Concordant and discordant breast density patterns by different approaches for assessing breast density and breast cancer risk.

PURPOSE: To examine the discrepancy in breast density assessments by radiologists, LIBRA software, and AI algorithm and their association with breast cancer risk. METHODS: Among 74,610 Korean women aged ≥ 34 years, who underwent screening mammography, density estimates obtained from both LIBRA and the AI algorithm were compared to radiologists using BI-RADS density categories (A-D, designating C and D as dense breasts). The breast cancer risks were compared according to concordant or discordant dense breasts identified by radiologists, LIBRA, and AI. Cox-proportional hazards models were used to determine adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)]. RESULTS: During a median follow-up of 9.9 years, 479 breast cancer cases developed. Compared to the reference non-dense breast group, the aHRs (95% CIs) for breast cancer were 2.37 (1.68-3.36) for radiologist-classified dense breasts, 1.30 (1.05-1.62) for LIBRA, and 2.55 (1.84-3.56) for AI. For different combinations of breast density assessment, aHRs (95% CI) for breast cancer were 2.40 (1.69-3.41) for radiologist-dense/LIBRA-non-dense, 11.99 (1.64-87.62) for radiologist-non-dense/LIBRA-dense, and 2.99 (1.99-4.50) for both dense breasts, compared to concordant non-dense breasts. Similar trends were observed with radiologists/AI classification: the aHRs (95% CI) were 1.79 (1.02-3.12) for radiologist-dense/AI-non-dense, 2.43 (1.24-4.78) for radiologist-non-dense/AI-dense, and 3.23 (2.15-4.86) for both dense breasts. CONCLUSION: The risk of breast cancer was highest in concordant dense breasts. Discordant dense breast cases also had a significantly higher risk of breast cancer, especially when identified as dense by either AI or LIBRA, but not radiologists, compared to concordant non-dense breast cases.

Height and breast cancer risk in premenopausal Korean women aged under 40 years of age.

BACKGROUND: Taller women are at an increased risk of breast cancer; however, evidence regarding this in younger women is limited. This study investigated the association between body height and breast cancer risk in premenopausal Korean women aged <40 years. METHODS: Premenopausal women aged <40 years enroled in the Kangbuk Samsung Health Study (KSHS) and National Health Insurance Service-National Health Information Database (NHIS-NHID) were included in the analysis. Trained staff members performed anthropometry, including height measurements. Breast cancer incidence was followed up until December 2019. Cox regression model and restricted cubic- spline regression were applied. RESULTS: The mean (standard deviation [SD]) age was 33.3 (3.6) years and 32.9 (4.2) in KSHS and NHIS-NHID cohorts, respectively. After adjusting for age at baseline and other confounders, every 10 cm of height was associated with a 1.44-fold increased risk of developing breast cancer (adjusted hazard ratio [aHR], 1.44; 95% confidence interval [CI], 1.17-1.78) in the KSHS. The restricted cubic spline regression showed an almost linear association between height and breast cancer risk. Compared to women with height <155 cm, aHRs (95% CI) among those with height 160-165 cm, 165-170 cm, and ≥170 cm were 1.67 (1.07-2.60), 1.75 (1.09-2.81), and 2.31 (1.18-3.86), respectively (P = 0.009). Results were similar in the NHIS-NHID cohort (aHR, 1.20 [95% CI, 1.10-1.31] per 10-cm increase in height). CONCLUSION: In young Korean women, greater body height was associated with increased breast cancer risk.

Sex-specific association between carbohydrate antigen 19-9 and incident type 2 diabetes.

Carbohydrate antigen 19-9 (CA19-9) levels are associated with glycemic control, insulin resistance, and chronic complications in patients with type 2 diabetes (T2D). Women generally show higher CA19-9 levels despite a greater T2D prevalence in men. We evaluated the sex-specific longitudinal associations between CA19-9 levels and T2D incidence. Korean adults (n = 329,380) without previous cancer or T2D were categorized into four groups based on their CA19-9 levels. The study end point was the development of incident T2D during follow-up. Cox proportional hazards models were used to estimate hazard ratios (HR) according to CA19-9 levels. During a median follow-up of 6.1 years (3.3-9.3 years), the incidence rates of T2D were 9.9 per 1,000 person-years in men and 3.6 per 1,000 person-years in women. In the time-dependent analysis, adjusted HRs (95% confidence intervals) for incident T2D comparing CA19-9 levels of 10.0-19.9, 20.0-29.9, and ≥ 30 U/mL to the reference (< 10 U/mL) were 1.08 (1.04-1.13), 1.18 (1.07-1.30), and 1.64 (1.35-1.99), respectively, among men. However, this association was not observed in women. The association between CA19-9 category and incident T2D significantly differed by sex (Pinteraction = 0.006). Among young and middle-aged Korean adults, elevated CA19-9 levels were significantly associated with increased risk of type 2 diabetes in men but not in women. Elevated CA19-9 levels in men could be a useful marker for identifying individuals at high risk of developing T2D. Evaluation approaches for individuals with elevated CA19-9 levels should be sex-specific.

