Association Between a Germline OCA2 Polymorphism at Chromosome 15q13.1 and Estrogen Receptor-Negative Breast Cancer Survival

被引：43

作者：

Azzato, Elizabeth M. ^{[1
,2
]}

Tyrer, Jonathan ^{[1
]}

Fasching, Peter A. ^{[3
,6
]}

Beckmann, Matthias W. ^{[3
]}

Ekici, Arif B. ^{[5
]}

Schulz-Wendtland, Ruediger ^{[4
]}

Bojesen, Stig E. ^{[7
,8
,9
]}

Nordestgaard, Borge G. ^{[7
,8
,9
]}

Flyger, Henrik ^{[7
,8
,9
]}

Milne, Roger L. ^{[10
]}

Arias, Jose Ignacio ^{[12
]}

Menendez, Primitiva ^{[13
]}

Benitez, Javier ^{[11
]}

Chang-Claude, Jenny ^{[14
]}

Hein, Rebecca ^{[14
]}

Wang-Gohrke, Shan ^{[15
]}

Nevanlinna, Heli ^{[16
]}

Heikkinen, Tuomas ^{[16
]}

Aittomaki, Kristiina ^{[17
]}

Blomqvist, Carl ^{[18
]}

Margolin, Sara ^{[19
]}

Mannermaa, Arto ^{[19
,20
,21
,22
]}

Kosma, Veli-Matti ^{[20
,21
,22
]}

Kataja, Vesa ^{[20
,22
]}

Beesley, Jonathan ^{[24
]}

Chen, Xiaoqing ^{[24
]}

Chenevix-Trench, Georgia ^{[24
]}

Couch, Fergus J. ^{[25
,26
]}

Olson, Janet E. ^{[26
]}

Fredericksen, Zachary S. ^{[26
]}

Wang, Xianshu ^{[25
]}

Giles, Graham G. ^{[27
]}

Severi, Gianluca ^{[27
]}

Baglietto, Laura ^{[27
]}

Southey, Melissa C. ^{[28
]}

Devilee, Peter ^{[29
,30
]}

Tollenaar, Rob A. E. M. ^{[31
]}

Seynaeve, Caroline ^{[32
]}

Garcia-Closas, Montserrat ^{[33
]}

Lissowska, Jolanta ^{[34
,35
]}

Sherman, Mark E. ^{[33
]}

Bolton, Kelly L. ^{[33
]}

Hall, Per ^{[36
]}

Czene, Kamila ^{[36
]}

Cox, Angela ^{[37
]}

Brock, Ian W. ^{[37
]}

Elliott, Graeme C. ^{[37
]}

Reed, Malcolm W. R. ^{[38
]}

Greenberg, David ^{[39
]}

Anton-Culver, Hoda ^{[40
]}

机构：

[1] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cambridge, England

[2] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[3] Univ Breast Ctr, Bavarian Breast Canc Cases & Controls BBCC, Erlangen, Germany

[4] Univ Hosp Erlangen, Inst Diagnost Radiol, BBCC, Erlangen, Germany

[5] Univ Erlangen Nurnberg, Inst Human Genet, BBCC, D-8520 Erlangen, Germany

[6] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, BBCC, Los Angeles, CA 90095 USA

[7] Univ Copenhagen, Herlev Univ Hosp, Copenhagen Breast Canc Study, Copenhagen, Denmark

[8] Univ Copenhagen, Herlev Univ Hosp, CGPS, Dept Clin Biochem, Copenhagen, Denmark

[9] Univ Copenhagen, Herlev Univ Hosp, CGPS, Dept Breast Surg, Copenhagen, Denmark

[10] Spanish Natl Canc Ctr, Breast Canc Study CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain

[11] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, CNIO BCS, Madrid, Spain

[12] Hosp Monte Naranco, CNIO BCS, Oviedo, Spain

[13] HUCA Oviedo, CNIO BCS, Oviedo, Spain

[14] German Canc Res Ctr, Div Canc Epidemiol, Genet Epidemiol Study Breast Canc Age GESBC 50, D-6900 Heidelberg, Germany

[15] Univ Ulm, Dept Obstet & Gynecol, GESBC, Ulm, Germany

[16] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki Breast Canc Study HEBCS, FIN-00290 Helsinki, Finland

[17] Univ Helsinki, Cent Hosp, Dept Clin Genet, HEBCS, FIN-00290 Helsinki, Finland

[18] Univ Helsinki, Cent Hosp, Dept Oncol, HEBCS, FIN-00290 Helsinki, Finland

[19] Karolinska Inst, Dept Pathol & Oncol, Karolinska Breast Canc Study KARBAC, Stockholm, Sweden

[20] Univ Kuopio, Inst Clin Med Pathol & Forens Med, Kuopio Breast Canc Project, FIN-70211 Kuopio, Finland

[21] Kuopio Univ Hosp, Dept Pathol, KBCP, SF-70210 Kuopio, Finland

[22] Kuopio Univ Hosp, Dept Oncol, KBCP, SF-70210 Kuopio, Finland

[23] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[24] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[25] Mayo Clin, Dept Lab Med & Pathol, MCBCS, Rochester, MN USA

[26] Mayo Clin, Dept Hlth Sci Res, MCBCS, Rochester, MN USA

[27] Canc Council Victoria, Canc Epidemiol Ctr, MCCS, Melbourne, Vic, Australia

[28] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, MCCS, Melbourne, Vic, Australia

[29] Leiden Univ, Med Ctr, Breast Canc Study ORIGO, Dept Human Genet, Leiden, Netherlands

[30] Leiden Univ, Med Ctr, ORIGO, Dept Pathol, Leiden, Netherlands

[31] Leiden Univ, Med Ctr, Dept Surg Oncol, ORIGO, Leiden, Netherlands

[32] Erasmus MC Daniel den Hoed Canc Ctr, Rotterdam Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands

[33] NCI, PBCS, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA

[34] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, PBCS, Warsaw, Poland

[35] Inst Oncol, Warsaw, Poland

[36] Karolinska Inst, Dept Med Epidemiol & Biostat, Singapore & Swedish Breast Canc Study SASBAC, Stockholm, Sweden

[37] Univ Sheffield, Dept Oncol, Inst Canc Studies, SBCS, Sheffield, S Yorkshire, England

[38] Univ Sheffield, Acad Unit Surg Oncol, SBCS, Sheffield, S Yorkshire, England

[39] Eastern Canc Registrat & Informat Ctr, Unit Magog Court C, Cambridge, England

[40] Univ Calif Irvine, Dept Epidemiol, UCIBCS, Irvine, CA USA

[41] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Canc Res UK Genet Epidemiol Unit, Cambridge, England

来源：

JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2010年 / 102卷 / 09期

基金：

美国国家卫生研究院; 英国医学研究理事会; 芬兰科学院;

关键词：

SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; GENETIC-VARIATION; OVARIAN-CANCER; TUMOR CHARACTERISTICS; COMMON POLYMORPHISMS; BRCA1; MUTATIONS; REPAIR GENES; RISK; POPULATION;

