PHIP : a novel candidate breast cancer susceptibility locus on 6q14.1

Xiang Jiao; Christos Aravidis; Rajeshwari Marikkannu; Johanna Rantala; Simone Picelli; Tatjana Adamovic; Tao Liu; Paula Maguire; Barbara Kremeyer; Liping Luo; Susanna von Holst; Vinaykumar Kontham; Jessada Thutkawkorapin; Sara Margolin; Quan Du; Johanna Lundin; Kyriaki Michailidou; Manjeet K. Bolla; Qin Wang; Joe Dennis; Michael Lush; Christine B. Ambrosone; Irene L. Andrulis; Hoda Anton-Culver; Natalia N. Antonenkova; Volker Arndt; Matthias W. Beckmann; Carl Blomqvist; William Blot; Bram Boeckx; Stig E. Bojesen; Bernardo Bonanni; Judith S. Brand; Hiltrud Brauch; Hermann Brenner; Annegien Broeks; Thomas Brüning; Barbara Burwinkel; Qiuyin Cai; Jenny Chang-Claude; Collaborators NBCS Collaborators; Fergus J. Couch; Angela Cox; Simon S. Cross; Sandra L. Deming-Halverson; Peter Devilee; Isabel dos-Santos-Silva; Thilo Dörk; Mikael Eriksson; Peter A. Fasching; Jonine Figueroa; Dieter Flesch-Janys; Henrik Flyger; Marike Gabrielson; Montserrat García-Closas; Graham G. Giles; Anna González-Neira; Pascal Guénel; Qi Guo; Melanie Gündert; Christopher A. Haiman; Emily Hallberg; Ute Hamann; Patricia Harrington; Maartje J. Hooning; John L. Hopper; Guanmengqian Huang; Anna Jakubowska; Michael E. Jones; Michael J. Kerin; Veli Matti Kosma; Vessela N. Kristensen; Diether Lambrechts; Loic Le Marchand; Jan Lubinski; Arto Mannermaa; John W.M. Martens; Alfons Meindl; Roger L. Milne; Anna Marie Mulligan; Susan L. Neuhausen; Heli Nevanlinna; Julian Peto; Katri Pylkäs; Paolo Radice; Valerie Rhenius; Elinor J. Sawyer; Marjanka K. Schmidt; Rita K. Schmutzler; Caroline Seynaeve; Mitul Shah; Jacques Simard; Melissa C. Southey; Anthony J. Swerdlow; Thérèse Truong; Camilla Wendt; Robert Winqvist; Wei Zheng; Investigators kConFab/AOCS Investigators; Javier Benitez; Alison M. Dunning; Paul D.P. Pharoah; Douglas F. Easton; Kamila Czene; Per Hall; Annika Lindblom