Artificial Intelligence-Powered Imaging Biomarker Based on Mammography for Breast Cancer Risk Prediction.

The purposes of this study were to develop an artificial intelligence (AI) model for future breast cancer risk prediction based on mammographic images, investigate the feasibility of the AI model, and compare the AI model, clinical statistical risk models, and Mirai, a state of-the art deep learning algorithm based on screening mammograms for 1-5-year breast cancer risk prediction. We trained and developed a deep learning model using a total of 36,995 serial mammographic examinations from 21,438 women (cancer-enriched mammograms, 17.5%). To determine the feasibility of the AI prediction model, mammograms and detailed clinical information were collected. C-indices and area under the receiver operating characteristic curves (AUCs) for 1-5-year outcomes were obtained. We compared the AUCs of our AI prediction model, Mirai, and clinical statistical risk models, including the Tyrer-Cuzick (TC) model and Gail model, using DeLong's test. A total of 16,894 mammograms were independently collected for external validation, of which 4002 were followed by a cancer diagnosis within 5 years. Our AI prediction model obtained a C-index of 0.76, with AUCs of 0.90, 0.84, 0.81, 0.78, and 0.81, to predict the 1-5-year risks. Our AI prediction model showed significantly higher AUCs than those of the TC model (AUC: 0.57; p < 0.001) and Gail model (AUC: 0.52; p < 0.001), and achieved similar performance to Mirai. The deep learning AI model using mammograms and AI-powered imaging biomarkers has substantial potential to advance accurate breast cancer risk prediction.

Glycemic status, insulin resistance, and mortality from lung cancer among individuals with and without diabetes.

BACKGROUND: The effects of glycemic status and insulin resistance on lung cancer remain unclear. We investigated the associations between both glycemic status and insulin resistance, and lung cancer mortality, in a young and middle-aged population with and without diabetes. METHODS: This cohort study involved individuals who participated in routine health examinations. Lung cancer mortality was identified using national death records. Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% CIs for lung cancer mortality risk. RESULTS: Among 666,888 individuals (mean age 39.9 ± 10.9 years) followed for 8.3 years (interquartile range, 4.6-12.7), 602 lung cancer deaths occurred. Among individuals without diabetes, the multivariable-adjusted HRs (95% CI) for lung cancer mortality comparing hemoglobin A1c categories (5.7-5.9, 6.0-6.4, and ≥ 6.5% or 39-41, 42-46, and ≥ 48 mmol/mol, respectively) with the reference (< 5.7% or < 39 mmol/mol) were 1.39 (1.13-1.71), 1.72 (1.33-2.20), and 2.22 (1.56-3.17), respectively. Lung cancer mortality was associated with fasting blood glucose categories in a dose-response manner (P for trend = 0.001) and with previously diagnosed diabetes. Insulin resistance (HOMA-IR ≥ 2.5) in individuals without diabetes was also associated with lung cancer mortality (multivariable-adjusted HR, 1.41; 95% CI, 1.13-1.75). These associations remained after adjusting for changing status in glucose, hemoglobin A1c, insulin resistance, smoking status, and other confounders during follow-up as time-varying covariates. CONCLUSIONS: Glycemic status within both diabetes and prediabetes ranges and insulin resistance were independently associated with an increased risk of lung cancer mortality.

Mammographic breast features and risk of cardiovascular diseases in korean women.

