Breast Cancer Susceptibility and Tumor Characteristics

Breast cancer is the most frequent cancer in women. Therefore it is of certain interest to elucidate risk factors and improve breast cancer prevention. Recent efforts showed that sporadic breast cancer is a polygenic disease and several relevant polymorphisms in FGFR2, COX8, TNRC9, MAP3K1, LSP1, PTEN, CHEK2 have been identified so far. We were involved in the validation of some of these factors and our ongoing projects aim to further clarify the role of genetic and epigenetic risk factors to understand the molecular basis of breast carcinogenesis and may be improve cancer screening strategies. In addition to genetic variations epidemiological and life style factors are suspected to impact breast cancer risk. At this postmenopausal hormone replacement therapy in particular long-term use or combined estrogen-progestagen therapy are supposed to be crucial. Our investigations showed that the carcinogenic effect of exogenous steroid hormones may be interfered by constitutional genetic polymorphisms. Accordingly the identification of polymorphisms affecting the individual risk of postmenopausal women may be facilitate the decision in favour or against the use of hormone replacement therapy in the future. Beside the identification of risk factors in general it is of particular interest to understand the risk for certain types of mamma carcinoma. It is of note that breast tumors are highly diverse in histological and clinical features and these factors are essential for prognosis and prediction. Therefore we aim to find genetic and epigenetic variations that affect tumor characteristics to support therapy decision and improve event free survival of breast cancer patients.

Major Projects

Breast cancer susceptibility
Characteristics of mamma carcinoma
Identification of potential drug targets
Prognosis and prediction
Genomics and epigenomics

PD Dr.rer.nat. Christina Justenhoven

phone: ++49-711-8101 5765

christina.justenhoven@ikp-stuttgart.de

Selected References

Yang XR, Chang-Claude J, Goode EL, Couch FJ, Nevanlinna H, Milne RL, Gaudet M, Schmidt MK, Broeks A, Cox A, Fasching PA, Hein R, Spurdle AB, Blows F, Driver K, Flesch-Janys D, Heinz J, Sinn P, Vrieling A, Heikkinen T, Aittomäki K, Heikkilä P, Blomqvist C, Lissowska J, Peplonska B, Chanock S, Figueroa J, Brinton L, Hall P, Czene K, Humphreys K, Darabi H, Liu J, Van 't Veer LJ, van Leeuwen FE, Andrulis IL, Glendon G, Knight JA, Mulligan AM, O'Malley FP, Weerasooriya N, John EM, Beckmann MW, Hartmann A, Weihbrecht SB, Wachter DL, Jud SM, Loehberg CR, Baglietto L, English DR, Giles GG, McLean CA, Severi G, Lambrechts D, Vandorpe T, Weltens C, Paridaens R, Smeets A, Neven P, Wildiers H, Wang X, Olson JE, Cafourek V, Fredericksen Z, Kosel M, Vachon C, Cramp HE, Connley D, Cross SS, Balasubramanian SP, Reed MW, Dörk T, Bremer M, Meyer A, Karstens JH, Ay A, Park-Simon TW, Hillemanns P, Arias Pérez JI, Menéndez Rodríguez P, Zamora P, Benítez J, Ko YD, Fischer HP, Hamann U, Pesch B, Brüning T, Justenhoven C, Brauch H, Eccles DM, Tapper WJ, Gerty SM, Sawyer EJ, Tomlinson IP, Jones A, Kerin M, Miller N, McInerney N, Anton-Culver H, Ziogas A, Shen CY, Hsiung CN, Wu PE, Yang SL, Yu JC, Chen ST, Hsu GC, Haiman CA, Henderson BE, Le Marchand L, Kolonel LN, Lindblom A, Margolin S, Jakubowska A, Lubiński J, Huzarski T, Byrski T, Górski B, Gronwald J, Hooning MJ, Hollestelle A, van den Ouweland AM, Jager A, Kriege M, Tilanus-Linthorst MM, Collée M, Wang-Gohrke S, Pylkäs K, Jukkola-Vuorinen A, Mononen K, Grip M, Hirvikoski P, Winqvist R, Mannermaa A, Kosma VM, Kauppinen J, Kataja V, Auvinen P, Soini Y, Sironen R, Bojesen SE, Ørsted DD, Kaur-Knudsen D, Flyger H, Nordestgaard BG, Holland H, Chenevix-Trench G, Manoukian S, Barile M, Radice P, Hankinson SE, Hunter DJ, Tamimi R, Sangrajrang S, Brennan P, McKay J, Odefrey F, Gaborieau V, Devilee P, Huijts PE, Tollenaar RA, Seynaeve C, Dite GS, Apicella C, Hopper JL, Hammet F, Tsimiklis H, Smith LD, Southey MC, Humphreys MK, Easton D, Pharoah P, Sherman ME, Garcia-Closas M. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst. 2011, 103(3):250-63
Justenhoven C, Obazee O, Winter S, Couch FJ, Olson JE, Hall P, Hannelius U, Li J, Humphreys K, Severi G, Giles G, Southey M, Baglietto L, Fasching PA, Beckmann MW, Ekici AB, Hamann U, Baisch C, Harth V, Rabstein S, Lotz A, Pesch B, Brüning T, Ko YD, Brauch H. The postmenopausal hormone replacement therapy-related breast cancer risk is decreased in women carrying the CYP2C19*17 variant. Breast Cancer Res Treat. 2011 Oct 26. [Epub ahead of print]

