Vessela N. Kristensen

• Chen, Hongjie; Fan, Shaoqi; Stone, Jennifer; Thompson, Deborah J.; Douglas, Julie & Li, Shuai [Show all 56 contributors for this article] (2022). Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci. Breast Cancer Research. ISSN 1465-5411. 24(1). doi: 10.1186/s13058-022-01524-0.
• Mo, Torgeir; Brandal, Siri Helene Bertelsen; Kohn Luque, Alvaro; Engebråten, Olav; Kristensen, Vessela N. & Fleischer, Thomas [Show all 8 contributors for this article] (2022). Quantification of Tumor Hypoxia through Unsupervised Modelling of Consumption and Supply Hypoxia MR Imaging in Breast Cancer. Cancers. ISSN 2072-6694. 14(5). doi: 10.3390/cancers14051326.
• Normann, Lisa Svartdal; Haugen, Mads Haugland; Aure, Miriam Ragle; Kristensen, Vessela N.; Mælandsmo, Gunhild Mari & Sahlberg, Kristine Kleivi (2022). miR-101-5p Acts as a Tumor Suppressor in HER2-Positive Breast Cancer Cells and Improves Targeted Therapy. Breast Cancer: Targets and Therapy. ISSN 1179-1314. 14, p. 25–39. doi: 10.2147/BCTT.S338404.
• Mavaddat, Nasim; Dorling, Leila; Carvalho, Sara; Allen, Jamie; González-Neira, Anna & Keeman, Renske [Show all 94 contributors for this article] (2022). Pathology of tumors associated with pathogenic germline variants in 9 breast cancer susceptibility genes. JAMA Oncology. ISSN 2374-2437. 8(3). doi: 10.1001/jamaoncol.2021.6744.
• Dennis, Joe; Tyrer, Jonathan P.; Walker, Logan C.; Michailidou, Kyriaki; Dorling, Leila & Bolla, Manjeet K. [Show all 120 contributors for this article] (2022). Rare germline copy number variants (CNVs) and breast cancer risk. Communications Biology. ISSN 2399-3642. 5(1). doi: 10.1038/s42003-021-02990-6.
• Ahearn, Thomas U.; Zhang, Haoyu; Michailidou, Kyriaki; Milne, Roger L.; Bolla, Manjeet K. & Dennis, Joe [Show all 205 contributors for this article] (2022). Common variants in breast cancer risk loci predispose to distinct tumor subtypes. Breast Cancer Research. ISSN 1465-5411. 24(1). doi: 10.1186/s13058-021-01484-x.
• Lemma, Roza Berhanu; Fleischer, Thomas; Martinsen, Emily; Ledsaak, Marit; Kristensen, Vessela N. & Eskeland, Ragnhild [Show all 8 contributors for this article] (2022). Pioneer transcription factors are associated with the modulation of DNA methylation patterns across cancers. Epigenetics & Chromatin. ISSN 1756-8935. 15. doi: 10.1186/s13072-022-00444-9.
• Dorling, Leila; Carvalho, Sara; Allen, Jamie; González-Neira, Anna; Luccarini, Craig & Wahlström, Cecilia [Show all 176 contributors for this article] (2021). Breast cancer risk genes - Association analysis in more than 113,000 women. New England Journal of Medicine. ISSN 0028-4793. 384(5), p. 428–439. doi: 10.1056/NEJMoa1913948.