BACKGROUND: There is a growing amount of evidence on the association between cardiovascular diseases (CVDs) and breast calcification. Thus, mammographic breast features have recently gained attention as CVD predictors. OBJECTIVE: This study assessed the association of mammographic features, including benign calcification, microcalcification, and breast density, with cardiovascular diseases. METHODS: This study comprised 6,878,686 women aged ≥40 who underwent mammographic screening between 2009 and 2012 with follow-up until 2020. The mammographic features included benign calcification, microcalcification, and breast density. The cardiovascular diseases associated with the mammographic features were assessed using logistic regression. RESULTS: The prevalence of benign calcification, microcalcification, and dense breasts were 9.6 %, 0.9 % and 47.3 % at baseline, respectively. Over a median follow-up of 10 years, benign calcification and microcalcification were positively associated with an increased risk of chronic ischaemic heart disease whereas breast density was inversely associated with it; the corresponding aOR (95 % CI) was 1.14 (1.10-1.17), 1.19 (1.03-1.15), and 0.88 (0.85-0.90), respectively. A significantly increased risk of chronic ischaemic heart disease (IHD) was observed among women with benign calcifications (aHR, 1.14; 95 % CI 1.10-1.17) and microcalcifications (aOR, 1.19; 95 % CI 1.06-1.33). Women with microcalcifications had a 1.16-fold (95 % CI 1.03-1.30) increased risk of heart failure. CONCLUSIONS: Mammographic calcifications were associated with an increased risk of chronic ischaemic heart diseases, whereas dense breast was associated with a decreased risk of cardiovascular disease. Thus, the mammographic features identified on breast cancer screening may provide an opportunity for cardiovascular disease risk identification and prevention.

Screening mammography performance according to breast density: a comparison between radiologists versus standalone intelligence detection.

BACKGROUND: Artificial intelligence (AI) algorithms for the independent assessment of screening mammograms have not been well established in a large screening cohort of Asian women. We compared the performance of screening digital mammography considering breast density, between radiologists and AI standalone detection among Korean women. METHODS: We retrospectively included 89,855 Korean women who underwent their initial screening digital mammography from 2009 to 2020. Breast cancer within 12 months of the screening mammography was the reference standard, according to the National Cancer Registry. Lunit software was used to determine the probability of malignancy scores, with a cutoff of 10% for breast cancer detection. The AI's performance was compared with that of the final Breast Imaging Reporting and Data System category, as recorded by breast radiologists. Breast density was classified into four categories (A-D) based on the radiologist and AI-based assessments. The performance metrics (cancer detection rate [CDR], sensitivity, specificity, positive predictive value [PPV], recall rate, and area under the receiver operating characteristic curve [AUC]) were compared across breast density categories. RESULTS: Mean participant age was 43.5 ± 8.7 years; 143 breast cancer cases were identified within 12 months. The CDRs (1.1/1000 examination) and sensitivity values showed no significant differences between radiologist and AI-based results (69.9% [95% confidence interval [CI], 61.7-77.3] vs. 67.1% [95% CI, 58.8-74.8]). However, the AI algorithm showed better specificity (93.0% [95% CI, 92.9-93.2] vs. 77.6% [95% CI, 61.7-77.9]), PPV (1.5% [95% CI, 1.2-1.9] vs. 0.5% [95% CI, 0.4-0.6]), recall rate (7.1% [95% CI, 6.9-7.2] vs. 22.5% [95% CI, 22.2-22.7]), and AUC values (0.8 [95% CI, 0.76-0.84] vs. 0.74 [95% CI, 0.7-0.78]) (all P < 0.05). Radiologist and AI-based results showed the best performance in the non-dense category; the CDR and sensitivity were higher for radiologists in the heterogeneously dense category (P = 0.059). However, the specificity, PPV, and recall rate consistently favored AI-based results across all categories, including the extremely dense category. CONCLUSIONS: AI-based software showed slightly lower sensitivity, although the difference was not statistically significant. However, it outperformed radiologists in recall rate, specificity, PPV, and AUC, with disparities most prominent in extremely dense breast tissue.

The association of blood eosinophil counts and FEV1 decline: a cohort study.

