Genome- and transcriptome-wide association studies of 386,000 Asian and European-ancestry women provide new insights into breast cancer genetics.

By combining data from 160,500 individuals with breast cancer and 226,196 controls of Asian and European ancestry, we conducted genome- and transcriptome-wide association studies of breast cancer. We identified 222 genetic risk loci and 137 genes that were associated with breast cancer risk at a p < 5.0 × 10-8 and a Bonferroni-corrected p < 4.6 × 10-6, respectively. Of them, 32 loci and 15 genes showed a significantly different association between ER-positive and ER-negative breast cancer after Bonferroni correction. Significant ancestral differences in risk variant allele frequencies and their association strengths with breast cancer risk were identified. Of the significant associations identified in this study, 17 loci and 14 genes are located 1Mb away from any of the previously reported breast cancer risk variants. Pathways analyses including 221 putative risk genes identified multiple signaling pathways that may play a significant role in the development of breast cancer. Our study provides a comprehensive understanding of and new biological insights into the genetics of this common malignancy.

Ex vivo kidney machine perfusion: meta-analysis of randomized clinical trials.

BACKGROUND: Machine perfusion is an organ preservation strategy used to improve function over simple storage in a cold environment. This article presents an updated systematic review and meta-analysis of machine perfusion in deceased donor kidneys. METHODS: RCTs from November 2018 to July 2023 comparing machine perfusion versus static cold storage in kidney transplantation were evaluated for systematic review. The primary outcome in meta-analysis was delayed graft function. RESULTS: A total 19 studies were included, and 16 comparing hypothermic machine perfusion with static cold storage were analysed. The risk of delayed graft function was lower with hypothermic machine perfusion (risk ratio (RR) 0.77, 95% c.i. 0.69 to 0.86), even in kidneys after circulatory death (RR 0.78, 0.68 to 0.90) or brain death (RR 0.73, 0.63 to 0.84). Full hypothermic machine perfusion decreased the risk of delayed graft function (RR 0.69, 0.60 to 0.79), whereas partial hypothermic machine perfusion did not (RR 0.92, 0.69 to 1.22). Normothermic machine perfusion or short-term oxygenated hypothermic machine perfusion preservation after static cold storage was equivalent to static cold storage in terms of delayed graft function and 1-year graft survival. CONCLUSION: Hypothermic machine perfusion reduces delayed graft function risks and normothermic approaches show promise.

An Epidemiological Study on Legionnaires' Disease in Gyeonggi Province, Korea: Occurrence, Infection Routes, and Risk Factors for Mortality (2016-2022).

Background and Objectives: Legionnaires' disease (LD) is an acute respiratory disease with increasing annual numbers of reported domestic and global cases. This study aimed to establish foundational data for the prevention and control of LD by investigating the occurrence and infection routes of reported and suspected cases of LD in Gyeonggi Province, Korea, from January 2016 to December 2022, and by and analyzing the risk factors for death. Materials and Methods: A sex-and-age standardization was performed on LD patients and suspected cases reported in Gyeonggi Province. The monthly average number of confirmed cases was visualized using graphs, and a survival analysis was performed using Kaplan-Meier survival curves. The mortality risk ratio was estimated using the Cox proportional hazards model. Results: The incidence of LD in Gyeonggi Province mirrored the national trend, peaking in July with the highest number of confirmed and suspected cases. While there was no significant difference in survival rates by age, the survival rate was higher for suspected cases when analyzed separately. Comparing the death ratio by infection route, nosocomial infections showed the highest death ratio, and intensive care unit (ICU) admission and the presence of coinfections were significantly correlated with mortality. Factors such as nosocomial infection, admission within 1 to 3 days following diagnosis, and the development of complications were factors contributing to a higher risk of death. Conclusions: The general characteristics of patients with LD were similar to those suggested by previous studies. The proportion of community-acquired infections was lower than in previous studies, but the length of hospital stay was similar for survivors and the deceased, and the mortality rate within 30 days after diagnosis was higher for nosocomial infections. In conclusion, nosocomial infection, a period of up to 3 days from admission to diagnosis, and complications were significantly related to the mortality rate of LD.

