Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations
Copyright © 2023 American Society of Human Genetics. All rights reserved..
Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies (GWASs) of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here, we report a GWAS in 1,686 African individuals with ESCC and 3,217 population-matched control individuals to investigate its genetic etiology. We identified a genome-wide-significant risk locus on chromosome 9 upstream of FAM120A (rs12379660, p = 4.58 × 10-8, odds ratio = 1.28, 95% confidence interval = 1.22-1.34), as well as a potential African-specific risk locus on chromosome 2 (rs142741123, p = 5.49 × 10-8) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized with highly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC-affected individuals and 5,918 control individuals, which identified three genome-wide-significant loci on chromosome 9 at FAM120A (rs12379660, pmeta = 9.36 × 10-10), chromosome 10 at PLCE1 (rs7099485, pmeta = 1.48 × 10-8), and chromosome 22 at CHEK2 (rs1033667, pmeta = 1.47 × 10-9). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations. Our GWAS of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:110 |
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| Enthalten in: |
American journal of human genetics - 110(2023), 10 vom: 05. Okt., Seite 1690-1703 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Wenlong Carl [VerfasserIn] |
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| Links: |
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| Themen: |
African cancer genome-wide association study |
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| Anmerkungen: |
Date Completed 10.10.2023 Date Revised 06.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ajhg.2023.08.007 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations |
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| 520 | |a Copyright © 2023 American Society of Human Genetics. All rights reserved. | ||
| 520 | |a Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies (GWASs) of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here, we report a GWAS in 1,686 African individuals with ESCC and 3,217 population-matched control individuals to investigate its genetic etiology. We identified a genome-wide-significant risk locus on chromosome 9 upstream of FAM120A (rs12379660, p = 4.58 × 10-8, odds ratio = 1.28, 95% confidence interval = 1.22-1.34), as well as a potential African-specific risk locus on chromosome 2 (rs142741123, p = 5.49 × 10-8) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized with highly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC-affected individuals and 5,918 control individuals, which identified three genome-wide-significant loci on chromosome 9 at FAM120A (rs12379660, pmeta = 9.36 × 10-10), chromosome 10 at PLCE1 (rs7099485, pmeta = 1.48 × 10-8), and chromosome 22 at CHEK2 (rs1033667, pmeta = 1.47 × 10-9). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations. Our GWAS of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa | ||
| 650 | 4 | |a Meta-Analysis | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a African cancer genome-wide association study | |
| 650 | 4 | |a ESCC GWAS | |
| 650 | 4 | |a ESCC genetics | |
| 650 | 4 | |a ESCC meta-analysis | |
| 650 | 4 | |a esophageal squamous cell carcinoma | |
| 700 | 1 | |a Brandenburg, Jean-Tristan |e verfasserin |4 aut | |
| 700 | 1 | |a Choudhury, Ananyo |e verfasserin |4 aut | |
| 700 | 1 | |a Hayat, Mahtaab |e verfasserin |4 aut | |
| 700 | 1 | |a Sengupta, Dhriti |e verfasserin |4 aut | |
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| 700 | 1 | |a Babb de Villiers, Chantal |e verfasserin |4 aut | |
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| 700 | 1 | |a Aldous, Colleen |e verfasserin |4 aut | |
| 700 | 1 | |a Soo, Cassandra C |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Sang |e verfasserin |4 aut | |
| 700 | 1 | |a Curtis, Charles |e verfasserin |4 aut | |
| 700 | 1 | |a Newton, Rob |e verfasserin |4 aut | |
| 700 | 1 | |a Waterboer, Tim |e verfasserin |4 aut | |
| 700 | 1 | |a Sitas, Freddy |e verfasserin |4 aut | |
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| 700 | 1 | |a Lewis, Cathryn M |e verfasserin |4 aut | |
| 700 | 1 | |a Mathew, Christopher G |e verfasserin |4 aut | |
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