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 (US) |
|---|---|
| Pages (from-to) | 102769-102782 |
| Number of pages | 14 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 61 |
| DOIs | |
| State | Published - 2017 |
Keywords
- Familial breast cancer
- Linkage analysis
- Risk haplotype
- Sequencing
ASJC Scopus subject areas
- Oncology
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PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1. / Jiao, Xiang; Aravidis, Christos; Marikkannu, Rajeshwari; Rantala, Johanna; Picelli, Simone; Adamovic, Tatjana; Liu, Tao; Maguire, Paula; Kremeyer, Barbara; Luo, Liping; von Holst, Susanna; Kontham, Vinaykumar; Thutkawkorapin, Jessada; Margolin, Sara; Du, Quan; Lundin, Johanna; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Lush, Michael; Ambrosone, Christine B.; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arndt, Volker; Beckmann, Matthias W.; Blomqvist, Carl; Blot, William; Boeckx, Bram; Bojesen, Stig E.; Bonanni, Bernardo; Brand, Judith S.; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Cai, Qiuyin; Chang-Claude, Jenny; NBCS Collaborators, Collaborators; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Deming-Halverson, Sandra L.; Devilee, Peter; dos-Santos-Silva, Isabel; Dörk, Thilo; Eriksson, Mikael; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Flyger, Henrik; Gabrielson, Marike; García-Closas, Montserrat; Giles, Graham G.; González-Neira, Anna; Guénel, Pascal; Guo, Qi; Gündert, Melanie; Haiman, Christopher A.; Hallberg, Emily; Hamann, Ute; Harrington, Patricia; Hooning, Maartje J.; Hopper, John L.; Huang, Guanmengqian; Jakubowska, Anna; Jones, Michael E.; Kerin, Michael J.; Kosma, Veli Matti; Kristensen, Vessela N.; Lambrechts, Diether; Marchand, Loic Le; Lubinski, Jan; Mannermaa, Arto; Martens, John W.M.; Meindl, Alfons; Milne, Roger L.; Mulligan, Anna Marie; Neuhausen, Susan L.; Nevanlinna, Heli; Peto, Julian; Pylkäs, Katri; Radice, Paolo; Rhenius, Valerie; Sawyer, Elinor J.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Seynaeve, Caroline; Shah, Mitul; Simard, Jacques; Southey, Melissa C.; Swerdlow, Anthony J.; Truong, Thérèse; Wendt, Camilla; Winqvist, Robert; Zheng, Wei; kConFab/AOCS Investigators, Investigators; Benitez, Javier; Dunning, Alison M.; Pharoah, Paul D.P.; Easton, Douglas F.; Czene, Kamila; Hall, Per; Lindblom, Annika.
In: Oncotarget, Vol. 8, No. 61, 2017, p. 102769-102782.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - PHIP - 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
N1 - Funding Information: We are grateful to the patients who contributed to this study. We thank Charles M. Perou, Anne-Lise Børresen-Dale and Lambert Skoog for their valuable contribution. The iCOGS study would not have been possible without the contributions of the following: Andrew Berchuck (OCAC), Rosalind A. Eeles, Ali Amin Al Olama, Zsofia Kote-Jarai, Sara Benlloch (PRACTICAL), Antonis Antoniou, Lesley McGuffog and Ken Offit (CIMBA), Andrew Lee, and Ed Dicks, Craig Luccarini, and the staff of the Centre for Genetic Epidemiology Laboratory, the staff of the CNIO genotyping unit, Daniel C. Tessier, Francois Bacot, Daniel Vincent, Sylvie LaBoissière and Frederic Robidoux and the staff of the McGill University and Génome Québec Innovation Centre, Sune F. Nielsen, Borge G. Nordestgaard, and the staff of the Copenhagen DNA laboratory, and Julie M. Cunningham, Sharon A. Windebank, Christopher A. Hilker, Jeffrey Meyer and the staff of Mayo Clinic Genotyping Core Facility. Acknowledgements of individual BCAC studies are listed in the Supplemental Note. The study was supported by grants provided by the Swedish Cancer Society (Cancerfonden), the Stockholm County Council (ALF project), the Swedish Research Council (Vetenskapsrådet), the Stockholm Cancer Society (Radiumhemsfonderna) and Bert von Kantzows and Nilsson-Ehle's foundations. BCAC is funded by Cancer Research UK (C1287/A16563, C1287/A10118), the European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community's Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112-the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. Funding of individual BCAC studies is listed in the Supplemental Note. Publisher Copyright: © Jiao et al.
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
UR - http://www.scopus.com/inward/record.url?scp=85035357496&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85035357496&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.21800
DO - 10.18632/oncotarget.21800
M3 - Article
AN - SCOPUS:85035357496
VL - 8
SP - 102769
EP - 102782
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 61
ER -