East Asian Women Research Articles

Interaction of base excision repair gene polymorphism and estrogen-DNA adducts in breast cancer risk among East Asian women.

In East Asia, the incidence of breast cancer has been increasing rapidly, particularly among premenopausal women. An elevated ratio of estrogen-DNA adducts was linked to a higher risk of breast cancer. The present study explored the influence of the interaction between base excision repair (BER) gene polymorphisms and estrogen-DNA adducts on breast cancer risk. We conducted a case-control study comprising healthy volunteers and individuals with benign breast disease (control arm, n = 176) and patients with invasive carcinoma or carcinoma in situ (case arm, n = 177). Genotyping for BER-related genes, including SMUG1, OGG1, ERCC5, and APEX1, was performed. A logistic regression model, incorporating interactions between gene polymorphisms, estrogen-DNA adduct ratio, and clinical variables, was used to identify the risk factors for breast cancer. Univariate analysis indicated marginal associations between breast cancer risk and APEX1 rs1130409 T > G (P = 0.057) and APEX1 rs1760944 T > G (P = 0.065). Multivariate regression analysis revealed significant associations with increased breast cancer risk for APEX1_rs1130409 (GT/GG versus TT) combined with a natural logarithmic value of the estrogen-DNA adduct ratio (estimated OR 1.164, P = 0.023) and premenopausal status with an estrogen-DNA adduct ratio > 2.93 (estimated OR 2.433, P = 0.001). APEX1_rs1130409 (GT/GG versus TT) polymorphisms, which are related to decreased BER activity, combined with an increased ratio of estrogen-DNA adducts, increase the risk of breast cancer in East Asian women.

Intermanufacturer assessment of diagnostic performance of angiogenic ratio vs glycosylated fibronectin in women with suspected pre-eclampsia.

To compare the diagnostic performance of different manufacturers' immunoassays for the soluble fms-like tyrosine kinase-1 (sFlt-1)-to-placental growth factor (PlGF) ratio with that of a point-of-care test for glycosylated fibronectin (GlyFn) in women with suspected pre-eclampsia (PE). This was a prospective, single-center, double-blinded, non-interventional study of East Asian women with a singleton pregnancy who presented with hypertension with or without clinical features of PE after 20 weeks' gestation between January 2020 and March 2022. Maternal serum samples were collected at the time of presentation, and subsequent management followed the departmental protocol, based on gestational age, severity of hypertension, fetal condition and presence of severe PE features. Women diagnosed with PE at presentation were excluded. PE was diagnosed according to the 2018 International Society for the Study of Hypertension in Pregnancy classification. Levels of sFlt-1 and PlGF were measured using the Cobas e411 (Roche Diagnostics), BRAHMS KRYPTOR (ThermoFisher Scientific) and iMAGIN 1800 (Ningbo-Aucheer) platforms. GlyFn levels were measured using the Lumella™ GlyFn PoC test (Diabetomics). The predictive performance of each test to rule out PE within 7 days and rule in PE within 28 days from the date of presentation was assessed. Based on the PROGNOSIS study, a sFlt-1/PlGF ratio of ≤ 38 on the Roche platform was used to predict the absence of PE within 7 days. The sFlt-1/PlGF ratio was classified as high or low using platform-specific thresholds equivalent to a Roche sFlt-1/PlGF ratio of 38, which were derived using Passing-Bablok regression. GlyFn was categorized as high or low using two reported clinical management thresholds (263 μg/mL and 510 μg/mL). Overall, 236 women with suspected PE were included, of whom 70 (29.7%) were diagnosed with PE; 36 (51.4%) and 70 (100%) developed PE within 7 days and 28 days, respectively. Eighty-eight (37.3%) women had a sFlt-1/PlGF ratio of > 38 on the Roche platform, 79 (33.5%) women had a sFlt-1/PlGF ratio of > 55 on the KRYPTOR platform and 96 (40.7%) women had a sFlt-1/PlGF ratio of > 40 on the iMAGIN 1800 platform. Furthermore, 62 (26.3%) and four (1.7%) women had a GlyFn level of > 263 μg/mL and > 510 μg/mL, respectively. The negative predictive value (NPV) of the sFlt-1/PlGF ratio measured on the Roche, KRYPTOR and iMAGIN 1800 platforms to rule out PE within 7 days after presentation was 83.3%, 82.0% and 82.9%, respectively, while that for GlyFn > 263 μg/mL and > 510 μg/mL was 82.6% and 70.4%, respectively. The corresponding positive predictive values (PPV) to rule in PE within 28 days after presentation were 50.5%, 52.3% and 46.7%, respectively, for the sFlt-1/PlGF ratio, and 35.4% and 50.0%, respectively, for GlyFn > 263 μg/mL and > 510 μg/mL. The predictive performance of different manufacturers' assays for the sFlt-1/PlGF ratio to rule in and rule out PE were similar once standardized to a common threshold. Our findings suggest that the sFlt-1/PlGF ratio and GlyFn using a cut-off of 263 μg/mL can both be utilized to rule out PE within 7 days after assessment, with a moderate NPV. The PPV for ruling in PE within 28 days remains poor. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