doi:10.18632/oncotarget.21800

PHIP : a novel candidate breast cancer susceptibility locus on 6q14.1

Xiang Jiao, Christos Aravidis, Rajeshwari Marikkannu, Johanna Rantala, Simone Picelli, Tatjana Adamovic, Tao Liu, Paula Maguire, Barbara Kremeyer, Liping Luo, Susanna von Holst, Vinaykumar Kontham, Jessada Thutkawkorapin, Sara Margolin, Quan Du, Johanna Lundin, Kyriaki Michailidou, Manjeet K. Bolla, Qin Wang, Joe DennisMichael Lush, Christine B. Ambrosone, Irene L. Andrulis, Hoda Anton-Culver, Natalia N. Antonenkova, Volker Arndt, Matthias W. Beckmann, Carl Blomqvist, William Blot, Bram Boeckx, Stig E. Bojesen, Bernardo Bonanni, Judith S. Brand, Hiltrud Brauch, Hermann Brenner, Annegien Broeks, Thomas Brüning, Barbara Burwinkel, Qiuyin Cai, Jenny Chang-Claude, Collaborators NBCS Collaborators, Fergus J. Couch, Angela Cox, Simon S. Cross, Sandra L. Deming-Halverson, Peter Devilee, Isabel dos-Santos-Silva, Thilo Dörk, Mikael Eriksson, Peter A. Fasching, Jonine Figueroa, Dieter Flesch-Janys, Henrik Flyger, Marike Gabrielson, Montserrat García-Closas, Graham G. Giles, Anna González-Neira, Pascal Guénel, Qi Guo, Melanie Gündert, Christopher A. Haiman, Emily Hallberg, Ute Hamann, Patricia Harrington, Maartje J. Hooning, John L. Hopper, Guanmengqian Huang, Anna Jakubowska, Michael E. Jones, Michael J. Kerin, Veli Matti Kosma, Vessela N. Kristensen, Diether Lambrechts, Loic Le Marchand, Jan Lubinski, Arto Mannermaa, John W.M. Martens, Alfons Meindl, Roger L. Milne, Anna Marie Mulligan, Susan L. Neuhausen, Heli Nevanlinna, Julian Peto, Katri Pylkäs, Paolo Radice, Valerie Rhenius, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Caroline Seynaeve, Mitul Shah, Jacques Simard, Melissa C. Southey, Anthony J. Swerdlow, Thérèse Truong, Camilla Wendt, Robert Winqvist, Wei Zheng, Investigators kConFab/AOCS Investigators, Javier Benitez, Alison M. Dunning, Paul D.P. Pharoah, Douglas F. Easton, Kamila Czene, Per Hall, Annika Lindblom^*

^*Corresponding author for this work

Department of Clinical Medicine

2 Citations (Scopus)

43 Downloads (Pure)

Abstract

Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderaterisk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.

Original language	English
Journal	OncoTarget
Volume	8
Issue number	61
Pages (from-to)	102769-102782
Number of pages	14
ISSN	1949-2553
DOIs	https://doi.org/10.18632/oncotarget.21800
Publication status	Published - 2017

Keywords

Familial breast cancer
Linkage analysis
Risk haplotype
Sequencing

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.21800Licence: CC BY

PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1Final published version, 1.15 MBLicence: CC BY

Cite this

Jiao, X., Aravidis, C., Marikkannu, R., Rantala, J., Picelli, S., Adamovic, T., Liu, T., Maguire, P., Kremeyer, B., Luo, L., von Holst, S., Kontham, V., Thutkawkorapin, J., Margolin, S., Du, Q., Lundin, J., Michailidou, K., Bolla, M. K., Wang, Q., ... Lindblom, A. (2017). PHIP : a novel candidate breast cancer susceptibility locus on 6q14.1. OncoTarget, 8(61), 102769-102782. https://doi.org/10.18632/oncotarget.21800

Jiao, X, Aravidis, C, Marikkannu, R, Rantala, J, Picelli, S, Adamovic, T, Liu, T, Maguire, P, Kremeyer, B, Luo, L, von Holst, S, Kontham, V, Thutkawkorapin, J, Margolin, S, Du, Q, Lundin, J, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Lush, M, Ambrosone, CB, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Beckmann, MW, Blomqvist, C, Blot, W, Boeckx, B, Bojesen, SE, Bonanni, B, Brand, JS, Brauch, H, Brenner, H, Broeks, A, Brüning, T, Burwinkel, B, Cai, Q, Chang-Claude, J, NBCS Collaborators, C, Couch, FJ, Cox, A, Cross, SS, Deming-Halverson, SL, Devilee, P, dos-Santos-Silva, I, Dörk, T, Eriksson, M, Fasching, PA, Figueroa, J, Flesch-Janys, D, Flyger, H, Gabrielson, M, García-Closas, M, Giles, GG, González-Neira, A, Guénel, P, Guo, Q, Gündert, M, Haiman, CA, Hallberg, E, Hamann, U, Harrington, P, Hooning, MJ, Hopper, JL, Huang, G, Jakubowska, A, Jones, ME, Kerin, MJ, Kosma, VM, Kristensen, VN, Lambrechts, D, Marchand, LL, Lubinski, J, Mannermaa, A, Martens, JWM, Meindl, A, Milne, RL, Mulligan, AM, Neuhausen, SL, Nevanlinna, H, Peto, J, Pylkäs, K, Radice, P, Rhenius, V, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Seynaeve, C, Shah, M, Simard, J, Southey, MC, Swerdlow, AJ, Truong, T, Wendt, C, Winqvist, R, Zheng, W, kConFab/AOCS Investigators, I, Benitez, J, Dunning, AM, Pharoah, PDP, Easton, DF, Czene, K, Hall, P & Lindblom, A 2017, 'PHIP : a novel candidate breast cancer susceptibility locus on 6q14.1', OncoTarget, vol. 8, no. 61, pp. 102769-102782. https://doi.org/10.18632/oncotarget.21800

