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Genome-wide association study of colorectal cancer in Hispanics
Genome-wide association studies (GWAS) have identified 58 susceptibility alleles across 37 regions associated with the risk of colorectal cancer (CRC) with P < 5×10(−8). Most studies have been conducted in non-Hispanic whites and East Asians; however, the generalizability of these findings and th...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876992/ https://www.ncbi.nlm.nih.gov/pubmed/27207650 http://dx.doi.org/10.1093/carcin/bgw046 |
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author | Schmit, Stephanie L. Schumacher, Fredrick R. Edlund, Christopher K. Conti, David V. Ihenacho, Ugonna Wan, Peggy Van Den Berg, David Casey, Graham Fortini, Barbara K. Lenz, Heinz-Josef Tusié-Luna, Teresa Aguilar-Salinas, Carlos A. Moreno-Macías, Hortensia Huerta-Chagoya, Alicia Ordóñez-Sánchez, María Luisa Rodríguez-Guillén, Rosario Cruz-Bautista, Ivette Rodríguez-Torres, Maribel Muñóz-Hernández, Linda Liliana Arellano-Campos, Olimpia Gómez, Donají Alvirde, Ulices González-Villalpando, Clicerio González-Villalpando, María Elena Le Marchand, Loic Haiman, Christopher A. Figueiredo, Jane C. |
author_facet | Schmit, Stephanie L. Schumacher, Fredrick R. Edlund, Christopher K. Conti, David V. Ihenacho, Ugonna Wan, Peggy Van Den Berg, David Casey, Graham Fortini, Barbara K. Lenz, Heinz-Josef Tusié-Luna, Teresa Aguilar-Salinas, Carlos A. Moreno-Macías, Hortensia Huerta-Chagoya, Alicia Ordóñez-Sánchez, María Luisa Rodríguez-Guillén, Rosario Cruz-Bautista, Ivette Rodríguez-Torres, Maribel Muñóz-Hernández, Linda Liliana Arellano-Campos, Olimpia Gómez, Donají Alvirde, Ulices González-Villalpando, Clicerio González-Villalpando, María Elena Le Marchand, Loic Haiman, Christopher A. Figueiredo, Jane C. |
author_sort | Schmit, Stephanie L. |
collection | PubMed |
description | Genome-wide association studies (GWAS) have identified 58 susceptibility alleles across 37 regions associated with the risk of colorectal cancer (CRC) with P < 5×10(−8). Most studies have been conducted in non-Hispanic whites and East Asians; however, the generalizability of these findings and the potential for ethnic-specific risk variation in Hispanic and Latino (HL) individuals have been largely understudied. We describe the first GWAS of common genetic variation contributing to CRC risk in HL (1611 CRC cases and 4330 controls). We also examine known susceptibility alleles and implement imputation-based fine-mapping to identify potential ethnicity-specific association signals in known risk regions. We discovered 17 variants across 4 independent regions that merit further investigation due to suggestive CRC associations (P < 1×10(−6)) at 1p34.3 (rs7528276; Odds Ratio (OR) = 1.86 [95% confidence interval (CI): 1.47–2.36); P = 2.5×10(−7)], 2q23.3 (rs1367374; OR = 1.37 (95% CI: 1.21–1.55); P = 4.0×10(−7)), 14q24.2 (rs143046984; OR = 1.65 (95% CI: 1.36–2.01); P = 4.1×10(−7)) and 16q12.2 [rs142319636; OR = 1.69 (95% CI: 1.37–2.08); P=7.8×10(−7)]. Among the 57 previously published CRC susceptibility alleles with minor allele frequency ≥1%, 76.5% of SNPs had a consistent direction of effect and 19 (33.3%) were nominally statistically significant (P < 0.05). Further, rs185423955 and rs60892987 were identified as novel secondary susceptibility variants at 3q26.2 (P = 5.3×10(–5)) and 11q12.2 (P = 6.8×10(−5)), respectively. Our findings demonstrate the importance of fine mapping in HL. These results are informative for variant prioritization in functional studies and future risk prediction modeling in minority populations. |
format | Online Article Text |
