Genome-wide association study of gastric adenocarcinoma in Asia: A comparison of associations between cardia and non-cardia tumours

Nan Hu; Zhaoming Wang; Xin Song; Lixuan Wei; Byung Sik Kim; Neal D. Freedman; Jiwon Baek; Laurie Burdette; Jiang Chang; Charles Chung; Sanford M. Dawsey; Ti DIng; Yu Tang Gao; Carol Giffen; Yaling Han; Myunghee Hong; Jia Huang; Hee Sung Kim; Woon Puay Koh; Linda M. Liao; Yi Min Mao; You Lin Qiao; Xiao Ou Shu; Wen Tan; Chaoyu Wang; Chen Wu; Min Jie Wu; Yong Bing Xiang; Meredith Yeager; Jeong Hwan Yook; Jian Min Yuan; Peng Zhang; Xue Ke Zhao; Wei Zheng; Kyuyoung Song; Li Dong Wang; Dongxin Lin; Stephen J. Chanock; Alisa M. Goldstein; Philip R. Taylor; Christian C. Abnet

doi:10.1136/gutjnl-2015-309340

Genome-wide association study of gastric adenocarcinoma in Asia: A comparison of associations between cardia and non-cardia tumours

Nan Hu
, Zhaoming Wang
, Xin Song
, Lixuan Wei
, Byung Sik Kim
, Neal D. Freedman
, Jiwon Baek
, Laurie Burdette
, Jiang Chang
, Charles Chung
, Sanford M. Dawsey
, Ti DIng
, Yu Tang Gao
, Carol Giffen
, Yaling Han
, Myunghee Hong
, Jia Huang
, Hee Sung Kim
, Woon Puay Koh
, Linda M. Liao

Yi Min Mao, You Lin Qiao, Xiao Ou Shu, Wen Tan, Chaoyu Wang, Chen Wu, Min Jie Wu, Yong Bing Xiang, Meredith Yeager, Jeong Hwan Yook, Jian Min Yuan, Peng Zhang, Xue Ke Zhao, Wei Zheng, Kyuyoung Song, Li Dong Wang, Dongxin Lin, Stephen J. Chanock, Alisa M. Goldstein, Philip R. Taylor, Christian C. Abnet^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

117 Citations (Scopus)

Abstract

Objective Genome-wide association studies (GWAS) of gastric cancer have reported differences in single-nucleotide polymorphism (SNP) associations for tumour subtypes, particularly when divided by location into the gastric cardia versus the non-cardia. Design Here we present results for a GWAS using 2350 East Asian gastric cancer cases divided as 1189 gastric cardia and 1027 gastric non-cardia cases and 2708 controls. We also included up to 3042 cardia cases, 4359 non-cardia cases and 7548 controls for replication from two Chinese studies and one Korean study. From the GWAS, we selected 12 top SNPs for each gastric cancer subtype, 4 top SNPs for total gastric cancer and 1 SNP in MUC1 for replication testing. Results We observed genome-wide significant associations for rs10074991 in PRKAA1 at 5p13.1 for cardia (p=7.36×10 -12) and non-cardia cancers (p=2.42×10 -23) with per allele OR (95% CI) for the combined endpoint of 0.80 (0.77 to 0.83). At 6p21.1, rs2294693 near UNC5CL was significantly associated with gastric non-cardia cancer risk (p=2.50×10 -8), with OR (95% CI) of 1.18 (1.12 to 1.26), but there was only a nominal association for cardia cancer (p=1.47×10 -2). We also confirmed a previously reported association for rs4072037 in MUC1 with p=6.59×10 -8 for total gastric cancer and similar estimates for cardia and non-cardia cancers. Three SNPs in PSCA previously reported to be associated with gastric non-cardia cancer showed no apparent association for cardia cancer. Conclusions Our results suggest that associations for SNPs with gastric cancer show some different results by tumour location in the stomach.

Original language	English
Pages (from-to)	1611-1618
Number of pages	8
Journal	Gut
Volume	65
Issue number	10
DOIs	https://doi.org/10.1136/gutjnl-2015-309340
Publication status	Published - 1 Oct 2016
Externally published	Yes

Bibliographical note

Publisher Copyright:
© Published by the BMJ Publishing Group Limited.