BACKGROUND: Accelerated lung function decline is characteristic of COPD. However, the association between blood eosinophil counts and lung function decline, accounting for current smoking status, in young individuals without prevalent lung disease is not fully understood. METHODS: This is a cohort study of 629 784 Korean adults without COPD or a history of asthma at baseline who participated in health screening examinations including spirometry and differential white blood cell counts. We used a linear mixed-effects model to estimate the annual change in forced expiratory volume in 1 s (FEV1) (mL) by baseline blood eosinophil count, adjusting for covariates including smoking status. In addition, we performed a stratified analysis by baseline and time-varying smoking status. RESULTS: During a mean follow-up of 6.5 years (maximum 17.8 years), the annual change in FEV1 (95% CI) in participants with eosinophil counts <100, 100-199, 200-299, 300-499 and ≥500 cells·µL-1 in the fully adjusted model were -23.3 (-23.9--22.7) mL, -24.3 (-24.9--23.7) mL, -24.8 (-25.5--24.2) mL, -25.5 (-26.2--24.8) mL and -26.8 (-27.7--25.9) mL, respectively. When stratified by smoking status, participants with higher eosinophil count had a faster decline in FEV1 than those with lower eosinophil count in both never- and ever-smokers, which persisted when time-varying smoking status was used. CONCLUSIONS: Higher blood eosinophil counts were associated with a faster lung function decline among healthy individuals without lung disease, independent of smoking status. The findings suggest that higher blood eosinophil counts contribute to the risk of faster lung function decline, particularly among younger adults without a history of lung disease.

Adiposity, Body Composition Measures, and Breast Cancer Risk in Korean Premenopausal Women.

Objective: To investigate the association between body composition parameters and breast cancer (BC) risk in premenopausal women. Design, Setting, and Participants: Prospective cohort study using data from the Kangbuk Samsung Cohort Study. Participants were women aged 20 to 54 years who were enrolled from 2011 to 2019 and followed up for BC development until December 31, 2020. Data were analyzed from June to August 2023. Exposures: Trained nurses conducted anthropometric measurements and assessed body composition using segmental bioelectric impedance analysis. The analysis encompassed adiposity measures such as body mass index (BMI), waist circumference, and body composition parameters, including muscle mass, fat mass, ratio of muscle mass to weight, ratio of fat mass to weight, and fat mass index. Main outcomes and measures: Adjusted hazard ratios (aHR) for BC during the follow-up period. Results: Among 125 188 premenopausal women, the mean (SD) age was 34.9 (6.3) years. During a mean (range) follow-up of 6.7 (0.5-9.9) years, 1110 incident BC cases were identified. The mean (SD) BMI and waist circumference were 21.6 (3.1) and 75.3 (8.2) cm, respectively. Higher BMI and waist circumference were associated with decreased risk, with an aHR of 0.89 (95% CI, 0.84-0.95) per SD increase in BMI and 0.92 (95% CI, 0.86-0.98) per SD increase in waist circumference. A higher ratio of fat mass to weight was associated with decreased BC risk (aHR, 0.92; 95% CI, 0.86-0.99 per SD increase), whereas the opposite trend was observed for the ratio of muscle mass to weight, with an aHR of 1.08 (95% CI, 1.02-1.15) per SD increase. The results remained consistent even after additional adjustments for height in the model. The fat mass index was also inversely associated with BC risk, with an HR of 0.90 (95% CI, 0.85-0.97) per SD increase. Conclusions and Relevance: In this cohort study of premenopausal women, a higher level of adiposity, represented by increased BMI, waist circumference, and fat mass, was consistently associated with decreased breast cancer risk. Conversely, muscle mass and its ratio to weight displayed opposite or inconsistent patterns. These findings suggest an inverse association between excess adiposity and the risk of BC in premenopausal women, confirming earlier findings that BMI is an indirect measure of adiposity.

Risk prediction model for gastric cancer within 5 years in healthy Korean adults.

BACKGROUND: Although endoscopy is commonly used for gastric cancer screening in South Korea, predictive models that integrate endoscopy results are scarce. We aimed to develop a 5-year gastric cancer risk prediction model using endoscopy results as a predictor. METHODS: We developed a predictive model using the cohort data of the Kangbuk Samsung Health Study from 2011 to 2019. Among the 260,407 participants aged ≥20 years who did not have any previous history of cancer, 435 cases of gastric cancer were observed. A Cox proportional hazard regression model was used to evaluate the predictors and calculate the 5-year risk of gastric cancer. Harrell's C-statistics and Nam-D'Agostino χ2 test were used to measure the quality of discrimination and calibration ability, respectively. RESULTS: We included age, sex, smoking status, alcohol consumption, family history of cancer, and previous results for endoscopy in the risk prediction model. This model showed sufficient discrimination ability [development cohort: C-Statistics: 0.800, 95% confidence interval (CI) 0.770-0.829; validation cohort: C-Statistics: 0.799, 95% CI 0.743-0.856]. It also performed well with effective calibration (development cohort: χ2 = 13.65, P = 0.135; validation cohort: χ2 = 15.57, P = 0.056). CONCLUSION: Our prediction model, including young adults, showed good discrimination and calibration. Furthermore, this model considered a fixed time interval of 5 years to predict the risk of developing gastric cancer, considering endoscopic results. Thus, it could be clinically useful, especially for adults with endoscopic results.

Human papillomavirus infection and cardiovascular mortality: a cohort study.

BACKGROUND AND AIMS: High-risk human papillomavirus (HR-HPV) infection-a well-established risk factor for cervical cancer-has associations with cardiovascular disease (CVD). However, its relationship with CVD mortality remains uncertain. This study examined the associations between HR-HPV infection and CVD mortality. METHODS: As part of a health examination, 163 250 CVD-free Korean women (mean age: 40.2 years) underwent HR-HPV screening and were tracked for up to 17 years (median: 8.6 years). National death records identified the CVD mortality cases. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD mortality were estimated using Cox proportional hazard regression analyses. RESULTS: During 1 380 953 person-years of follow-up, 134 CVD deaths occurred, with a mortality rate of 9.1 per 105 person-years for HR-HPV(-) women and 14.9 per 105 person-years for HR-HPV(+) women. After adjustment for traditional CVD risk factors and confounders, the HRs (95% CI) for atherosclerotic CVD (ASCVD), ischaemic heart disease (IHD), and stroke mortality in women with HR-HPV infection compared with those without infection were 3.91 (1.85-8.26), 3.74 (1.53-9.14), and 5.86 (0.86-40.11), respectively. The association between HR-HPV infection and ASCVD mortality was stronger in women with obesity than in those without (P for interaction = .006), with corresponding HRs (95% CI) of 4.81 (1.55-14.93) for obese women and 2.86 (1.04-7.88) for non-obese women. CONCLUSIONS: In this cohort study of young and middle-aged Korean women, at low risks for CVD mortality, those with HR-HPV infection had higher death rates from CVD, specifically ASCVD and IHD, with a more pronounced trend in obese individuals.

Impact of metabolic unhealthiness and its changes on the risk of erosive esophagitis: a cohort study.

BACKGROUND AND AIM: We aimed to compare the risk of erosive esophagitis (EE) among individuals with different phenotypes based on metabolic health status and obesity and investigate the role of changes in metabolic health in EE risk. METHODS: A cohort of 258 892 asymptomatic adults without EE at baseline who underwent ollow-up esophagogastroduodenoscopy (EGD) were categorized into the following four groups according to metabolic health and obesity status: (i) metabolically healthy (MH) non-obese; (ii) metabolically unhealthy (MU) non-obese; (iii) MH obese; and (iv) MU obese. EE was defined as the presence of grade A or higher mucosal breaks on EGD. RESULTS: During a median follow-up of 4.5 years, the incidence rates of EE were 0.6/103 person-years (PY), 1.7/103 PY, 1.7/103 PY, and 3.1/103 PY in the MH non-obese, MU non-obese, MH obese, and MU obese groups, respectively. The multivariable-adjusted hazard ratio (HR) (95% confidence intervals [CI]) for developing EE comparing the MH obese, MU non-obese, and MU obese groups with the MH non-obese group were 1.49 (1.29-1.71), 1.56 (1.25-1.94), and 2.18 (1.90-2.49), respectively. The multivariable-adjusted HR (95% CI) comparing the progression of MH to MU, regression of MU to MH, and persistent MU with the persistent MH group were 1.39 (1.10-1.76), 1.39 (1.09-1.77), and 1.86 (1.56-2.21), respectively. The increased risk of EE among the persistent MU group was consistently observed in individuals without obesity or abdominal obesity. CONCLUSION: Metabolic unhealthiness and obesity were independent risk factors for the development of EE, suggesting that maintaining both normal weight and metabolic health may help reduce the risk of EE.

Mammography-based deep learning model for coronary artery calcification.

