Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Causes & Control
Published in: Cancer Causes & Control 3/2014

01-03-2014 | Original Paper

The influence of genetic ancestry and ethnicity on breast cancer survival associated with genetic variation in the TGF-β-signaling pathway: The Breast Cancer Health Disparities Study

Authors: Martha L. Slattery, Abbie Lundgreen, Marianna C. Stern, Lisa Hines, Roger K. Wolff, Anna R. Giuliano, Kathy B. Baumgartner, Esther M. John

Published in: Cancer Causes & Control | Issue 3/2014

Login to get access

Abstract

The TGF-β signaling pathway regulates cellular proliferation and differentiation. We evaluated genetic variation in this pathway, its association with breast cancer survival, and survival differences by genetic ancestry and self-reported ethnicity. The Breast Cancer Health Disparities Study includes participants from the 4-Corners Breast Cancer Study (n = 1,391 cases) and the San Francisco Bay Area Breast Cancer Study (n = 946 cases) who have been followed for survival. We evaluated 28 genes in the TGF-β signaling pathway using a tagSNP approach. Adaptive rank truncated product (ARTP) was used to test the gene and pathway significance by Native American (NA) ancestry and by self-reported ethnicity (non-Hispanic white (NHW) and Hispanic/NA). Genetic variation in the TGF-β signaling pathway was associated with overall breast cancer survival (P ARTP = 0.05), especially for women with low NA ancestry (P ARTP = 0.007) and NHW women (P ARTP = 0.006). BMP2, BMP4, RUNX1, and TGFBR3 were significantly associated with breast cancer survival overall (P ARTP = 0.04, 0.02, 0.002, and 0.04, respectively). Among women with low NA, ancestry associations were as follows: BMP4 (P ARTP = 0.007), BMP6 (P ARTP = 0.001), GDF10 (P ARTP = 0.05), RUNX1 (P ARTP = 0.002), SMAD1 (P ARTP = 0.05), and TGFBR2 (P ARTP = 0.02). A polygenic risk model showed that women with low NA ancestry and high numbers of at-risk alleles had twice the risk of dying from breast cancer as did women with high NA ancestry. Our data suggest that genetic variation in the TGF-β signaling pathway influences breast cancer survival. Associations were similar when the analyses were stratified by genetic ancestry or by self-reported ethnicity.
Appendix
Available only for authorised users
Literature
1.
Gordon KJ, Blobe GC (2008) Role of transforming growth factor-beta superfamily signaling pathways in human disease. Biochim Biophys Acta 1782(4):197–228PubMedCrossRef
2.
Wharton K, Derynck R (2009) TGFbeta family signaling: novel insights in development and disease. Development 136(22):3691–3697PubMedCrossRef
3.
4.
Blyth K, Cameron ER, Neil JC (2005) The RUNX genes: gain or loss of function in cancer. Nat Rev Cancer 5(5):376–387PubMedCrossRef
5.
Lee KS, Hong SH, Bae SC (2002) Both the Smad and p38 MAPK pathways play a crucial role in Runx2 expression following induction by transforming growth factor-beta and bone morphogenetic protein. Oncogene 21(47):7156–7163PubMedCrossRef
6.
Cameron ER, Blyth K, Hanlon L, Kilbey A, Mackay N, Stewart M, Terry A, Vaillant F, Wotton S, Neil JC (2003) The Runx genes as dominant oncogenes. Blood Cells Mol Dis 30(2):194–200PubMedCrossRef
7.
Ito Y, Osato M, Ito K (2003) RUNX and cancer. Ann Acad Med Singapore 32(5 Suppl):S6–S7PubMed
8.
de Kruijf EM, Dekker TJ, Hawinkels LJ, Putter H, Smit VT, Kroep JR, Kuppen PJ, van de Velde CJ, Ten Dijke P, Tollenaar RA et al (2013) The prognostic role of TGF-beta signaling pathway in breast cancer patients. Ann Oncol Off J Eur Soc Med Oncol ESMO 24(2):384–390CrossRef
9.
Desruisseau S, Palmari J, Giusti C, Romain S, Martin PM, Berthois Y (2006) Determination of TGFbeta1 protein level in human primary breast cancers and its relationship with survival. Br J Cancer 94(2):239–246PubMedCentralPubMedCrossRef
10.
Figueroa JD, Flanders KC, Garcia-Closas M, Anderson WF, Yang XR, Matsuno RK, Duggan MA, Pfeiffer RM, Ooshima A, Cornelison R et al (2010) Expression of TGF-beta signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics. Breast Cancer Res Treat 121(3):727–735PubMedCrossRef
11.
Jacobs EJ, Feigelson HS, Bain EB, Brady KA, Rodriguez C, Stevens VL, Patel AV, Thun MJ, Calle EE (2006) Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the cancer prevention study II cohort. Breast Cancer Res BCR 8(2):R22CrossRef
12.