Causes of death and associated factors with death after liver transplantation: a nationwide database study.

BACKGROUND/AIMS: This study investigated overall, 1-year, and 5-year mortality rate, the causes of death, and associated factors with death in liver transplantation recipients. METHODS: A total of 11,590 liver transplant recipients identified from National Health Insurance Service database between 2006 and 2017 were included. Factors associated with all-cause of death were analyzed by Cox proportional regression models. Cumulative mortality rate according to the underlying indication was estimated by Kaplan-Meier method. RESULTS: The 12-year survival rate for all liver transplant recipients was 68%. In the overall, 1-year, and 5-year mortality of liver transplant recipients, hepatic death was the highest contributing risk, accounting for >65% of the causes of death. Deaths from cirrhosis and liver failure accounted for a high proportion of deaths within 1 year after transplantation, and deaths from malignant tumors such as hepatocellular carcinoma were high among late-stage deaths. DISCUSSION: Although the most common cause of death from liver transplantation is due to primary disease, there was a difference in the pattern of major causes of death according to the period from transplantation to death. If appropriate medical intervention is performed at each period after transplantation, the survival rate can be improved.

Trends for syndromic surveillance of norovirus in emergency department data based on chief complaints.

BACKGROUND: This study compared the trends in norovirus cases to determine whether chief complaint-based emergency department (ED) visits data could reflect trends of norovirus in Korea. METHODS: The ED visits from the National Emergency Department Information System (NEDIS) database and the weekly reported number of noroviruses from the sentinel surveillance system were collected between August 2017 and December 2020. The correlation between weekly norovirus cases and weekly ED visits considering the chief complaint and discharge diagnosis code was estimated using a three-week moving average. RESULTS: In total, 6,399,774 patients with chief complaints of digestive system disease visited ED. A higher correlation between reported norovirus cases and ED visit with chief complaint of vomiting and discharge diagnosis code of gastroenteritis and colitis of unspecified origin or other and unspecified gastroenteritis and colitis of infectious origin was observed (R=0.88, p<.0001). The correlation was highest for the 0-4-years age group (R=0.89, p<.0001). However, no correlation was observed between the reported norovirus cases and the number of emergency department visits with norovirus identified as a discharge diagnosis code. CONCLUSIONS: ED visit data considering a combination of chief complaints and discharged diagnosis code would be available for early detection of infectious disease trends.

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.

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.

Association of Longitudinal Mammographic Breast Density Changes with Subsequent Breast Cancer Risk.

Background Although Breast Imaging Reporting and Data System (BI-RADS) density classification has been used to assess future breast cancer risk, its reliability and validity are still debated in literature. Purpose To determine the association between overall longitudinal changes in mammographic breast density and breast cancer risk stratified by menopausal status. Materials and Methods In a retrospective cohort study using the Korean National Health Insurance Service database, women aged at least 40 years without a history of cancer who underwent three consecutive biennial mammographic screenings in 2009-2014 were followed up through December 2020. Participants were divided according to baseline breast density: fatty (BI-RADS categories a, b) versus dense (BI-RADS categories c, d) and then into subgroups on the basis of changes from the first to second and from second to third screenings. Women without change in breast density were used as the reference group. Main outcomes were incident breast cancer events, both invasive breast cancer and ductal carcinoma in situ. Cox proportion hazard regression was used to calculate the hazard ratio (HR) with adjustment for other covariables. Results Among 2 253 963 women (mean age, 59 years ± 9) there were 22 439 detected breast cancers. Premenopausal women with fatty breasts at the first screening had a higher risk of breast cancer as density increased in the second and third screenings (fatty-to-dense HR, 1.45 [95% CI: 1.27, 1.65]; dense-to-fatty HR, 1.53 [95% CI: 1.34, 1.74]; dense-to-dense HR, 1.93 [95% CI: 1.75, 2.13]). In premenopausal women with dense breasts at baseline, those in whom density continuously decreased had a 0.62-fold lower risk (95% CI: 0.56, 0.69). Similar results were observed in postmenopausal women, remaining significant after adjustment for baseline breast density or changes in body mass index (fatty-to-dense HR, 1.50 [95% CI: 1.39, 1.62]; dense-to-fatty HR, 1.42 [95% CI: 1.31, 1.53]; dense-to-dense HR, 1.62 [95% CI: 1.51, 1.75]). Conclusion In both premenopausal and postmenopausal women undergoing three consecutive biennial mammographic screenings, a consecutive increase in breast density augmented the future breast cancer risk whereas a continuous decrease was associated with a lower risk. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kataoka et al in this issue.