의미 네트워크(Semantic Network)를 활용한 중국 독자의 한국 여성 서사 수용 연구: 최은영 『밝은 밤』의 정동(Affect)적 접근

This study analyzes Chinese readers' rating reviews of Eunyoung Choi's Bright Night using a semantic network to explore Chinese readers' acceptance of Korean female narratives in terms of affect. Eunyoung Choi's Bright Night was ranked second overall and first in the foreign fiction category in the 2023 annual book rankings on Douban, China's largest book rating site. The novel centers on the stories of four women: a great-grandmother, a grandmother, a mother, and a daughter. The relationship between the great-grandmother, aunt, and neighboring women who lived through the Japanese occupation and the Korean War, as well as the conflict and reconciliation between grandmother, mother, and me, are important narrative devices in the novel. Affect refers to the continuous transformation of potential states inherent in the body into reality through ‘encounter’. The bodies that are encountered are not only human bodies, but also literary works such as Bright Night. The idea transformed by the encounter between bodies is affect, and the actual state is objectified in language. The analysis showed that Chinese readers were most affected by the matriarchal narratives of the four women, and the women's painful lives and internal conflicts, and the friendship and solidarity of other women to help them overcome them. Cluster analysis of the reviewed texts to identify specific emotional patterns revealed four patterns: ‘empathizing with women's suffering and pain’, ‘emotions of healing and hope for female characters’ ‘friendship and reconciliation’, ‘literary emotions of female solidarity’, and ‘heart-to-heart encounters’. This study confirms that Korean women's narratives can reach readers with different national systems and social structures and cause emotional changes, which can be extended to East Asian women's narratives.

Association between thermogenic brown fat and genes under positive natural selection in circumpolar populations

BackgroundAdaptation to cold was essential for human migration across Eurasia. Non-shivering thermogenesis through brown adipose tissue (BAT) participates in cold adaptation because some genes involved in the differentiation and function of BAT exhibit signatures of positive natural selection in populations at high latitudes. Whether these genes are associated with the inter-individual variability in BAT thermogenesis remains unclear. In this study, we evaluated the potential associations between BAT activity and single nucleotide polymorphisms (SNPs) in candidate gene regions in East Asian populations.MethodsBAT activity induced by mild cold exposure was measured in 399 healthy Japanese men and women using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). The capacity for cold-induced thermogenesis and fat oxidation was measured in 56 men. Association analyses with physiological traits were performed for 11 SNPs at six loci (LEPR, ANGPTL8, PLA2G2A, PLIN1, TBX15-WARS2, and FADS1) reported to be under positive natural selection. Associations found in the FDG-PET/CT population were further validated in 84 healthy East Asian men and women, in whom BAT activity was measured using infrared thermography. Associations between the SNP genotypes and BAT activity or other related traits were tested using multiple logistic and linear regression models.ResultsOf the 11 putative adaptive alleles of the six genes, two intronic SNPs in LEPR (rs1022981 and rs12405556) tended to be associated with higher BAT activity. However, these did not survive multiple test comparisons. Associations with lower body fat percentage, plasma triglyceride, insulin, and HOMA-IR levels were observed in the FDG-PET/CT population (P < 0.05). Other loci, including TBX15-WARS2, which is speculated to mediate cold adaptation in Greenland Inuits, did not show significant differences in BAT thermogenesis.ConclusionsOur results suggest a marginal but significant association between LEPR SNPs. However, robust supporting evidence was not established for the involvement of other loci under positive natural selection in cold adaptation through BAT thermogenesis in East Asian adults. Given the pleiotropic function of these genes, factors other than cold adaptation through BAT thermogenesis, such as diet adaptation, may contribute to positive natural selection at these loci.

The Critical Discourse Analysis of Domestic Helper Abuse Case by Different News and Social Media Platforms A Case Study of Erwiana Sulistyaningsih

The paper discusses the unfair treatment of Indonesian domestic worker (DHs) based on a case study of Erwiana Sulistyaningsih using a critical discourse analysis (CDA) approach. Both official statements and unofficial comments are thoroughly analyzed to demonstrate the media's hidden power in influencing public opinion. We identify polarity in attitude (positive and negative) towards the case in NGOs (non-governmental organization) and comments from social media and Hong Kong forums. NGO are essential in raising awareness about the discrimination and racism faced by domestic helpers and in shaping public opinion to support more inclusive policies for immigrants. Conversely, discussions on social media and Hong Kong forums show that opinions on Erwiana's case were not unanimous. Some comments even displayed racial discrimination. However, these descriptions and labels of foreign domestic helpers can be seen as objective statements or based on life experiences. Commenters are unaware of the stereotypes and discrimination against East Asian women that are concealed within the racial ideology of Hongkongers.

