Genome-wide association study (GWAS) of ovarian cancer in Japanese predicted regulatory variants in 22q13.1.

• Main Authors: Varalee Yodsurang, Yaqi Tang, Yukie Takahashi, Chizu Tanikawa, Yoichiro Kamatani, Atsushi Takahashi, Yukihide Momozawa, Nobuo Fuse, Junichi Sugawara, Atsushi Shimizu, Akimune Fukushima, Asahi Hishida, Norihiro Furusyo, Mariko Naito, Kenji Wakai, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Shoichiro Tsugane, Makoto Hirata, Yoshinori Murakami, Michiaki Kubo, Koichi Matsuda
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2018-01-01
• Series: PLoS ONE
• Online Access: https://doi.org/10.1371/journal.pone.0209096

Genome-wide association studies (GWAS) have identified greater than 30 variants associated with ovarian cancer, but most of these variants were investigated in European populations. Here, we integrated GWAS and subsequent functional analyses to identify the genetic variants with potential regulatory effects. We conducted GWAS for ovarian cancer using 681 Japanese cases and 17,492 controls and found that rs137672 on 22q13.1 exhibited a strong association with a P-value of 1.05 × 10(-7) and an odds ratio of 0.573 with a 95% confidence interval of 0.466-0.703. In addition, three previously reported SNPs, i.e., rs10088218, rs9870207 and rs1400482, were validated in the Japanese population (P < 0.05) with the same risk allele as noted in previous studies. Functional studies including regulatory feature analysis and electrophoretic mobility shift assay (EMSA) revealed two regulatory SNPs in 22q13.1, rs2072872 and rs6509, that affect the binding affinity to some nuclear proteins in ovarian cancer cells. The plausible regulatory proteins whose motifs could be affected by the allele changes of these two SNPs were also proposed. Moreover, the protective G allele of rs6509 was associated with a decreased SYNGR1 expression level in normal ovarian tissues. Our findings elucidated the regulatory variants in 22q13.1 that are associated with ovarian cancer risk.