Publications by authors named "I-Shou Chang"

Article Synopsis
  • * Results showed that a higher PRS was more strongly related to EGFR-positive LUAD cases (OR=8.63) than to EGFR-negative cases (OR=3.50), indicating a significant association based on mutation status.
  • * These findings imply that genetic susceptibility to LUAD differs in never-smoking East Asian women depending on whether the cancer has specific mutations, which could affect public health strategies and clinical practices.*
View Article and Find Full Text PDF
Article Synopsis
  • * The newly developed multi-ancestry PRS showed a strong correlation with LUAD risk, indicating that individuals in the highest PRS percentile had significantly increased risk compared to those in the lowest.
  • * Findings suggest that those in the highest risk category have a lifetime risk of about 6.69%, and they reach the average population's 10-year risk for LUAD by age 41, highlighting the importance of multi-ancestry PRS for better risk assessment in this group.
View Article and Find Full Text PDF

Lung cancer in never smokers (LCINS) accounts for up to 25% of all lung cancers and has been associated with exposure to secondhand tobacco smoke and air pollution in observational studies. Here, we evaluate the mutagenic exposures in LCINS by examining deep whole-genome sequencing data from a large international cohort of 871 treatment-naïve LCINS recruited from 28 geographical locations within the Sherlock- study. mutations were 3.

View Article and Find Full Text PDF
Article Synopsis
  • The study analyzed the age at lung cancer diagnosis and sex differences in individuals who never smoked, involving 33,793 participants from various regions including East Asia, the US, and the UK.
  • Results showed that in Chinese individuals, females were diagnosed at a younger age than males, with significant differences recorded in several locations, while patterns in other racial groups were inconsistent.
  • The findings suggest that there are notable sex differences in the age of diagnosis for lung cancer among non-smokers, highlighting the need for further research in this area.
View Article and Find Full Text PDF

Type 2 diabetes (T2D) and hypertension are common comorbidities and, along with hyperlipidemia, serve as risk factors for cardiovascular diseases. This study aimed to evaluate the predictive value of polygenic risk scores (PRSs) on cardiometabolic traits related to T2D, hypertension, and hyperlipidemia and the incidence of these three diseases in Taiwan Biobank samples. Using publicly available, large-scale genome-wide association studies summary statistics, we constructed cross-ethnic PRSs for T2D, hypertension, body mass index, and nine quantitative traits typically used to define the three diseases.

View Article and Find Full Text PDF
Article Synopsis
  • Estimating the absolute risk of lung cancer in never-smokers is key for developing effective lung cancer screening programs, particularly in relation to the influence of environmental tobacco smoke (ETS).
  • This study focused on never-smoking women in Taiwan, integrating their genetic susceptibility (via a polygenic risk score) and exposure to ETS to evaluate the risk of lung adenocarcinoma (LUAD).
  • Findings revealed that the estimated lifetime risk of LUAD in women with no ETS exposure was 2.5%, highlighting the variability based on genetic and environmental factors, and the study examined how these elements interact in determining lung cancer risk.
View Article and Find Full Text PDF

Importance: Knowing whether the effects of smoking and other risk factors with lung adenocarcinoma (ADC) incidence varies by sex would provide information on lung cancer prevention strategies.

Objective: To evaluate whether women in Taiwan have higher age- and tumor stage-specific lung ADC incidence rates than men irrespective of smoking status (ie, ever smoker or never smoker).

Design, Setting, And Participants: This population-based cohort study used data sets synthesized from the Taiwan Cancer Registry (TCR) from 1979 to 2019; the TCR Long Form (TCRLF) from 2011 to 2019, which provides individual-level smoking and tumor stage information; the Taiwan Cause of Death Database (TCOD) from 1985 to 2019; the National Health Insurance Research Database (NHIRD) from 2000 to 2020; the Monthly Bulletin of Interior Statistics (MBIS) from 2011 to 2019; the National Health Interview Survey from 2001, 2005, 2009, 2013, and 2017; and Taiwan Biobank data from 2008 to 2021.

View Article and Find Full Text PDF
Article Synopsis
  • Lung adenocarcinoma is the most prevalent form of lung cancer, and existing known genetic risk factors account for only a small portion of its heritability.
  • A comprehensive genome-wide association study involving nearly 22,000 cases and over 150,000 controls identified 12 new genetic variants linked to the disease, raising the count to 28 variants across 25 distinct locations in the genome.
  • The study emphasized that these genetic markers are particularly significant in East Asian populations, especially among never-smokers, and indicates that further research could inform better prevention and treatment strategies tailored to these populations.
View Article and Find Full Text PDF
Article Synopsis
  • Due to increasing cancer cases and an aging population in Taiwan, researchers aimed to analyze cancer prevalence and the comorbidities of older patients with the five most common cancers: breast, colorectal, liver, lung, and oral.
  • They created the Taiwan Cancer Comorbidity Index (TCCI) using data from multiple health databases to assess the actual prognosis of these patients based on age, cancer stage, and comorbidities.
  • Findings showed that cancer prevalence nearly doubled from 2004 to 2014, with stage being a key predictor of prognosis; interestingly, patients in Taiwan faced lower noncancer-related death rates than in the US, but higher cancer death rates, aiding in clinical treatment decisions and health policy planning
View Article and Find Full Text PDF

Background: Methods synthesizing multiple data sources without prospective datasets have been proposed for absolute risk model development. This study proposed methods for adapting risk models for another population without prospective cohorts, which would help alleviate the health disparities caused by advances in absolute risk models. To exemplify, we adapted the lung cancer risk model PLCOM2012, well studied in the west, for Taiwan.