Fantasised and fantastical Nordic imaginaries: Contextualising Nordic life vlogs by East Asian YouTube vloggers

Abstract Nordic life vlogs are a popular genre among avid watchers of YouTube influencers across East Asia. The vlogs showcase “a slice of life” content, documenting the simple living, daily routines, beautiful landscapes, cultural festivals, and everyday norms of what it is like to live in the Nordic region. While there are many Nordic life vloggers, in this article, we focus on a subset: young immigrant women from Japan and South Korea living in the Nordics. By attending to the genre, content, and interactions between vloggers and viewers, we explore how female East Asian YouTube vloggers who have immigrated to Nordic countries construct fantasised and fantastical narratives around Nordic imaginaries. The discussion of multifaceted layers of Nordic imaginaries explains how Nordic life vlogs serve as a platform for young East Asian women to project their desire for a better life and cultivate subtle resilience at the juncture of postfeminism and postcolonialism.

P-327 A multicenter retrospective study of the investigation of detailed immunological inflammatory grading for chronic endometritis and their correlation with the endometrial microbiome

Abstract Study question There exists refractory chronic endometritis which does not respond to antibiotic treatment. This study aims to elucidate its pathogenesis and develop detection methods. Summary answer Through treatment intervention for chronic endometritis (CE), the inflammatory grade decreased overall and the bacteria most associated with endometritis were Lactobacillus iners. What is known already CE and endometrial dysbiosis have been reported to be associated with recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), but there is insufficient data confirming the interrelation between them. Moreover, the diagnosis of CE typically involves single immunohistochemical staining with CD138, but the diagnostic criteria vary across reports (e.g., McQueen’s method, Liu’s method, etc.) and moreover, use of this classical inflammatory assessment methods raises concerns about their sufficiency in evaluating the pathogenesis of endometritis in cases of RPL and RIF. Study design, size, duration A retrospective analysis was conducted on 206 samples of endometrial specimens collected from infertile patients at seven participating assisted reproductive healthcare facilities from 2021 to 2023. Among these, 73 samples (from 48 cases) had undergone both histological examination and simultaneous endometrial microbiome testing, and data on pregnancy outcomes (including implantation success and ongoing pregnancy rate) were collected until December 2023 for these cases. Participants/materials, setting, methods The endometrial specimens from cases with RIF or RPL were obtained through intrauterine aspiration in luteal phase. Immunohistochemical staining using CD138, CD56, and CD8 antibodies was performed. A composite grading for endometritis, based on histological findings and immunohistochemistry intensity, was established (INF grading; grade 0 to 5). Furthermore, a portion of the specimens underwent microbiome analysis using next-generation sequencing targeting the 16SrRNA, exploring correlations between bacterial taxa, abundance, histological findings, and pregnancy outcomes. Main results and the role of chance Among analyzed 48 cases, 11 cases underwent repeated endometrial microbiome analysis post-treatment again, while 7 cases had additional testing without improvement in chronic endometritis (CE) or endometrial dysbiosis. The McQueen’s method diagnosed 27 cases with CE, while the Liu method identified 4 cases. According to our INF grading, 11 cases were classified as endometritis grade 3 or above. Successful embryo implantation was achieved in 18 cases (37.5%), with ongoing pregnancy in 13 cases (27.1%). CE treatment involved broad-spectrum oral antibiotics, mainly doxycycline and metronidazole, resulting in improvement to grade 2 or below in 9 out of 11 cases with INF grade 3 or above. However, clear associations between pregnancy outcomes and INF grades were not apparent, with the most significant correlation found in CE diagnosis using Liu’s method. Analyzing biomarkers for CE through LEfSe (Linear discriminant analysis effect size), both McQueen’s method and INF grading 2 or above were associated with the intrauterine presence of Lactobacillus iners. Estimating endometrial inflammation based on intrauterine Lactobacillus iners presence yielded an AUC of 0.733 for McQueen’s CE and 0.723 for INF grade 2 or above. Limitations, reasons for caution This study is a retrospective analysis, and the treatment protocols and intervention criteria for chronic endometritis vary among different facilities. The number of cases is also limited, and it is desirable to conduct a unified prospective multicenter cohort study with consistent protocols. Wider implications of the findings The combination of the endometrial microbiome testing and detailed inflammatory grading suggests the potential for establishing appropriate treatment intervention strategies and predicting the success rate of infertile treatment. Since Lactobacillus iners tends to colonize extensively in the vaginal environment of East Asian women, it is necessary to explore region-specific measures. Trial registration number not appicable

Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.

