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 - 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 - Flyger, Henrik

AU - NBCS Collaborators

PY - 2017/11/28

Y1 - 2017/11/28

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 moderate-risk 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 moderate-risk 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 - Journal Article

U2 - 10.18632/oncotarget.21800

DO - 10.18632/oncotarget.21800

M3 - Journal article

VL - 8

SP - 102769

EP - 102782

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 61

ER -