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.

Synthetic Extracellular Matrix of Polyvinyl Alcohol Nanofibers for Three-Dimensional Cell Culture.

An ideal extracellular matrix (ECM) replacement scaffold in a three-dimensional cell (3D) culture should induce in vivo-like interactions between the ECM and cultured cells. Highly hydrophilic polyvinyl alcohol (PVA) nanofibers disintegrate upon contact with water, resulting in the loss of their fibrous morphology in cell cultures. This can be resolved by using chemical crosslinkers and post-crosslinking. A crosslinked, water-stable, porous, and optically transparent PVA nanofibrous membrane (NM) supports the 3D growth of various cell types. The binding of cells attached to the porous PVA NM is low, resulting in the aggregation of cultured cells in prolonged cultures. PVA NMs containing integrin-binding peptides of fibronectin and laminin were produced to retain the blended peptides as cell-binding substrates. These peptide-blended PVA NMs promote peptide-specific cell adherence and growth. Various cells, including epithelial cells, cultured on these PVA NMs form layers instead of cell aggregates and spheroids, and their growth patterns are similar to those of the cells cultured on an ECM-coated PVA NM. The peptide-retained PVA NMs are non-stimulatory to dendritic cells cultured on the membranes. These peptide-retaining PVA NMs can be used as an ECM replacement matrix by providing in vivo-like interactions between the matrix and cultured cells.

Trends in breast density and other risk factors for breast cancer and associations with trends in the incidence of breast cancer in Korean women.

INTRODUCTION: This study investigated the trends in breast density in Korean women and their association with the incidence of breast cancer, incorporating the trends in the known risk factors for breast cancer from an ecological perspective. METHODS: The prevalence of risk factors for breast cancer from the National Health and Nutrition Survey, breast density from Korea's national breast cancer screening program, and breast cancer incidence from the Korea Central Cancer Registry during 2010-2018 were applied after age-standardization to the population at the middle of the year 2000. The association between the prevalence of risk factors for breast cancer, the prevalence of dense breast, and the incidence rate of breast cancer was estimated using linear regression. RESULTS: The proportion of age-standardized dense breasts steadily increased from 45.8 % in 2010 to 51.5 % in 2018. The increased prevalence of dense breasts in women was positively related to the prevalence of smoking, drinking, lack of exercise, early menarche age (<15 years old), premenopausal status, nulliparity, and no history of breastfeeding, and negatively related to the prevalence of obesity. The increased prevalence of the dense breast was associated with an increase in the incidence of breast cancer, and 96 % of the variation in breast cancer incidence could be explained by the variation in the prevalence of dense breast. The factors associated with dense breast and breast cancer incidence overlapped. CONCLUSIONS: Trends in breast cancer risk factors were associated with an increased prevalence of dense breast, which, in turn, was associated with an increased incidence of breast cancer in Korea.

Accounting for time-varying exposures and covariates in the relationship between obesity and diabetes: analysis using parametric g-formula.

BACKGROUND: Previous studies investigating the association between obesity and diabetes often did not consider the role of time-varying covariates affected by previous obesity status. This study quantified the association between obesity and diabetes using parametric g-formula. METHODS: We included 8924 participants without diabetes from the Korean Genome and Epidemiology Study-Ansan and Ansung study(2001-2002)-with up to the seventh biennial follow-up data from 2015 to 2016. Obesity status was categorised as normal (body mass index (BMI) <23.5 kg/m2), overweight (23.5-24.9 kg/m2), obese 1 (25.0-27.4 kg/m2) and obese 2 (≥27.5 kg/m2). Hazard ratios (HRs) comparing baseline or time-varying obesity status were estimated using Cox models, whereas risk ratio (RR) was estimated using g-formula. RESULTS: The Cox model for baseline obesity status demonstrated an increased risk of diabetes in overweight (HR 1.85; 95% CI=1.48-2.31), obese 1 (2.40; 1.97-2.93) and obese 2 (3.65; 2.98-4.47) statuses than that in normal weight status. Obesity as a time-varying exposure with time-varying covariates had HRs of 1.31 (1.07-1.60), 1.55 (1.29-1.86) and 2.58 (2.14-3.12) for overweight, obese 1 and obese 2 statuses. Parametric g-formula comparing if everyone had been in each obesity category versus normal over 15 years showed increased associations of RRs of 1.37 (1.34-1.40), 1.78 (1.76-1.80) and 2.42 (2.34-2.50). CONCLUSIONS: Higher BMI classification category was associated with increased risk of diabetes after accounting for time-varying covariates using g-formula. The results from g-formula were smaller than when considering baseline obesity status only but comparable with the results from time-varying Cox model.

