Dataset Information

Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer.

ABSTRACT: Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10^-8), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is rs78193826 (odds ratio = 1.46, 95% confidence interval = 1.29-1.66, P = 4.28 × 10^-9), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant. Associations between selected GP2 gene variants and pancreatic cancer are replicated in 10,822 additional cases and controls of East Asian origin. Functional analyses using cell lines provide supporting evidence of the effect of rs78193826 on KRAS activity. These findings suggest that GP2 gene variants are probably associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

SUBMITTER: Lin Y

PROVIDER: S-EPMC7314803 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer.

Lin Yingsong Y Nakatochi Masahiro M Hosono Yasuyuki Y Ito Hidemi H Kamatani Yoichiro Y Inoko Akihito A Sakamoto Hiromi H Kinoshita Fumie F Kobayashi Yumiko Y Ishii Hiroshi H Ozaka Masato M Sasaki Takashi T Matsuyama Masato M Sasahira Naoki N Morimoto Manabu M Kobayashi Satoshi S Fukushima Taito T Ueno Makoto M Ohkawa Shinichi S Egawa Naoto N Kuruma Sawako S Mori Mitsuru M Nakao Haruhisa H Adachi Yasushi Y Okuda Masumi M Osaki Takako T Kamiya Shigeru S Wang Chaochen C Hara Kazuo K Shimizu Yasuhiro Y Miyamoto Tatsuo T Hayashi Yuko Y Ebi Hiromichi H Kohmoto Tomohiro T Imoto Issei I Kasugai Yumiko Y Murakami Yoshinori Y Akiyama Masato M Ishigaki Kazuyoshi K Matsuda Koichi K Hirata Makoto M Shimada Kazuaki K Okusaka Takuji T Kawaguchi Takahisa T Takahashi Meiko M Watanabe Yoshiyuki Y Kuriki Kiyonori K Kadota Aya A Okada Rieko R Mikami Haruo H Takezaki Toshiro T Suzuki Sadao S Yamaji Taiki T Iwasaki Motoki M Sawada Norie N Goto Atsushi A Kinoshita Kengo K Fuse Nobuo N Katsuoka Fumiki F Shimizu Atsushi A Nishizuka Satoshi S SS Tanno Kozo K Suzuki Ken K Okada Yukinori Y Horikoshi Momoko M Yamauchi Toshimasa T Kadowaki Takashi T Yu Herbert H Zhong Jun J Amundadottir Laufey T LT Doki Yuichiro Y Ishii Hideshi H Eguchi Hidetoshi H Bogumil David D Haiman Christopher A CA Le Marchand Loic L Mori Masaki M Risch Harvey H Setiawan Veronica W VW Tsugane Shoichiro S Wakai Kenji K Yoshida Teruhiko T Matsuda Fumihiko F Kubo Michiaki M Kikuchi Shogo S Matsuo Keitaro K

Nature communications 20200624 1

Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10<sup>-8</sup>), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is ...[more]

PMID: 32581250

Similar Datasets

Project description:Childhood acute lymphoblastic leukemia (ALL) occurs more frequently in males. Reasons behind sex differences in childhood ALL risk are unknown. In the present genome-wide association study (GWAS), we explored the genetic basis of sex differences by comparing genotype frequencies between male and female cases in a case-only study to assess effect-modification by sex.The case-only design included 236 incident cases of childhood ALL consecutively recruited at the Texas Children's Cancer Center in Houston, Texas from 2007 to 2012. All cases were non-Hispanic whites, aged 1 to 10 years, and diagnosed with confirmed B-cell precursor ALL. Genotyping was performed using the Illumina HumanCoreExome BeadChip on the Illumina Infinium platform. Besides the top 100 statistically most significant results, results were also analyzed by the top 100 highest effect size with a nominal statistical significance (P <0.05).The statistically most significant sex-specific association (P = 4 × 10) was with the single nucleotide polymorphism (SNP) rs4813720 (RASSF2), an expression quantitative trait locus (eQTL) for RASSF2 in peripheral blood. rs4813720 is also a strong methylation QTL (meQTL) for a CpG site (cg22485289) within RASSF2 in pregnancy, at birth, childhood, and adolescence. cg22485289 is one of the hypomethylated CpG sites in ALL compared with pre-B cells. Two missense SNPs, rs12722042 and 12722039, in the HLA-DQA1 gene yielded the highest effect sizes (odds ratio [OR] ∼ 14; P <0.01) for sex-specific results. The HLA-DQA1 SNPs belong to DQA1*01 and confirmed the previously reported male-specific association with DQA1*01. This finding supports the proposed infection-related etiology in childhood ALL risk for males. Further analyses revealed that most SNPs (either direct effect or through linkage disequilibrium) were within active enhancers or active promoter regions and had regulatory effects on gene expression levels.Cumulative data suggested that RASSF2 rs4813720, which correlates with increased RASSF2 expression, may counteract the suppressor effect of estrogen-regulated miR-17-92 on RASSF2 resulting in protection in males. Given the amount of sex hormone-related mechanisms suggested by our findings, future studies should examine prenatal or early postnatal programming by sex hormones when hormone levels show a large variation.

Dataset Information

Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer.

Publications

Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets