Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31

Jennifer Permuth-Wey; Kate Lawrenson; Howard C Shen; Aneliya Velkova; Jonathan P Tyrer; Zhihua Chen; Hui-Yi Lin; Y Ann Chen; Ya-Yu Tsai; Xiaotao Qu; Susan J Ramus; Rod Karevan; Janet Lee; Nathan Lee; Melissa C Larson; Katja K Aben; Hoda Anton-Culver; Natalia Antonenkova; Antonis C Antoniou; Sebastian M Armasu; François Bacot; Laura Baglietto; Elisa V Bandera; Jill Barnholtz-Sloan; Matthias W Beckmann; Michael J Birrer; Greg Bloom; Natalia Bogdanova; Louise A Brinton; Angela Brooks-Wilson; Robert James (Jim) Brown; Ralf Butzow; Qiuyin Cai; Ian Campbell; Jenny Chang-Claude; Stephen Chanock; Georgia Chenevix-Trench; Jin Q Cheng; Mine S Cicek; Gerhard A Coetzee; Linda S Cook; Fergus J Couch; Daniel W Cramer; Julie M Cunningham; Claus K Høgdall; Estrid Høgdall; Allan Jensen; Susanne Krüger Kjaer; Lotte Nedergaard; Australian Cancer Study; Thomas van Overeem Hansen

doi:10.1038/ncomms2613

Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31

Jennifer Permuth-Wey
, Kate Lawrenson
, Howard C Shen
, Aneliya Velkova
, Jonathan P Tyrer
, Zhihua Chen
, Hui-Yi Lin
, Y Ann Chen
, Ya-Yu Tsai
, Xiaotao Qu
, Susan J Ramus
, Rod Karevan
, Janet Lee
, Nathan Lee
, Melissa C Larson
, Katja K Aben
, Hoda Anton-Culver
, Natalia Antonenkova
, Antonis C Antoniou
, Sebastian M Armasu

François Bacot, Laura Baglietto, Elisa V Bandera, Jill Barnholtz-Sloan, Matthias W Beckmann, Michael J Birrer, Greg Bloom, Natalia Bogdanova, Louise A Brinton, Angela Brooks-Wilson, Robert James (Jim) Brown, Ralf Butzow, Qiuyin Cai, Ian Campbell, Jenny Chang-Claude, Stephen Chanock, Georgia Chenevix-Trench, Jin Q Cheng, Mine S Cicek, Gerhard A Coetzee, Linda S Cook, Fergus J Couch, Daniel W Cramer, Julie M Cunningham, Claus K Høgdall, Estrid Høgdall, Allan Jensen, Susanne Krüger Kjaer, Lotte Nedergaard, Australian Cancer Study, Thomas van Overeem Hansen

103 Citationer (Scopus)

Abstract

Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.

Originalsprog	Engelsk
Tidsskrift	Nature Communications
Vol/bind	4
Sider (fra-til)	1627
ISSN	2041-1722
DOI	https://doi.org/10.1038/ncomms2613
Status	Udgivet - 2013

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10.1038/ncomms2613

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Permuth-Wey, J., Lawrenson, K., Shen, H. C., Velkova, A., Tyrer, J. P., Chen, Z., Lin, H.-Y., Chen, Y. A., Tsai, Y.-Y., Qu, X., Ramus, S. J., Karevan, R., Lee, J., Lee, N., Larson, M. C., Aben, K. K., Anton-Culver, H., Antonenkova, N., Antoniou, A. C., ... Hansen, T. V. O. (2013). Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31. Nature Communications, 4, 1627. https://doi.org/10.1038/ncomms2613

Permuth-Wey, J, Lawrenson, K, Shen, HC, Velkova, A, Tyrer, JP, Chen, Z, Lin, H-Y, Chen, YA, Tsai, Y-Y, Qu, X, Ramus, SJ, Karevan, R, Lee, J, Lee, N, Larson, MC, Aben, KK, Anton-Culver, H, Antonenkova, N, Antoniou, AC, Armasu, SM, Bacot, F, Baglietto, L, Bandera, EV, Barnholtz-Sloan, J, Beckmann, MW, Birrer, MJ, Bloom, G, Bogdanova, N, Brinton, LA, Brooks-Wilson, A, Brown, RJ, Butzow, R, Cai, Q, Campbell, I, Chang-Claude, J, Chanock, S, Chenevix-Trench, G, Cheng, JQ, Cicek, MS, Coetzee, GA, Cook, LS, Couch, FJ, Cramer, DW, Cunningham, JM, Høgdall, CK , Høgdall, E, Jensen, A, Kjaer, SK, Nedergaard, L, Australian Cancer Study & Hansen, TVO 2013, 'Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31', Nature Communications, bind 4, s. 1627. https://doi.org/10.1038/ncomms2613