Schneider BP, Winer EP, Foulkes WD, Garber J, Perou CM, Richardson A, Sledge GW, Carey LA (2008) Triple-negative breast cancer: risk factors to potential targets. Clinical Cancer Res Off J Am Assoc Cancer Res 14(24):8010–8018CrossRef
13.
Kesler KA, Rieger KM, Hammoud ZT, Kruter LE, Perkins SM, Turrentine MW, Schneider BP, Einhorn LH, Brown JW (2008) A 25-year single institution experience with surgery for primary mediastinal nonseminomatous germ cell tumors. Ann Thorac Surg 85(2):371–378PubMedCrossRef
14.
Slattery ML, John EM, Torres-Mejia G, Lundgreen A, Herrick JS, Baumgartner KB, Hines LM, Stern MC, Wolff RK (2012) Genetic variation in genes involved in hormones, inflammation and energetic factors and breast cancer risk in an admixed population. Carcinogenesis 33(8):1512–1521PubMedCrossRef
15.
Swan J, Edwards BK (2003) Cancer rates among American Indians and Alaska Natives: is there a national perspective. Cancer 98(6):1262–1272PubMedCrossRef
16.
Gilliland FD, Hunt WC, Baumgartner KB, Crumley D, Nicholson CS, Fetherolf J, Samet JM (1998) Reproductive risk factors for breast cancer in Hispanic and non-Hispanic white women: the New Mexico Women’s Health Study. Am J Epidemiol 148(7):683–692PubMedCrossRef
17.
Slattery ML, Sweeney C, Edwards S, Herrick J, Baumgartner K, Wolff R, Murtaugh M, Baumgartner R, Giuliano A, Byers T (2007) Body size, weight change, fat distribution and breast cancer risk in Hispanic and non-Hispanic white women. Breast Cancer Res Treat 102(1):85–101PubMedCrossRef
18.
John EM, Horn-Ross PL, Koo J (2003) Lifetime physical activity and breast cancer risk in a multiethnic population: the San Francisco Bay area breast cancer study. Cancer Epidemiol Biomark Prev 12(11 Pt 1):1143–1152
19.
John EM, Phipps AI, Davis A, Koo J (2005) Migration history, acculturation, and breast cancer risk in Hispanic women. Cancer Epidemiol Biomark Prev 14(12):2905–2913CrossRef
20.
Falush D, Stephens M, Pritchard JK (2003) Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 164(4):1567–1587PubMed
21.
Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155(2):945–959PubMed
22.
Yu K, Li Q, Bergen AW, Pfeiffer RM, Rosenberg PS, Caporaso N, Kraft P, Chatterjee N (2009) Pathway analysis by adaptive combination of P-values. Genet Epidemiol 33(8):700–709PubMedCentralPubMedCrossRef
23.
Kai Yu OL (2011) William Wheeler: ARTP gene and pathway p-values computed using the adaptive rank truncated product. In., 2.0.0 edn; R package
24.
Ye L, Bokobza SM, Jiang WG (2009) Bone morphogenetic proteins in development and progression of breast cancer and therapeutic potential (review). Int J Mol Med 24(5):591–597PubMedCrossRef
25.
Ye L, Lewis-Russell JM, Kyanaston HG, Jiang WG (2007) Bone morphogenetic proteins and their receptor signaling in prostate cancer. Histol Histopathol 22(10):1129–1147PubMed
26.
27.
Clement JH, Raida M, Sanger J, Bicknell R, Liu J, Naumann A, Geyer A, Waldau A, Hortschansky P, Schmidt A et al (2005) Bone morphogenetic protein 2 (BMP-2) induces in vitro invasion and in vivo hormone independent growth of breast carcinoma cells. Int J Oncol 27(2):401–407PubMed
28.
Alarmo EL, Parssinen J, Ketolainen JM, Savinainen K, Karhu R, Kallioniemi A (2009) BMP7 influences proliferation, migration, and invasion of breast cancer cells. Cancer Lett 275(1):35–43PubMedCrossRef
29.
Katsuno Y, Hanyu A, Kanda H, Ishikawa Y, Akiyama F, Iwase T, Ogata E, Ehata S, Miyazono K, Imamura T (2008) Bone morphogenetic protein signaling enhances invasion and bone metastasis of breast cancer cells through Smad pathway. Oncogene 27(49):6322–6333PubMedCrossRef
30.
Bokobza SM, Ye L, Kynaston HE, Mansel RE, Jiang WG (2009) Reduced expression of BMPR-IB correlates with poor prognosis and increased proliferation of breast cancer cells. Cancer Genomics Proteomics 6(2):101–108PubMed
31.
Alarmo EL, Kallioniemi A (2010) Bone morphogenetic proteins in breast cancer: dual role in tumourigenesis? Endocr Relat Cancer 17(2):R123–R139PubMedCrossRef
32.
Tandon M, Gokul K, Ali SA, Chen Z, Lian J, Stein GS, Pratap J (2012) Runx2 mediates epigenetic silencing of the bone morphogenetic protein-3B (BMP-3B/GDF10) in lung cancer cells. Mol Cancer 11:27PubMedCentralPubMedCrossRef
33.
Takahashi M, Otsuka F, Miyoshi T, Otani H, Goto J, Yamashita M, Ogura T, Makino H, Doihara H (2008) Bone morphogenetic protein 6 (BMP6) and BMP7 inhibit estrogen-induced proliferation of breast cancer cells by suppressing p38 mitogen-activated protein kinase activation. J Endocrinol 199(3):445–455PubMedCrossRef