View Article and Find Full Text PDF
Article Synopsis
  • - The study focuses on assessing cardiovascular mortality risk in an aging population through a combined score based on electrocardiographic (ECG) parameters, aiming for primary prevention strategies.
  • - Conducted on over 5,300 elderly subjects in Taiwan, results showed that specific ECG abnormalities like left ventricular hypertrophy (LVH) and prolonged QTc and PR intervals were significantly linked to all-cause and cardiovascular death.
  • - The research developed predictive models using an ECG abnormality score, which effectively identified high-risk groups, demonstrating robust statistical improvements in predicting outcomes related to mortality.
View Article and Find Full Text PDF

Objectives: Lung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of programmed death-1 (encoded by ) and its ligands, programmed death ligand 1 () and 2 (), associated with lung cancer risk in never-smoking women.

Materials And Methods: During September 2002 and July 2012, we enrolled never-smoking female patients with lung adenocarcinoma (LUAD) (n=1153) and healthy women (n=1022) from six tertiary hospitals in Taiwan.

View Article and Find Full Text PDF
Article Synopsis
  • Genetic background plays a significant role in the cognitive decline of Alzheimer's disease (AD) patients, with specific focus on risk genes in a study involving 255 AD and 44 mild cognitive impairment (MCI) patients.
  • The study used a 4-year follow-up and data-driven analysis to investigate how certain genetic variants influenced the onset age and rate of cognitive decline among the Han Chinese population.
  • Key findings showed that the ε4 allele was linked to an earlier onset of cognitive decline, while other alleles also had varying impacts on age and rate of decline, identifying important genetic factors in this demographic.
View Article and Find Full Text PDF

Aims/hypothesis: An elevated fasting glucose level in non-diabetic individuals is a key predictor of type 2 diabetes. Genome-wide association studies (GWAS) have identified hundreds of SNPs for fasting glucose but most of their functional roles in influencing the trait are unclear. This study aimed to identify the mediation effects of DNA methylation between SNPs identified as significant from GWAS and fasting glucose using Mendelian randomisation (MR) analyses.

View Article and Find Full Text PDF

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA.

View Article and Find Full Text PDF

Background: High disease burden suggests the desirability to identify high-risk Asian never-smoking females (NSF) who may benefit from low-dose CT (LDCT) screening. In North America, one is eligible for LDCT screening if one satisfies the U.S.

View Article and Find Full Text PDF

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS.

View Article and Find Full Text PDF

Assuming Cox's regression model, we consider penalized full likelihood approach to conduct variable selection under nested case-control (NCC) sampling. Penalized non-parametric maximum likelihood estimates (PNPMLEs) are characterized by self-consistency equations derived from score functions. A cross-validation method based on profile likelihood is used to choose the tuning parameter within a family of penalty functions.

View Article and Find Full Text PDF

Mitochondrial Lon is a multi-function matrix protease with chaperone activity. However, little literature has been undertaken into detailed investigations on how Lon regulates apoptosis through its chaperone activity. Accumulating evidences indicate that various stresses induce transportation of p53 to mitochondria and activate apoptosis in a transcription-independent manner.

View Article and Find Full Text PDF

Objective: A policy initiated in 2001 by Taiwan's National Health Insurance (NHI) Administration has effectively reduced outpatient antibiotic use except fluoroquinolones (FQs). The influence of differential regulation policy of narrow-spectrum versus broad-spectrum FQs on the prescriptions is unknown.

Methods: This study analyzed the claim records of oral FQs prescription at outpatient visits during 2000-2010 using the NHI Research Database and compared prescriptions for narrow-spectrum FQs, which are inactive against Streptococcus pneumoniae and lack formulary restriction, with those for broad-spectrum FQs.

View Article and Find Full Text PDF

The early onset breast cancer patients (age ≤ 40) often display higher incidence of axillary lymph node metastasis, and poorer five-year survival than the late-onset patients. To identify the genes and molecules associated with poor prognosis of early onset breast cancer, we examined gene expression profiles from paired breast normal/tumor tissues, and coupled with Gene Ontology and public data base analysis. Our data showed that the expression of GAS7b gene was lower in the early onset breast cancer patients as compared to the elder patients.

View Article and Find Full Text PDF

Background: The effect of cardio-metabolic profile on the relationship of body mass index (BMI) with mortality is unclear. The aim of this study was to explore association between BMI and mortality at all ages, taking account of cardio-metabolic disorders.

Methods: We followed 377,929 individuals (≥ 20 years), who registered for health checkups in 1996-2007, until 2008 and found 9490 deaths.

View Article and Find Full Text PDF
Article Synopsis
  • Advances in early cancer diagnosis and treatment in high-income countries have helped improve survival rates, but socioeconomic disparities in survival persist for some adult cancers.
  • A study in Taiwan assessed net survival rates for 20 common adult cancers across different age and socioeconomic groups, revealing improvements in survival for many, but persistent inequalities for some cancers.
  • The findings highlight the importance of addressing socioeconomic disparities, especially in age groups with significant gaps, to enhance overall cancer survival and inform targeted interventions.
View Article and Find Full Text PDF

Background: Phthalic acid esters are ubiquitous and antiandrogenic, and may cause systemic effects in humans, particularly with in utero exposure. Epigenetic modification, such as DNA methylation, has been hypothesized to be an important mechanism that mediates certain biological processes and pathogenic effects of in utero phthalate exposure.

Objective: The aim of this study was to examine the association between genome-wide DNA methylation at birth and prenatal exposure to phthalate.

View Article and Find Full Text PDF