Cancer medicine · 2026
Exploring Genetic Contributions to Prostate Cancer Risk in an Asian Population-Based Study.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Geng Jiun-Hung, Yu Chia-Cheng, Huang Chao-Yuan, Lin Victor C, Li Chia-Yang, Wu Ming-Tsang, Chen Szu-Chia, Bao Bo-Ying, Huang Shu-Pin
Аннотация
BACKGROUND: Genetic susceptibility to prostate cancer (PCa) varies across populations, yet East Asian men remain underrepresented in genome-wide association studies (GWAS). This study aimed to identify genetic variants associated with PCa in a Taiwanese cohort and to explore their potential biological relevance using integrative annotation approaches.
METHODS: We analyzed 961 PCa patients and 3792 age-matched controls from the Taiwan Biobank. Genotyping and imputation were performed using the Taiwan Biobank 2.0 array and the 1000 Genomes East Asian reference panel. Association testing was conducted using logistic regression adjusted for age and population structure. Gene-based analysis using Multi-marker Analysis of GenoMic Annotation (MAGMA), functional annotation using HaploReg, and prostate tissue cis-expression quantitative trait loci (cis-eQTL) and splicing QTL (sQTL) evaluation using the Genotype-Tissue Expression project (GTEx) were performed to explore functional relevance.
RESULTS: We identified 371 genome-wide significant variants and 47 independent risk loci, including established regions (8q24.21, ZNF365, NCOR2, and PRKCB) as well as loci not previously reported in major GWAS (CCDC36, RAB6B, TTLL3, and PARD3B). MAGMA analysis identified 80 PCa-associated genes, and pathway analysis highlighted sphingolipid metabolism and leukocyte transendothelial migration. Integrative annotation indicated that several variants are located in regulatory elements and are associated with prostate-specific eQTL and sQTL effects. Additional analyses showed that several variants were associated with clinical indicators of disease aggressiveness, and age-stratified sensitivity analyses demonstrated consistent associations across age groups. Sensitivity analyses using alternative modeling approaches yielded comparable results.
CONCLUSIONS: This study identifies both established and putatively novel genetic loci associated with PCa in a Taiwanese cohort and provides functional insights through integrative annotation. These findings contribute to understanding the genetic architecture of PCa in East Asian populations and highlight candidate loci that require independent validation in future studies.
METHODS: We analyzed 961 PCa patients and 3792 age-matched controls from the Taiwan Biobank. Genotyping and imputation were performed using the Taiwan Biobank 2.0 array and the 1000 Genomes East Asian reference panel. Association testing was conducted using logistic regression adjusted for age and population structure. Gene-based analysis using Multi-marker Analysis of GenoMic Annotation (MAGMA), functional annotation using HaploReg, and prostate tissue cis-expression quantitative trait loci (cis-eQTL) and splicing QTL (sQTL) evaluation using the Genotype-Tissue Expression project (GTEx) were performed to explore functional relevance.
RESULTS: We identified 371 genome-wide significant variants and 47 independent risk loci, including established regions (8q24.21, ZNF365, NCOR2, and PRKCB) as well as loci not previously reported in major GWAS (CCDC36, RAB6B, TTLL3, and PARD3B). MAGMA analysis identified 80 PCa-associated genes, and pathway analysis highlighted sphingolipid metabolism and leukocyte transendothelial migration. Integrative annotation indicated that several variants are located in regulatory elements and are associated with prostate-specific eQTL and sQTL effects. Additional analyses showed that several variants were associated with clinical indicators of disease aggressiveness, and age-stratified sensitivity analyses demonstrated consistent associations across age groups. Sensitivity analyses using alternative modeling approaches yielded comparable results.
CONCLUSIONS: This study identifies both established and putatively novel genetic loci associated with PCa in a Taiwanese cohort and provides functional insights through integrative annotation. These findings contribute to understanding the genetic architecture of PCa in East Asian populations and highlight candidate loci that require independent validation in future studies.