id | pubmed-4876992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-48769922016-05-26 Genome-wide association study of colorectal cancer in Hispanics Schmit, Stephanie L. Schumacher, Fredrick R. Edlund, Christopher K. Conti, David V. Ihenacho, Ugonna Wan, Peggy Van Den Berg, David Casey, Graham Fortini, Barbara K. Lenz, Heinz-Josef Tusié-Luna, Teresa Aguilar-Salinas, Carlos A. Moreno-Macías, Hortensia Huerta-Chagoya, Alicia Ordóñez-Sánchez, María Luisa Rodríguez-Guillén, Rosario Cruz-Bautista, Ivette Rodríguez-Torres, Maribel Muñóz-Hernández, Linda Liliana Arellano-Campos, Olimpia Gómez, Donají Alvirde, Ulices González-Villalpando, Clicerio González-Villalpando, María Elena Le Marchand, Loic Haiman, Christopher A. Figueiredo, Jane C. Carcinogenesis Original Manuscript Genome-wide association studies (GWAS) have identified 58 susceptibility alleles across 37 regions associated with the risk of colorectal cancer (CRC) with P < 5×10(−8). Most studies have been conducted in non-Hispanic whites and East Asians; however, the generalizability of these findings and the potential for ethnic-specific risk variation in Hispanic and Latino (HL) individuals have been largely understudied. We describe the first GWAS of common genetic variation contributing to CRC risk in HL (1611 CRC cases and 4330 controls). We also examine known susceptibility alleles and implement imputation-based fine-mapping to identify potential ethnicity-specific association signals in known risk regions. We discovered 17 variants across 4 independent regions that merit further investigation due to suggestive CRC associations (P < 1×10(−6)) at 1p34.3 (rs7528276; Odds Ratio (OR) = 1.86 [95% confidence interval (CI): 1.47–2.36); P = 2.5×10(−7)], 2q23.3 (rs1367374; OR = 1.37 (95% CI: 1.21–1.55); P = 4.0×10(−7)), 14q24.2 (rs143046984; OR = 1.65 (95% CI: 1.36–2.01); P = 4.1×10(−7)) and 16q12.2 [rs142319636; OR = 1.69 (95% CI: 1.37–2.08); P=7.8×10(−7)]. Among the 57 previously published CRC susceptibility alleles with minor allele frequency ≥1%, 76.5% of SNPs had a consistent direction of effect and 19 (33.3%) were nominally statistically significant (P < 0.05). Further, rs185423955 and rs60892987 were identified as novel secondary susceptibility variants at 3q26.2 (P = 5.3×10(–5)) and 11q12.2 (P = 6.8×10(−5)), respectively. Our findings demonstrate the importance of fine mapping in HL. These results are informative for variant prioritization in functional studies and future risk prediction modeling in minority populations. Oxford University Press 2016-06 2016-04-18 /pmc/articles/PMC4876992/ /pubmed/27207650 http://dx.doi.org/10.1093/carcin/bgw046 Text en © The Author 2016. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Manuscript Schmit, Stephanie L. Schumacher, Fredrick R. Edlund, Christopher K. Conti, David V. Ihenacho, Ugonna Wan, Peggy Van Den Berg, David Casey, Graham Fortini, Barbara K. Lenz, Heinz-Josef Tusié-Luna, Teresa Aguilar-Salinas, Carlos A. Moreno-Macías, Hortensia Huerta-Chagoya, Alicia Ordóñez-Sánchez, María Luisa Rodríguez-Guillén, Rosario Cruz-Bautista, Ivette Rodríguez-Torres, Maribel Muñóz-Hernández, Linda Liliana Arellano-Campos, Olimpia Gómez, Donají Alvirde, Ulices González-Villalpando, Clicerio González-Villalpando, María Elena Le Marchand, Loic Haiman, Christopher A. Figueiredo, Jane C. Genome-wide association study of colorectal cancer in Hispanics |
title | Genome-wide association study of colorectal cancer in Hispanics |
title_full | Genome-wide association study of colorectal cancer in Hispanics |
title_fullStr | Genome-wide association study of colorectal cancer in Hispanics |
title_full_unstemmed | Genome-wide association study of colorectal cancer in Hispanics |
title_short | Genome-wide association study of colorectal cancer in Hispanics |
title_sort | genome-wide association study of colorectal cancer in hispanics |
topic | Original Manuscript |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876992/ https://www.ncbi.nlm.nih.gov/pubmed/27207650 http://dx.doi.org/10.1093/carcin/bgw046 |
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