Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium

被引:39
作者
Canzian, Federico [1 ]
Cox, David G. [2 ,3 ,4 ]
Setiawan, V. Wendy [5 ]
Stram, Daniel O. [5 ]
Ziegler, Regina G. [6 ]
Dossus, Laure [1 ]
Beckmann, Lars [1 ]
Blanche, Helene [8 ]
Barricarte, Aurelio [9 ]
Berg, Christine D. [7 ]
Bingham, Sheila [10 ]
Buring, Julie [11 ,12 ]
Buys, Saundra S. [13 ]
Calle, Eugenia E. [14 ]
Chanock, Stephen J.
Clavel-Chapelon, Francoise [15 ]
DeLancey, John Oliver L. [14 ]
Diver, W. Ryan [14 ]
Dorronsoro, Miren [16 ]
Haiman, Christopher A. [5 ]
Hallmans, Goeran [17 ]
Hankinson, Susan E. [11 ,12 ]
Hunter, David J. [2 ]
Huesing, Anika [1 ]
Isaacs, Claudine [18 ]
Khaw, Kay-Tee [10 ]
Kolonel, Laurence N. [19 ]
Kraft, Peter [2 ]
Le Marchand, Loic [19 ]
Lund, Eiliv [20 ]
Overvad, Kim [21 ]
Panico, Salvatore [22 ]
Peeters, Petra H. M. [23 ]
Pollak, Michael [24 ]
Thun, Michael J. [14 ]
Tjonneland, Anne [25 ]
Trichopoulos, Dimitrios [26 ]
Tumino, Rosario [27 ]
Yeager, Meredith [28 ]
Hoover, Robert N.
Riboli, Elio [4 ]
Thomas, Gilles
Henderson, Brian E.
Kaaks, Rudolf [1 ]
Feigelson, Heather Spencer [13 ,29 ]
机构
[1] German Canc Res Ctr, D-69120 Heidelberg, Germany
[2] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA
[3] Ctr Leon Berard, INSERM U590, Lyon, France
[4] Imperial Coll, Fac Med, Sch Publ Hlth, London, England
[5] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA
[6] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA
[7] NCI, Canc Prevent Div, Bethesda, MD 20892 USA
[8] Fdn Jean Dausset CEPH, Biol Resource Ctr, Paris, France
[9] Publ Hlth Inst Navarra, Pamplona, Spain
[10] Univ Cambridge, Sch Clin Med, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England
[11] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA
[12] Harvard Univ, Sch Med, Boston, MA USA
[13] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA
[14] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA
[15] Inst Gustave Roussy, Villejuif, France
[16] Dept Publ Hlth Guipuzcoa, San Sebastian, Spain
[17] Umea Univ, Umea, Sweden
[18] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA
[19] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA
[20] Univ Tromso, Inst Community Med, Tromso, Norway
[21] Aarhus Univ Hosp, Aalborg, Denmark
[22] Univ Naples Federico II, Naples, Italy
[23] Univ Med Ctr, Julius Ctr, Utrecht, Netherlands
[24] McGill Univ, Dept Oncol, Montreal, PQ, Canada
[25] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark
[26] Acad Athens, Bur Epidemiol Res, Athens, Greece
[27] Civile MP Arezzo Hosp, Dept Oncol, Canc Regis & Histopathol Unit, Ragusa, Italy
[28] SAIC Frederick Inc, Core Genotyping Facil, Adv Technol Program, Frederick, MD USA
[29] Kaiser Permanente, Inst Hlth Res, Denver, CO USA
基金
美国国家卫生研究院;
关键词
GENOME-WIDE ASSOCIATION; BASE-LINE CHARACTERISTICS; ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; CIRCULATING LEVELS; IGF-I; MULTIETHNIC COHORT; BINDING-PROTEINS; DEHYDROEPIANDROSTERONE-SULFATE; CONFER SUSCEPTIBILITY;
D O I
10.1093/hmg/ddq291
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
There is extensive evidence that increases in blood and tissue concentrations of steroid hormones and of insulin-like growth factor I (IGF-I) are associated with breast cancer risk. However, studies of common variation in genes involved in steroid hormone and IGF-I metabolism have yet to provide convincing evidence that such variants predict breast cancer risk. The Breast and Prostate Cancer Cohort Consortium (BPC3) is a collaboration of large US and European cohorts. We genotyped 1416 tagging single nucleotide polymorphisms (SNPs) in 37 steroid hormone metabolism genes and 24 IGF-I pathway genes in 6292 cases of breast cancer and 8135 controls, mostly Caucasian, postmenopausal women from the BPC3. We also imputed 3921 additional SNPs in the regions of interest. None of the SNPs tested was significantly associated with breast cancer risk, after correction for multiple comparisons. The results remained null when cases and controls were stratified by age at diagnosis/recruitment, advanced or nonadvanced disease, body mass index, with or without in situ cases; or restricted to Caucasians. Among 770 estrogen receptor-negative cases, an SNP located 3' of growth hormone receptor (GHR) was marginally associated with increased risk after correction for multiple testing (P-trend = 1.5 x 10(-4)). We found no significant overall associations between breast cancer and common germline variation in 61 genes involved in steroid hormone and IGF-I metabolism in this large, comprehensive study. Although previous studies have shown that variations in these genes can influence endogenous hormone levels, the magnitude of the effect of single SNPs does not appear to be sufficient to alter breast cancer risk.
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收藏
页码:3873 / 3884
页数:12
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