Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk

Ernest K Amankwah; Hui-Yi Lin; Jonathan P Tyrer; Kate Lawrenson; Joe Dennis; Ganna Chornokur; Katja K H Aben; Hoda Anton-Culver; Natalia Antonenkova; Fiona Bruinsma; Elisa V Bandera; Yukie T Bean; Matthias W Beckmann; Maria Bisogna; Line Bjorge; Natalia Bogdanova; Louise A Brinton; Angela Brooks-Wilson; Clareann H Bunker; Ralf Butzow; Ian G Campbell; Karen Carty; Zhihua Chen; Y Ann Chen; Jenny Chang-Claude; Linda S Cook; Daniel W Cramer; Julie M Cunningham; Cezary Cybulski; Agnieszka Dansonka-Mieszkowska; Andreas du Bois; Evelyn Despierre; Ed Dicks; Jennifer A Doherty; Thilo Dörk; Matthias Dürst; Douglas F Easton; Diana M Eccles; Robert P Edwards; Arif B Ekici; Peter A Fasching; Brooke L Fridley; Yu-Tang Gao; Aleksandra Gentry-Maharaj; Graham G Giles; Claus K Hogdall; Estrid Hogdall; Susanne K Kjaer; Lene Lundvall; Lotte Thomsen; Georgia Chenevix-Trench on behalf of the AOCS management group

doi:10.1002/gepi.21921

Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk

Ernest K Amankwah, Hui-Yi Lin, Jonathan P Tyrer, Kate Lawrenson, Joe Dennis, Ganna Chornokur, Katja K H Aben, Hoda Anton-Culver, Natalia Antonenkova, Fiona Bruinsma, Elisa V Bandera, Yukie T Bean, Matthias W Beckmann, Maria Bisogna, Line Bjorge, Natalia Bogdanova, Louise A Brinton, Angela Brooks-Wilson, Clareann H Bunker, Ralf ButzowIan G Campbell, Karen Carty, Zhihua Chen, Y Ann Chen, Jenny Chang-Claude, Linda S Cook, Daniel W Cramer, Julie M Cunningham, Cezary Cybulski, Agnieszka Dansonka-Mieszkowska, Andreas du Bois, Evelyn Despierre, Ed Dicks, Jennifer A Doherty, Thilo Dörk, Matthias Dürst, Douglas F Easton, Diana M Eccles, Robert P Edwards, Arif B Ekici, Peter A Fasching, Brooke L Fridley, Yu-Tang Gao, Aleksandra Gentry-Maharaj, Graham G Giles, Claus K Hogdall, Estrid Hogdall, Susanne K Kjaer, Lene Lundvall, Lotte Thomsen, Georgia Chenevix-Trench on behalf of the AOCS management group

22 Citationer (Scopus)

Abstract

Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC.

Originalsprog	Engelsk
Tidsskrift	Genetic Epidemiology
Vol/bind	39
Udgave nummer	8
Sider (fra-til)	689-697
ISSN	0741-0395
DOI	https://doi.org/10.1002/gepi.21921
Status	Udgivet - 24 sep. 2015

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10.1002/gepi.21921

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Amankwah, E. K., Lin, H.-Y., Tyrer, J. P., Lawrenson, K., Dennis, J., Chornokur, G., Aben, K. K. H., Anton-Culver, H., Antonenkova, N., Bruinsma, F., Bandera, E. V., Bean, Y. T., Beckmann, M. W., Bisogna, M., Bjorge, L., Bogdanova, N., Brinton, L. A., Brooks-Wilson, A., Bunker, C. H., ... Georgia Chenevix-Trench on behalf of the AOCS management group (2015). Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk. Genetic Epidemiology, 39(8), 689-697. https://doi.org/10.1002/gepi.21921

Amankwah, EK, Lin, H-Y, Tyrer, JP, Lawrenson, K, Dennis, J, Chornokur, G, Aben, KKH, Anton-Culver, H, Antonenkova, N, Bruinsma, F, Bandera, EV, Bean, YT, Beckmann, MW, Bisogna, M, Bjorge, L, Bogdanova, N, Brinton, LA, Brooks-Wilson, A, Bunker, CH, Butzow, R, Campbell, IG, Carty, K, Chen, Z, Chen, YA, Chang-Claude, J, Cook, LS, Cramer, DW, Cunningham, JM, Cybulski, C, Dansonka-Mieszkowska, A, du Bois, A, Despierre, E, Dicks, E, Doherty, JA, Dörk, T, Dürst, M, Easton, DF, Eccles, DM, Edwards, RP, Ekici, AB, Fasching, PA, Fridley, BL, Gao, Y-T, Gentry-Maharaj, A, Giles, GG, Hogdall, CK , Hogdall, E , Kjaer, SK, Lundvall, L, Thomsen, L & Georgia Chenevix-Trench on behalf of the AOCS management group 2015, 'Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk', Genetic Epidemiology, bind 39, nr. 8, s. 689-697. https://doi.org/10.1002/gepi.21921

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title = "Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk",

abstract = "Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC.",

author = "Amankwah, {Ernest K} and Hui-Yi Lin and Tyrer, {Jonathan P} and Kate Lawrenson and Joe Dennis and Ganna Chornokur and Aben, {Katja K H} and Hoda Anton-Culver and Natalia Antonenkova and Fiona Bruinsma and Bandera, {Elisa V} and Bean, {Yukie T} and Beckmann, {Matthias W} and Maria Bisogna and Line Bjorge and Natalia Bogdanova and Brinton, {Louise A} and Angela Brooks-Wilson and Bunker, {Clareann H} and Ralf Butzow and Campbell, {Ian G} and Karen Carty and Zhihua Chen and Chen, {Y Ann} and Jenny Chang-Claude and Cook, {Linda S} and Cramer, {Daniel W} and Cunningham, {Julie M} and Cezary Cybulski and Agnieszka Dansonka-Mieszkowska and {du Bois}, Andreas and Evelyn Despierre and Ed Dicks and Doherty, {Jennifer A} and Thilo D{\"o}rk and Matthias D{\"u}rst and Easton, {Douglas F} and Eccles, {Diana M} and Edwards, {Robert P} and Ekici, {Arif B} and Fasching, {Peter A} and Fridley, {Brooke L} and Yu-Tang Gao and Aleksandra Gentry-Maharaj and Giles, {Graham G} and Hogdall, {Claus K} and Estrid Hogdall and Kjaer, {Susanne K} and Lene Lundvall and Lotte Thomsen and {Georgia Chenevix-Trench on behalf of the AOCS management group}",

note = "{\textcopyright} 2015 WILEY PERIODICALS, INC.",

year = "2015",

month = sep,

day = "24",

doi = "10.1002/gepi.21921",

language = "English",

volume = "39",

pages = "689--697",

journal = "Genetic Epidemiology",

issn = "0741-0395",

publisher = "Wiley-Liss Inc.",

number = "8",

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TY - JOUR

T1 - Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk

AU - Amankwah, Ernest K

AU - Lin, Hui-Yi

AU - Tyrer, Jonathan P

AU - Lawrenson, Kate

AU - Dennis, Joe

AU - Chornokur, Ganna

AU - Aben, Katja K H

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia

AU - Bruinsma, Fiona

AU - Bandera, Elisa V

AU - Bean, Yukie T

AU - Beckmann, Matthias W

AU - Bisogna, Maria

AU - Bjorge, Line

AU - Bogdanova, Natalia

AU - Brinton, Louise A

AU - Brooks-Wilson, Angela

AU - Bunker, Clareann H

AU - Butzow, Ralf

AU - Campbell, Ian G

AU - Carty, Karen

AU - Chen, Zhihua

AU - Chen, Y Ann

AU - Chang-Claude, Jenny

AU - Cook, Linda S

AU - Cramer, Daniel W

AU - Cunningham, Julie M

AU - Cybulski, Cezary

AU - Dansonka-Mieszkowska, Agnieszka

AU - du Bois, Andreas

AU - Despierre, Evelyn

AU - Dicks, Ed

AU - Doherty, Jennifer A

AU - Dörk, Thilo

AU - Dürst, Matthias

AU - Easton, Douglas F

AU - Eccles, Diana M

AU - Edwards, Robert P

AU - Ekici, Arif B

AU - Fasching, Peter A

AU - Fridley, Brooke L

AU - Gao, Yu-Tang

AU - Gentry-Maharaj, Aleksandra

AU - Giles, Graham G

AU - Hogdall, Claus K

AU - Hogdall, Estrid

AU - Kjaer, Susanne K

AU - Lundvall, Lene

AU - Thomsen, Lotte

AU - Georgia Chenevix-Trench on behalf of the AOCS management group

PY - 2015/9/24

Y1 - 2015/9/24

N2 - Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC.

AB - Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC.

U2 - 10.1002/gepi.21921

DO - 10.1002/gepi.21921

M3 - Journal article

C2 - 26399219

SN - 0741-0395

VL - 39

SP - 689

EP - 697

JO - Genetic Epidemiology

JF - Genetic Epidemiology

IS - 8

ER -

Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk

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