Characterizing Genetic Susceptibility to Colorectal Cancer in Taiwan Through Genome‐Wide Association Study
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
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| Veröffentlicht in: | Molecular carcinogenesis 2025-01, Vol.64 (1), p.25-32 |
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| creator | Bau, Da‐Tian Liu, Ting‐Yuan Yang, Jai‐Sing Chen, William Tzu‐Liang Tsai, Chia‐Wen Chang, Wen‐Shin Ke, Tao‐Wei Liao, Chi‐Chou Chen, Yu‐Chia Chang, Yen‐Ting Tsai, Fuu‐Jen |
| description | 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 |
| doi_str_mv | 10.1002/mc.23823 |
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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 × 10−8). The lead SNPs in these three regions were: rs12778523 (OR = 1.18, 95% CI, 1.15–1.23, p = 4.51 × 10−13), an intergenic SNP between RNA5SP299 and LINC02676 at chromosome 10p14; rs647161 (OR = 1.14, 95% CI, 1.09–1.19, p = 2.21 × 10−9), an intronic SNP in PITX1 at 5q31.1, and rs10427139 (OR = 1.20, 95% CI, 1.14–1.28, p = 3.62 × 10−9), 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.</description><identifier>ISSN: 0899-1987</identifier><identifier>ISSN: 1098-2744</identifier><identifier>EISSN: 1098-2744</identifier><identifier>DOI: 10.1002/mc.23823</identifier><identifier>PMID: 39392253</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Aged ; AUC ; Biomarkers ; Cancer therapies ; Case-Control Studies ; Cell cycle ; Chromosome 10 ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; DNA repair ; E-cadherin ; Extracellular matrix ; Female ; Genetic Predisposition to Disease ; genetic risk score ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Humans ; Male ; Middle Aged ; Molecular modelling ; Polymorphism, Single Nucleotide ; ROC curve ; Single-nucleotide polymorphism ; SNP ; Susceptibility ; Taiwan - epidemiology ; Tumorigenesis</subject><ispartof>Molecular carcinogenesis, 2025-01, Vol.64 (1), p.25-32</ispartof><rights>2024 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2743-63e5fcbf837ffea0e215bcc92984840fe3b97bd8a13d27b6a1f034987c781aa43</cites><orcidid>0000-0002-5504-8656</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmc.23823$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmc.23823$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39392253$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bau, Da‐Tian</creatorcontrib><creatorcontrib>Liu, Ting‐Yuan</creatorcontrib><creatorcontrib>Yang, Jai‐Sing</creatorcontrib><creatorcontrib>Chen, William Tzu‐Liang</creatorcontrib><creatorcontrib>Tsai, Chia‐Wen</creatorcontrib><creatorcontrib>Chang, Wen‐Shin</creatorcontrib><creatorcontrib>Ke, Tao‐Wei</creatorcontrib><creatorcontrib>Liao, Chi‐Chou</creatorcontrib><creatorcontrib>Chen, Yu‐Chia</creatorcontrib><creatorcontrib>Chang, Yen‐Ting</creatorcontrib><creatorcontrib>Tsai, Fuu‐Jen</creatorcontrib><title>Characterizing Genetic Susceptibility to Colorectal Cancer in Taiwan Through Genome‐Wide Association Study</title><title>Molecular carcinogenesis</title><addtitle>Mol Carcinog</addtitle><description>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 × 10−8). The lead SNPs in these three regions were: rs12778523 (OR = 1.18, 95% CI, 1.15–1.23, p = 4.51 × 10−13), an intergenic SNP between RNA5SP299 and LINC02676 at chromosome 10p14; rs647161 (OR = 1.14, 95% CI, 1.09–1.19, p = 2.21 × 10−9), an intronic SNP in PITX1 at 5q31.1, and rs10427139 (OR = 1.20, 95% CI, 1.14–1.28, p = 3.62 × 10−9), 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.