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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.

SUBMITTER: Hu N 

PROVIDER: S-EPMC5568652 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Hu Nan N   Wang Zhaoming Z   Song Xin X   Wei Lixuan L   Kim Byung Sik BS   Freedman Neal D ND   Baek Jiwon J   Burdette Laurie L   Chang Jiang J   Chung Charles C   Dawsey Sanford M SM   Ding Ti T   Gao Yu-Tang YT   Giffen Carol C   Han Yaling Y   Hong Myunghee M   Huang Jia J   Kim Hee Sung HS   Koh Woon-Puay WP   Liao Linda M LM   Mao Yi Min YM   Qiao You-Lin YL   Shu Xiao-Ou XO   Tan Wen W   Wang Chaoyu C   Wu Chen C   Wu Min-Jie MJ   Xiang Yong-Bing YB   Yeager Meredith M   Yook Jeong Hwan JH   Yuan Jian-Min JM   Zhang Peng P   Zhao Xue-Ke XK   Zheng Wei W   Song Kyuyoung K   Wang Li-Dong LD   Lin Dongxin D   Chanock Stephen J SJ   Goldstein Alisa M AM   Taylor Philip R PR   Abnet Christian C CC  

Gut 20150630 10


<h4>Objective</h4>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.<h4>Design</h4>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  ...[more]

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