Visible-Light-Mediated TiO2-Catalyzed Aerobic Dehydrogenation of N-Heterocycles in Batch and Flow.

We report a simple and environmentally friendly method for synthesizing N-containing heterocycles via a visible-light-mediated aerobic dehydrogenation reaction. Using a nontoxic, stable, and inexpensive titanium dioxide catalyst, a variety of substituted quinoline, indole, quinoxaline, and 3,4-dihydroisoquinoline derivatives could be synthesized using the green oxidant molecular oxygen. Improved reactivity and scalability of this reaction were demonstrated by adapting the photochemical multiphasic reaction to a continuous flow system. To gain insight into the mechanism, we also conducted several mechanistic studies, including absorption analysis, light on-off testing, and NMR analysis. Especially, oxygen is reduced to hydrogen peroxide, and dimethyl sulfoxide is a critical scavenger of the oxidant byproduct for ensuring high yields.

One-Pot Synthesis of Unprotected 2-Acylpyrroles from 1,2,3-Triazoles and 2-Hydroxymethylallyl Carbonates.

An efficient, tandem one-pot approach to synthesize multisubstituted 2-acylpyrroles from readily prepared N-tosyl triazoles and 2-hydroxymethylallyl carbonates is reported. The reaction proceeds via Rh(II)-catalyzed O-H insertion, [3,3]-sigmatropic rearrangement, Pd(0)-catalyzed oxidative addition, intramolecular cyclization, DBU-promoted E1cB elimination, double bond isomerization, and aromatization, enabling the disconnection and formation of multiple bonds in one reactor. The approach represents a highly regioselective way to access di-, tri-, and tetra-substituted NH pyrroles with high efficiency.

Mutual association between family history of gastric and colorectal cancer and risk of gastric and colorectal cancer.

BACKGROUND AND AIM: We evaluated the associations between gastric cancer (GC) family history (FH) and colorectal cancer (CRC) risk and between CRC FH and GC/gastric adenoma risk. METHODS: We used data of participants who underwent national cancer screening between 2013 and 2014. Participants with GC or CRC FH in first-degree relatives (n = 1 172 750) and those without cancer FH (n = 3 518 250) were matched 1:3 by age and gender. RESULTS: Of the 1 172 750 participants with a FH, 871 104, 264 040, and 37 606 had FHs of only GC, only CRC, and both GC and CRC, respectively. The median follow-up time was 4.8 years. GC and CRC FHs were associated with increased GC and CRC risks, respectively. GC FH was associated with CRC risk (adjusted hazard ratio 1.05; 95% confidence interval [CI] 1.01-1.10), whereas CRC FH was not associated with the risk of GC or gastric adenoma. However, gastric adenoma risk increased 1.62-fold (95% CI 1.40-1.87) in participants with FHs of both GC and CRC, demonstrating a significant difference with the 1.39-fold (95% CI 1.34-1.44) increase in participants with only GC FH. Furthermore, GC risk increased by 5.32 times (95% CI 1.74-16.24) in participants with FHs of both GC and CRC in both parents and siblings. CONCLUSIONS: GC FH was significantly associated with a 5% increase in CRC risk. Although CRC FH did not increase GC risk, FH of both GC and CRC further increased the risk of gastric adenoma. FHs of GC and CRC may affect each other's neoplastic lesion risk.

Comparison of Proportional Mortality Between Korean Atomic Bomb Survivors and the General Population During 1992-2019.

