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 & 158 others 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 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, Agnieszka Dansonka-Mieszkowska, Evelyn Despierre, Jennifer A. Doherty, Thilo Dörk, Andreas Du Bois, Matthias Dürst, Douglas F. Easton, Diana Eccles, Robert Edwards, Arif B. Ekici, Peter A. Fasching, David A. Fenstermacher, James M. Flanagan, Montserrat Garcia-Closas, Aleksandra Gentry-Maharaj, Graham G. Giles, Rosalind M. Glasspool, Jesus Gonzalez-Bosquet, Marc T. Goodman, Martin Gore, Bohdan Górski, Jacek Gronwald, Per Hall, Mari K. Halle, Philipp Harter, Florian Heitz, Peter Hillemanns, Maureen Hoatlin, Claus K. Høgdall, Estrid Høgdall, Satoyo Hosono, Anna Jakubowska, Allan Jensen, Heather Jim, Kimberly R. Kalli, Beth Y. Karlan, Stanley B. Kaye, Linda E. Kelemen, Lambertus A. Kiemeney, Fumitaka Kikkawa, Gottfried E. Konecny, Camilla Krakstad, Susanne Krüger Kjaer, Jolanta Kupryjanczyk, Diether Lambrechts, Sandrina Lambrechts, Johnathan M. Lancaster, Nhu D. Le, Arto Leminen, Douglas A. Levine, Dong Liang, Boon Kiong Lim, Jie Lin, Jolanta Lissowska, Karen H. Lu, Jan Lubiński, Galina Lurie, Leon F A G Massuger, Keitaro Matsuo, Valerie McGuire, John R. McLaughlin, Usha Menon, Francesmary Modugno, Kirsten B. Moysich, Toru Nakanishi, Steven A. Narod, Lotte Nedergaard, Roberta B. Ness, Heli Nevanlinna, Stefan Nickels, Houtan Noushmehr, Kunle Odunsi, Sara H. Olson, Irene Orlow, James Paul, Celeste L. Pearce, Tanja Pejovic, Liisa M. Pelttari, Malcolm C. Pike, Elizabeth M. Poole, Paola Raska, Stefan P. Renner, Harvey A. Risch, Lorna Rodriguez-Rodriguez, Mary Anne Rossing, Anja Rudolph, Ingo B. Runnebaum, Iwona K. Rzepecka, Helga B. Salvesen, Ira Schwaab, Gianluca Severi, Viji Shridhar, Xiao Ou Shu, Yurii B. Shvetsov, Weiva Sieh, Honglin Song, Melissa C. Southey, Beata Spiewankiewicz, Daniel Stram, Rebecca Sutphen, Soo Hwang Teo, Kathryn L. Terry, Daniel C. Tessier, Pamela J. Thompson, Shelley S. Tworoger, Anne M. Van Altena, Ignace Vergote, Robert A. Vierkant, Daniel Vincent, Allison F. Vitonis, Shan Wang-Gohrke, Rachel Palmieri Weber, Nicolas Wentzensen, Alice S. Whittemore, Elisabeth Wik, Lynne R. Wilkens, Boris Winterhoff, Yin Ling Woo, Anna H. Wu, Yong Bing Xiang, Hannah P. Yang, Wei Zheng, Argyrios Ziogas, Famida Zulkifli, Catherine M. Phelan, Edwin Iversen, Joellen M. Schildkraut, Andrew Berchuck, Brooke L. Fridley, Ellen L. Goode, Paul D P Pharoah, Alvaro N A Monteiro, Thomas A. Sellers, Simon A. Gayther

Research output: Contribution to journalArticle

70 Citations (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.

Original languageEnglish (US)
Article number1627
JournalNature Communications
Volume4
DOIs
StatePublished - 2013

Fingerprint

loci
Polymorphism
Ovarian Neoplasms
cancer
MicroRNAs
magnetic permeability
polymorphism
Nucleotides
nucleotides
Genes
Single Nucleotide Polymorphism
genes
3' Untranslated Regions
Odds Ratio
inversions
Binding Sites
Neoplasm Genes
Ovarian epithelial cancer
coding

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Permuth-Wey, J., Lawrenson, K., Shen, H. C., Velkova, A., Tyrer, J. P., Chen, Z., ... Gayther, S. A. (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

Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31. / Permuth-Wey, Jennifer; Lawrenson, Kate; Shen, Howard C.; Velkova, Aneliya; Tyrer, Jonathan P.; Chen, Zhihua; Lin, Hui Yi; Ann Chen, Y.; Tsai, Ya Yu; Qu, Xiaotao; Ramus, Susan J.; Karevan, Rod; Lee, Janet; Lee, Nathan; Larson, Melissa C.; Aben, Katja K.; Anton-Culver, Hoda; Antonenkova, Natalia; Antoniou, Antonis C.; Armasu, Sebastian M.; Bacot, François; Baglietto, Laura; Bandera, Elisa V.; Barnholtz-Sloan, Jill; Beckmann, Matthias W.; Birrer, Michael J.; Bloom, Greg; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Cai, Qiuyin; Campbell, Ian; Chang-Claude, Jenny; Chanock, Stephen; Chenevix-Trench, Georgia; Cheng, Jin Q.; Cicek, Mine S.; Coetzee, Gerhard A.; Cook, Linda S.; Couch, Fergus J.; Cramer, Daniel W.; Cunningham, Julie M.; Dansonka-Mieszkowska, Agnieszka; Despierre, Evelyn; Doherty, Jennifer A.; Dörk, Thilo; Du Bois, Andreas; Dürst, Matthias; Easton, Douglas F.; Eccles, Diana; Edwards, Robert; Ekici, Arif B.; Fasching, Peter A.; Fenstermacher, David A.; Flanagan, James M.; Garcia-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind M.; Gonzalez-Bosquet, Jesus; Goodman, Marc T.; Gore, Martin; Górski, Bohdan; Gronwald, Jacek; Hall, Per; Halle, Mari K.; Harter, Philipp; Heitz, Florian; Hillemanns, Peter; Hoatlin, Maureen; Høgdall, Claus K.; Høgdall, Estrid; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Jim, Heather; Kalli, Kimberly R.; Karlan, Beth Y.; Kaye, Stanley B.; Kelemen, Linda E.; Kiemeney, Lambertus A.; Kikkawa, Fumitaka; Konecny, Gottfried E.; Krakstad, Camilla; Krüger Kjaer, Susanne; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Lancaster, Johnathan M.; Le, Nhu D.; Leminen, Arto; Levine, Douglas A.; Liang, Dong; Kiong Lim, Boon; Lin, Jie; Lissowska, Jolanta; Lu, Karen H.; Lubiński, Jan; Lurie, Galina; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Nakanishi, Toru; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Nickels, Stefan; Noushmehr, Houtan; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Pike, Malcolm C.; Poole, Elizabeth M.; Raska, Paola; Renner, Stefan P.; Risch, Harvey A.; Rodriguez-Rodriguez, Lorna; Anne Rossing, Mary; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schwaab, Ira; Severi, Gianluca; Shridhar, Viji; Shu, Xiao Ou; Shvetsov, Yurii B.; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Stram, Daniel; Sutphen, Rebecca; Teo, Soo Hwang; Terry, Kathryn L.; Tessier, Daniel C.; Thompson, Pamela J.; Tworoger, Shelley S.; Van Altena, Anne M.; Vergote, Ignace; Vierkant, Robert A.; Vincent, Daniel; Vitonis, Allison F.; Wang-Gohrke, Shan; Palmieri Weber, Rachel; Wentzensen, Nicolas; Whittemore, Alice S.; Wik, Elisabeth; Wilkens, Lynne R.; Winterhoff, Boris; Ling Woo, Yin; Wu, Anna H.; Xiang, Yong Bing; Yang, Hannah P.; Zheng, Wei; Ziogas, Argyrios; Zulkifli, Famida; Phelan, Catherine M.; Iversen, Edwin; Schildkraut, Joellen M.; Berchuck, Andrew; Fridley, Brooke L.; Goode, Ellen L.; Pharoah, Paul D P; Monteiro, Alvaro N A; Sellers, Thomas A.; Gayther, Simon A.

In: Nature Communications, Vol. 4, 1627, 2013.