Validation of self-reported morbidities of the Korean Atomic Bomb Survivor Cohort.

Objectives: This study aimed to evaluate the agreement of disease status collected through a survey of the Korean Atomic Bomb Survivor Cohort (K-ABC), compared with medical claim records from the Korean National Health Insurance Service (NHIS) database and the Korean Central Cancer Registry (KCCR). Methods: Data on the lifetime physician-diagnosed morbidities of 1,215 K-ABC participants were collected through an interviewer-administered questionnaire between 2020 and 2022. Survey data were linked to the NHIS and KCCR databases. Eleven diseases were included for validation. We evaluated the following indicators: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, the area under the curve (AUC), and the kappa coefficient. Results: The mean (standard deviation) age was 62.1 (18.7) years, and 42.6% of the participants were aged ≥70 years. Hypertension and cataracts showed the highest prevalence rates (33.8% and 28.8%, respectively). Hypertension, diabetes, and cancer demonstrated high sensitivity (>0.8) and specificity (>0.9), whereas diabetes, cancer, myocardial infarction, angina pectoris, and asthma exhibited high accuracy (>0.9). In contrast, arthritis, allergic rhinitis, and asthma showed low sensitivity (<0.4) and kappa values (<0.3). In the participants aged ≥70 years, the kappa value was ≥0.4 for all diseases except arthritis, allergic rhinitis, and asthma. Conclusion: The results from this initial analysis showed relatively high agreement between the survey and NHIS/KCCR databases, especially for hypertension, diabetes, and cancer. Our findings suggest that the information on morbidities collected through the questionnaires in this cohort was valid for both younger and older individuals.

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.

Recent progress in machine learning approaches for predicting carcinogenicity in drug development.

INTRODUCTION: This review explores the transformative impact of machine learning (ML) on carcinogenicity prediction within drug development. It discusses the historical context and recent advancements, emphasizing the significance of ML methodologies in overcoming challenges related to data interpretation, ethical considerations, and regulatory acceptance. AREAS COVERED: The review comprehensively examines the integration of ML, deep learning, and diverse artificial intelligence (AI) approaches in various aspects of drug development safety assessments. It explores applications ranging from early-phase compound screening to clinical trial optimization, highlighting the versatility of ML in enhancing predictive accuracy and efficiency. EXPERT OPINION: Through the analysis of traditional approaches such as in vivo rodent bioassays and in vitro assays, the review underscores the limitations and resource intensity associated with these methods. It provides expert insights into how ML offers innovative solutions to address these challenges, revolutionizing safety assessments in drug development.

Risk Factors and Mortality Among Women With Interval Breast Cancer vs Screen-Detected Breast Cancer.

