Genome-wide association study identifies a possible susceptibility locus for endometrial cancer

Long, Jirong, Zheng, Wei, Xiang, Yong-Bing, Lose, Felicity, Thompson, Deborah, Tomlinson, Ian, Yu, Herbert, Wentzensen, Nicolas, Lambrechts, Diether, Dork, Thilo, Dubrowinskaja, Natalia, Goodman, Marc T., Salvesen, Helga B., Fasching, Peter A., Scott, Rodney J., Delahanty, Ryan, Zheng, Ying, O'Mara, Tracy, Healey, Catherine S., Hodgson, Shirley, Risch, Harvey, Yang, Hannah P., Amant, Frederic, Turmanov, Nurzhan, Schwake, Anita, Lurie, Galina, Trovik, Jone, Beckmann, Matthias W., Ashton, Katie, Ji, Bu-Tian, Bao, Ping-Ping, Howarth, Kimberly, Lu, Lingeng, Lissowska, Jolanta, Coenegrachts, Lieve, Kaidarova, Dilyara, Durst, Matthias, Thompson, Pamela J., Krakstad, Camilla, Ekici, Arif B., Otton, Geoffrey, Shi, Jiajun, Zhang, Ben, Gorman, Maggie, Brinton, Louise, Coosemans, An, Matsuno, Rayna K., Halle, Mari K., Hein, Alexander, Proietto, Anthony, Cai, Hui, Lu, Wei, Dunning, Alison, Easton, Douglas, Gao, Yu-Tang, Cai, Qiuyin, Spurdle, Amanda B. and Shu, Xiao-Ou (2012) Genome-wide association study identifies a possible susceptibility locus for endometrial cancer. Cancer Epidemiology Biomarkers and Prevention, 21 6: 980-987. doi:10.1158/1055-9965.EPI-11-1160

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Author Long, Jirong
Zheng, Wei
Xiang, Yong-Bing
Lose, Felicity
Thompson, Deborah
Tomlinson, Ian
Yu, Herbert
Wentzensen, Nicolas
Lambrechts, Diether
Dork, Thilo
Dubrowinskaja, Natalia
Goodman, Marc T.
Salvesen, Helga B.
Fasching, Peter A.
Scott, Rodney J.
Delahanty, Ryan
Zheng, Ying
O'Mara, Tracy
Healey, Catherine S.
Hodgson, Shirley
Risch, Harvey
Yang, Hannah P.
Amant, Frederic
Turmanov, Nurzhan
Schwake, Anita
Lurie, Galina
Trovik, Jone
Beckmann, Matthias W.
Ashton, Katie
Ji, Bu-Tian
Bao, Ping-Ping
Howarth, Kimberly
Lu, Lingeng
Lissowska, Jolanta
Coenegrachts, Lieve
Kaidarova, Dilyara
Durst, Matthias
Thompson, Pamela J.
Krakstad, Camilla
Ekici, Arif B.
Otton, Geoffrey
Shi, Jiajun
Zhang, Ben
Gorman, Maggie
Brinton, Louise
Coosemans, An
Matsuno, Rayna K.
Halle, Mari K.
Hein, Alexander
Proietto, Anthony
Cai, Hui
Lu, Wei
Dunning, Alison
Easton, Douglas
Gao, Yu-Tang
Cai, Qiuyin
Spurdle, Amanda B.
Shu, Xiao-Ou
Total Author Count Override 58
Title Genome-wide association study identifies a possible susceptibility locus for endometrial cancer
Journal name Cancer Epidemiology Biomarkers and Prevention   Check publisher's open access policy
ISSN 1055-9965
1538-7755
Publication date 2012-06
Sub-type Article (original research)
DOI 10.1158/1055-9965.EPI-11-1160
Volume 21
Issue 6
Start page 980
End page 987
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Collection year 2013
Language eng
Formatted abstract Background:
Genome-wide association studies (GWAS) have identified more than 100 genetic loci for various cancers. However, only one is for endometrial cancer.

Methods:
We conducted a three-stage GWAS including 8,492 endometrial cancer cases and 16,596 controls. After analyzing 585,963 single-nucleotide polymorphisms (SNP) in 832 cases and 2,682 controls (stage I) from the Shanghai Endometrial Cancer Genetics Study, we selected the top 106 SNPs for in silico replication among 1,265 cases and 5,190 controls from the Australian/British Endometrial Cancer GWAS (stage II). Nine SNPs showed results consistent in direction with stage I with P < 0.1. These nine SNPs were investigated among 459 cases and 558 controls (stage IIIa) and six SNPs showed a direction of association consistent with stages I and II. These six SNPs, plus two additional SNPs selected on the basis of linkage disequilibrium and P values in stage II, were investigated among 5,936 cases and 8,166 controls from an additional 11 studies (stage IIIb).

Results:
SNP rs1202524, near the CAPN9 gene on chromosome 1q42.2, showed a consistent association with endometrial cancer risk across all three stages, with ORs of 1.09 [95% confidence interval (CI), 1.03–1.16] for the A/G genotype and 1.17 (95% CI, 1.05–1.30) for the G/G genotype (P = 1.6 × 10−4 in combined analyses of all samples). The association was stronger when limited to the endometrioid subtype, with ORs (95% CI) of 1.11 (1.04–1.18) and 1.21 (1.08–1.35), respectively (P = 2.4 × 10−5).

Conclusions:
Chromosome 1q42.2 may host an endometrial cancer susceptibility locus.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
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Created: Mon, 16 Jul 2012, 13:11:12 EST by Matthew Lamb on behalf of School of Medicine