Research output: Contribution to journalArticle

Permuth-Wey, J, Lawrenson, K, Shen, HC, Velkova, A, Tyrer, JP, Chen, Z, Lin, HY, Ann Chen, Y, Tsai, YY, 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, R, 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, Dansonka-Mieszkowska, A, Despierre, E, Doherty, JA, Dörk, T, Du Bois, A, Dürst, M, Easton, DF, Eccles, D, Edwards, R, Ekici, AB, Fasching, PA, Fenstermacher, DA, Flanagan, JM, Garcia-Closas, M, Gentry-Maharaj, A, Giles, GG, Glasspool, RM, Gonzalez-Bosquet, J, Goodman, MT, Gore, M, Górski, B, Gronwald, J, Hall, P, Halle, MK, Harter, P, Heitz, F, Hillemanns, P, Hoatlin, M, Høgdall, CK, Høgdall, E, Hosono, S, Jakubowska, A, Jensen, A, Jim, H, Kalli, KR, Karlan, BY, Kaye, SB, Kelemen, LE, Kiemeney, LA, Kikkawa, F, Konecny, GE, Krakstad, C, Krüger Kjaer, S, Kupryjanczyk, J, Lambrechts, D, Lambrechts, S, Lancaster, JM, Le, ND, Leminen, A, Levine, DA, Liang, D, Kiong Lim, B, Lin, J, Lissowska, J, Lu, KH, Lubiński, J, Lurie, G, Massuger, LFAG, Matsuo, K, McGuire, V, McLaughlin, JR, Menon, U, Modugno, F, Moysich, KB, Nakanishi, T, Narod, SA, Nedergaard, L, Ness, RB, Nevanlinna, H, Nickels, S, Noushmehr, H, Odunsi, K, Olson, SH, Orlow, I, Paul, J, Pearce, CL, Pejovic, T, Pelttari, LM, Pike, MC, Poole, EM, Raska, P, Renner, SP, Risch, HA, Rodriguez-Rodriguez, L, Anne Rossing, M, Rudolph, A, Runnebaum, IB, Rzepecka, IK, Salvesen, HB, Schwaab, I, Severi, G, Shridhar, V, Shu, XO, Shvetsov, YB, Sieh, W, Song, H, Southey, MC, Spiewankiewicz, B, Stram, D, Sutphen, R, Teo, SH, Terry, KL, Tessier, DC, Thompson, PJ, Tworoger, SS, Van Altena, AM, Vergote, I, Vierkant, RA, Vincent, D, Vitonis, AF, Wang-Gohrke, S, Palmieri Weber, R, Wentzensen, N, Whittemore, AS, Wik, E, Wilkens, LR, Winterhoff, B, Ling Woo, Y, Wu, AH, Xiang, YB, Yang, HP, Zheng, W, Ziogas, A, Zulkifli, F, Phelan, CM, Iversen, E, Schildkraut, JM, Berchuck, A, Fridley, BL, Goode, EL, Pharoah, PDP, Monteiro, ANA, Sellers, TA & Gayther, SA 2013, 'Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31', Nature Communications, vol. 4, 1627. https://doi.org/10.1038/ncomms2613
Permuth-Wey, Jennifer ; Lawrenson, Kate ; Shen, Howard C. ; Velkova, Aneliya ; Tyrer, Jonathan P. ; Chen, Zhihua ; Lin, Hui Yi ; Ann Chen, Y. ; Tsai, Ya Yu ; Qu, Xiaotao ; Ramus, Susan J. ; Karevan, Rod ; Lee, Janet ; Lee, Nathan ; Larson, Melissa C. ; Aben, Katja K. ; Anton-Culver, Hoda ; Antonenkova, Natalia ; Antoniou, Antonis C. ; Armasu, Sebastian M. ; Bacot, François ; Baglietto, Laura ; Bandera, Elisa V. ; Barnholtz-Sloan, Jill ; Beckmann, Matthias W. ; Birrer, Michael J. ; Bloom, Greg ; Bogdanova, Natalia ; Brinton, Louise A. ; Brooks-Wilson, Angela ; Brown, Robert ; Butzow, Ralf ; Cai, Qiuyin ; Campbell, Ian ; Chang-Claude, Jenny ; Chanock, Stephen ; Chenevix-Trench, Georgia ; Cheng, Jin Q. ; Cicek, Mine S. ; Coetzee, Gerhard A. ; Cook, Linda S. ; Couch, Fergus J. ; Cramer, Daniel W. ; Cunningham, Julie M. ; Dansonka-Mieszkowska, Agnieszka ; Despierre, Evelyn ; Doherty, Jennifer A. ; Dörk, Thilo ; Du Bois, Andreas ; Dürst, Matthias ; Easton, Douglas F. ; Eccles, Diana ; Edwards, Robert ; Ekici, Arif B. ; Fasching, Peter A. ; Fenstermacher, David A. ; Flanagan, James M. ; Garcia-Closas, Montserrat ; Gentry-Maharaj, Aleksandra ; Giles, Graham G. ; Glasspool, Rosalind M. ; Gonzalez-Bosquet, Jesus ; Goodman, Marc T. ; Gore, Martin ; Górski, Bohdan ; Gronwald, Jacek ; Hall, Per ; Halle, Mari K. ; Harter, Philipp ; Heitz, Florian ; Hillemanns, Peter ; Hoatlin, Maureen ; Høgdall, Claus K. ; Høgdall, Estrid ; Hosono, Satoyo ; Jakubowska, Anna ; Jensen, Allan ; Jim, Heather ; Kalli, Kimberly R. ; Karlan, Beth Y. ; Kaye, Stanley B. ; Kelemen, Linda E. ; Kiemeney, Lambertus A. ; Kikkawa, Fumitaka ; Konecny, Gottfried E. ; Krakstad, Camilla ; Krüger Kjaer, Susanne ; Kupryjanczyk, Jolanta ; Lambrechts, Diether ; Lambrechts, Sandrina ; Lancaster, Johnathan M. ; Le, Nhu D. ; Leminen, Arto ; Levine, Douglas A. ; Liang, Dong ; Kiong Lim, Boon ; Lin, Jie ; Lissowska, Jolanta ; Lu, Karen H. ; Lubiński, Jan ; Lurie, Galina ; Massuger, Leon F A G ; Matsuo, Keitaro ; McGuire, Valerie ; McLaughlin, John R. ; Menon, Usha ; Modugno, Francesmary ; Moysich, Kirsten B. ; Nakanishi, Toru ; Narod, Steven A. ; Nedergaard, Lotte ; Ness, Roberta B. ; Nevanlinna, Heli ; Nickels, Stefan ; Noushmehr, Houtan ; Odunsi, Kunle ; Olson, Sara H. ; Orlow, Irene ; Paul, James ; Pearce, Celeste L. ; Pejovic, Tanja ; Pelttari, Liisa M. ; Pike, Malcolm C. ; Poole, Elizabeth M. ; Raska, Paola ; Renner, Stefan P. ; Risch, Harvey A. ; Rodriguez-Rodriguez, Lorna ; Anne Rossing, Mary ; Rudolph, Anja ; Runnebaum, Ingo B. ; Rzepecka, Iwona K. ; Salvesen, Helga B. ; Schwaab, Ira ; Severi, Gianluca ; Shridhar, Viji ; Shu, Xiao Ou ; Shvetsov, Yurii B. ; Sieh, Weiva ; Song, Honglin ; Southey, Melissa C. ; Spiewankiewicz, Beata ; Stram, Daniel ; Sutphen, Rebecca ; Teo, Soo Hwang ; Terry, Kathryn L. ; Tessier, Daniel C. ; Thompson, Pamela J. ; Tworoger, Shelley S. ; Van Altena, Anne M. ; Vergote, Ignace ; Vierkant, Robert A. ; Vincent, Daniel ; Vitonis, Allison F. ; Wang-Gohrke, Shan ; Palmieri Weber, Rachel ; Wentzensen, Nicolas ; Whittemore, Alice S. ; Wik, Elisabeth ; Wilkens, Lynne R. ; Winterhoff, Boris ; Ling Woo, Yin ; Wu, Anna H. ; Xiang, Yong Bing ; Yang, Hannah P. ; Zheng, Wei ; Ziogas, Argyrios ; Zulkifli, Famida ; Phelan, Catherine M. ; Iversen, Edwin ; Schildkraut, Joellen M. ; Berchuck, Andrew ; Fridley, Brooke L. ; Goode, Ellen L. ; Pharoah, Paul D P ; Monteiro, Alvaro N A ; Sellers, Thomas A. ; Gayther, Simon A. / Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31. In: Nature Communications. 2013 ; Vol. 4.
@article{8e5d93c8b5ac47358b4fb1f4719485c0,
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.",
author = "Jennifer Permuth-Wey and Kate Lawrenson and Shen, {Howard C.} and Aneliya Velkova and Tyrer, {Jonathan P.} and Zhihua Chen and Lin, {Hui Yi} and {Ann Chen}, Y. and Tsai, {Ya Yu} 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{\cc}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 Robert Brown 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 Agnieszka Dansonka-Mieszkowska and Evelyn Despierre and Doherty, {Jennifer A.} and Thilo D{\"o}rk and {Du Bois}, Andreas and Matthias D{\"u}rst and Easton, {Douglas F.