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title = "PHIP : a novel candidate breast cancer susceptibility locus on 6q14.1",

abstract = "Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderaterisk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.",

keywords = "Familial breast cancer, Linkage analysis, Risk haplotype, Sequencing",

author = "Xiang Jiao and Christos Aravidis and Rajeshwari Marikkannu and Johanna Rantala and Simone Picelli and Tatjana Adamovic and Tao Liu and Paula Maguire and Barbara Kremeyer and Liping Luo and {von Holst}, Susanna and Vinaykumar Kontham and Jessada Thutkawkorapin and Sara Margolin and Quan Du and Johanna Lundin and Kyriaki Michailidou and Bolla, {Manjeet K.} and Qin Wang and Joe Dennis and Michael Lush and Ambrosone, {Christine B.} and Andrulis, {Irene L.} and Hoda Anton-Culver and Antonenkova, {Natalia N.} and Volker Arndt and Beckmann, {Matthias W.} and Carl Blomqvist and William Blot and Bram Boeckx and Bojesen, {Stig E.} and Bernardo Bonanni and Brand, {Judith S.} and Hiltrud Brauch and Hermann Brenner and Annegien Broeks and Thomas Br{\"u}ning and Barbara Burwinkel and Qiuyin Cai and Jenny Chang-Claude and {NBCS Collaborators}, Collaborators and Couch, {Fergus J.} and Angela Cox and Cross, {Simon S.} and Deming-Halverson, {Sandra L.} and Peter Devilee and Isabel dos-Santos-Silva and Thilo D{\"o}rk and Mikael Eriksson and Fasching, {Peter A.} and Jonine Figueroa and Dieter Flesch-Janys and Henrik Flyger and Marike Gabrielson and Montserrat Garc{\'i}a-Closas and Giles, {Graham G.} and Anna Gonz{\'a}lez-Neira and Pascal Gu{\'e}nel and Qi Guo and Melanie G{\"u}ndert and Haiman, {Christopher A.} and Emily Hallberg and Ute Hamann and Patricia Harrington and Hooning, {Maartje J.} and Hopper, {John L.} and Guanmengqian Huang and Anna Jakubowska and Jones, {Michael E.} and Kerin, {Michael J.} and Kosma, {Veli Matti} and Kristensen, {Vessela N.} and Diether Lambrechts and Marchand, {Loic Le} and Jan Lubinski and Arto Mannermaa and Martens, {John W.M.} and Alfons Meindl and Milne, {Roger L.} and Mulligan, {Anna Marie} and Neuhausen, {Susan L.} and Heli Nevanlinna and Julian Peto and Katri Pylk{\"a}s and Paolo Radice and Valerie Rhenius and Sawyer, {Elinor J.} and Schmidt, {Marjanka K.} and Schmutzler, {Rita K.} and Caroline Seynaeve and Mitul Shah and Jacques Simard and Southey, {Melissa C.} and Swerdlow, {Anthony J.} and Th{\'e}r{\`e}se Truong and Camilla Wendt and Robert Winqvist and Wei Zheng and {kConFab/AOCS Investigators}, Investigators and Javier Benitez and Dunning, {Alison M.} and Pharoah, {Paul D.P.} and Easton, {Douglas F.} and Kamila Czene and Per Hall and Annika Lindblom",