34.
Zhang M, Yan JD, Zhang L, Wang Q, Lu SJ, Zhang J, Zhu TH (2005) Activation of bone morphogenetic protein-6 gene transcription in MCF-7 cells by estrogen. Chin Med J 118(19):1629–1636PubMed
35.
Du J, Yang S, Wang Z, Zhai C, Yuan W, Lei R, Zhang J, Zhu T (2008) Bone morphogenetic protein 6 inhibit stress-induced breast cancer cells apoptosis via both Smad and p38 pathways. J Cell Biochem 103(5):1584–1597PubMedCrossRef
36.
37.
Pratap J, Lian JB, Javed A, Barnes GL, van Wijnen AJ, Stein JL, Stein GS (2006) Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone. Cancer Metastasis Rev 25(4):589–600PubMedCrossRef
38.
Mendoza-Villanueva D, Deng W, Lopez-Camacho C, Shore P (2010) The Runx transcriptional co-activator, CBFbeta, is essential for invasion of breast cancer cells. Mol Cancer 9:171
39.
Subramaniam MM, Chan JY, Soong R, Ito K, Ito Y, Yeoh KG, Salto-Tellez M, Putti TC (2009) RUNX3 inactivation by frequent promoter hypermethylation and protein mislocalization constitute an early event in breast cancer progression. Breast Cancer Res Treat 113(1):113–121PubMedCrossRef
40.
Stender JD, Kim K, Charn TH, Komm B, Chang KC, Kraus WL, Benner C, Glass CK, Katzenellenbogen BS (2010) Genome-wide analysis of estrogen receptor alpha DNA binding and tethering mechanisms identifies Runx1 as a novel tethering factor in receptor-mediated transcriptional activation. Mol Cell Biol 30(16):3943–3955PubMedCentralPubMedCrossRef
41.
Ellis MJ, Ding L, Shen D, Luo J, Suman VJ, Wallis JW, Van Tine BA, Hoog J, Goiffon RJ, Goldstein TC et al (2012) Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature 486(7403):353–360PubMedCentralPubMed
42.
Buck MB, Fritz P, Dippon J, Zugmaier G, Knabbe C (2004) Prognostic significance of transforming growth factor beta receptor II in estrogen receptor-negative breast cancer patients. Clinical Cancer Res Off J Am Assoc Cancer Res 10(2):491–498CrossRef
43.
Koumoundourou D, Kassimatis T, Zolota V, Tzorakoeleftherakis E, Ravazoula P, Vassiliou V, Kardamakis D, Varakis J (2007) Prognostic significance of TGFbeta-1 and pSmad2/3 in breast cancer patients with T1–2, N0 tumours. Anticancer Res 27(4C):2613–2620PubMed
44.
Ivanovic V, Demajo M, Krtolica K, Krajnovic M, Konstantinovic M, Baltic V, Prtenjak G, Stojiljkovic B, Breberina M, Neskovic-Konstantinovic Z et al (2006) Elevated plasma TGF-beta1 levels correlate with decreased survival of metastatic breast cancer patients. Clinica Chimica Acta Int J Clin Chem 371(1–2):191–193CrossRef
45.
Mu L, Katsaros D, Lu L, Preti M, Durando A, Arisio R, Yu H (2008) TGF-beta1 genotype and phenotype in breast cancer and their associations with IGFs and patient survival. Br J Cancer 99(8):1357–1363PubMedCentralPubMedCrossRef
46.
Zheng W (2009) Genetic polymorphisms in the transforming growth factor-beta signaling pathways and breast cancer risk and survival. Methods Mol Biol 472:265–277PubMedCrossRef
Metadata
Title
The influence of genetic ancestry and ethnicity on breast cancer survival associated with genetic variation in the TGF-β-signaling pathway: The Breast Cancer Health Disparities Study
Authors
Martha L. Slattery
Abbie Lundgreen
Marianna C. Stern
Lisa Hines
Roger K. Wolff
Anna R. Giuliano
Kathy B. Baumgartner
Esther M. John
Publication date
01-03-2014
Publisher
Springer International Publishing
Published in
Cancer Causes & Control / Issue 3/2014
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-013-0331-9

Other articles of this Issue 3/2014

Cancer Causes & Control 3/2014 Go to the issue

Original paper

Association between endogenous sex steroid hormones and insulin-like growth factor proteins in US men

Letter to the Editor

Reply to comments by Dr. Frisch and Dr. Van Howe

Original paper

A collaborative study of the etiology of breast cancer subtypes in African American women: the AMBER consortium

Original paper

Exposure to household painting and floor treatments, and parental occupational paint exposure and risk of childhood brain tumors: results from an Australian case–control study

Original paper

Fasting insulin and endogenous hormones in relation to premenopausal breast density (Canada)

Original paper

Type 2 diabetes and the risk of mortality among patients with prostate cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits