updated status of insulin and other covariates over time were treated as time-varying covariates.
Conclusion
Our findings do not support the positive relationship of IR with the development of breast cancer in premenopausal women, unlike in postmenopausal women. Thus, the role of IR as a risk factor for breast cancer may differ by menopausal status.
The impact of glycemic status and insulin resistance on the risk of pancreatic cancer in the nondiabetic population remains uncertain. We aimed to examine the association of glycemic status and ...insulin resistance with pancreatic cancer mortality in individuals with and without diabetes.
This is a cohort study of 572,021 Korean adults without cancer at baseline, who participated in repeat screening examinations which included fasting blood glucose, hemoglobin A1c, and insulin, and were followed for a median of 8.4 years (interquartile range, 5.3 -13.2 years). Vital status and pancreatic cancer mortality were ascertained through linkage to national death records.
During 5,211,294 person-years of follow-up, 260 deaths from pancreatic cancer were identified, with a mortality rate of 5.0 per 10 person-years. In the overall population, the risk of pancreatic cancer mortality increased with increasing levels of glucose and hemoglobin A1c in a dose-response manner, and this association was observed even in individuals without diabetes. In nondiabetic individuals without previously diagnosed or screen-detected diabetes, insulin resistance and hyperinsulinemia were positively associated with increased pancreatic cancer mortality. Specifically, the multivariable-adjusted hazard ratio (95% confidence intervals) for pancreatic cancer mortality comparing the homeostatic model assessment of insulin resistance ≥75th percentile to the <75th percentile was 1.49 (1.08-2.05), and the corresponding hazard ratio comparing the insulin ≥75th percentile to the <75th percentile was 1.43 (1.05-1.95). These associations remained significant when introducing changes in insulin resistance, hyperinsulinemia, and other confounders during follow-up as time-varying covariates.
Glycemic status, insulin resistance, and hyperinsulinemia, even in individuals without diabetes, were independently associated with an increased risk of pancreatic cancer mortality.
The effect of modest alcohol consumption on fibrosis progression in the general population with nonalcoholic fatty liver disease (NAFLD) remains unclear. We examined the association of nonheavy ...alcohol consumption with worsening of noninvasive fibrosis indices in a large‐scale, low‐risk population with NAFLD. A cohort study was performed in 58,927 Korean adults with NAFLD and low fibrosis scores who were followed for a median of 4.9 years. Non‐, light, and moderate drinkers were defined as 0 g/day, 1‐9.9 g/day, and 10‐29.9 g/day (10‐19.9 g/day for women), respectively. Progression from low to intermediate or high probability of advanced fibrosis was assessed using noninvasive indices including NAFLD fibrosis score (NFS) and Fibrosis‐4 Index (FIB‐4). A parametric proportional hazards model was used to estimate the multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). During 347,925.4 person‐years of follow‐up, 5,630 subjects with low FIB‐4 progressed to intermediate or high FIB‐4. The multivariable‐adjusted HRs (95% CI) for worsening of FIB‐4 comparing light and moderate drinkers with nondrinkers were 1.06 (0.98‐1.16) and 1.29 (1.18‐1.40), respectively. Similarly, using NFS, corresponding HRs (95% CI) comparing light and moderate drinkers with nondrinkers were 1.09 (1.02‐1.16) and 1.31 (1.23‐1.40), respectively. Furthermore, the association of moderate drinkers with worsening of either FIB‐4 or NFS remained significant after introducing alcohol use and confounders treated as time‐varying covariates. Conclusion: In this large‐scale cohort of young and middle‐aged individuals with NAFLD, nonheavy alcohol consumption, especially moderate alcohol consumption, was significantly and independently associated with worsening of noninvasive markers of fibrosis, indicating that even moderate alcohol consumption might be harmful.
Although obesity is associated with numerous diseases, the risks of disease may depend on metabolic health. Associations between the gut microbiota, obesity, and metabolic syndrome have been ...reported, but differences in microbiomes according to metabolic health in the obese population have not been explored in previous studies. Here, we investigated the composition of gut microbiota according to metabolic health status in obese and overweight subjects. A total of 747 overweight or obese adults were categorized by metabolic health status, and their fecal microbiota were profiled using 16S ribosomal RNA gene sequencing. We classified these adults into a metabolically healthy group (MH, N = 317) without any components of metabolic syndrome or a metabolically unhealthy group (MU, N = 430) defined as having at least one metabolic abnormality. The phylogenetic and non-phylogenetic alpha diversity for gut microbiota were lower in the MU group than the MH group, and there were significant differences in gut microbiota bacterial composition between the two groups. We found that the genus Oscillospira and the family Coriobacteriaceae were associated with good metabolic health in the overweight and obese populations. This is the first report to describe gut microbial diversity and composition in metabolically healthy and unhealthy overweight and obese individuals. Modulation of the gut microbiome may help prevent metabolic abnormalities in the obese population.
PDF
