Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer

被引：574

作者：

Stacey, Simon N.

Manolescu, Andrei

Sulem, Patrick

Rafnar, Thorunn

Gudmundsson, Julius

Gudjonsson, Sigurjon A.

Masson, Gisli

Jakobsdottir, Margret

Thorlacius, Steinunn

Helgason, Agnar

Aben, Katja K.

Strobbe, Luc J.

Albers-Akkers, Marjo T.

Swinkels, Dorine W.

Henderson, Brian E.

Kolonel, Laurence N.

Le Marchand, Loic

Millastre, Esther

Andres, Raquel

Godino, Javier

Garcia-Prats, Maria Dolores

Polo, Eduardo

Tres, Alejandro

Mouy, Magali

Saemundsdottir, Jona

Backman, Valgerdur M.

Gudmundsson, Larus

Kristjansson, Kristleifur

Bergthorsson, Jon T.

Kostic, Jelena

Frigge, Michael L.

Geller, Frank

Gudbjartsson, Daniel

Sigurdsson, Helgi

Jonsdottir, Thora

Hrafnkelsson, Jon

Johannsson, Jakob

Sveinsson, Thorarinn

Myrdal, Gardar

Grimsson, Hlynur Niels

Jonsson, Thorvaldur

von Holst, Susanna

Werelius, Barbro

Margolin, Sara

Lindblom, Annika

Mayordomo, Jose I.

Haiman, Christopher A.

Kiemeney, Lambertus A.

Johannsson, Oskar Th

Gulcher, Jeffrey R.

机构：

[1] deCODE Genet, IS-101 Reykjavik, Iceland

[2] Ctr Comprehens Canc, NL-6501 BG Nijmegen, Netherlands

[3] Radboud Univ Nijmegen Med Ctr, Dept Epidemiol & Biostat, NL-6500 HB Nijmegen, Netherlands

[4] Radboud Univ Nijmegen Med Ctr, Dept Clin Chem, NL-6500 HB Nijmegen, Netherlands

[5] Canisius Wilhelmina Hosp, Dept Surg, NL-6500 GS Nijmegen, Netherlands

[6] INR Thrombosis Serv, NL-6525 ED Nijmegen, Netherlands

[7] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[8] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA

[9] Univ Hosp, Div Med Oncol, Zaragoza 50009, Spain

[10] Nanotechnol Inst Aragon, Hlth Sci Inst, Zaragoza, Spain

[11] San Jorge Gen Hosp, Div Pathol, Huesca 22004, Spain

[12] Ernest Lluch Hosp, Div Med Oncol, Calatayud 50300, Spain

[13] Univ Hosp, Landspitali, Dept Oncol, Reykjavik, Iceland

[14] Univ Hosp, Landspitali, Dept Surg, Reykjavik, Iceland

[15] Univ Hosp, Landspitali, Dept Radiat Phys, Reykjavik, Iceland

[16] Karolinska Inst, Dept Mol Med, S-17176 Stockholm, Sweden

[17] Karolinska Univ Hosp, Sodersjukhuset, S-11883 Stockholm, Sweden

来源：

NATURE GENETICS | 2007年 / 39卷 / 07期

关键词：

D O I：

10.1038/ng2064

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Familial clustering studies indicate that breast cancer risk has a substantial genetic component(1-3). To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: similar to 25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44- fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64- fold greater risk. Risk from both alleles was confined to estrogen receptor - positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5' end of TNRC9, a high mobility group chromatin - associated protein whose expression is implicated in breast cancer metastasis to bone(4).

引用

页码：865 / 869

页数：5

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