Justenhoven C, Winter S, Hamann U, Haas S, Fischer HP, Pesch B, Brüning T, Ko YD, Brauch H; GENICA Network. The frameshift polymorphism CYP3A43_74_delA is associated with poor differentiation of breast tumors. Cancer. 2010, 116(23):5358-64 (FREE ARTICLE)

The MARIE-GENICA Consortium on Genetic Susceptibility for Menopausal Hormone Therapy Related Breast Cancer Risk. Genetic Polymorphisms in Phase I and Phase II Enzymes and Breast Cancer Risk Associated with Menopausal Hormone Therapy in Postmenopausal Woman. Breast Cancer Res Treat. 2010, 119(2): 463-474
C Justenhoven, U Hamann CB Pierl, C Baisch, V Harth, S Rabstein, A Spickenheuer, B Pesch, T Bruning, S Winter, YD Ko, H Brauch. CYP2C19*17 is Associated with Decreased Breast Cancer Risk. Breast Cancer Res Treat. 2009, 115(2): 391-396
C Justenhoven, CB Pierl, S Haas, HP Fischer, C Baisch, U Hamann, V Harth, B Pesch, T Bruning, C Vollmert, T Illig, J Dippon, YD Ko, H Brauch. Polymorphic loci of E2F2, CCND1 and CCND3 are associated with HER2 status of breast tumors. Int J Cancer. 2009, 124(9): 2077-2081

M Garcia-Closas, P Hall, H Nevanlinna, K Pooley, J Morrison, D Richesson, SE Bojesen, BG Nordestgaard, CK Axelsson, JI Arias, RL Milne, G Ribas, A Gonzalez-Neira, J Benitez, P Zamora, H Brauch, C Justenhoven, U Hamann, YD Ko, T Bruning, S Haas, T Dork, P Schurmann, P Hillemanns, N Bogdanova, M Bremer, JH Karstens, R Fagerholm, K Aaltonen, K Aittomaki, K v Smitten, C Blomqvist, A Mannermaa, M Uusitupa, M Eskelinen, M Tengstrom, VM Kosma, V Kataja, G Chenevix-Trench, AB Spurdle, J Beesley, X Chen, Australian Ovarian Cancer Management Group, The Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, P Devilee, CJ v Asperen, CE Jacobi, RAEM Tollenaar, P Huijts, J Klijn, J Chang-Claude, S Kropp, T Slanger, D Flesch-Janys, E Mutschelknauss, R Salazar, F Couch, EL Goode, JE Olson, C Vachon, ZS Fredericksen, GG Giles, L Baglietto, G Severi, JL Hopper, DR English, MC Southey, CA Haiman, BE Henderson, LN Kolonel, L LeMarchand, DO Stram, DJ Hunter, SE Hankinson, DG Cox, R Tamimi, P Kraft, M Sherman, S Chanock, J Lissowska, L Brinton, B Peplonska, J Liu, LY Lin, L Yuqing, K Humphreys, K Czene, A Cox, SP Balasubramanian, SS Cross, MWR Reed, F Blows, K Driver, A Dunning, BAJ Ponder, S Sangrajrang, P Brennan, J McKay, F Odefrey, V Gabrieau, A Sigurdson, M Doody, J Struewing, B Alexander, DF Easton, P Pharoah. Heterogeneity of Breast Cancer Associations with Five Susceptibility Loci by Clinical and Pathological Characteristics. PLoS Genetics. 2008, 4(4): e1000054 (FREE ARTICLE)

C Justenhoven, CB Pierl, S Haas, HP Fischer, C Baisch, U Hamann, V Harth, B Pesch, T Bruning, C Vollmert, T Illig, J Dippon, YD Ko, H Brauch. The CYP1B1_1358_GG Genotype is Associated with Estrogen Receptor-Negative Breast Cancer. Breast Cancer Res Treat. 2008, 111(1): 171-177
M Jaremko, C Justenhoven, W Schoth, BK Abraham, P Fritz, C Vollmert, T Illig, W Simon, M Schwab, H Brauch. A Polymorphism of the DNA Repair Enzyme XRCC1 is Associated with Treatment Prediction in Anthracycline and CMF-Based Chemotherapy of Patients with Primary Invasive Breast Cancer. Pharmacogenet and Genomics. 2007, 17(7): 529-538

