Open AccessGenome‐wide association study identifies gastric cancer susceptibility loci at 12q24.11‐12 and 20q11.21
Author(s) -
Tanikawa Chizu,
Kamatani Yoichiro,
Toyoshima Osamu,
Sakamoto Hiromi,
Ito Hidemi,
Takahashi Atsushi,
Momozawa Yukihide,
Hirata Makoto,
Fuse Nobuo,
TakaiIgarashi 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
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13815
Subject(s) - biology , cancer , locus (genetics) , genetics , genome wide association study , helicobacter pylori , population , genetic association , odds ratio , gene , pathogenesis , expression quantitative trait loci , abo blood group system , genotype , single nucleotide polymorphism , medicine , immunology , environmental health
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 CUX 2 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). CUX 2 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.