</description><subject>Aged</subject><subject>AUC</subject><subject>Biomarkers</subject><subject>Cancer therapies</subject><subject>Case-Control Studies</subject><subject>Cell cycle</subject><subject>Chromosome 10</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>DNA repair</subject><subject>E-cadherin</subject><subject>Extracellular matrix</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>genetic risk score</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Molecular modelling</subject><subject>Polymorphism, Single Nucleotide</subject><subject>ROC curve</subject><subject>Single-nucleotide polymorphism</subject><subject>SNP</subject><subject>Susceptibility</subject><subject>Taiwan - epidemiology</subject><subject>Tumorigenesis</subject><issn>0899-1987</issn><issn>1098-2744</issn><issn>1098-2744</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1O3DAURq0KBNMpUp8AWWLTTQb_ZWIvR1FLkaZiMaAuI8e5mTFK4sF2hKYrHoFn7JPUMEAlJFbf5tyj-92L0FdKZpQQdt6bGeOS8U9oQomSGSuEOEATIpXKqJLFMfocwi0hlBY5OULHXHHFWM4nqCs32msTwds_dljjCxggWoNXYzCwjba2nY07HB0uXec8mKg7XOrBgMd2wNfa3usUG-_G9eZp2vXw9-Hxt20AL0Jwxupo3YBXcWx2X9Bhq7sAJy85RTc_vl-XP7Pl1cVluVhmJi3OszmHvDV1K3nRtqAJMJrXxiimpJCCtMBrVdSN1JQ3rKjnmraEi1TTFJJqLfgUfdt7t97djRBi1dtUp-v0AG4MFac0zwmXRCb07B1660Y_pO0SJTgTc0HIf6HxLgQPbbX1ttd-V1FSPX2g6k31_IGEnr4Ix7qH5g18PXkCsj1wbzvYfSiqfpV74T_vHI_e</recordid><startdate>202501</startdate><enddate>202501</enddate><creator>Bau, Da‐Tian</creator><creator>Liu, Ting‐Yuan</creator><creator>Yang, Jai‐Sing</creator><creator>Chen, William Tzu‐Liang</creator><creator>Tsai, Chia‐Wen</creator><creator>Chang, Wen‐Shin</creator><creator>Ke, Tao‐Wei</creator><creator>Liao, Chi‐Chou</creator><creator>Chen, Yu‐Chia</creator><creator>Chang, Yen‐Ting</creator><creator>Tsai, Fuu‐Jen</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5504-8656</orcidid></search><sort><creationdate>202501</creationdate><title>Characterizing Genetic Susceptibility to Colorectal Cancer in Taiwan Through Genome‐Wide Association Study</title><author>Bau, Da‐Tian ; 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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 × 10−8). The lead SNPs in these three regions were: rs12778523 (OR = 1.18, 95% CI, 1.15–1.23, p = 4.51 × 10−13), an intergenic SNP between RNA5SP299 and LINC02676 at chromosome 10p14; rs647161 (OR = 1.14, 95% CI, 1.09–1.19, p = 2.21 × 10−9), an intronic SNP in PITX1 at 5q31.1, and rs10427139 (OR = 1.20, 95% CI, 1.14–1.28, p = 3.62 × 10−9), 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.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>39392253</pmid><doi>10.1002/mc.23823</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-5504-8656</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aged AUC Biomarkers Cancer therapies Case-Control Studies Cell cycle Chromosome 10 Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology DNA repair E-cadherin Extracellular matrix Female Genetic Predisposition to Disease genetic risk score Genome-wide association studies Genome-Wide Association Study Genomes Humans Male Middle Aged Molecular modelling Polymorphism, Single Nucleotide ROC curve Single-nucleotide polymorphism SNP Susceptibility Taiwan - epidemiology Tumorigenesis |
| title | Characterizing Genetic Susceptibility to Colorectal Cancer in Taiwan Through Genome‐Wide Association Study |
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