DF Easton, KA Pooley, AM Dunning, PD Pharoah, D Thompson, DG Ballinger, JP Struewing, J Morrison, H Field, R Luben, N Wareham, S Ahmed, CS Healey, the Search collaborators, C Haiman, L Kolonel, B Henderson, L Le Marchand, P Brennan, S Sangrajrang, V Gaborieau, F Godfrey, CY Shen, PE Wu, HC Wang, D Eccles, DG Evans, O Fletcher, J Peto, N Johnson, MR Stratton, N Rahman, G Chenevix-Trench, SE Bojesen, BG Nordestgaard, CK Axelsson, M Garcia-Closas, L Brinton, S Chanock, J Lissowska, H Nevanlinna, R Fagerholm, H Eerola, D Kang, KY Yoo, DY Noh, SH Ahn, DJ Hunter, Hankinson SE, Cox DG, Hall P, Wedren S, Liu JJ, Low YL, Bogdanova N, Schurmann P, T Dork, RAEM Tollenaar, CE Jacobi, JGM Klijn, P Devilee, A Sigurdson, MM Doody, BH Alexander, J Zhang, A Cox, IW Brock, GM Pherson, MWR Read, F Couch, E Goode, J Olson, H Meijers-Hiejboer, A Unterlinden, R Milne, G Ribas, A Gonzalez, J Benitez, J Hopper, M McCredie, M Southey, G Giles, C Schroen, C Justenhoven, H Brauch, U Hamann, YD Ko, M Spurdle, J Beesley, X Chen, kConFab, AOCS Management Group, A Mannermaa, VM Kosma, V Kataja, J Hartikainen, NE Day, DR Cox, BAJ Ponder. Genome-Wide Association Study Identifies Novel Breast Cancer Susceptibility Loci. Nature. 2007, 447(7148): 1087-1093 (FREE ARTICLE)

Major Networks and Collaborations

GENICA: Gene Environment Interactions and Breast Cancer in Germany a collaboration of Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University Tübingen; Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn;Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum; Germany. The population-based study includes 1.143 breast cancer patients and 1.155 age-matched controls

The MARIE-GENICA Consortium on Genetic Susceptibility for Menopausal Hormone Therapy Related Breast Cancer Risk: A Collaboration of Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University Tübingen; Division of Cancer Epidemiology and Division ofMolecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn;Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum; Department of Medical Biometry and Epidemiology, Center for Experimental Medicine and Department of Gynecological Endocrinology and Reproductive Medicine, Center for Gynaecology, Obstetrics and Paediatrics, University Medical Center Hamburg-Eppendorf, Hamburg; Congenics AG, Hamburg; Germany. The joint project includes 3.155 postmenopausal breast cancer patients and 5.496 age-matched controls

BCAC: breast cancer association consortium, collaboration of more that 45 international breast cancer case control studies, including more than 66.000 cases and more that 77.000 controls

Curriculum Vitae Christina Justenhoven, PhD

Affiliation

Postdoctoral fellow at the Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart and University of Tübingen

Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
Auerbachstr. 112
D-70376 Stuttgart
phone: ++49-711-8101 5765
fax: ++49-711-859295
email: christina.justenhoven@ikp-stuttgart.de

Education and Professional Career

1990-1996	Study of biology, Free University of Berlin, Germany
1996	Diploma degree of biology, Free University of Berlin, Germany
1997-2000	PhD study at the German Institute of Human Nutrition Potsdam-Rehbrücke, Germany (head of the institute: Christian Barth, MD, Professor; section: Nutritional Toxicology, section head: Hansruedi Glatt, PhD, Professor)
2001	Doctoral degree of molecular biology, Faculty of Mathematics and Natural Sciencesof the University of Potsdam, Germany
since 2001	Postdoctoral fellow at the Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart (Susceptibility and Pharmacogenomic of Mammacarcinoma: Hiltrud Brauch, PhD, Professor)
2005	AACR-Women in Cancer Research Brigid G Leventhal Scholar Award in Cancer Research, 96th AACR Annual Meeting, Anaheim, CA, USA
2011	Habilitation, University of Tuebingen, Germany
2011	Wellcome Trust - Genome Medicine Poster Prize, Cold Spring Harbor Laboratories Conference: Pharmacogenomics and Personalized Medicine, 2011, Hinxton, UK

Professional Memberships

since 2000: GBM Gesellschaft für Biochemie und Molekularbiologie
since 2004: AACR American Association of Cancer Research, Associated Member
since 2004: AACR WICR Women in Cancer Research

Scientific Journal Editorial Board Memberships

since 2010: Review Editor of “Frontiers in Pharmacogenetics and Pharmacogenomics”