D O I：

10.1093/jnci/djq057

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Traditional prognostic factors for survival and treatment response of patients with breast cancer do not fully account for observed survival variation. We used available genotype data from a previously conducted two-stage, breast cancer susceptibility genome-wide association study (ie, Studies of Epidemiology and Risk factors in Cancer Heredity [SEARCH]) to investigate associations between variation in germline DNA and overall survival. We evaluated possible associations between overall survival after a breast cancer diagnosis and 10 621 germline single-nucleotide polymorphisms (SNPs) from up to 3761 patients with invasive breast cancer (including 647 deaths and 26 978 person-years at risk) that were genotyped previously in the SEARCH study with high-density oligonucleotide microarrays (ie, hypothesis-generating set). Associations with all-cause mortality were assessed for each SNP by use of Cox regression analysis, generating a per rare allele hazard ratio (HR). To validate putative associations, we used patient genotype information that had been obtained with 5' nuclease assay or mass spectrometry and overall survival information for up to 14 096 patients with invasive breast cancer (including 2303 deaths and 70 019 person-years at risk) from 15 international case-control studies (ie, validation set). Fixed-effects meta-analysis was used to generate an overall effect estimate in the validation dataset and in combined SEARCH and validation datasets. All statistical tests were two-sided. In the hypothesis-generating dataset, SNP rs4778137 (C > G) of the OCA2 gene at 15q13.1 was statistically significantly associated with overall survival among patients with estrogen receptor-negative tumors, with the rare G allele being associated with increased overall survival (HR of death per rare allele carried = 0.56, 95% confidence interval [CI] = 0.41 to 0.75, P = 9.2 x 10(-5)). This association was also observed in the validation dataset (HR of death per rare allele carried = 0.88, 95% CI = 0.78 to 0.99, P = .03) and in the combined dataset (HR of death per rare allele carried = 0.82, 95% CI = 0.73 to 0.92, P = 5 x 10(-4)). The rare G allele of the OCA2 polymorphism, rs4778137, may be associated with improved overall survival among patients with estrogen receptor-negative breast cancer.

引用

页码：650 / 662

页数：13

共 60 条

[21]

Goode EL, 2002, CANCER RES, V62, P3052

[22] A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation [J].

Han, Jiali ;

Kraft, Peter ;

Nan, Hongmei ;

Guo, Qun ;

Chen, Constance ;

Qureshi, Abrar ;

Hankinson, Susan E. ;

Hu, Frank B. ;

Duffy, David L. ;

Zhao, Zhen Zhen ;

Martin, Nicholas G. ;

Montgomery, Grant W. ;

Hayward, Nicholas K. ;

Thomas, Gilles ;

Hoover, Robert N. ;

Chanock, Stephen ;

Hunter, David J. .

PLOS GENETICS, 2008, 4 (05)

[23] Refinement of the 22q12-q13 breast cancer-associated region:: Evidence of TMPRSS6 as a candidate gene in an eastern Finnish population [J].

Hartikainen, JM ;

Tuhkanen, H ;

Kataja, V ;

Eskelinen, M ;

Uusitupa, M ;

Kosma, VM ;

Mannermaa, A .

CLINICAL CANCER RESEARCH, 2006, 12 (05) :1454-1462

[24]

Hartikainen JM, 2005, CANCER EPIDEM BIOMAR, V14, P75

[25] Is breast cancer prognosis inherited? [J].

Hartman, Mikael ;

Lindstom, Linda ;

Dickman, Paul W. ;

Adami, Hans-Olov ;

Hall, Per ;

Czene, Kamila .

BREAST CANCER RESEARCH, 2007, 9 (03)

[26] Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer [J].

Harvey, JM ;

Clark, GM ;

Osborne, CK ;

Allred, DC .

JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (05) :1474-1481

[27] Quantifying heterogeneity in a meta-analysis [J].

Higgins, JPT ;

Thompson, SG .

STATISTICS IN MEDICINE, 2002, 21 (11) :1539-1558

[28]

Hsieh S M, 2006, Breast Dis, V26, P157

[29] Matrix metalloproteinase single-nucleotide polymorphisms and haplotypes predict breast cancer progression [J].

Hughes, Simon ;

Agbaje, Olorunsola ;

Bowen, Rebecca L. ;

Holliday, Deborah L. ;

Shaw, Jacqueline A. ;

Duffy, Stephen ;

Jones, J. Louise .

CLINICAL CANCER RESEARCH, 2007, 13 (22) :6673-6680

[30] Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases [J].

Huijts, Petra E. A. ;

Vreeswijk, Maaike P. G. ;

Kroeze-Jansema, Karin H. G. ;

Jacobi, Catharina E. ;

Seynaeve, Caroline ;

Krol-Warmerdam, Elly M. M. ;

Wijers-Koster, Pauline M. ;

Blom, Jannet C. ;

Pooley, Karen A. ;

Klijn, Jan G. M. ;

Tollenaar, Rob A. E. M. ;

Devilee, Peter ;

van Asperen, Christi J. .

BREAST CANCER RESEARCH, 2007, 9 (06)

← 1 2 3 4 5 6 →