Genome-wide association study for colorectal cancer identifies risk polymorphisms in German familial cases and implicates MAPK signalling pathways in disease susceptibility
(2010) In Carcinogenesis 31(9). p.1612-1619- Abstract
- Genetic susceptibility accounts for similar to 35% of all colorectal cancer (CRC). Ten common low-risk variants contributing to CRC risk have been identified through genome-wide association studies (GWASs). In our GWAS, 610 664 genotyped single-nucleotide polymorphisms (SNPs) passed the quality control filtering in 371 German familial CRC patients and 1263 controls, and replication studies were conducted in four additional case-control sets (4915 cases and 5607 controls). Known risk loci at 8q24.21 and 11q23 were confirmed, and a previously unreported association, rs12701937, located between the genes GLI3 (GLI family zinc finger 3) and INHBA (inhibin, beta A) [P = 1.1 x 10(-3), odds ratio (OR) 1.14, 95% confidence interval (CI) 1.05-1.23,... (More)
- Genetic susceptibility accounts for similar to 35% of all colorectal cancer (CRC). Ten common low-risk variants contributing to CRC risk have been identified through genome-wide association studies (GWASs). In our GWAS, 610 664 genotyped single-nucleotide polymorphisms (SNPs) passed the quality control filtering in 371 German familial CRC patients and 1263 controls, and replication studies were conducted in four additional case-control sets (4915 cases and 5607 controls). Known risk loci at 8q24.21 and 11q23 were confirmed, and a previously unreported association, rs12701937, located between the genes GLI3 (GLI family zinc finger 3) and INHBA (inhibin, beta A) [P = 1.1 x 10(-3), odds ratio (OR) 1.14, 95% confidence interval (CI) 1.05-1.23, dominant model in the combined cohort], was identified. The association was stronger in familial cases compared with unselected cases (P = 2.0 x 10(-4), OR 1.36, 95% CI 1.16-1.60, dominant model). Two other unreported SNPs, rs6038071, 40 kb upstream of CSNK2A1 (casein kinase 2, alpha 1 polypeptide) and an intronic marker in MYO3A (myosin IIIA), rs11014993, associated with CRC only in the familial CRC cases (P = 2.5 x 10(-3), recessive model, and P = 2.7 x 10(-4), dominant model). Three software tools successfully pointed to the overrepresentation of genes related to the mitogen-activated protein kinase (MAPK) signalling pathways among the 1340 most strongly associated markers from the GWAS (allelic P value < 10(-3)). The risk of CRC increased significantly with an increasing number of risk alleles in seven genes involved in MAPK signalling events (P-trend = 2.2 x 10(-16), ORper allele = 1.34, 95% CI 1.11-1.61). (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1697835
- author
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Carcinogenesis
- volume
- 31
- issue
- 9
- pages
- 1612 - 1619
- publisher
- Oxford University Press
- external identifiers
-
- wos:000281530400015
- scopus:77956281205
- ISSN
- 0143-3334
- DOI
- 10.1093/carcin/bgq146
- language
- English
- LU publication?
- yes
- id
- c402e24f-dc8c-4070-a274-6a05903ca9b6 (old id 1697835)
- date added to LUP
- 2016-04-01 10:42:55
- date last changed
- 2022-01-26 01:47:11
@article{c402e24f-dc8c-4070-a274-6a05903ca9b6,
abstract = {{Genetic susceptibility accounts for similar to 35% of all colorectal cancer (CRC). Ten common low-risk variants contributing to CRC risk have been identified through genome-wide association studies (GWASs). In our GWAS, 610 664 genotyped single-nucleotide polymorphisms (SNPs) passed the quality control filtering in 371 German familial CRC patients and 1263 controls, and replication studies were conducted in four additional case-control sets (4915 cases and 5607 controls). Known risk loci at 8q24.21 and 11q23 were confirmed, and a previously unreported association, rs12701937, located between the genes GLI3 (GLI family zinc finger 3) and INHBA (inhibin, beta A) [P = 1.1 x 10(-3), odds ratio (OR) 1.14, 95% confidence interval (CI) 1.05-1.23, dominant model in the combined cohort], was identified. The association was stronger in familial cases compared with unselected cases (P = 2.0 x 10(-4), OR 1.36, 95% CI 1.16-1.60, dominant model). Two other unreported SNPs, rs6038071, 40 kb upstream of CSNK2A1 (casein kinase 2, alpha 1 polypeptide) and an intronic marker in MYO3A (myosin IIIA), rs11014993, associated with CRC only in the familial CRC cases (P = 2.5 x 10(-3), recessive model, and P = 2.7 x 10(-4), dominant model). Three software tools successfully pointed to the overrepresentation of genes related to the mitogen-activated protein kinase (MAPK) signalling pathways among the 1340 most strongly associated markers from the GWAS (allelic P value < 10(-3)). The risk of CRC increased significantly with an increasing number of risk alleles in seven genes involved in MAPK signalling events (P-trend = 2.2 x 10(-16), ORper allele = 1.34, 95% CI 1.11-1.61).}},
author = {{Lascorz, Jesus and Försti, Asta and Chen, Bowang and Buch, Stephan and Steinke, Verena and Rahner, Nils and Holinski-Feder, Elke and Morak, Monika and Schackert, Hans K. and Goergens, Heike and Schulmann, Karsten and Goecke, Timm and Kloor, Matthias and Engel, Cristoph and Buettner, Reinhard and Kunkel, Nelli and Weires, Marianne and Hoffmeister, Michael and Pardini, Barbara and Naccarati, Alessio and Vodickova, Ludmila and Novotny, Jan and Schreiber, Stefan and Krawczak, Michael and Broering, Clemens D. and Voelzke, Henry and Schafmayer, Clemens and Vodicka, Pavel and Chang-Claude, Jenny and Brenner, Hermann and Burwinkel, Barbara and Propping, Peter and Hampe, Jochen and Hemminki, Kari}},
issn = {{0143-3334}},
language = {{eng}},
number = {{9}},
pages = {{1612--1619}},
publisher = {{Oxford University Press}},
series = {{Carcinogenesis}},
title = {{Genome-wide association study for colorectal cancer identifies risk polymorphisms in German familial cases and implicates MAPK signalling pathways in disease susceptibility}},
url = {{http://dx.doi.org/10.1093/carcin/bgq146}},
doi = {{10.1093/carcin/bgq146}},
volume = {{31}},
year = {{2010}},
}