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10.1136/gutjnl-2015-309340

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Hu, N., Wang, Z., Song, X., Wei, L., Kim, B. S., Freedman, N. D., Baek, J., Burdette, L., Chang, J., Chung, C., Dawsey, S. M., DIng, T., Gao, Y. T., Giffen, C., Han, Y., Hong, M., Huang, J., Kim, H. S., Koh, W. P., ... Abnet, C. C. (2016). Genome-wide association study of gastric adenocarcinoma in Asia: A comparison of associations between cardia and non-cardia tumours. Gut, 65(10), 1611-1618. https://doi.org/10.1136/gutjnl-2015-309340

@article{309a79e0f349499bb613a5b0d7161591,

title = "Genome-wide association study of gastric adenocarcinoma in Asia: A comparison of associations between cardia and non-cardia tumours",

abstract = "Objective Genome-wide association studies (GWAS) of gastric cancer have reported differences in single-nucleotide polymorphism (SNP) associations for tumour subtypes, particularly when divided by location into the gastric cardia versus the non-cardia. Design Here we present results for a GWAS using 2350 East Asian gastric cancer cases divided as 1189 gastric cardia and 1027 gastric non-cardia cases and 2708 controls. We also included up to 3042 cardia cases, 4359 non-cardia cases and 7548 controls for replication from two Chinese studies and one Korean study. From the GWAS, we selected 12 top SNPs for each gastric cancer subtype, 4 top SNPs for total gastric cancer and 1 SNP in MUC1 for replication testing. Results We observed genome-wide significant associations for rs10074991 in PRKAA1 at 5p13.1 for cardia (p=7.36×10 -12) and non-cardia cancers (p=2.42×10 -23) with per allele OR (95\% CI) for the combined endpoint of 0.80 (0.77 to 0.83). At 6p21.1, rs2294693 near UNC5CL was significantly associated with gastric non-cardia cancer risk (p=2.50×10 -8), with OR (95\% CI) of 1.18 (1.12 to 1.26), but there was only a nominal association for cardia cancer (p=1.47×10 -2). We also confirmed a previously reported association for rs4072037 in MUC1 with p=6.59×10 -8 for total gastric cancer and similar estimates for cardia and non-cardia cancers. Three SNPs in PSCA previously reported to be associated with gastric non-cardia cancer showed no apparent association for cardia cancer. Conclusions Our results suggest that associations for SNPs with gastric cancer show some different results by tumour location in the stomach.",

author = "Nan Hu and Zhaoming Wang and Xin Song and Lixuan Wei and Kim, \{Byung Sik\} and Freedman, \{Neal D.\} and Jiwon Baek and Laurie Burdette and Jiang Chang and Charles Chung and Dawsey, \{Sanford M.\} and Ti DIng and Gao, \{Yu Tang\} and Carol Giffen and Yaling Han and Myunghee Hong and Jia Huang and Kim, \{Hee Sung\} and Koh, \{Woon Puay\} and Liao, \{Linda M.\} and Mao, \{Yi Min\} and Qiao, \{You Lin\} and Shu, \{Xiao Ou\} and Wen Tan and Chaoyu Wang and Chen Wu and Wu, \{Min Jie\} and Xiang, \{Yong Bing\} and Meredith Yeager and Yook, \{Jeong Hwan\} and Yuan, \{Jian Min\} and Peng Zhang and Zhao, \{Xue Ke\} and Wei Zheng and Kyuyoung Song and Wang, \{Li Dong\} and Dongxin Lin and Chanock, \{Stephen J.\} and Goldstein, \{Alisa M.\} and Taylor, \{Philip R.\} and Abnet, \{Christian C.\}",

note = "Publisher Copyright: {\textcopyright} Published by the BMJ Publishing Group Limited.",

year = "2016",

month = oct,

day = "1",

doi = "10.1136/gutjnl-2015-309340",

language = "English",

volume = "65",

pages = "1611--1618",

journal = "Gut",

issn = "0017-5749",

publisher = "BMJ Publishing Group",

number = "10",

}

Hu, N, Wang, Z, Song, X, Wei, L, Kim, BS, Freedman, ND, Baek, J, Burdette, L, Chang, J, Chung, C, Dawsey, SM, DIng, T, Gao, YT, Giffen, C, Han, Y, Hong, M, Huang, J, Kim, HS, Koh, WP, Liao, LM, Mao, YM, Qiao, YL, Shu, XO, Tan, W, Wang, C, Wu, C, Wu, MJ, Xiang, YB, Yeager, M, Yook, JH, Yuan, JM, Zhang, P, Zhao, XK, Zheng, W, Song, K, Wang, LD, Lin, D, Chanock, SJ, Goldstein, AM, Taylor, PR & Abnet, CC 2016, 'Genome-wide association study of gastric adenocarcinoma in Asia: A comparison of associations between cardia and non-cardia tumours', Gut, vol. 65, no. 10, pp. 1611-1618. https://doi.org/10.1136/gutjnl-2015-309340

TY - JOUR

T1 - Genome-wide association study of gastric adenocarcinoma in Asia

T2 - A comparison of associations between cardia and non-cardia tumours

AU - Hu, Nan

AU - Wang, Zhaoming

AU - Song, Xin

AU - Wei, Lixuan

AU - Kim, Byung Sik

AU - Freedman, Neal D.