AIMS: Mammography, commonly used for breast cancer screening in women, can also predict cardiovascular disease. We developed mammography-based deep learning models for predicting coronary artery calcium (CAC) scores, an established predictor of coronary events. METHODS AND RESULTS: We evaluated a subset of Korean adults who underwent image mammography and CAC computed tomography and randomly selected approximately 80% of the participants as the training dataset, used to develop a convolutional neural network (CNN) to predict detectable CAC. The sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), and overall accuracy of the model's performance were evaluated. The training and validation datasets included 5235 and 1208 women, respectively [mean age, 52.6 (±10.2) years], including non-zero cases (46.8%). The CNN-based deep learning prediction model based on the Resnet18 model showed the best performance. The model was further improved using contrastive learning strategies based on positive and negative samples: sensitivity, 0.764 (95% CI, 0.667-0.830); specificity, 0.652 (95% CI, 0.614-0.710); AUROC, 0.761 (95% CI, 0.742-0.780); and accuracy, 70.8% (95% CI, 68.8-72.4). Moreover, including age and menopausal status in the model further improved its performance (AUROC, 0.776; 95% CI, 0.762-0.790). The Framingham risk score yielded an AUROC of 0.736 (95% CI, 0.712-0.761). CONCLUSION: Mammography-based deep learning models showed promising results for predicting CAC, performing comparably to conventional risk models. This indicates mammography's potential for dual-risk assessment in breast cancer and cardiovascular disease. Further research is necessary to validate these findings in diverse populations, with a particular focus on representation from national breast screening programmes.

Potential role of Fibrosis-4 score in hepatocellular carcinoma screening: The Kangbuk Samsung Health Study.

AIM: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death, with low survival rates worldwide. Fatty liver disease (FLD) significantly contributes to HCC. We studied the screening performance of different methods for identifying HCC in patients with FLD or with metabolic risk factors for FLD. METHODS: Korean adults (n = 340 825) without a prior HCC diagnosis were categorized into four groups: normal (G1), ≥2 metabolic risk factors (G2), FLD (G3), and viral liver disease or liver cirrhosis (G4). The National Cancer Registry data were used to identify HCC cases within 12 months. We assessed the area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of individual or combined screening methods. RESULTS: In 93 HCC cases, 71 were identified in G4, whereas 20 cases (21.5%) in G2 and G3 combined where ultrasound and Fibrosis-4 performed similarly to alpha-fetoprotein and ultrasound. In G2, Fibrosis-4 and ultrasound had the highest area under the receiver operating characteristic curve (0.93 [0.87-0.99]), whereas in G3, the combined screening methods had the highest area under the receiver operating characteristic curve (0.98 [0.95-1.00]). The positive predictive value was lower in G2 and G3 than in G4, but was >5% when restricted to a high Fibrosis-4 score. CONCLUSIONS: More than 21% of HCC cases were observed in patients with diagnosed FLD or at risk of FLD with metabolic risk factors. Nevertheless, screening for HCC in individuals without cirrhosis or viral hepatitis yielded very low results, despite the potential value of the Fibrosis-4 score in identifying individuals at high risk of HCC.

Mammographic breast density and cardiovascular disease risk in women.

AIMS: We aimed to determine the predictive role of mammographic breast density in addition to the Framingham Risk Score (FRS) on subsequent CVD events in women. METHODS AND RESULTS: This cohort study included 4,268,579 women aged ≥40 years who underwent mammography screening between 2009 and 2010 with follow-up until 2020. Breast density was reported following the Breast Imaging Reporting and Data System. Primary outcomes included coronary heart disease, cerebrovascular disease, peripheral arterial disease, and heart failure. The incremental predictive ability of breast density added to the FRS model was assessed using the ROC and net reclassification index (NRI) among all women and strata based on FRS risk categories (<5% as low-risk, 5%-10% as moderate-risk, and ≥10% as high-risk). In total, 135,475 CVD events were recorded after a median follow-up of 10.9 years. A lower category of breast density was associated with a higher risk of CVD. Compared to the extremely dense breast group, the hazard ratios (95% CI) for CVDs were 1.12 (1.09-1.14), 1.19 (1.17-1.22), and 1.29 (1.26-1.32) in women with heterogeneously dense, scattered fibroglandular densities, and almost entirely fat breast density, respectively. Adding breast density to the FRS showed a slight improvement in AUROC but a modest improvement in NRI; the C-statistic difference was 0.083% (95% CI 0.069-0.096) with a 7.15% (6.85-7.69) increase in NRI, with the strongest improvement observed in the low-risk group. CONCLUSIONS: Mammographic breast density is an independent predictor of incident CVD among women. The addition of mammographic breast density to FRS improves the prediction of CVDs, especially in low-risk individuals.

Metabolic-associated fatty liver disease is associated with colorectal adenomas in young and older Korean adults.

