A genome-wide association study yields five novel thyroid cancer risk loci

被引：123

作者：

Gudmundsson, Julius ^{[1
]}

Thorleifsson, Gudmar ^{[1
]}

Sigurdsson, Jon K. ^{[1
]}

Stefansdottir, Lilja ^{[1
]}

Jonasson, Jon G. ^{[2
,3
,4
]}

Gudjonsson, Sigurjon A. ^{[1
]}

Gudbjartsson, Daniel F. ^{[1
]}

Masson, Gisli ^{[1
]}

Johannsdottir, Hrefna ^{[1
]}

Halldorsson, Gisli H. ^{[1
]}

Stacey, Simon N. ^{[1
]}

Helgason, Hannes ^{[1
,5
]}

Sulem, Patrick ^{[1
]}

Senter, Leigha ^{[6
]}

He, Huiling ^{[7
]}

Liyanarachchi, Sandya ^{[7
]}

Ringel, Matthew D. ^{[8
]}

Aguillo, Esperanza ^{[9
]}

Panadero, Angeles ^{[10
]}

Prats, Enrique ^{[11
]}

Garcia-Castano, Almudena ^{[12
]}

De Juan, Ana ^{[12
]}

Rivera, Fernando ^{[12
]}

Xu, Li ^{[13
]}

Kiemeney, Lambertus A. ^{[14
]}

Eyjolfsson, Gudmundur I. ^{[15
]}

Sigurdardottir, Olof ^{[16
]}

Olafsson, Isleifur ^{[2
]}

Kristvinsson, Hoskuldur ^{[2
]}

Netea-Maier, Romana T. ^{[17
]}

Jonsson, Thorvaldur ^{[2
,3
]}

Mayordomo, Jose I. ^{[18
]}

Plantinga, Theo S. ^{[19
]}

Hjartarson, Hannes ^{[2
]}

Hrafnkelsson, Jon ^{[2
]}

Sturgis, Erich M. ^{[13
]}

Thorsteinsdottir, Unnur ^{[1
,3
]}

Rafnar, Thorunn ^{[1
]}

de la Chapelle, Albert ^{[7
]}

Stefansson, Kari ^{[1
,3
]}

机构：

[1] Amgen Inc, DeCODF Genet, IS-101 Reykjavik, Iceland

[2] Landspitali Univ Hosp, IS-101 Reykjavik, Iceland

[3] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland

[4] Iceland Canc Registry, IS-105 Reykjavik, Iceland

[5] Univ Iceland, Sch Engn & Nat Sci, IS-101 Reykjavik, Iceland

[6] Ohio State Univ, Ctr Comprehens Canc, Div Human Genet, Columbus, OH 43210 USA

[7] Ohio State Univ, Ctr Comprehens Canc, Dept Canc Biol & Genet, Columbus, OH 43210 USA

[8] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA

[9] Univ Hosp, Div Endocrinol, Zaragoza 50009, Spain

[10] Ciudad Coria Hosp, Div Med Oncol, Coria 10800, Spain

[11] Univ Hosp, Div Nucl Med, Zaragoza 50009, Spain

[12] Marques Valdecilla Univ Hosp, Div Med Oncol, Santander 39008, Spain

[13] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA

[14] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6500 HB Nijmegen, Netherlands

[15] Lab Mjodd, IS-109 Reykjavik, Iceland

[16] Akureyri Hosp, Dept Clin Biochem, IS-600 Akureyri, Iceland

[17] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Internal Med,Div Endocrinol, NL-6500 HB Nijmegen, Netherlands

[18] Univ Colorado Hosp, Aurora, CO 80045 USA

[19] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Pathol, NL-6500 HB Nijmegen, Netherlands

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

美国国家卫生研究院;

关键词：

SUSCEPTIBILITY LOCI; GENETIC-VARIANTS; COMMON VARIANTS; CARCINOMA; IDENTIFICATION; 9Q22.33; PROTEIN; FOXE1; DNA;

D O I：

10.1038/ncomms14517

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with P-combined <3 x 10(-8)): 1q42.2 (rs12129938 in PCNXL2), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10q24.33 (rs7902587 near OBFC1), and two independently associated variants at 15q22.33 (rs2289261 and rs56062135; both in SMAD3). We also confirm recently published association results from a Chinese study of a variant on 5p15.33 (rs2736100 near the TERT gene) and present a stronger association result for a moderately correlated variant (rs10069690; OR = 1.20, P = 3.2 x 10(-7)) based on our study of individuals of European ancestry. In combination, these results raise several opportunities for future studies of the pathogenesis of thyroid cancer.

引用

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