Importance: The risk factors for interval breast cancer (IBC) compared with those for screen-detected breast cancer (SBC) and their association with mortality outcomes have not yet been evaluated among Korean women. Objective: To evaluate risk factors associated with IBC and survival among Korean women with IBC compared with those with SBC. Design, Setting, and Participants: This retrospective cohort study used data from the Korean National Health Insurance Service Database. Women who participated in a national mammographic breast cancer screening program between January 1, 2009, and December 31, 2012, were included. Mortality outcomes were calculated from the date of breast cancer diagnosis to the date of death or December 31, 2020. Data were analyzed from March 1 to June 30, 2023. Exposure: Breast cancer diagnosed within 6 to 24 months after a negative screening result (ie, IBC) or within 6 months after a positive screening result (ie, SBC). Main Outcomes and Measures: Risk factors and survival rates for IBC and SBC. Results: This study included 8702 women with IBC (mean [SD] age, 53.3 [8.6] years) and 9492 women with SBC (mean [SD] age, 54.1 [9.0] years). Compared with SBC, the probability of IBC decreased as mammographic density increased. Lower body mass index, menopausal status, hormone replacement therapy (HRT) use, and lack of family history of breast cancer were associated with a higher likelihood of IBC. When stratified by detection time, younger age at breast cancer diagnosis and family history of breast cancer were associated with an increased likelihood of IBC diagnosed at 6 to 12 months but a decreased likelihood of IBC diagnosed at 12 to 24 months. Overall mortality of IBC was comparable with SBC, but total mortality and cancer-related mortality of IBC diagnosed between 6 and 12 months was higher than that of SBC. Conclusions and Relevance: The findings of this cohort study suggest that breast density, obesity, and HRT use were associated with IBC compared with SBC. These findings also suggest that higher supplemental breast ultrasound use among Korean women, especially those with dense breasts, could be attributed to a lower incidence of IBC among women with dense breasts compared with women with SBC, due to greater detection. Finally, overall mortality of IBC was comparable with that of SBC.

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.

Associations between breast cancer risk factors and mammographic breast density in a large cross-section of Korean women.

BACKGROUND: We investigated the association between established risk factors for breast cancer and mammographic breast density in Korean women. METHODS: This large cross-sectional study included 8 460 928 women aged >40 years, who were screened for breast cancer between 2009 and 2018. Breast density was assessed using the Breast Imaging Reporting and Data System. This study used multiple logistic regression analyses of age, BMI, age at menarche, menopausal status, menopausal age, parity, breastfeeding status, oral contraceptive use, family history of breast cancer, physical activity, smoking, drinking and hormone replacement therapy use to investigate their associations with mammographic breast density. Analyses were performed using SAS software. RESULTS: Of 8 460 928 women, 4 139 869 (48.9%) had nondense breasts and 4 321 059 (51.1%) had dense breasts. Factors associated with dense breasts were: earlier age at menarche [<15 vs. ≥15; adjusted odds ratio (aOR), 1.18; 95% confidence interval (CI), 1.17-1.18], premenopausal status (aOR, 2.01; 95% CI, 2.00-2.02), later age at menopause (≥52 vs. <52; aOR, 1.23; 95% CI, 1.22-1.23), nulliparity (aOR, 1.64; 95% CI, 1.63-1.65), never breastfed (aOR, 1.23; 95% CI, 1.23-1.24) and use of hormone replacement therapy (aOR, 1.29; 95% CI, 1.28-1.29). Women with a higher BMI and the use of oral contraceptives were more likely to have nondense breasts. CONCLUSION: Lower BMI, reproductive health and behavioral factors were associated with dense breasts in Korean women. Additional research should investigate the relationship between mammographic breast density, breast cancer risk factors and breast cancer risk.

Temporal Trend in Uptake of the National General Health Checkups and Cancer Screening Program among Korean Women with Breast Cancer.

PURPOSE: This study assessed the temporal trends of uptake of national general health and cancer screening among women with breast cancer in Korea between 2009 and 2016. MATERIALS AND METHODS: We retrospectively analyzed the claims data from the Korean National Health Insurance Service database. Participants included 101,403 breast cancer patients diagnosed between 2009 and 2016. Information on participation in national screening programs, including breast cancer screening, general health, and gastric, colorectal, and cervical cancers, up to 2020 was collected. Screening participation rates within the first 2 and 5 years postdiagnosis were calculated by diagnosis year and fitted with joinpoint regression models to assess temporal trends. RESULTS: Overall, the participation rate in breast cancer screening within 2 years postdiagnosis increased from 10.9% to 14.0% from 2009-2016, with an annual percentage change (APC) of 3.7% (p < 0.05). The participation rate in breast cancer screening was lower than that in general health checkup and screening for other cancers within 2 and 5 years postdiagnosis. A steady increase in screening trends was also observed for general health, gastric, colorectal, and cervical cancers, with APC of 5.3%, 5.7%, 6.9%, and 7.6% in the 2-year postdiagnosis rate, and APC of 3.6%, 3.7%, 3.7%, and 4.4% in 5-year postdiagnosis rate, respectively. The screening rate was highest among age groups 50-59 and 60-69 in 2009 and significant upward trends were observed in all age groups for general health checkup and gastric, colorectal, and cervical cancer screening. CONCLUSION: Among female breast cancer survivors in Korea, the uptake rate of screenings for general health and various cancers, including breast, gastric, colorectal, and cervical cancers, has shown a gradual increase in recent years.