} and Diana Eccles and Robert Edwards and Ekici, {Arif B.} and Fasching, {Peter A.} and Fenstermacher, {David A.} and Flanagan, {James M.} and Montserrat Garcia-Closas and Aleksandra Gentry-Maharaj and Giles, {Graham G.} and Glasspool, {Rosalind M.} and Jesus Gonzalez-Bosquet and Goodman, {Marc T.} and Martin Gore and Bohdan G{\'o}rski and Jacek Gronwald and Per Hall and Halle, {Mari K.} and Philipp Harter and Florian Heitz and Peter Hillemanns and Maureen Hoatlin and H{\o}gdall, {Claus K.} and Estrid H{\o}gdall and Satoyo Hosono and Anna Jakubowska and Allan Jensen and Heather Jim and Kalli, {Kimberly R.} and Karlan, {Beth Y.} and Kaye, {Stanley B.} and Kelemen, {Linda E.} and Kiemeney, {Lambertus A.} and Fumitaka Kikkawa and Konecny, {Gottfried E.} and Camilla Krakstad and {Kr{\"u}ger Kjaer}, Susanne and Jolanta Kupryjanczyk and Diether Lambrechts and Sandrina Lambrechts and Lancaster, {Johnathan M.} and Le, {Nhu D.} and Arto Leminen and Levine, {Douglas A.} and Dong Liang and {Kiong Lim}, Boon and Jie Lin and Jolanta Lissowska and Lu, {Karen H.} and Jan Lubiński and Galina Lurie and Massuger, {Leon F A G} and Keitaro Matsuo and Valerie McGuire and McLaughlin, {John R.} and Usha Menon and Francesmary Modugno and Moysich, {Kirsten B.} and Toru Nakanishi and Narod, {Steven A.} and Lotte Nedergaard and Ness, {Roberta B.} and Heli Nevanlinna and Stefan Nickels and Houtan Noushmehr and Kunle Odunsi and Olson, {Sara H.} and Irene Orlow and James Paul and Pearce, {Celeste L.} and Tanja Pejovic and Pelttari, {Liisa M.} and Pike, {Malcolm C.} and Poole, {Elizabeth M.} and Paola Raska and Renner, {Stefan P.} and Risch, {Harvey A.} and Lorna Rodriguez-Rodriguez and {Anne Rossing}, Mary and Anja Rudolph and Runnebaum, {Ingo B.} and Rzepecka, {Iwona K.} and Salvesen, {Helga B.} and Ira Schwaab and Gianluca Severi and Viji Shridhar and Shu, {Xiao Ou} and Shvetsov, {Yurii B.} and Weiva Sieh and Honglin Song and Southey, {Melissa C.} and Beata Spiewankiewicz and Daniel Stram and Rebecca Sutphen and Teo, {Soo Hwang} and Terry, {Kathryn L.} and Tessier, {Daniel C.} and Thompson, {Pamela J.} and Tworoger, {Shelley S.} and {Van Altena}, {Anne M.} and Ignace Vergote and Vierkant, {Robert A.} and Daniel Vincent and Vitonis, {Allison F.} and Shan Wang-Gohrke and {Palmieri Weber}, Rachel and Nicolas Wentzensen and Whittemore, {Alice S.} and Elisabeth Wik and Wilkens, {Lynne R.} and Boris Winterhoff and {Ling Woo}, Yin and Wu, {Anna H.} and Xiang, {Yong Bing} and Yang, {Hannah P.} and Wei Zheng and Argyrios Ziogas and Famida Zulkifli and Phelan, {Catherine M.} and Edwin Iversen and Schildkraut, {Joellen M.} and Andrew Berchuck and Fridley, {Brooke L.} and Goode, {Ellen L.} and Pharoah, {Paul D P} and Monteiro, {Alvaro N A} and Sellers, {Thomas A.} and Gayther, {Simon A.}",
year = "2013",
doi = "10.1038/ncomms2613",
language = "English (US)",
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journal = "Nature Communications",
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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 - Ann Chen, Y.