BACKGROUND AND AIMS: Given that the majority of colorectal cancers (CRCs) develop from high-risk adenomas, identifying risk factors for high-risk adenomas is important. The relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and the risk of colorectal adenoma in young adults remains unclear. We aimed to evaluate this relationship in adults <50 (younger) and ≥50 (older) years of age. METHODS: This cross-sectional study included 184 792 Korean adults (80% <50 years of age) who all underwent liver ultrasound and colonoscopy. Participants were grouped into those with and without MAFLD and classified by adenoma presence into no adenoma, low-risk adenoma, or high-risk adenoma (defined as ≥3 adenomas, any ≥10 mm, or adenoma with high-grade dysplasia/villous features). RESULTS: The prevalence of low- and high-risk adenomas among young and older adults was 9.6% and 0.8% and 22.3% and 4.8%, respectively. MAFLD was associated with an increased prevalence of low- and high-risk adenomas in young and older adults. Young adults with MAFLD had a 1.30 (95% CIs 1.26-1.35) and 1.40 (1.23-1.59) times higher prevalence of low- and high-risk adenomas, respectively, compared to those without MAFLD. These associations were consistent even in lean adults (BMI < 23 kg/m2 ) and those without a family history of CRC. CONCLUSIONS: MAFLD is associated with an increased prevalence of low- and high-risk adenomas in Korean adults, regardless of age or obesity status. Whether reducing metabolic risk factors, such as MAFLD, reduces the risk of precancerous lesions and ultimately reduces the risk of early-onset CRC requires further investigation.

Diagnostic performance of screening mammography according to menstrual cycle among Asian women.

PURPOSE: To investigate the performance metrics of screening mammography according to menstrual cycle week in premenopausal Asian women. METHODS: This retrospective study included 69,556 premenopausal Asian women who underwent their first screening mammography between 2011 and 2019. The presence or absence of a breast cancer diagnosis within 12 months after the index screening mammography served as the reference standard, determined by linking the study data to the national cancer registry data. Menstrual cycles were calculated, and participants were assigned to groups according to weeks 1-4. The performance metrics included cancer detection rate (CDR), sensitivity, specificity, and positive predictive value (PPV), with comparisons across menstrual cycles. RESULTS: Among menstrual cycles, the lowest CDR at 4.7 per 1000 women (95% confidence interval [CI], 3.8-5.8 per 1000 women) was observed in week 4 (all P < 0.05). The highest sensitivity of 72.7% (95% CI, 61.4-82.3) was observed in week 1, although the results failed to reach statistical significance. The highest specificity of 80.4% (95% CI, 79.5-81.3%) was observed in week 1 (P = 0.01). The lowest PPV of 2.2% (95% CI, 1.8-2.7) was observed in week 4 (all P < 0.05). CONCLUSION: Screening mammography tended to show a higher performance during week 1 and a lower performance during week 4 of the menstrual cycle among Asian women. These results emphasize the importance of timing recommendations that consider menstrual cycles to optimize the effectiveness of screening mammography for breast cancer detection.

Longitudinal analysis for the risk of depression according to the consumption of sugar-sweetened carbonated beverage in non-diabetic and diabetic population.

Studies have presented that high intake of sugar-sweetened carbonated beverage (SSCB) was more associated with the prevalence of depression. However, longitudinal evidence is still insufficient to identify whether the effect of SSCB on incident depression is independent of metabolic factors. Therefore, to evaluate the effect of SSCB consumption on the risk of depression, we analyzed the risk of depression according to the consumption of SSCB in 87,115 working aged Koreans who responded to Center for Epidemiologic Studies Depression (CES-D) scale. They were categorized into 5 groups by SSCB consumption based on one serving dose (200 ml) with never/almost never, < 1 serving/week, 1 ≤ serving/week < 3, 3 ≤ serving/week < 5, and 5 ≤ serving/week. During follow-up, CES-D ≥ 16 was determined as incident depressive symptom. Cox proportional hazards model was used to calculate the multivariable-adjusted hazard ratio (HR) and 95% confidence intervals (CI) for depressive symptom. In analysis for all study participants, the risk of depressive symptom significantly increased proportionally to SSCB consumption (never/almost never: reference, < 1 serving/week: 1.12 [1.07-1.17], 1 ≤ ~ < 3 serving/week: 1.26 [1.19-1.33], 3 ≤ ~ < 5 serving/week: 1.32 [1.23-1.42], and ≥ 5 serving/week: 1.45 [1.33-1.59]). This association was identically observed in men, women, normal glycemic subgroup and prediabetes subgroup.