Longitudinal Changes in Smoking Behaviors and Cancer-Related Mortality Risk in Middle-Aged Korean Women.

PURPOSE: This study investigated association between smoking habit change and cancer-related mortality risk in Korean women. MATERIALS AND METHODS: Study population were women aged ≥ 40 years who underwent two biennial cancer screenings during 2009-2012 and were followed up until 2020. Participants were grouped into sustained nonsmokers, sustained quitters, new quitters, relapsers/smoking initiators, and sustained smokers. Outcomes included all-cause and cancer-related deaths. Cox regression and competing risk analysis was used to assess association between smoking habit change and mortality risk. RESULTS: Of 2,892,590 women, 54,443 death cases were recorded (median follow-up of 9.0 years). Compared with sustained nonsmokers, mortality risk from all causes and cancer-related causes increased in all other smoking groups. Cancer-related risk increased 1.22-fold among sustained quitters (95% confidence interval [CI], 1.10 to 1.36), 1.56-fold (95% CI, 1.40 to 1.75) in new quitters, 1.40-fold (95% CI, 1.21 to 1.62) in relapsers/smoking initiators, and 1.61-fold (95% CI, 1.46 to 1.78) in sustained smokers compared with sustained nonsmokers. Women who were sustained smokers with higher smoking intensity had a higher mortality risk in terms of hazard ratios compared to nonsmokers (< 5 pack-years 2.12-fold, 5-10 pack-years 2.15-fold, and > 10 pack-years 2.27-fold). CONCLUSION: Quitting smoking earlier is critical for preventing death from all causes and cancer among female smokers.

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.

Health-related quality of life in long-term early-stage breast cancer survivors compared to general population in Korea.

PURPOSE: This study assessed health-related quality of life (HRQoL) of long-term breast cancer (BC) survivors diagnosed at early stages and compare with cancer-free, age-matched women. METHODS: The study population included BC survivors diagnosed with ductal carcinoma in situ (DCIS) or breast cancer stages I-II, who had undergone lumpectomy/mastectomy, with time since diagnosis ranging from 9 to 16 years. Survey was conducted at two tertiary hospitals in 2020. Data for cancer-free female controls was randomly drawn from a population-based survey and age-, education-matched with 1 case: 3 controls ratio. Self-reported HRQoL was assessed using EQ-5D with five dimentions. EQ-5D utility index score was calculated. Difference in EQ-5D score was evaluated using the Tobit regression model with adjustment for other covariates. RESULTS: Of 273 survivors. 88% and 12% underwent mastectomy and lumpectomy, respectively. The mean (standard deviation, SD) age at survey was 57.3 (8.5) years old. BC survivors reported significantly more problems performing daily activities (11% vs. 5%, p < 0.001), pain/discomfort (46% vs. 23%, p < 0.001), and anxious/depressed feelings (44% vs. 8%, p < 0.001) relative to the controls. Difference in EQ-5D score between BC survivors and the general population was higher in older age groups. The overall EQ-5D score of BC survivors was statistically lower than that of the control subjects (adjusted [Formula: see text]=0.117, p < 0.001). CONCLUSION: Long-term BC survivors who survived beyond ten years post-diagnosis experience more pain, anxiety, and distress, leading to an overall poorer HRQoL. IMPLICATIONS FOR CANCER SURVIVORS: This study suggest the importance of follow-up care, particularly focusing on pain, anxiety, and distress management to enhance the HRQoL of long-term BC survivors.

Mammographic Breast Density and Risk of Ovarian Cancer in Korean Women.

BACKGROUND: This study aimed to investigate the potential association between mammographic breast density and ovarian cancer risk. METHODS: This retrospective cohort study included women ≥40 years of age who underwent a mammography screening from 2009 to 2014. Breast density was assessed using the Breast Imaging-Reporting and Data System. The primary outcome was ovarian cancer development, and the cases were recorded until 2020. Cox proportional hazards regression was used to assess the association between breast density and ovarian cancer development. Subgroup analyses stratified by age, menopausal status, and body mass index (BMI) were conducted. RESULTS: Of the 8,556,914 women included in this study, 9,246 ovarian cancer events were recorded during a median follow-up period of 10 years (interquartile range, 8.1-11.0 years). Compared with women with almost entirely fat density, those with scattered fibroglandular density, heterogeneous density, and extreme density had an increased risk of ovarian cancer with adjusted HRs of 1.08 [95% confidence interval (CI), 1.02-1.15], 1.16 (95% CI, 1.09-1.24), and 1.24 (95% CI, 1.15-1.34), respectively. The strongest association was observed in the ≥60 years age group; subgroup analysis indicated a significant increase in association between the higher-density category and ovarian cancer risk, regardless of BMI or menopausal status. CONCLUSIONS: Higher levels of breast density are associated with an increased risk of ovarian cancer. IMPACT: Breast density may have a relationship with ovarian cancer risk and could be used to assess future risk.

Increased risk of cancer and cancer-related mortality in middle-aged Korean women with prediabetes and diabetes: a population-based study.

OBJECTIVES: This study investigated the risk of developing and dying from all types of cancer, as well as cancer-specific mortality, in women diagnosed with prediabetes and diabetes. METHODS: We included women aged ≥40 years who underwent cancer screening from 2009 to 2014 with follow-up until 2020. Diabetes status was determined based on fasting plasma glucose levels, self-reported history of diabetes, and the use of antidiabetic medication. We quantified the risk of cancer and mortality in the prediabetes and diabetes groups, relative to the normoglycemia group, by calculating adjusted hazard ratios (aHRs). RESULTS: The study included 8,309,393 participants with a mean age of 52.7±9.7 years. Among these participants, 522,894 cases of cancer and 193,283 deaths were detected. An increased risk of cancer was observed in both the prediabetes group (aHR, 1.03; 95% confidence interval [CI], 1.02 to 1.04) and the diabetes group (aHR, 1.13; 95% CI, 1.12 to 1.14). The highest risk was identified in those with diabetes who developed liver (aHR, 1.72; 95% CI, 1.66 to 1.79), pancreatic (aHR, 1.68; 95% CI, 1.60 to 1.76), and gallbladder cancer (aHR, 1.43; 95% CI, 1.36 to 1.51). Women with prediabetes and diabetes exhibited a 1.07-fold (95% CI, 1.05 to 1.08) and 1.38-fold (95% CI, 1.36 to 1.41) increased risk of death from cancer, respectively. CONCLUSIONS: Both prediabetes and diabetes were associated with an elevated risk of cancer, as well as an increased risk of death from cancer, in middle-aged Korean women. However, the degree of risk varied depending on the specific site of the cancer.

Changes in metabolic syndrome and the risk of breast and endometrial cancer according to menopause in Korean women.

