Genome‐wide association study identifies gastric cancer susceptibility loci at 12q24.11‐12 and 20q11.21

Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein,...

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Bibliographic Details
Published in:Cancer science 2018-12, Vol.109 (12), p.4015-4024
Main Authors: Tanikawa, Chizu, Kamatani, Yoichiro, Toyoshima, Osamu, Sakamoto, Hiromi, Ito, Hidemi, Takahashi, Atsushi, Momozawa, Yukihide, Hirata, Makoto, Fuse, Nobuo, Takai‐Igarashi, Takako, Shimizu, Atsushi, Sasaki, Makoto, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Tsugane, Shoichiro, Naito, Mariko, Hishida, Asahi, Wakai, Kenji, Furusyo, Norihiro, Murakami, Yoshinori, Nakamura, Yusuke, Imoto, Issei, Inazawa, Johji, Oze, Isao, Sato, Naomi, Tanioka, Fumihiko, Sugimura, Haruhiko, Hirose, Hiroshi, Yoshida, Teruhiko, Matsuo, Keitaro, Kubo, Michiaki, Matsuda, Koichi
Format: Article
Language:English
Subjects:
ABO
ABO Blood-Group System - genetics
Adult
Aged
Aged, 80 and over
beta-Defensins - genetics
Biopsy
Blood groups
Case-Control Studies
Chromosome 12
Chromosome 9
Chromosomes, Human, Pair 12 - genetics
Chromosomes, Human, Pair 20 - genetics
Chromosomes, Human, Pair 9 - genetics
Collaboration
CUX2
DEFB
Disease
Female
Gastric cancer
Gene expression
Gene Expression Regulation
Genetic diversity
Genetic factors
Genetic Predisposition to Disease
Genome-wide association studies
Genome-Wide Association Study - methods
Genomes
genome‐wide association study
Health risk assessment
Helicobacter Infections - genetics
Homeodomain Proteins - genetics
Humans
Infections
Japan
Male
Medical research
Middle Aged
Mucosa
Original
Polymorphism
Polymorphism, Single Nucleotide
Population
Principal components analysis
Public health
Stomach Neoplasms - genetics
Stomach Neoplasms - microbiology
Studies
Young Adult
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Summary:Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein, we carried out a large‐scale genome‐wide association study using 6171 cases and 27 178 controls followed by three replication analyses. Analysis using a total of 11 507 cases and 38 904 controls identified two novel loci on 12q24.11‐12 (rs6490061, P = 3.20 × 10−8 with an odds ratio [OR] of 0.905) and 20q11.21 (rs2376549, P = 8.11 × 10−10 with an OR of 1.109). rs6490061 is located at intron 19 of the CUX2 gene, and its expression was suppressed by Helicobacter pylori infection. rs2376549 is included within the gene cluster of DEFB families that encode antibacterial peptides. We also found a significant association of rs7849280 in the ABO gene locus on 9q34.2 (P = 2.64 × 10−13 with an OR of 1.148). CUX2 and ABO expression in gastric mucosal tissues was significantly associated with rs6490061 and rs7849280 (P = 0.0153 and 8.00 × 10−11), respectively. Our findings show the crucial roles of genetic variations in the pathogenesis of gastric cancer. Manhattan plot of gastric cancer GWAS.
ISSN:1347-9032
1349-7006
DOI:10.1111/cas.13815