AU - Baek, Jiwon

AU - Burdette, Laurie

AU - Chang, Jiang

AU - Chung, Charles

AU - Dawsey, Sanford M.

AU - DIng, Ti

AU - Gao, Yu Tang

AU - Giffen, Carol

AU - Han, Yaling

AU - Hong, Myunghee

AU - Huang, Jia

AU - Kim, Hee Sung

AU - Koh, Woon Puay

AU - Liao, Linda M.

AU - Mao, Yi Min

AU - Qiao, You Lin

AU - Shu, Xiao Ou

AU - Tan, Wen

AU - Wang, Chaoyu

AU - Wu, Chen

AU - Wu, Min Jie

AU - Xiang, Yong Bing

AU - Yeager, Meredith

AU - Yook, Jeong Hwan

AU - Yuan, Jian Min

AU - Zhang, Peng

AU - Zhao, Xue Ke

AU - Zheng, Wei

AU - Song, Kyuyoung

AU - Wang, Li Dong

AU - Lin, Dongxin

AU - Chanock, Stephen J.

AU - Goldstein, Alisa M.

AU - Taylor, Philip R.

AU - Abnet, Christian C.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Objective Genome-wide association studies (GWAS) of gastric cancer have reported differences in single-nucleotide polymorphism (SNP) associations for tumour subtypes, particularly when divided by location into the gastric cardia versus the non-cardia. Design Here we present results for a GWAS using 2350 East Asian gastric cancer cases divided as 1189 gastric cardia and 1027 gastric non-cardia cases and 2708 controls. We also included up to 3042 cardia cases, 4359 non-cardia cases and 7548 controls for replication from two Chinese studies and one Korean study. From the GWAS, we selected 12 top SNPs for each gastric cancer subtype, 4 top SNPs for total gastric cancer and 1 SNP in MUC1 for replication testing. Results We observed genome-wide significant associations for rs10074991 in PRKAA1 at 5p13.1 for cardia (p=7.36×10 -12) and non-cardia cancers (p=2.42×10 -23) with per allele OR (95% CI) for the combined endpoint of 0.80 (0.77 to 0.83). At 6p21.1, rs2294693 near UNC5CL was significantly associated with gastric non-cardia cancer risk (p=2.50×10 -8), with OR (95% CI) of 1.18 (1.12 to 1.26), but there was only a nominal association for cardia cancer (p=1.47×10 -2). We also confirmed a previously reported association for rs4072037 in MUC1 with p=6.59×10 -8 for total gastric cancer and similar estimates for cardia and non-cardia cancers. Three SNPs in PSCA previously reported to be associated with gastric non-cardia cancer showed no apparent association for cardia cancer. Conclusions Our results suggest that associations for SNPs with gastric cancer show some different results by tumour location in the stomach.

AB - Objective Genome-wide association studies (GWAS) of gastric cancer have reported differences in single-nucleotide polymorphism (SNP) associations for tumour subtypes, particularly when divided by location into the gastric cardia versus the non-cardia. Design Here we present results for a GWAS using 2350 East Asian gastric cancer cases divided as 1189 gastric cardia and 1027 gastric non-cardia cases and 2708 controls. We also included up to 3042 cardia cases, 4359 non-cardia cases and 7548 controls for replication from two Chinese studies and one Korean study. From the GWAS, we selected 12 top SNPs for each gastric cancer subtype, 4 top SNPs for total gastric cancer and 1 SNP in MUC1 for replication testing. Results We observed genome-wide significant associations for rs10074991 in PRKAA1 at 5p13.1 for cardia (p=7.36×10 -12) and non-cardia cancers (p=2.42×10 -23) with per allele OR (95% CI) for the combined endpoint of 0.80 (0.77 to 0.83). At 6p21.1, rs2294693 near UNC5CL was significantly associated with gastric non-cardia cancer risk (p=2.50×10 -8), with OR (95% CI) of 1.18 (1.12 to 1.26), but there was only a nominal association for cardia cancer (p=1.47×10 -2). We also confirmed a previously reported association for rs4072037 in MUC1 with p=6.59×10 -8 for total gastric cancer and similar estimates for cardia and non-cardia cancers. Three SNPs in PSCA previously reported to be associated with gastric non-cardia cancer showed no apparent association for cardia cancer. Conclusions Our results suggest that associations for SNPs with gastric cancer show some different results by tumour location in the stomach.

UR - https://www.scopus.com/pages/publications/84996471012

U2 - 10.1136/gutjnl-2015-309340

DO - 10.1136/gutjnl-2015-309340

M3 - Article

C2 - 26129866

AN - SCOPUS:84996471012

SN - 0017-5749

VL - 65

SP - 1611

EP - 1618

JO - Gut

JF - Gut

IS - 10

ER -

Genome-wide association study of gastric adenocarcinoma in Asia: A comparison of associations between cardia and non-cardia tumours

Abstract

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