OBJECTIVES: This study investigated how changes in metabolic syndrome (MetS) are associated with the subsequent risk of breast and endometrial cancer according to menopausal status. METHODS: This cohort study, using data from the National Health Insurance Service database, included women aged ≥40 years who underwent 2 biennial cancer screenings (2009-2010 and 2011-2012) and were followed up until 2020. Participants were grouped into MetS-free, MetS-recovery, MetS-development, and MetS-persistent groups. Menopausal status (premenopausal, perimenopausal, and postmenopausal) was assessed at 2 screenings. Cox proportional hazard regression was used to assess the association between MetS changes and cancer risk. RESULTS: In 3,031,980 women, breast and endometrial cancers were detected in 39,184 and 4,298, respectively. Compared with the MetS-free group, those who recovered, developed, or had persistent MetS showed an increased risk of breast cancer, with adjusted hazard ratios (aHRs) of 1.05, 1.05, and 1.11, respectively (p<0.005). MetS persistence was associated with an increased risk of breast cancer in postmenopausal women (aHR, 1.12, 95% confidence interval [CI], 1.08 to 1.16) but not in premenopausal or perimenopausal women. MetS persistence was associated with an increased risk of endometrial cancer in premenopausal, perimenopausal, and postmenopausal women, with aHRs of 1.41 (95% CI, 1.17 to 1.70), 1.59 (95% CI, 1.19 to 2.12), and 1.47 (95% CI, 1.32 to 1.63), respectively. CONCLUSIONS: Increased breast cancer risk was associated with recovered, developed, and persistent MetS in postmenopausal women. Meanwhile, increased endometrial cancer risk was found in obese women who recovered from MetS or persistently had MetS, regardless of menopausal status, when compared to MetS-free women.

Increased risk of pancreatic, thyroid, prostate and breast cancers in men with a family history of breast cancer: A population-based study.

The association between a family history of breast cancer (FHBC) in female first-degree relatives (FDRs) and cancer risk in men has not been evaluated. This study aimed to compare the risks of overall and site-specific cancers in men with and without FHBC. A population-based study was conducted with 3 329 106 men aged ≥40 years who underwent national cancer screening between 2013 and 2014. Men with and without FHBC in their female FDRs were age-matched in a 1:4 ratio. Men without FHBC were defined as those without a family history of any cancer type in their FDRs. Data from 69 124 men with FHBC and 276 496 men without FHBC were analyzed. The mean follow-up period was 4.7 ± 0.9 years. Men with an FHBC in any FDR (mother or sister) had a higher risk of pancreatic, thyroid, prostate and breast cancers than those without an FHBC (adjusted hazard ratios [aHRs] (95% confidence interval [CI]): 1.35 (1.07-1.70), 1.33 (1.12-1.56), 1.28 (1.13-1.44) and 3.03 (1.130-8.17), respectively). Although an FHBC in any one of the FDRs was not associated with overall cancer risk, FHBC in both mother and sibling was a significant risk factor for overall cancer (aHR: 1.69, 95% CI:1.11-2.57) and increased the risk of thyroid cancer by 3.41-fold (95% CI: 1.10-10.61). FHBC in the mother or sister was a significant risk factor for pancreatic, thyroid, prostate and breast cancers in men; therefore, men with FHBC may require more careful BRCA1/2 mutation-related cancer surveillance.

Identifying the impact of land use land cover change on streamflow and nitrate load following modeling approach: a case study in the upstream Dong Nai River basin, Vietnam.

Tri An Reservoir is a vital source of water for agriculture, industry, hydropower, and public usage in Southern Vietnam. Due to human activities, water eutrophication has become a serious problem in recent decades. This study investigated for the first time the impact of land use and land cover (LULC) change on streamflow and nitrate load from the upstream Dong Nai River basin, which is the largest watershed of the reservoir. The study utilized several LULC scenarios, including LULC 2000, 2010, and 2020. The SWAT model was applied to model the watershed during the period 1997-2009. Results showed that the hydrological model performed satisfactorily based on the Nash-Sutcliffe efficiency (NSE) coefficient, the root mean square error observations standard deviation ratio (RSR), and the percent bias (PBIAS). The average simulated values of monthly streamflow and nitrate load were 453.7, 450.0, 446.7 m3/s and 17,699.43, 17,869.13, 17,590.81 tonnes for the LULC 2000, 2010, and 2020 scenarios, respectively. There were no significant differences in streamflow and nitrate load at the basin level under the different LULC scenarios. However, when looking at the subbasin level, there were differences in nitrate load among the scenarios. This suggests that the impacts of LULC on nitrate load may be more pronounced at smaller scales. Overall, our finding underscores the importance of modeling techniques in predicting the impacts of LULC change on streamflow and water quality, which can ultimately aid in the sustainable management of water resources.

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.