Association of breast cancer risk loci with breast cancer survival

被引：28

作者：

Barrdahl, Myrto ^{[1
]}

Canzian, Federico ^{[2
]}

Lindstroem, Sara ^{[3
]}

Shui, Irene ^{[4
]}

Black, Amanda ^{[5
]}

Hoover, Robert N. ^{[5
]}

Ziegler, Regina G. ^{[5
]}

Buring, Julie E. ^{[6
,7
,8
,9
,10
]}

Chanock, Stephen J. ^{[5
,11
]}

Diver, W. Ryan ^{[12
]}

Gapstur, Susan M. ^{[12
,17
]}

Gaudet, Mia M. ^{[12
]}

Giles, Graham G. ^{[13
,14
]}

Haiman, Christopher ^{[15
]}

Henderson, Brian E. ^{[15
]}

Hankinson, Susan ^{[4
,16
]}

Hunter, David J. ^{[3
]}

Joshi, Amit D. ^{[4
]}

Kraft, Peter ^{[4
]}

Lee, I-Min ^{[4
,18
]}

Le Marchand, Loic ^{[19
]}

Milne, Roger L. ^{[13
,14
]}

Southey, Melissa C. ^{[20
]}

Willett, Walter ^{[21
]}

Gunter, Marc ^{[22
]}

Panico, Salvatore ^{[23
]}

Sund, Malin ^{[24
]}

Weiderpass, Elisabete ^{[25
,26
,27
,28
]}

Sanchez, Maria-Jose ^{[29
,30
]}

Overvad, Kim ^{[31
]}

Dossus, Laure ^{[32
,33
,34
]}

Peeters, Petra H. ^{[35
,36
]}

Khaw, Kay-Tee ^{[37
]}

Trichopoulos, Dimitrios ^{[4
,38
,39
]}

Kaaks, Rudolf ^{[1
]}

Campa, Daniele ^{[1
]}

机构：

[1] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany

[2] German Canc Res Ctr, Genom Epidemiol Grp, D-69120 Heidelberg, Germany

[3] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA

[4] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[5] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[6] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA

[7] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA

[8] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA

[9] Harvard Univ, Sch Med, Boston, MA 02115 USA

[10] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[11] Core Genotyping Facil Frederick Natl Lab Canc Res, Gaithersburg, MD USA

[12] Amer Canc Soc, Epidemiol Res Program, NW Atlanta, GA USA

[13] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia

[14] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia

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

[16] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Epidemiol, Amherst, MA 01003 USA

[17] Brigham & Womens Hosp, Canc Res Ctr, Boston, MA 02115 USA

[18] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[19] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96822 USA

[20] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia

[21] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[22] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol Biostat, London, England

[23] Dipartimento Med Clin E Chirurgia, Naples, Italy

[24] Umea Univ, Dept Surg & Perioperat Sci, S-90187 Umea, Sweden

[25] Univ Tromso, Fac Hlth Sci, Dept Community Med, N-9001 Tromso, Norway

[26] Canc Registry Norway, Dept Res, Oslo, Norway

[27] Karolinska Inst, Dept Med Epidemiol & Biostat, Solna, Sweden

[28] Samfundet Folkhalsan, Helsinki, Finland

[29] Univ Granada, Hosp Univ Granada, Escuela Andaluza Salud Publ, Inst Invest Biosanitaria Ibs Granada, E-18071 Granada, Spain

[30] CIBERESP, Barcelona, Spain

[31] Aarhus Univ, Dept Publ Hlth, Epidemiol Sect, DK-8000 Aarhus C, Denmark

[32] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, Nutr Hormones & Womens Hlth Team, U1018, Villejuif, France

[33] Univ Paris 11, UMRS 1018, Villejuif, France

[34] IGR, Villejuif, France

[35] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands

[36] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England

[37] Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England

[38] Acad Athens, Bur Epidemiol Res, Athens, Greece

[39] Hellen Hlth Fdn, Athens, Greece

来源：

INTERNATIONAL JOURNAL OF CANCER | 2015年 / 137卷 / 12期

基金：

美国国家卫生研究院;

关键词：

breast cancer; SNP; survival; BPC3; meta-analysis; GENOME-WIDE ASSOCIATION; MAMMOGRAPHIC DENSITY; SUSCEPTIBILITY LOCI; COMMON VARIANTS; CONFER SUSCEPTIBILITY; GENETIC-VARIANTS; IDENTIFIES; POLYMORPHISM; COHORT; P57(KIP2);

D O I：

10.1002/ijc.29446

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele=0.70; 95% CI: 0.58-0.85; p(trend)=2.84 x 10(-4); HRheterozygotes=0.71; 95% CI: 0.55-0.92; HRhomozygotes=0.48; 95% CI: 0.31-0.76; p(2DF)=1.45 x 10(-3)). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; p(trend)=6.6 x 10(-4); HRheterozygotes=0.96 95% CI: 0.90-1.03; HRhomozygotes=1.21; 95% CI: 1.09-1.35; p(2DF)=1.25 x 10(-4)). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662. What's new? Genetic factors are known to influence the risk of breast cancer, but inherited genetic variation may also affect disease prognosis and response to treatment. In this study, the we investigated whether single nucleotide polymorphisms (SNPs) that are known to be associated with breast cancer risk might also influence the survival of breast-cancer patients. While two of the investigated SNPs may influence survival, there was otherwise no indication that SNP alleles related to breast cancer risk also play a role in the survival of breast cancer patients.

引用

页码：2837 / 2845

页数：9

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