Multi-Ancestry Transcriptome-wide Association Studies Uncover New Insights into Breast Cancer Genetics and Biology.

Genome-wide association studies (GWAS) have identified over 200 genetic risk loci for breast cancer, yet the target genes in these loci remain largely unknown. To address this knowledge gap, we conducted a series of multi-ancestry transcriptome-wide association studies (TWAS) to discover potential breast cancer susceptibility genes. We developed and validated ancestry-specific genetic models to predict levels of gene expression, alternative splicing, and 3' UTR alternative polyadenylation, using genomic and transcriptomic data from normal breast tissue samples of 652 females of African, Asian, or European ancestry.

Integrating multi-ancestry genomic and proteomic data to identify blood risk biomarkers and target proteins for breast cancer genetic risk loci.

Genome-wide association studies (GWAS) have identified more than 200 risk loci for breast cancer. However, target genes and their encoded proteins in these loci remain largely unknown. In this study, we utilized genetic prediction models for 1349 circulating proteins derived from individuals of African (n = 1871) and European (n = 7213) ancestry to investigate genetically predicted protein levels in association with breast cancer risk among females of African (n = 40,138), Asian (n = 137,677), and European (n = 247,173) ancestry.

Role of oligandrin in enhancing post-harvest disease resistance in cherry tomato through salicylic acid and jasmonic acid signaling pathways.

Salicylic acid (SA) and jasmonic acid (JA) pathways are crucial components of plant defense mechanisms; however, their roles in post-harvest preservation remain inadequately explored. Cherry tomatoes are highly susceptible to fungal pathogens, such as , after harvest, leading to significant post-harvest losses. This study investigates the effects of oligandrin, an elicitin protein derived from , on enhancing the resistance of harvested cherry tomatoes to .

Association Between Cardiometabolic Multimorbidity and 15-year Mortality in the Asia Cohort Consortium.

Background: Studies on the association between multimorbidity and mortality in large populations have mainly been conducted in European and North American populations. This study aimed to identify the association between cardiometabolic multimorbidity and all-cause and cardiovascular disease (CVD) mortality in the Asia Cohort Consortium.

Methods: In this prospective cohort study, pooled analysis was performed to evaluate the association between cardiometabolic diseases (hypertension, diabetes, ischemic heart disease, and stroke), multimorbidity, and all-cause and CVD mortality, including premature mortality, among participants from 11 Asian cohort studies.

Lipid peroxidation and colorectal cancer risk: a time-varying relationship.

Importance: We recently observed an inverse and time-dependent association between systemic oxidative stress (OxS), measured by urinary biomarkers of nucleic acid oxidation, and colorectal cancer (CRC) risk. Further investigations into other types of OxS markers are warranted.

Objective: To extend the investigation into systemic lipid peroxidation and CRC risk.

Time-dependent relationship between urinary biomarkers of nucleic acid oxidation and colorectal cancer risk.

Purpose: Randomized controlled trials have failed to validate that neutralizing oxidative stress (OxS) through antioxidant supplementation reduces cancer risk. This study aims to prospectively investigate whether the relationship between systemic OxS and colorectal cancer (CRC) risk changes over the course of cancer development.

Methods: This study utilized a nested case-control design in two Shanghai cohorts for primary analysis and one US cohort for replication analysis.

Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

Mutational signatures define immune and Wnt-associated subtypes of ampullary carcinoma.

Background And Objective: Ampullary carcinoma (AMPAC) taxonomy is based on morphology and immunohistochemistry. This classification lacks prognostic reliability and unique genetic associations. We applied an approach of integrative genomics characterising patients with AMPAC exploring molecular subtypes that may guide personalised treatments.

Reproductive factors and risk of epithelial ovarian cancer: results from the Asia Cohort Consortium.

Background: There are scarce data on risk factors for epithelial ovarian cancer (EOC) in Asian populations. Our goal was to advance knowledge on reproductive -related risk factors for EOC in a large population of Asian women.

Methods: This study used pooled individual data from baseline questionnaires in 11 prospective cohorts (baseline years, 1958-2015) in the Asia Cohort Consortium.

The Epstein-Barr Virus Nuclear Antigen 1 Variant Associated with Nasopharyngeal Carcinoma Defines the Sequence Criteria for Serologic Risk Prediction.

Purpose: Antibodies to select Epstein-Barr virus proteins can diagnose early-stage nasopharyngeal carcinoma (NPC). We have previously shown that IgA against Epstein-Barr virus nuclear antigen 1 (EBNA1) can predict incident NPC in high- and intermediate-risk cohorts 4 years before diagnosis. Here, we tested EBNA1 variants, with mutants, to define the sequence requirements for an NPC risk assay.

Occupational exposure to benzene and risk of non-Hodgkin lymphoma in an extended follow-up of two population-based prospective cohorts of Chinese men and women.

The carcinogenicity of benzene was reevaluated by the International Agency for Research on Cancer in 2017, with the Working Group reaffirming positive yet inconclusive associations with non-Hodgkin lymphoma (NHL). To extend our previous observation of a significant exposure-response for cumulative occupational benzene exposure and NHL risk among Chinese women in a population-based cohort in Shanghai, we extended follow-up of this cohort and pooled the data with a similarly designed population-based cohort of men in Shanghai. Cumulative exposure estimates were derived for 134,449 participants in the pooled analysis by combining ordinal job-exposure matrix intensity ratings with quantitative benzene measurements from an inspection database of Shanghai factories.

TPPP-BRD9 fusion-related gallbladder carcinomas are frequently associated with intracholecystic neoplasia, neuroendocrine carcinoma, and a distinctive small tubular-type adenocarcinoma commonly accompanied with a syringomatous pattern.

A fusion between tubulin polymerization-promoting protein (TPPP), a regulatory cytoskeletal gene, and the chromatin remodeling factor, bromodomain-containing protein 9 (BRD9), TPPP-BRD9 fusion has been found in rare cancer cases, including lung and gallbladder cancers (GBC). In this study, we investigated the histopathological features of 16 GBCs previously shown by RNA sequencing to harbor the TPPP-BRD9 fusion. Findings in the fusion-positive GBCs were compared with 645 GBC cases from the authors' database.

Diabetes and gastric cancer incidence and mortality in the Asia Cohort Consortium: A pooled analysis of more than a half million participants.

Background: Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes.

Methods: A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium.

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV.

A nested case-control study of untargeted plasma metabolomics and lung cancer among never-smoking women within the prospective Shanghai Women's Health Study.

The etiology of lung cancer in never-smokers remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Here, we aimed to enhance our understanding of lung cancer pathogenesis among never-smokers using untargeted metabolomics. This nested case-control study included 395 never-smoking women who developed lung cancer and 395 matched never-smoking cancer-free women from the prospective Shanghai Women's Health Study with 15,353 metabolic features quantified in pre-diagnostic plasma using liquid chromatography high-resolution mass spectrometry.

Family history and gastric cancer incidence and mortality in Asia: a pooled analysis of more than half a million participants.

Background: The family history of gastric cancer holds important implications for cancer surveillance and prevention, yet existing evidence predominantly comes from case-control studies. We aimed to investigate the association between family history of gastric cancer and gastric cancer risk overall and by various subtypes in Asians in a prospective study.

Methods: We included 12 prospective cohorts with 550,508 participants in the Asia Cohort Consortium.