year = "2017",

doi = "10.18632/oncotarget.21800",

language = "English",

volume = "8",

pages = "102769--102782",

journal = "OncoTarget",

issn = "1949-2553",

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number = "61",

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TY - JOUR

T1 - PHIP

T2 - a novel candidate breast cancer susceptibility locus on 6q14.1

AU - Jiao, Xiang

AU - Aravidis, Christos

AU - Marikkannu, Rajeshwari

AU - Rantala, Johanna

AU - Picelli, Simone

AU - Adamovic, Tatjana

AU - Liu, Tao

AU - Maguire, Paula

AU - Kremeyer, Barbara

AU - Luo, Liping

AU - von Holst, Susanna

AU - Kontham, Vinaykumar

AU - Thutkawkorapin, Jessada

AU - Margolin, Sara

AU - Du, Quan

AU - Lundin, Johanna

AU - Michailidou, Kyriaki

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Dennis, Joe

AU - Lush, Michael

AU - Ambrosone, Christine B.

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia N.

AU - Arndt, Volker

AU - Beckmann, Matthias W.

AU - Blomqvist, Carl

AU - Blot, William

AU - Boeckx, Bram

AU - Bojesen, Stig E.

AU - Bonanni, Bernardo

AU - Brand, Judith S.

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Broeks, Annegien

AU - Brüning, Thomas

AU - Burwinkel, Barbara

AU - Cai, Qiuyin

AU - Chang-Claude, Jenny

AU - NBCS Collaborators, Collaborators

AU - Couch, Fergus J.

AU - Cox, Angela

AU - Cross, Simon S.

AU - Deming-Halverson, Sandra L.

AU - Devilee, Peter

AU - dos-Santos-Silva, Isabel

AU - Dörk, Thilo

AU - Eriksson, Mikael

AU - Fasching, Peter A.

AU - Figueroa, Jonine

AU - Flesch-Janys, Dieter

AU - Flyger, Henrik

AU - Gabrielson, Marike

AU - García-Closas, Montserrat

AU - Giles, Graham G.

AU - González-Neira, Anna

AU - Guénel, Pascal

AU - Guo, Qi

AU - Gündert, Melanie

AU - Haiman, Christopher A.

AU - Hallberg, Emily

AU - Hamann, Ute

AU - Harrington, Patricia

AU - Hooning, Maartje J.

AU - Hopper, John L.

AU - Huang, Guanmengqian

AU - Jakubowska, Anna

AU - Jones, Michael E.

AU - Kerin, Michael J.

AU - Kosma, Veli Matti

AU - Kristensen, Vessela N.

AU - Lambrechts, Diether

AU - Marchand, Loic Le

AU - Lubinski, Jan

AU - Mannermaa, Arto

AU - Martens, John W.M.

AU - Meindl, Alfons

AU - Milne, Roger L.

AU - Mulligan, Anna Marie

AU - Neuhausen, Susan L.

AU - Nevanlinna, Heli

AU - Peto, Julian

AU - Pylkäs, Katri

AU - Radice, Paolo

AU - Rhenius, Valerie

AU - Sawyer, Elinor J.

AU - Schmidt, Marjanka K.

AU - Schmutzler, Rita K.

AU - Seynaeve, Caroline

AU - Shah, Mitul

AU - Simard, Jacques

AU - Southey, Melissa C.

AU - Swerdlow, Anthony J.

AU - Truong, Thérèse

AU - Wendt, Camilla

AU - Winqvist, Robert

AU - Zheng, Wei

AU - kConFab/AOCS Investigators, Investigators

AU - Benitez, Javier

AU - Dunning, Alison M.

AU - Pharoah, Paul D.P.

AU - Easton, Douglas F.

AU - Czene, Kamila

AU - Hall, Per

AU - Lindblom, Annika

PY - 2017

Y1 - 2017

N2 - Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderaterisk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.

AB - Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderaterisk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.

KW - Familial breast cancer

KW - Linkage analysis

KW - Risk haplotype

KW - Sequencing

U2 - 10.18632/oncotarget.21800

DO - 10.18632/oncotarget.21800

M3 - Journal article

C2 - 29262523

AN - SCOPUS:85035357496

SN - 1949-2553

VL - 8

SP - 102769

EP - 102782

JO - OncoTarget

JF - OncoTarget

IS - 61

ER -