BACKGROUND: Atomic bombs dropped on Hiroshima and Nagasaki in Japan in August 1945 were estimated to have killed approximately 70,000 Koreans. In Japan, studies on the health status and mortality of atomic bomb survivors compared with the non-exposed population have been conducted. However, there have been no studies related to the mortality of Korean atomic bomb survivors. Therefore, we aimed to study the cause of death of atomic bomb survivors compared to that of the general population. METHODS: Of 2,299 atomic bomb survivors registered with the Korean Red Cross, 2,176 were included in the study. In the general population, the number of deaths by age group was calculated from 1992 to 2019, and 6,377,781 individuals were assessed. Causes of death were categorized according to the Korean Standard Classification of Diseases. To compare the proportional mortality between the two groups, the P value for the ratio test was confirmed, and the Cochran-Armitage trend test and χ² test were performed to determine the cause of death according to the distance from the hypocenter. RESULTS: Diseases of the circulatory system were the most common cause of death (25.4%), followed by neoplasms (25.1%) and diseases of the respiratory system (10.6%) in atomic bomb survivors who died between 1992 and 2019. The proportional mortality associated with respiratory diseases, nervous system diseases, and other diseases among atomic bomb survivors was higher than that of the general population. Of the dead people between 1992 and 2019, the age at death of survivors who were exposed at a close distance was younger than those who were exposed at a greater distance. CONCLUSION: Overall, proportional mortality of respiratory diseases and nervous system diseases was high in atomic bomb survivors, compared with the general population. Further studies on the health status of Korean atomic bomb survivors are needed.

Early clinical outcome prediction based on the initial National Early Warning Score + Lactate (News+L) Score among adult emergency department patients.

BACKGROUND: The National Early Warning Score + Lactate (NEWS+L) Score has been previously shown to outperform NEWS alone in prediction of mortality and need for critical care in a small adult ED study. We validated the score in a large patient data set and constructed a model that allows early prediction of the probability of clinical outcomes based on the individual's NEWS+L Score. METHODS: In this retrospective study, we included all adult patients who visited the ED of a single urban academic tertiary-care university hospital in South Korea for five consecutive years (1 January 2015 to 31 December 2019). The initial (<1 hour) NEWS+L Score is routinely recorded electronically at our ED and was abstracted for each visit. The outcomes were hospital death or a composite of hospital death and intensive care unit admission at 24 hours, 48 hours and 72 hours. The data set was randomly split into train and test sets (1:1) for internal validation. The area under the receiver operating characteristic curve (AUROC) value and area under the precision and recall curve (AUPRC) value were evaluated and logistic regression models were used to develop an equation to calculate the predicted probabilities for each of these outcomes according to the NEWS+L Score. RESULTS: After excluding 808 patients (0.5%) from 149 007 patients in total, the study cohort consisted of 148 199 patients. The mean NEWS+L Score was 3.3±3.8. The AUROC value was 0.789~0.813 for the NEWS+L Score with good calibration (calibration-in-the-large=-0.082~0.001, slope=0.964~0.987, Brier Score=0.011~0.065). The AUPRC values of the NEWS+L Score for outcomes were 0.331~0.415. The AUROC and AUPRC values of the NEWS+L Score were greater than those of NEWS alone (AUROC 0.744~0.806 and AUPRC 0.316~0.380 for NEWS). Using the equation, 48 hours hospital mortality rates for NEWS+L Score of 5, 10 and 15 were found to be 1.1%, 3.1% and 8.8%, and for the composite outcome 9.2%, 27.5% and 58.5%, respectively. CONCLUSION: The NEWS+L Score has acceptable to excellent performance for risk estimation among undifferentiated adult ED patients, and outperforms NEWS alone.

Disparity in access for people with disabilities to outpatient dental care services: a retrospective cohort study.

BACKGROUND: People with disabilities face difficulties in oral health management and gaining access to dental care. The availability of a regular source of dental care (RSDC) is an important factor that influences the access to health services and care management. The purpose of this study was to determine the effect of the availability of RSDC on the number of annual dental visits and dental expenses per visit among people with disabilities. METHODS: Data of 7,896,251 patients with dental problems in South Korea were analyzed using the 2002-2018 National Health Insurance claims data. A generalized estimating equation was applied to analyze the repeated-measurement data, and the interaction effect between RSDC and the disability severity was evaluated. RESULTS: The number of annual dental visits was higher among people with (2.62) than among those without (2.23) disabilities. Despite their increased dental needs, both annual dental visits and dental expenses per visit were low among older individuals (p < 0.001). The proportion and frequency of annual dental visits was lower among women than among men with disabilities. RSDC had differential effects on the severity of disability. Compared to people without disabilities, RSDC increased the number of annual dental visits (p = 0.067) and the dental expenses per visit (p < 0.05) among those with severe disabilities, but the effect on the number of annual dental visits was not significant among those with mild disabilities (p = 0.698). CONCLUSIONS: Our results suggest a need for a special dental care system for people with disabilities, to ensure an RSDC, particularly for women and for older people with disabilities.

Occupational hazards among dental hygienists: Risk level assessment of scaling work.

OBJECTIVES: This study aimed to classify occupational hazards of ultrasonic scaling by factor and to identify the distribution of occupational risk levels of the study participants according to occupational hazards. In addition, the relationship between the general characteristics of dental hygienists and the occupational risk level of scaling was investigated. METHODS: This study was conducted on 237 dental hygienists. Exposure frequency and the degree of work loss were investigated on a five-point scale for each of the 15 occupational hazards of scaling. RESULTS: Among occupational hazards, the proportion of high-risk individuals for biological hazards (32.9%) was the highest. Dental clinics (33.6%) were found to have a higher proportion of high-risk individuals than dental hospitals (16.5%) (p < 0.05). The proportion of high-risk individuals was higher in the absence of an infection control coordinator (33.9%) (p < 0.05) and infection control education in the preceding 2 years (28.6%) (p < 0.05). CONCLUSION: To create a safe dental work environment, appropriate measures according to the risk level and measurement of occupational risk should be discussed.

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

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

Microcalcifications, mammographic breast density, and risk of breast cancer: a cohort study.

BACKGROUND: Breast density and microcalcifications are strongly associated with the risk of breast cancer. However, few studies have evaluated the combined association between these two factors and breast cancer risk. We investigated the association between breast density, microcalcifications, and risk of breast cancer. METHODS: This cohort study included 3,910,815 women aged 40-74 years who were screened for breast cancer between 2009 and 2010 and followed up until 2020. The National Health Insurance Service database includes national health-screening results from the national breast cancer screening program, which is an organized screening program provided every 2 years for all women aged 40 years or older. Breast density was assessed based on the Breast Imaging Reporting and Data System (BI-RADS) 4th edition, mostly through visual assessment by radiologists. The presence or absence of microcalcifications was obtained from the mammographic results. Cox proportional hazard regression for breast cancer risk was used to estimate hazard ratios (aHRs) adjusted for breast cancer risk factors. RESULTS: A total of 58,315 women developed breast cancer during a median follow-up of 10.8 years. Women with breast cancer had a higher proportion of microcalcifications than women without breast cancer (0.9% vs. 0.3%). After adjusting for breast density, women with microcalcification had a 3.07-fold (95% confidence interval [CI] 2.82-3.35) increased risk of breast cancer compared to women without microcalcification. The combined association between microcalcification and breast density dramatically increased the risk of breast cancer, corresponding to a higher level of breast density. Among postmenopausal women, the highest risk group was women with BI-RADS 4 and microcalcification. These women had more than a sevenfold higher risk than women with BI-RADS 1 and non-microcalcification (aHR, 7.26; 95% CI 5.01-10.53). CONCLUSION: Microcalcification is an independent risk factor for breast cancer, and its risk is elevated when combined with breast density.

Changes in weight and waist circumference during menopausal transition and postmenopausal breast cancer risk.