Lung adenocarcinoma (LUAD) among never-smokers is a public health burden especially prevalent in East Asian (EAS) women. Polygenic risk scores (PRSs), which quanefy geneec suscepebility, are promising for straefying risk, yet have mainly been developed in European (EUR) populaeons. We developed and validated single-and mule-ancestry PRSs for LUAD in EAS never-smokers, using the largest available genome-wide associaeon study (GWAS) dataset. We used GWAS summary staesecs from both EAS (8,002 cases; 20,782 controls) and EUR (2,058 cases; 5,575 controls) populaeons, as well as independent EAS individual level data. We evaluated several PRSs approaches: a single-ancestry PRS using 25 variants that reached genome-wide significance (PRS-25), a genome-wide Bayesian based approach (LDpred2), and a mule-ancestry approach that models geneec correlaeons across ancestries (CT-SLEB). PRS performance was evaluated based on the associaeon with LUAD and AUC values. We then esemated the lifeeme absolute risk of LUAD (age 30-80) and projected the AUC at different sample sizes using EAS-derived effect-size distribueon and heritability esemates. The CT-SLEB PRS showed a strong associaeon with LUAD risk (odds raeo=1.71, 95% confidence interval (CI): 1.61, 1.82) with an AUC of 0.640 (95% CI: 0.629, 0.653). Individuals in the 95 th percenele of the PRS had an esemated 6.69% lifeeme absolute risk of LUAD. Comparison of LUAD risk between individuals in the highest and lowest 20% PRS quaneles revealed a 3.92-fold increase. Projeceon analyses indicated that achieving an AUC of 0.70, which approaches the maximized prediceon poteneal of the PRS given the esemated geneec variance, would require a future study encompassing 55,000 EAS LUAD cases with a 1:10 case-control raeo. Our study underscores the poteneal of mule-ancestry PRS approaches to enhance LUAD risk straeficaeon in never-smokers, parecularly in EAS populaeons, and highlights the necessary scale of future research to uncover the geneec underpinnings of LUAD.

Quantitative CT lumbar spine BMD cutpoint value for classifying osteoporosis among older Chinese men can be the same as that of older Chinese women, both much lower than the value for Caucasians.

For older Caucasian women and men, the QCT (quantitative CT) lumbar spine (LS) bone mineral density (BMD) threshold for classifying osteoporosis is 80mg/ml. It was recently proposed that, for older East Asian women, the QCT LS BMD value equivalent to the Caucasian women's threshold of 80mg/mL is about 45∼50mg/ml. For a data of 328 cases of Chinese men (age: 73.6 ± 4.4years) who had QCT LS BMD and DXA LS BMD at the same time and with the DXA BMD value of ≤ 0.613g/cm2 to classify osteoporosis, the corresponding QCT LS BMD threshold is 53mg/ml. Osteoporotic-like vertebral fracture sum score (OLVFss) ≤ -2.5 has been proposed to diagnose osteoporosis. For 316 cases of Chinese men(age:73.7±4.5 years), OLVFss ≤ -2.5 defines an osteoporosis prevalence of 4.4%; to achieve this osteoporosis prevalence, the corresponding QCT LS BMD value is < 47.5mg/ml. In the China Action on Spine and Hip Status study, a Genant grades 2/3 radiographic 'osteoporotic vertebral fracture' prevalence was 2.84% for Chinese men (total n = 1267, age: 62.77 ± 9.20years); to achieve this osteoporosis prevalence, the corresponding BMD value was < 42.5mg/ml. In a study of 357 Beijing older men, according to the clinical fragility fracture prevalence and femoral neck DXA T-score, the QCT LS BMD value to classify osteoporosis was between 39.45mg/ml and 51.38mg/ml. For older Chinese men (≥ 50years), we recommend the cutpoint for the QCT LS BMD definition of osteoporosis to be 45∼50mg/ml which is the same as the value for Chinese women.

Assessing Glycosylated Hemoglobin Thresholds for Development of Cardiovascular Disease by Racial and Ethnic Groups.

Diabetes is the strongest risk factor for cardiovascular disease, and although glycosylated hemoglobin (HbA1c) levels are known to vary by race, no racial and ethnic-specific diagnostic thresholds exist for diabetes in prediction of cardiovascular disease events. The purpose of this study is to determine whether HbA1c thresholds for predicting major adverse cardiovascular events (MACEs) differ among racial and ethnic groups. This is a retrospective cohort study of Kaiser Permanente Northern California adult members (n=309 636) with no history of cardiovascular disease who had HbA1c values and race and ethnicity data available between 2014 and 2019. Multivariable logistic regression was used to evaluate the odds of MACEs by the following racial and ethnic groups: Filipino, South Asian, East Asian, Black, White, and Hispanic. A Youden index was used to calculate HbA1c thresholds for MACE prediction by each racial and ethnic group, stratified by sex. Among studied racial and ethnic groups, South Asian race was associated with the greatest odds of MACEs (1.641 [95% CI, 1.456-1.843]; P<0.0001). HbA1c was a positive predictor for MACEs, with an odds ratio of 1.024 (95% CI, 1.022-1.025) for each 0.1% increment increase in HbA1c. HbA1c values varied between 6.0% and 7.6% in MACE prediction by race and ethnicity and sex. White individuals, South Asian individuals, East Asian women, and Black men had HbA1c thresholds for MACE prediction in the prediabetic range, between 6.0% and 6.2%. Black women, Hispanic men, and East Asian men had HbA1c thresholds of 6.2% to 6.6%, less than the typical threshold of 7.0% that is used as a treatment goal. Findings suggest that the use of race and ethnic- and sex-specific HbA1c thresholds may need to be considered in treatment goals and cardiovascular disease risk estimation.

Abstract PS10-07: A second-generation polygenic risk score (PRS) based on genetic ancestry improves breast cancer (BC) risk prediction for all ancestries

Abstract Background: Common genetic variants, mainly single-nucleotide polymorphisms (SNPs) explain substantial genetic susceptibility to BC. PRS have been developed to quantify the combined effects of BC-associated SNPs, providing important information about BC risk. Historically, genome-wide association studies have been conducted in predominantly European populations, resulting in miscalibrated and inaccurate PRS for non-Europeans. We previously described a multiple-ancestry PRS (MA-PRS-149) based on 56 ancestry-informative and 93 BC-associated SNPs. The MA-PRS-149 achieved accuracy for all women by characterizing the genetic ancestry of each BC-associated SNP in terms of three reference ancestries (African, East Asian, and European), applying ancestry-specific SNP risks and frequencies, and combining the results as a weighted sum of three ancestry-specific PRS. Here, we aimed to improve the predictive accuracy of MA-PRS-149, particularly for non-Europeans, through the inclusion of additional BC-associated SNPs. Methods: Women referred for hereditary cancer testing and negative for pathogenic variants in BC-associated genes were divided into consecutive study cohorts to (1) quantify ancestry-specific SNP risks, (2) combine the three ancestry-specific PRS, and (3) pre-specified clinical validation. To select an optimal set of BC-associated SNPs, we developed a novel synthetic stepwise regression methodology that accounts for linkage disequilibrium. Ancestry-specific SNP risks were determined from meta-analyses of literature with clinical cohorts of 57,827 Black/African and 26,992 East Asian women. Ancestry-specific PRS were combined based on a diverse cohort of 157,740 women. Clinical validation was conducted in an independent cohort of 77,774 women. We used multivariable logistic regression adjusted for age, ancestry, and cancer history to test for improved BC risk prediction over clinical factors. We tested for improvement over the MA-PRS-149, and a European PRS, by including additional PRS as covariates. Calibration was assessed through goodness-of-fit tests. All analyses were conducted within the full cohort and ancestral subpopulations. Odds ratios (ORs) and 95% confidence intervals (CIs) are reported per standard deviation within the corresponding population. Results: An optimal set of 383 SNPs (56 ancestry-informative and 327 BC-associated) was included in the final PRS (MA-PRS-383). MA-PRS-383 added significant predictive information to clinical factors in the full cohort and within each ancestry (Table 1). MA-PRS-383 had greater predictive accuracy than MA-PRS-149 or a 383-SNP PRS with European weights. Goodness-of-fit tests showed that MA-PRS-383 was well-calibrated and predicted risk accurately in the tails of the distribution for both European and non-European women. Conclusion: MA-PRS-383 was well-calibrated and substantially improved upon existing PRS in all tested ancestral populations. Incorporation of MA-PRS-383 into BC risk assessment may lead to more accurate identification of women who are most likely to benefit from screening and preventive medications. Citation Format: Timothy Simmons, Elisha Hughes, Dmitry Pruss, Matthew Kucera, Benjamin Roa, Thaddeus Judkins, Thomas Slavin, Victor Abkevich, Ryan Hoff, Srikanth Jammulapati, Susanne Wagner, Dale Muzzey, Jerry Lanchbury, Alexander Gutin. A second-generation polygenic risk score (PRS) based on genetic ancestry improves breast cancer (BC) risk prediction for all ancestries [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS10-07.

Efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms associated with menopause among women in East Asia: a phase 3 randomized study (MOONLIGHT I).

To evaluate the efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms (VMS) associated with menopause in East Asian women. In this phase 3, randomized, double-blind study, postmenopausal women with moderate to severe VMS (minimum average frequency in the 10 days before randomization, ≥7/day or 50/week) received fezolinetant 30 mg/day or placebo (weeks 1-12), followed by an open-label extension phase with fezolinetant 30 mg/day (weeks 13-24). The co-primary endpoints were the mean changes in the daily frequency and severity of VMS at weeks 4 and 12. Among 301 participants, the difference in the least squares mean change (95% confidence interval) from baseline in the daily frequency of moderate to severe VMS versus placebo was -0.65 (-1.41 to 0.12) at week 4 and -0.55 (-1.35 to 0.26) at week 12. The differences in the least squares mean change from baseline in the VMS severity score versus placebo were -0.06 (-0.14 to 0.03) and -0.13 (-0.27 to 0.01) at weeks 4 and 12, respectively. Serious adverse events occurred in 0.7% of participants receiving fezolinetant in weeks 1 to 12, compared with 1.3% of those receiving placebo. Fezolinetant was generally safe but did not reduce the frequency or severity of VMS versus placebo in postmenopausal women in this study.ClinicalTrials.Gov Identifier: NCT04234204.

Abstract 6149: Polygenic risk score and lung adenocarcinoma risk among never-smokers by EGFR mutation status

Abstract Background: Lung cancer is the leading cause of cancer mortality worldwide, and incidence rates for the disease in never-smokers is among the highest in East Asian (EAS) women. Epidermal growth factor receptor (EGFR) is a transmembrane protein that regulates cellular proliferation and apoptosis, and mutations in the EGFR gene have been found to be a defining hallmark of lung adenocarcinoma (LUAD). We investigated if overall genetic susceptibility to LUAD, defined as a polygenic risk score (PRS), is differentially associated with LUAD by EGFR mutation status. Methods: The study consists of 998 female never-smoking histologically confirmed LUAD cases with data on EGFR mutation status and 4,544 female never-smoking controls from the Female Lung Cancer Consortium in Asia. Germline DNA samples were genotyped using the 370K, 610Q, or 660W microarrays. Genomic DNA extracted from fresh, frozen or formalin-fixed paraffin-embedded tumor tissue samples of LUAD cases were genotyped for EGFR mutations on exons 19 and 21. We defined cases with EGFR mutation on either exon as EGFR+ (n=518) and cases without such EGFR mutation as EGFR- (n=480). Weights from 942,592 single nucleotide variants derived from a previously conducted genome-wide association study were used in a Bayesian-based approach, LDpred2, to derive a PRS for all participants. We estimated the odds ratios (OR) and 95% confidence intervals (CI) for the association between continuous PRS, PRS quartiles and tumor EGFR mutation status using logistic regression models in a case-case analysis, as well as using a multinomial logistic regression treating controls as the reference. All models were adjusted for age, study and the top 10 principal components. Results: In case-case comparisons, compared to EGFR- LUAD, we found a positive association between continuous PRS and risk of EGFR+ LUAD (OR=1.17, 95% CI: 1.02, 1.34), as well as a dose-response relationship between quartiles of the PRS and EGFR+ LUAD (p-trend=0.003). We further found that the association between the fourth quartile of the PRS with EGFR+ LUAD (OR=8.63, 95% CI: 5.67, 13.14) was significantly higher than the association between the fourth quartile of the PRS with EGFR- LUAD (OR=3.50, 95% CI: 2.44, 5.00) compared to controls (p-heterogeneity=0.004). Conclusions: We found that the PRS developed for LUAD in EAS individuals was more strongly associated with EGFR+ LUAD compared to EGFR- LUAD, suggesting that germline genetic susceptibility may be differentially associated with LUAD in never-smoking female EAS patients depending on the cancer’s mutation status. Given that patients with LUAD respond differently to treatments that are used as targeted therapy depending on their EGFR mutation status, our findings may have important public health and clinical implications, which may guide risk stratification, screening, and treatment. Citation Format: Batel Blechter, Chao Agnes Hsiung, Keitaro Matsuo, Kouya Shiraishi, Kevin Wang, Haoyu Zhang, Wei Jie Seow, Jianxin Shi, Nilanjan Chatterjee, Jason Y.Y. Wong, Juncheng Dai, H. Dean Hosgood, I-Shou Chang, Jiyeon Choi, Wei Hu, Wei Zheng, Young Tae Kim, Xiao-Ou Shu, Qiuyin Cai, Pan-Chyr Yang, Dongxin Lin, Kexin Chen, Yi-Long Wu, Hongbin Shen, Takashi Kohno, Stephen J. Chanock, Nathaniel Rothman, Qing Lan. Polygenic risk score and lung adenocarcinoma risk among never-smokers by EGFR mutation status [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6149.

East Asia Superciliary Arch Augmentation With Silicone Implant.

A flat superciliary arch is relatively common in East Asian women. Superciliary arch augmentation aims to increase the facial three-dimensionality of the upper face. However, there are few reports in the literature specifically introducing the surgery. In this study, the authors present the clinical outcomes after a series of superciliary arch augmentation with silicone implants. From May 2020 to December 2022, 54 patients underwent superciliary arch augmentation with silicone implants. Silicone implants generally have a length of 50 to 60 mm, a width of 13 to 14 mm, and an arc of 170 degrees. The thickness was 2 to 7 mm. The implant was placed subperiosteal at the lower edges of the eyebrows through a 7 mm incision below the brow tail. All patients evaluated the outcome according to the Global Esthetic Improvement Scale. Four plastic surgeons evaluated postsurgery results with a 5-point Likert Scale (5 = excellent, 4 = good, 3 = fair, 2 = no change, and 1 = worse). Fifty-four patients were successfully enrolled. The mean follow-up period was 12.02 ± 3.38 months. The mean thickness was 4.55 ± 0.67 mm for the thickest part of the implant. The minor complication rate was 44.44%. They all subsided within 1 month without treatment. Patients' outcome ratings were 4.45 ± 0.55 (3 mo), 4.51 ± 0.48 (6 mo), and 4.51 ± 0.45 (1 y). The surgeons' outcome scoring was 4.49 ± 0.31. Superciliary arch augmentation with silicone implants is a quite simple, effective, inexpensive, and safe strategy to improve the three-dimensionality and contour of the upper face in East Asians.

Lack of Association between TP73 G4C14-A4T14 Polymorphism and Cervical Cancer Risk in Overall and Asian Women: A Meta-Analysis.

Growing studies revealed the association between polymorphisms in Tumor Protein TP73 (TP73) and susceptibility to cancer, especially with gynecological cancers. but, the results remained inconsistent. This meta-analysis was carried out to examine the relationship of the TP73 G4C14-to-A4T14 polymorphism (hereafter, G4C14-to-A4T14) with susceptibility to cervical cancer globally and by ethnicity. Eligible studies were collected by retrieving PubMed, Scopus, Web of Science, Embase, Wan Fang, and CNKI published before 25 October, 2023. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of such association. A total of 10 case-control studies with 1804 cervical cancer cases and 2433 healthy controls were included to this study. The pooled results showed that TP73 G4C14-to-A4T14 polymorphism was not associated with cervical cancer risk in overall. in terms of stratified analyses by ethnicity, this polymorphism was not associated with risk of cervical cancer among East-Asian women. however, there was a significant association based source of control among hospital-based studies. Inconsistent with previous meta-analyses, our pooled results revealed that TP73 G4C14-to-A4T14 polymorphism might not be a risk factor for development of cervical cancer globally and among East-Asian women. Moreover, further studies examining the effect of gene-gene and gene-environment interactions may eventually provide a better knowledge.

The Influence of Confucian Cultural Values on the Social Roles of Contemporary Chinese, Japanese, and Korean Women

The background of the research is based on the problems and dilemmas faced by women in modern East Asian society. The research investigated how Confuciuss thoughts put social constraints on women in China, Japan, and South Korea because of their gender through the content of the books and the derived meaning of folk while looking at the ideological transformation of women in society to resist these regulations. People in those societies are often disciplined by thousands of years of traditional etiquette, hence the conflict between self-consciousness and cultural oppression brought about by Confucianism becomes an important topic among East Asian scholars. The paper aims to show how the Confucius norms build on the fixed gender role in different ways and analyze the social oppression of East Asian women, with the resistance and struggle that women are making in these countries. Hence a better understanding of the progress of women's rights in East Asian countries and the role of women in society. The significance of the paper is that it makes up the research gap on how Confucian culture oppresses women's social status and uses realistic scenes while demonstrating the transformation of women's self-consciousness under these regulations in a chronological sequence.

Gendered Perceptions of East and South Asian Men

Gendered race theory argues that in the United States, Asian men are perceived as more feminine and less masculine than Black and White men. However, extant research has focused predominantly on East Asians while overlooking South Asians. In five studies (N = 1,773 U.S. participants), we examined the perceived femininity-masculinity of East and South Asian men. East Asian men were perceived as more feminine and less masculine than South Asian, White, and Black men. South Asian men's perceived femininity-masculinity depends on whether they have facial hair or not. South Asian men with facial hair were perceived as less feminine, more masculine, and more threatening than men from other racial groups. This hyper-masculinization of South Asian men is likely due to alignment of the bearded terrorist stereotypes with facial hair cues. Results for South and East Asian women were inconsistent. This research highlights the importance of disaggregating Asian targets in social cognition theories.

Clinical Study on the Thoracodorsal Artery Perforator Flap in Breast-Conserving Reconstruction of T2 Breast Cancer.

Breast-conserving surgery combined with oncoplastic breast surgery has become the standard surgical treatment for early breast cancer. The purpose of this study was to investigate the safety and efficacy of the thoracodorsal artery perforator flap (TDAPF) in breast-conserving reconstruction of T2 breast cancer. Thirty patients with T2 breast cancer admitted to our hospital from January 2019 to December 2020 were enrolled to receive pedicled TDAPF for repairing breast defects after breast-conserving surgery. Intraoperative conditions, postoperative complications, and shape satisfaction after breast reconstruction were recorded. The operation was successfully completed in all 30 patients, with an operation time of 177.77 ± 24.39min, bleeding of 44.17 ± 7.67mL, and length of hospital stay of 5.23 ± .97d. There was no deformity or seroma at the donor site. Breast shape recovered well after operation. After operation, one patient had fat liquefaction in the recipient site, which healed well after wound treatment. The incidence of postoperative complications was 3.33%. Postoperative follow-up lasted 16-28months, with a median of 22months. The Breast-Q score for breast satisfaction was 61.83 ± 12.87 at 6months after operation, compared to 62.07 ± 11.78 before operation (P > .05). TDAPF, featuring a high survival rate, moderate flap area, fewer postoperative complications, and high satisfaction with breast shape after operation. For east asian women with moderate breast size, TDAPF is a safe, effective choice for repairing defects in breast-conserving surgery for T2 breast cancer.

Perinatal Trajectories of Maternal Depressive Symptoms in Prospective, Community-Based Cohorts Across 3 Continents

Depressive symptoms during pregnancy influence the development and health of the offspring, underscoring the need for timely intervention. However, the course of depressive symptoms across the perinatal period remains unclear, thus complicating screening and referral guidelines. To examine the course and stability of depressive symptoms across the perinatal period in multiple, ethnically diverse independent observational cohorts. This cohort study included self-reported depressive symptoms at multiple time points from 7 prospective cohorts spanning 3 continents (United Kingdom: Avon Longitudinal Study of Parents and Children from 1991 to 1995; Canada: Maternal Adversity, Vulnerability and Neurodevelopment from 2003 to 2007; Montreal Antenatal Well-being Study from 2019 to 2022; Alberta Pregnancy Outcomes and Nutrition from 2009 to 2014; and Singapore: Growing Up in Singapore Toward Healthy Outcomes from 2009 to 2013; Singapore Preconception Study of Long-Term Maternal and Child Outcomes from 2015 to 2019; and Mapping Antenatal Maternal Stress from 2019 to 2022). Participants were recruited either during preconception or pregnancy and observed into the postnatal period. All data from each cohort were analyzed from July 2022 to April 2023. Self-reported depressive symptoms from pregnancy to 2 years following childbirth using either the Edinburgh Postnatal Depression Scale or the Center for Epidemiological Studies Depression were analyzed independently within each cohort using item response theory (IRT) techniques. K-means clustering was used to identify groups of participants with similar trajectories. A total of 11 563 pregnant women (mean [SD] age, 29 [5] years; 569 [4.9%] East Asian women; 304 [2.6%] Southeast Asian women; 10 133 [87.6%] White women) self-reported depressive symptoms from pregnancy to 2 years following childbirth. Analytic methods from Item Response Theory identified 3 groups of mothers based on depressive symptoms: low, mild, and high levels in each of the 7 cohorts. Mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onwards. Mothers with clinical levels of depressive symptoms likewise showed stable trajectories from pregnancy into the postnatal period. In this study, trajectories of depressive symptoms remained stable from pregnancy across the perinatal period, a finding that conflicts with a continuing emphasis on postpartum or postnatal onset of depression that persists in some health policy guidelines. Interventions and public health initiatives should focus on reducing depressive symptoms during pregnancy in addition to following birth.

Asian facial recontouring surgery

Most East Asian women prefer a smaller and smoother facial contour. To meet this aesthetic preference, the concept and surgical techniques of modern facial bone contouring surgery have evolved. Initially, facial bone contouring surgery was limited to procedures like mandibular angle and malar reductions. However, contemporary Asian facial bone contouring surgery now places a stronger emphasis on addressing the entire facial profile from a three-dimensional perspective, a concept referred to as Profiloplasty. In this article, we review the evolution of surgical techniques in Asian facial bone contouring surgery and present its current surgical concepts, particularly focusing on the three-dimensional aspects.