Genome-Wide Association Study Identifies a Possible Susceptibility Locus for Endometrial Cancer

Jirong Long; Wei Zheng; Yong-Bing Xiang; Felicity Lose; Deborah Thompson; Ian Tomlinson; Herbert Yu; Nicolas Wentzensen; Diether Lambrechts; Thilo Dörk; Natalia Dubrowinskaja; Marc T. Goodman; Helga B. Salvesen; Peter A. Fasching; Rodney J. Scott; Ryan Delahanty; Ying Zheng; Tracy O'Mara; Catherine S. Healey; Shirley Hodgson; Harvey Risch; Hannah P. Yang; Frederic Amant; Nurzhan Turmanov; Anita Schwake; Galina Lurie; Jone Trovik; Matthias W. Beckmann; Katie Ashton; Bu-Tian Ji; Ping-Ping Bao; Kimberly Howarth; Lingeng Lu; Jolanta Lissowska; Lieve Coenegrachts; Dilyara Kaidarova; Matthias Dürst; Pamela J. Thompson; Camilla Krakstad; Arif B. Ekici; Geoffrey Otton; Jiajun Shi; Ben Zhang; Maggie Gorman; Louise Brinton; An Coosemans; Rayna K. Matsuno; Mari K. Halle; Alexander Hein; Anthony Proietto; Hui Cai; Wei Lu; Alison Dunning; Douglas Easton; Yu-Tang Gao; Qiuyin Cai; Amanda B. Spurdle; Xiao-Ou Shu

doi:https://doi.org/10.1158/1055-9965.EPI-11-1160

Genome-Wide Association Study Identifies a Possible Susceptibility Locus for Endometrial Cancer

Jirong Long, Wei Zheng, Yong-Bing Xiang, Felicity Lose, Deborah Thompson, Ian Tomlinson, Herbert Yu, Nicolas Wentzensen, Diether Lambrechts, Thilo Dörk, Natalia Dubrowinskaja, Marc T. Goodman, Helga B. Salvesen, Peter A. Fasching, Rodney J. Scott, Ryan Delahanty, Ying Zheng, Tracy O'Mara, Catherine S. Healey, Shirley HodgsonHarvey Risch, Hannah P. Yang, Frederic Amant, Nurzhan Turmanov, Anita Schwake, Galina Lurie, Jone Trovik, Matthias W. Beckmann, Katie Ashton, Bu-Tian Ji, Ping-Ping Bao, Kimberly Howarth, Lingeng Lu, Jolanta Lissowska, Lieve Coenegrachts, Dilyara Kaidarova, Matthias Dürst, Pamela J. Thompson, Camilla Krakstad, Arif B. Ekici, Geoffrey Otton, Jiajun Shi, Ben Zhang, Maggie Gorman, Louise Brinton, An Coosemans, Rayna K. Matsuno, Mari K. Halle, Alexander Hein, Anthony Proietto, Hui Cai, Wei Lu, Alison Dunning, Douglas Easton, Yu-Tang Gao, Qiuyin Cai, Amanda B. Spurdle, Xiao-Ou Shu

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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 silica 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 land H. 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 (Cl), 1.03-1.16] for the A/G genotype and 1.17(95% Cl, 1.05-1.30) for the GIG genotype (P = 1.6 x 10(-4) in combined analyses of all samples). The association was stronger when limited to the endometrioid subtype, with ORs (95% Cl) of 1.11 (1.04-1.18) and 1.21 (1.08-1.35), respectively (P = 2.4 x 10(-5)). Conclusions: Chromosome 1q42.2 may host an endometrial cancer susceptibility locus. Impact: This study identified a potential genetic locus for endometrial cancer risk. Cancer Epidemiol Biomarkers Prev; 21(6); 980-7. (C) 2012 AACR

Original language	English
Pages (from-to)	980-987
Journal	Cancer epidemiology, biomarkers & prevention
Volume	21
Issue number	6
DOIs	https://doi.org/10.1158/1055-9965.EPI-11-1160
Publication status	Published - 2012

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https://doi.org/10.1158/1055-9965.EPI-11-1160

