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Characterizing Genetic Susceptibility to Colorectal Cancer in Taiwan Through Genome-Wide Association Study.

Characterizing Genetic Susceptibility to Colorectal Cancer in Taiwan Through Genome-Wide Association Study.

Authors :
Bau DT
Liu TY
Yang JS
Chen WT
Tsai CW
Chang WS
Ke TW
Liao CC
Chen YC
Chang YT
Tsai FJ
Source :
Molecular carcinogenesis [Mol Carcinog] 2025 Jan; Vol. 64 (1), pp. 25-32. Date of Electronic Publication: 2024 Oct 11.
Publication Year :
2025

Abstract

We conducted the first genome-wide association study (GWAS) of colorectal cancer (CRC) in Taiwan with 5342 cases and 61,015 controls. Ninety-two SNPs in three genomic regions reached genome-wide significance (p < 5 × 10 <superscript>-8</superscript> ). The lead SNPs in these three regions were: rs12778523 (OR = 1.18, 95% CI, 1.15-1.23, p = 4.51 × 10 <superscript>-13</superscript> ), an intergenic SNP between RNA5SP299 and LINC02676 at chromosome 10p14; rs647161 (OR = 1.14, 95% CI, 1.09-1.19, p = 2.21 × 10 <superscript>-9</superscript> ), an intronic SNP in PITX1 at 5q31.1, and rs10427139 (OR = 1.20, 95% CI, 1.14-1.28, p = 3.62 × 10 <superscript>-9</superscript> ), an intronic SNP in GPATCH1 at 19q13.1. We further validated CRC susceptibility SNPs previously identified through GWAS in other populations. A total of 61 CRC susceptibility SNPs were confirmed in Taiwanese. The top validated putative CRC susceptibility genes included: POU2AF2, HAO1, LAMC1, EIF3H, BMP2, ZMIZ1, BMP4, POLD3, CDKN1A, PREX1, CDKN2B, CDH1, and LRIG1. The top enriched pathways included TGF-β signaling, BMP signaling, extracellular matrix organization, DNA repair, and cell cycle control. We could not validate SNPs in HLA-G at 6p22.1 and in NOTCH4 at 6p21.32. We generated a weighted genetic risk score (GRS) using the 61 SNPs and constructed receiver operating characteristic (ROC) curves using the GRS to predict CRC. The area under the ROC curve (AUC) was 0.589 for GRS alone and 0.645 for GRS, sex, and age. These susceptibility SNPs and genes provide important insights into the molecular mechanisms of CRC development and help identify high-risk individuals for CRC in Taiwan.<br /> (© 2024 Wiley Periodicals LLC.)

Details

Language :
English
ISSN :
1098-2744
Volume :
64
Issue :
1
Database :
MEDLINE
Journal :
Molecular carcinogenesis
Publication Type :
Academic Journal
Accession number :
39392253
Full Text :
https://doi.org/10.1002/mc.23823