@article{b4983118b0ad490d8fb5b35bc89b1f1c,

title = "Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31",

abstract = "Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.",

keywords = "Chromosomes, Human, Pair 17, Female, Genetic Predisposition to Disease, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Polymorphism, Single Nucleotide",

author = "Jennifer Permuth-Wey and Kate Lawrenson and Shen, \{Howard C\} and Aneliya Velkova and Tyrer, \{Jonathan P\} and Zhihua Chen and Hui-Yi Lin and Chen, \{Y Ann\} and Ya-Yu Tsai and Xiaotao Qu and Ramus, \{Susan J\} and Rod Karevan and Janet Lee and Nathan Lee and Larson, \{Melissa C\} and Aben, \{Katja K\} and Hoda Anton-Culver and Natalia Antonenkova and Antoniou, \{Antonis C\} and Armasu, \{Sebastian M\} and Fran{\c c}ois Bacot and Laura Baglietto and Bandera, \{Elisa V\} and Jill Barnholtz-Sloan and Beckmann, \{Matthias W\} and Birrer, \{Michael J\} and Greg Bloom and Natalia Bogdanova and Brinton, \{Louise A\} and Angela Brooks-Wilson and Brown, \{Robert James (Jim)\} and Ralf Butzow and Qiuyin Cai and Ian Campbell and Jenny Chang-Claude and Stephen Chanock and Georgia Chenevix-Trench and Cheng, \{Jin Q\} and Cicek, \{Mine S\} and Coetzee, \{Gerhard A\} and Cook, \{Linda S\} and Couch, \{Fergus J\} and Cramer, \{Daniel W\} and Cunningham, \{Julie M\} and H{\o}gdall, \{Claus K\} and Estrid H{\o}gdall and Allan Jensen and Kjaer, \{Susanne Kr{\"u}ger\} and Lotte Nedergaard and \{Australian Cancer Study\} and Hansen, \{Thomas van Overeem\}",

year = "2013",

doi = "10.1038/ncomms2613",

language = "English",

volume = "4",

pages = "1627",

journal = "Nature Communications",

issn = "2041-1722",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31

AU - Permuth-Wey, Jennifer

AU - Lawrenson, Kate

AU - Shen, Howard C

AU - Velkova, Aneliya

AU - Tyrer, Jonathan P

AU - Chen, Zhihua

AU - Lin, Hui-Yi

AU - Chen, Y Ann

AU - Tsai, Ya-Yu

AU - Qu, Xiaotao

AU - Ramus, Susan J

AU - Karevan, Rod

AU - Lee, Janet

AU - Lee, Nathan

AU - Larson, Melissa C

AU - Aben, Katja K

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia

AU - Antoniou, Antonis C

AU - Armasu, Sebastian M

AU - Bacot, François

AU - Baglietto, Laura

AU - Bandera, Elisa V

AU - Barnholtz-Sloan, Jill

AU - Beckmann, Matthias W

AU - Birrer, Michael J

AU - Bloom, Greg

AU - Bogdanova, Natalia

AU - Brinton, Louise A

AU - Brooks-Wilson, Angela

AU - Brown, Robert James (Jim)

AU - Butzow, Ralf

AU - Cai, Qiuyin

AU - Campbell, Ian

AU - Chang-Claude, Jenny

AU - Chanock, Stephen

AU - Chenevix-Trench, Georgia

AU - Cheng, Jin Q

AU - Cicek, Mine S

AU - Coetzee, Gerhard A

AU - Cook, Linda S

AU - Couch, Fergus J

AU - Cramer, Daniel W

AU - Cunningham, Julie M

AU - Høgdall, Claus K

AU - Høgdall, Estrid

AU - Jensen, Allan

AU - Kjaer, Susanne Krüger

AU - Nedergaard, Lotte

AU - Australian Cancer Study

AU - Hansen, Thomas van Overeem

PY - 2013

Y1 - 2013

N2 - Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.

AB - Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.

KW - Chromosomes, Human, Pair 17

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Neoplasms, Glandular and Epithelial

KW - Ovarian Neoplasms

KW - Polymorphism, Single Nucleotide

U2 - 10.1038/ncomms2613

DO - 10.1038/ncomms2613

M3 - Journal article

C2 - 23535648

SN - 2041-1722

VL - 4

SP - 1627

JO - Nature Communications

JF - Nature Communications

ER -

Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31

Abstract

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