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Long, J., Zheng, W., Xiang, Y.-B., Lose, F., Thompson, D., Tomlinson, I., Yu, H., Wentzensen, N., Lambrechts, D., Dörk, T., Dubrowinskaja, N., Goodman, M. T., Salvesen, H. B., Fasching, P. A., Scott, R. J., Delahanty, R., Zheng, Y., O'Mara, T., Healey, C. S., ... Shu, X.-O. (2012). Genome-Wide Association Study Identifies a Possible Susceptibility Locus for Endometrial Cancer. Cancer epidemiology, biomarkers & prevention, 21(6), 980-987. https://doi.org/10.1158/1055-9965.EPI-11-1160

@article{dd6eca110f3d43cb9a90a79afdba05d9,

title = "Genome-Wide Association Study Identifies a Possible Susceptibility Locus for Endometrial Cancer",

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 silica 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 land H. 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 (Cl), 1.03-1.16] for the A/G genotype and 1.17(95% Cl, 1.05-1.30) for the GIG genotype (P = 1.6 x 10(-4) in combined analyses of all samples). The association was stronger when limited to the endometrioid subtype, with ORs (95% Cl) of 1.11 (1.04-1.18) and 1.21 (1.08-1.35), respectively (P = 2.4 x 10(-5)). Conclusions: Chromosome 1q42.2 may host an endometrial cancer susceptibility locus. Impact: This study identified a potential genetic locus for endometrial cancer risk. Cancer Epidemiol Biomarkers Prev; 21(6); 980-7. (C) 2012 AACR",

author = "Jirong Long and Wei Zheng and Yong-Bing Xiang and Felicity Lose and Deborah Thompson and Ian Tomlinson and Herbert Yu and Nicolas Wentzensen and Diether Lambrechts and Thilo D{\"o}rk and Natalia Dubrowinskaja and Goodman, {Marc T.} and Salvesen, {Helga B.} and Fasching, {Peter A.} and Scott, {Rodney J.} and Ryan Delahanty and Ying Zheng and Tracy O'Mara and Healey, {Catherine S.} and Shirley Hodgson and Harvey Risch and Yang, {Hannah P.} and Frederic Amant and Nurzhan Turmanov and Anita Schwake and Galina Lurie and Jone Trovik and Beckmann, {Matthias W.} and Katie Ashton and Bu-Tian Ji and Ping-Ping Bao and Kimberly Howarth and Lingeng Lu and Jolanta Lissowska and Lieve Coenegrachts and Dilyara Kaidarova and Matthias D{\"u}rst and Thompson, {Pamela J.} and Camilla Krakstad and Ekici, {Arif B.} and Geoffrey Otton and Jiajun Shi and Ben Zhang and Maggie Gorman and Louise Brinton and An Coosemans and Matsuno, {Rayna K.} and Halle, {Mari K.} and Alexander Hein and Anthony Proietto and Hui Cai and Wei Lu and Alison Dunning and Douglas Easton and Yu-Tang Gao and Qiuyin Cai and Spurdle, {Amanda B.} and Xiao-Ou Shu",

year = "2012",

doi = "https://doi.org/10.1158/1055-9965.EPI-11-1160",

language = "English",

volume = "21",

pages = "980--987",

journal = "Cancer epidemiology, biomarkers & prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

number = "6",

}

Long, J, Zheng, W, Xiang, Y-B, Lose, F, Thompson, D, Tomlinson, I, Yu, H, Wentzensen, N, Lambrechts, D, Dörk, T, Dubrowinskaja, N, Goodman, MT, Salvesen, HB, Fasching, PA, Scott, RJ, Delahanty, R, Zheng, Y, O'Mara, T, Healey, CS, Hodgson, S, Risch, H, Yang, HP, Amant, F, Turmanov, N, Schwake, A, Lurie, G, Trovik, J, Beckmann, MW, Ashton, K, Ji, B-T, Bao, P-P, Howarth, K, Lu, L, Lissowska, J, Coenegrachts, L, Kaidarova, D, Dürst, M, Thompson, PJ, Krakstad, C, Ekici, AB, Otton, G, Shi, J, Zhang, B, Gorman, M, Brinton, L, Coosemans, A, Matsuno, RK, Halle, MK, Hein, A, Proietto, A, Cai, H, Lu, W, Dunning, A, Easton, D, Gao, Y-T, Cai, Q, Spurdle, AB & Shu, X-O 2012, 'Genome-Wide Association Study Identifies a Possible Susceptibility Locus for Endometrial Cancer', Cancer epidemiology, biomarkers & prevention, vol. 21, no. 6, pp. 980-987. https://doi.org/10.1158/1055-9965.EPI-11-1160

TY - JOUR

T1 - Genome-Wide Association Study Identifies a Possible Susceptibility Locus for Endometrial Cancer

AU - Long, Jirong

AU - Zheng, Wei

AU - Xiang, Yong-Bing

AU - Lose, Felicity

AU - Thompson, Deborah

AU - Tomlinson, Ian

AU - Yu, Herbert

AU - Wentzensen, Nicolas

AU - Lambrechts, Diether

AU - Dörk, Thilo

AU - Dubrowinskaja, Natalia

AU - Goodman, Marc T.

AU - Salvesen, Helga B.

AU - Fasching, Peter A.

AU - Scott, Rodney J.

AU - Delahanty, Ryan

AU - Zheng, Ying

AU - O'Mara, Tracy

AU - Healey, Catherine S.

AU - Hodgson, Shirley

AU - Risch, Harvey

AU - Yang, Hannah P.

AU - Amant, Frederic

AU - Turmanov, Nurzhan

AU - Schwake, Anita

AU - Lurie, Galina

AU - Trovik, Jone

AU - Beckmann, Matthias W.

AU - Ashton, Katie

AU - Ji, Bu-Tian

AU - Bao, Ping-Ping

AU - Howarth, Kimberly

AU - Lu, Lingeng

AU - Lissowska, Jolanta

AU - Coenegrachts, Lieve

AU - Kaidarova, Dilyara

AU - Dürst, Matthias

AU - Thompson, Pamela J.

AU - Krakstad, Camilla

AU - Ekici, Arif B.

AU - Otton, Geoffrey

AU - Shi, Jiajun

AU - Zhang, Ben

AU - Gorman, Maggie

AU - Brinton, Louise

AU - Coosemans, An

AU - Matsuno, Rayna K.

AU - Halle, Mari K.

AU - Hein, Alexander

AU - Proietto, Anthony

AU - Cai, Hui

AU - Lu, Wei

AU - Dunning, Alison

AU - Easton, Douglas

AU - Gao, Yu-Tang

AU - Cai, Qiuyin

AU - Spurdle, Amanda B.

AU - Shu, Xiao-Ou

PY - 2012

Y1 - 2012

N2 - 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 silica 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 land H. 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 (Cl), 1.03-1.16] for the A/G genotype and 1.17(95% Cl, 1.05-1.30) for the GIG genotype (P = 1.6 x 10(-4) in combined analyses of all samples). The association was stronger when limited to the endometrioid subtype, with ORs (95% Cl) of 1.11 (1.04-1.18) and 1.21 (1.08-1.35), respectively (P = 2.4 x 10(-5)). Conclusions: Chromosome 1q42.2 may host an endometrial cancer susceptibility locus. Impact: This study identified a potential genetic locus for endometrial cancer risk. Cancer Epidemiol Biomarkers Prev; 21(6); 980-7. (C) 2012 AACR

AB - 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 silica 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 land H. 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 (Cl), 1.03-1.16] for the A/G genotype and 1.17(95% Cl, 1.05-1.30) for the GIG genotype (P = 1.6 x 10(-4) in combined analyses of all samples). The association was stronger when limited to the endometrioid subtype, with ORs (95% Cl) of 1.11 (1.04-1.18) and 1.21 (1.08-1.35), respectively (P = 2.4 x 10(-5)). Conclusions: Chromosome 1q42.2 may host an endometrial cancer susceptibility locus. Impact: This study identified a potential genetic locus for endometrial cancer risk. Cancer Epidemiol Biomarkers Prev; 21(6); 980-7. (C) 2012 AACR

U2 - https://doi.org/10.1158/1055-9965.EPI-11-1160

DO - https://doi.org/10.1158/1055-9965.EPI-11-1160

M3 - Article

C2 - 22426144

SN - 1055-9965

VL - 21

SP - 980

EP - 987

JO - Cancer epidemiology, biomarkers & prevention

JF - Cancer epidemiology, biomarkers & prevention

IS - 6

ER -