@article{ac07f13ba0224200bf00c574263c1cf9,
title = "A novel colorectal cancer risk locus at 4q32.2 identified from an international genomewide association study",
abstract = "Only a fraction of colorectal cancer heritability is explained by known risk-conferring genetic variation. This study was designed to identify novel risk alleles in Europeans. We conducted a genomewide association study (GWAS) meta-analysis of colorectal cancer in participants from a population-based case-control study in Israel (n = 1616 cases, 1329 controls) and a consortium study from the Colon Cancer Family Registry (n = 1977 cases, 999 controls). We used a two-stage (discovery-replication) GWAS design, followed by a joint meta-analysis. A combined analysis identified a novel susceptibility locus that reached genome-wide significance on chromosome 4q32.2 [rs35509282, risk allele = A (minor allele frequency = 0.09); odds ratio (OR) per risk allele = 1.53; P value = 8.2 × 10-9; nearest gene = FSTL5]. The direction of the association was consistent across studies. In addition, we confirmed that 14 of 29 previously identified susceptibility variants were significantly associated with risk of colorectal cancer in this study. Genetic variation on chromosome 4q32.2 is significantly associated with risk of colorectal cancer in Ashkenazi Jews and Europeans in this study.",
author = "Schmit, {Stephanie L.} and Schumacher, {Fredrick R.} and Edlund, {Christopher K.} and Conti, {David V.} and Leon Raskin and Flavio Lejbkowicz and Mila Pinchev and Rennert, {Hedy S.} and Jenkins, {Mark A.} and Hopper, {John L.} and Buchanan, {Daniel D.} and Lindor, {Noralane M.} and {Le Marchand}, Loic and Steven Gallinger and Haile, {Robert W.} and Newcomb, {Polly A.} and Huang, {Shu Chen} and Gad Rennert and Graham Casey and Gruber, {Stephen B.}",
note = "Funding Information: The work of the Molecular Epidemiology of Colorectal Cancer (MECC) Study was supported by the National Cancer Institute at the National Institutes of Health [R01 CA81488, U19 CA148107, and P30 CA014089]; the National Human Genome Research Institute at the National Institutes of Health [T32 HG000040]; the National Institute of Environmental Health Sciences at the National Institutes of Health [T32 ES013678]; and the Rackham Graduate School at the University of Michigan [Rackham Predoctoral Fellowship]. This work of the Colon Cancer Family Registry (CFR) was supported by the National Cancer Institute, National Institutes of Health [CA-95-011] and through cooperative agreements with members of the Colon CFR and Principal Investigators. Collaborating centers include the Australasian Colorectal Cancer Family Registry[(U01 CA097735]; the Familial Colorectal Neoplasia Collaborative Group [U01 CA074799]; the Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [U01 CA074800]; the Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; the Seattle Colorectal Cancer Family Registry [U01 CA074794]; and University of Hawaii Colorectal Cancer Family Registry [U01 CA074806]. The Colon CFR GWAS and post-GWAS work was supported by the National Cancer Institute, National Institutes of Health [U01CA122839 and R01 CA143237]. Publisher Copyright: {\textcopyright} The Author 2014. Published by Oxford University Press. All rights reserved.",
year = "2014",
month = nov,
day = "1",
doi = "10.1093/carcin/bgu148",
language = "English (US)",
volume = "35",
pages = "2512--2519",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "11",
}