Serum 25-Hydroxyvitamin D Levels and Risk of Colorectal Cancer: An Age-Stratified Analysis.

BACKGROUND & AIMS: The role of circulating 25-hydroxyvitamin D (25(OH)D) in the prevention of early-onset colorectal cancer (CRC) in young adults aged <50 years is uncertain. We evaluated the age-stratified associations (<50 vs ≥50 years) between circulating 25(OH)D levels and the risk of CRC in a large sample of Korean adults. METHODS: Our cohort study included 236,382 participants (mean age, 38.0 [standard deviation, 9.0] years) who underwent a comprehensive health examination, including measurement of serum 25(OH)D levels. Serum 25(OH)D levels were categorized as <10, 10 to 20, and ≥20 ng/mL. CRC, along with the histologic subtype, site, and invasiveness, was ascertained through linkage with the national cancer registry. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CRC according to the serum 25(OH)D status, with adjustment for potential confounders. RESULTS: During the 1,393,741 person-years of follow-up (median, 6.5 years; interquartile range, 4.5-7.5 years), 341 participants developed CRC (incidence rate, 19.2 per 105 person-years). Among young individuals aged <50 years, serum 25(OH)D levels were inversely associated with the risk of incident CRC with HRs (95% CIs) of 0.61 (0.43-0.86) and 0.41 (0.27-0.63) for 25(OH)D 10 to 19 ng/mL and ≥20 ng/mL, respectively, with respect to the reference (<10 ng/mL) (P for trend <.001, time-dependent model). Significant associations were evident for adenocarcinoma, colon cancer, and invasive cancers. For those aged ≥50 years, associations were similar, although slightly attenuated compared with younger individuals. CONCLUSIONS: Serum 25(OH)D levels may have beneficial associations with the risk of developing CRC for both early-onset and late-onset disease.

Association of Breast Cancer Family History With Breast Density Over Time in Korean Women.

Importance: Evidence suggests that women with a family history of breast cancer (FHBC) in first-degree relatives have a higher level of breast density; however, studies of premenopausal women remain limited. Objective: To investigate the association between FHBC and mammographic breast density and breast density changes among premenopausal women. Design, Setting, and Participants: This retrospective cohort study used population-based data obtained from the National Health Insurance Service-National Health Information Database of Korea. We included premenopausal women aged 40 to 55 years who underwent mammography for breast cancer screening once between January 1, 2015, and December 31, 2016 (n = 1 174 214), and women who underwent mammography twice (first in 2015-2016 and again between January 1, 2017 and December 31, 2018) (n = 838 855). Exposures: Family history of breast cancer was assessed using a self-reported questionnaire, which included information on FHBC in the mother and/or sister. Main Outcomes and Measures: Breast density, based on the Breast Imaging Reporting and Data System, was categorized as dense (heterogeneously or extremely dense) and nondense (almost entirely fat or scattered fibroglandular areas). Multivariate logistic regression was used to assess the association among FHBC, breast density, and changes in breast density from the first to second screening. Data analysis was performed from June 1 to September 31, 2022. Results: Of the 1 174 214 premenopausal women, 34 003 (2.4%; mean [SD] age, 46.3 [3.2] years) reported having FHBC among their first-degree relatives, and 1 140 211 (97.1%; mean [SD] age, 46.3 [3.2] years) reported no FHBC. Odds of having dense breasts was 22% higher (adjusted odds ratio [aOR], 1.22; 95% CI, 1.19-1.26) in women with FHBC than in women without FHBC, and the association varied by affected relatives: mother alone (aOR, 1.15; 95% CI, 1.10-1.21), sister alone (aOR, 1.26; 95% CI, 1.22-1.31), and both mother and sister (aOR, 1.64; 95% CI, 1.20-2.25). Among women with fatty breasts at baseline, the odds of developing dense breasts was higher in women with FHBC than in those without FHBC (aOR, 1.19; 95% CI, 1.11-1.26), whereas among women with dense breasts, higher odds of having persistently dense breasts were observed in women with FHBC (aOR, 1.11; 95% CI, 1.05-1.16) than in those without FHBC. Conclusions and Relevance: In this cohort study of premenopausal Korean women, FHBC was positively associated with an increased incidence of having increased or persistently dense breasts over time. These findings suggest the need for a tailored breast cancer risk assessment for women with FHBC.