Our study aimed to investigate the association between changes in weight and waist circumference (WC) during menopausal transition and breast cancer risk in Asian women. In total, 184 931 women aged 40 to 59 years with a premenopausal status at the first screening in 2009 to 2010 and a postmenopausal status at the second screening in 2011 to 2012 were included in the analysis. Changes in weight and WC during menopausal transition were classified as loss (>2.5 kg; >2.5 cm), stable (±2.5 kg; ±2.5 cm), and gain (2.5-4.9 kg, ≥5 kg; 2.5-4.9 cm, ≥5 cm). WC gain of 5 cm or more during menopausal transition was associated with an increased risk of breast cancer with an HR of 1.15 (95% CI = 1.01-1.30), compared to stable WC (±2.5 cm). Among obese premenopausal women, increased WC ≥5 cm during menopausal transition was associated with increased breast cancer risk with an HR of 1.22 (95% CI = 1.03-1.44). Similarly, in women with premenopausal WC ≥80 cm, increased WC of ≥5 cm during menopausal transition was likely to increase the breast cancer risk (HR = 1.36, 95% CI = 1.13-1.88) than in women with stable WC. However, in premenopausal women with BMI <23 kg/m2 or WC <80 cm, changes in WC during menopausal transition did not show an association. Weight gain during menopausal transition was not associated with the risk of breast cancer. Changes in central obesity during menopausal transition in combination with premenopausal obesity status are associated with breast cancer risk after menopause.

Mammographic breast density, body mass index and risk of breast cancer in Korean women aged 75 years and older.

Mammographic breast density and body mass index (BMI) are strong risk factors of breast cancer, but few studies have investigated these factors in older women. Our study assessed the association between breast density, BMI and the breast cancer risk among women aged ≥75 years. We included women who underwent breast cancer screening between 2009 and 2014 and were followed up until 2020. Breast density was measured using Breast Imaging Reporting and Data System. BMI was classified into three groups: <23, 23 to <25 and ≥25. Cox proportional hazards models were used to estimate the association of breast density and BMI with breast cancer risk. In 483 564 women, 1885 developed breast cancer. The 5-year incidence increased with an increase in breast density and BMI. Increase in breast density was associated with an increased breast cancer risk in all BMI categories: among women with BMI <23, those with heterogeneous/extreme density had a 2.98-fold (95% CI: 2.23-3.80) increased risk of breast cancer compared to those with entirely fatty breasts. An increase in BMI was associated with increased breast cancer risk in women with the same breast density in all density categories. When the combined associations of breast density and BMI on the risk of breast cancer were considered, women with a BMI ≥25 and heterogeneous/extreme breast density had a 5.35-fold (95% CI: 4.26-6.72) increased risk of breast cancer compared to women with a BMI <23 and fatty breasts. Women aged ≥75 years, with dense breasts, regardless of BMI status, might benefit from a tailored screening strategy for early detection of breast cancer.

Association Between Family History of Gastric Cancer and the Risk of Gastric Cancer and Adenoma: A Nationwide Population-Based Study.

INTRODUCTION: A family history of gastric cancer (GC) is a well-known risk factor for GC. However, the association between family history of GC and the risk of GC and gastric adenoma according to the affected family members is unclear. METHODS: We analyzed the data of participants aged ≥40 years who underwent national GC screening between 2013 and 2014. Participants with and without a family history of GC among first-degree relatives were matched by age and sex in a 1:4 ratio. RESULTS: During a median follow-up of 4.9 years, 0.96% and 0.46% of 896,721 participants with a family history of GC and 0.65% and 0.32% of 3,586,884 participants without a family history of GC developed GC and gastric adenoma, respectively. A family history of GC among any first-degree relative was a risk factor for GC (adjusted hazard ratio [HR] 1.48, 95% confidence interval 1.45-1.52) and gastric adenoma (HR 1.44, 95% confidence interval 1.39-1.50). The HRs for GC and gastric adenoma were higher in participants with a family history of GC in parents and siblings (2.26 and 2.19, respectively) than in those with a family history of GC in parents only (1.40 and 1.41, respectively) or siblings only (1.59 and 1.47, respectively). The HRs for GC in participants with vs without a family history of GC were 1.62, 1.55, and 1.42 in the 40-49, 50-59, and ≥60 years' age groups of participants, respectively. Similarly, the HRs for gastric adenoma increased with decreasing age of participants. DISCUSSION: A family history of GC was a risk factor for both GC and gastric adenoma. The risk of GC and gastric adenoma of the participants was higher when both parents and siblings had GC.