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

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 - Dansonka-Mieszkowska, Agnieszka

AU - Despierre, Evelyn

AU - Doherty, Jennifer A.

AU - Dörk, Thilo

AU - Du Bois, Andreas

AU - Dürst, Matthias

AU - Easton, Douglas F.

AU - Eccles, Diana

AU - Edwards, Robert

AU - Ekici, Arif B.

AU - Fasching, Peter A.

AU - Fenstermacher, David A.

AU - Flanagan, James M.

AU - Garcia-Closas, Montserrat

AU - Gentry-Maharaj, Aleksandra

AU - Giles, Graham G.

AU - Glasspool, Rosalind M.

AU - Gonzalez-Bosquet, Jesus

AU - Goodman, Marc T.

AU - Gore, Martin

AU - Górski, Bohdan

AU - Gronwald, Jacek

AU - Hall, Per

AU - Halle, Mari K.

AU - Harter, Philipp

AU - Heitz, Florian

AU - Hillemanns, Peter

AU - Hoatlin, Maureen

AU - Høgdall, Claus K.

AU - Høgdall, Estrid

AU - Hosono, Satoyo

AU - Jakubowska, Anna

AU - Jensen, Allan

AU - Jim, Heather

AU - Kalli, Kimberly R.

AU - Karlan, Beth Y.

AU - Kaye, Stanley B.

AU - Kelemen, Linda E.

AU - Kiemeney, Lambertus A.

AU - Kikkawa, Fumitaka

AU - Konecny, Gottfried E.

AU - Krakstad, Camilla

AU - Krüger Kjaer, Susanne

AU - Kupryjanczyk, Jolanta

AU - Lambrechts, Diether

AU - Lambrechts, Sandrina

AU - Lancaster, Johnathan M.

AU - Le, Nhu D.

AU - Leminen, Arto

AU - Levine, Douglas A.

AU - Liang, Dong

AU - Kiong Lim, Boon

AU - Lin, Jie

AU - Lissowska, Jolanta

AU - Lu, Karen H.

AU - Lubiński, Jan

AU - Lurie, Galina

AU - Massuger, Leon F A G

AU - Matsuo, Keitaro

AU - McGuire, Valerie

AU - McLaughlin, John R.

AU - Menon, Usha

AU - Modugno, Francesmary

AU - Moysich, Kirsten B.

AU - Nakanishi, Toru

AU - Narod, Steven A.

AU - Nedergaard, Lotte

AU - Ness, Roberta B.

AU - Nevanlinna, Heli

AU - Nickels, Stefan

AU - Noushmehr, Houtan

AU - Odunsi, Kunle

AU - Olson, Sara H.

AU - Orlow, Irene

AU - Paul, James

AU - Pearce, Celeste L.

AU - Pejovic, Tanja

AU - Pelttari, Liisa M.

AU - Pike, Malcolm C.

AU - Poole, Elizabeth M.

AU - Raska, Paola

AU - Renner, Stefan P.

AU - Risch, Harvey A.

AU - Rodriguez-Rodriguez, Lorna

AU - Anne Rossing, Mary

AU - Rudolph, Anja

AU - Runnebaum, Ingo B.

AU - Rzepecka, Iwona K.

AU - Salvesen, Helga B.

AU - Schwaab, Ira

AU - Severi, Gianluca

AU - Shridhar, Viji

AU - Shu, Xiao Ou

AU - Shvetsov, Yurii B.

AU - Sieh, Weiva

AU - Song, Honglin

AU - Southey, Melissa C.

AU - Spiewankiewicz, Beata

AU - Stram, Daniel

AU - Sutphen, Rebecca

AU - Teo, Soo Hwang

AU - Terry, Kathryn L.

AU - Tessier, Daniel C.

AU - Thompson, Pamela J.

AU - Tworoger, Shelley S.

AU - Van Altena, Anne M.

AU - Vergote, Ignace

AU - Vierkant, Robert A.

AU - Vincent, Daniel

AU - Vitonis, Allison F.

AU - Wang-Gohrke, Shan

AU - Palmieri Weber, Rachel

AU - Wentzensen, Nicolas

AU - Whittemore, Alice S.

AU - Wik, Elisabeth

AU - Wilkens, Lynne R.

AU - Winterhoff, Boris

AU - Ling Woo, Yin

AU - Wu, Anna H.

AU - Xiang, Yong Bing

AU - Yang, Hannah P.

AU - Zheng, Wei

AU - Ziogas, Argyrios

AU - Zulkifli, Famida

AU - Phelan, Catherine M.

AU - Iversen, Edwin

AU - Schildkraut, Joellen M.

AU - Berchuck, Andrew

AU - Fridley, Brooke L.

AU - Goode, Ellen L.

AU - Pharoah, Paul D P

AU - Monteiro, Alvaro N A

AU - Sellers, Thomas A.

AU - Gayther, Simon A.

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.

UR - http://www.scopus.com/inward/record.url?scp=84875908264&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875908264&partnerID=8YFLogxK

U2 - 10.1038/ncomms2613

DO - 10.1038/ncomms2613

M3 - Article

VL - 4

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 1627

ER -