• Park, Hanla A.; Neumeyer, Sonja; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin & Kristensen, Vessela N. [Show all 50 contributors for this article] (2021). Mendelian randomisation study of smoking exposure in relation to breast cancer risk. British Journal of Cancer. ISSN 0007-0920. 125(8), p. 1135–1145. doi: 10.1038/s41416-021-01432-8. Full text in Research Archive
• Johnson, Nichola; Maguire, Sarah; Morra, Anna; Kapoor, Pooja Middha; Tomczyk, Katarzyna & Kristensen, Vessela N. [Show all 50 contributors for this article] (2021). CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers. British Journal of Cancer. ISSN 0007-0920. 124, p. 842–854. doi: 10.1038/s41416-020-01185-w. Full text in Research Archive
• Rye, Inga Hansine; Huse, Kanutte; Josefsson, Sarah Elisabet; Kildal, Wanja; Danielsen, Håvard Emil Greger & Schlichting, Ellen [Show all 28 contributors for this article] (2021). Breast cancer metastasis: immune profiling of lymph nodes reveals exhaustion of effector T cells and immunosuppression. Molecular Oncology. ISSN 1574-7891. 16(1), p. 88–103. doi: 10.1002/1878-0261.13047. Full text in Research Archive
• Morra, Anna; Jung, Audrey Y.; Behrens, Sabine; Keeman, Renske; Ahearn, Thomas U. & Anton-Culver, Hoda [Show all 134 contributors for this article] (2021). Breast cancer risk factors and survival by tumor subtype: Pooled analyses from the breast cancer association consortium. Cancer Epidemiology, Biomarkers and Prevention. ISSN 1055-9965. 30(4), p. 623–642. doi: 10.1158/1055-9965.EPI-20-0924.
• Baxter, Joseph S.; Johnson, Nichola; Tomczyk, Katarzyna; Gillespie, Andrea; Maguire, Sarah & Brough, Rachel [Show all 183 contributors for this article] (2021). Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element. American Journal of Human Genetics. ISSN 0002-9297. 108(7), p. 1190–1203. doi: 10.1016/j.ajhg.2021.05.013. Full text in Research Archive
• Morra, Anna; Escala-Garcia, Maria; Beesley, Jonathan; Keeman, Renske; Canisius, Sander & Ahearn, Thomas U. [Show all 50 contributors for this article] (2021). Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment. Breast Cancer Research. ISSN 1465-5411. 23:86(1), p. 1–18. doi: 10.1186/s13058-021-01450-7. Full text in Research Archive
• Escala-Garcia, Maria; Canisius, Sander; Keeman, Renske; Beesley, Jonathan; Anton-Culver, Hoda & Arndt, Volker [Show all 105 contributors for this article] (2021). Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis. Scientific Reports. ISSN 2045-2322. 11:19787, p. 1–11. doi: 10.1038/s41598-021-99409-3. Full text in Research Archive
• Fores-Martos, Jaume; Cervera-Vidal, Raimundo; Sierra-Roca, Julia; Lozano-Asencio, Carlos; Fedele, Vita & Cornelissen, Sten [Show all 19 contributors for this article] (2021). Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3 ^VNTR polymorphisms and gene co-expression. NPJ breast cancer. ISSN 2374-4677. 7(1). doi: 10.1038/s41523-021-00329-2.
• Park, JooYong; Choi, Ji-Yeob; Choi, Jaesung; Chung, Seokang; Song, Nan & Park, Sue K [Show all 50 contributors for this article] (2021). Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies? Cancers. ISSN 2072-6694. 13:2370(10), p. 1–21. doi: 10.3390/cancers13102370. Full text in Research Archive
• Galili, Ben; Tekpli, Xavier; Kristensen, Vessela N. & Yakhini, Zohar (2021). Efficient gene expression signature for a breast cancer immuno-subtype. PLOS ONE. ISSN 1932-6203. 16(1). doi: 10.1371/journal.pone.0245215.
• Bahrami, Nazli; Jabeen, Shakila; Tahiri, Andliena; Sauer, Torill; Ødegård, Hilde Presterud & Geisler, Stephanie Beate [Show all 11 contributors for this article] (2021). Lack of cross-resistance between non-steroidal and steroidal aromatase inhibitors in breast cancer patients: the potential role of the adipokine leptin. Breast Cancer Research and Treatment. ISSN 0167-6806. 190, p. 435–449. doi: 10.1007/s10549-021-06399-x. Full text in Research Archive
• Ben-Elazar, Shay; Aure, Miriam Ragle; Jonsdottir, Kristin; Leivonen, Suvi-Katri; Kristensen, Vessela N. & Janssen, Emiel [Show all 9 contributors for this article] (2021). miRNA normalization enables joint analysis of several datasets to increase sensitivity and to reveal novel miRNAs differentially expressed in breast cancer. PLoS Computational Biology. ISSN 1553-734X. 17(2). doi: 10.1371/JOURNAL.PCBI.1008608. Full text in Research Archive
• Aure, Miriam Ragle; Fleischer, Thomas; Bjørklund, Sunniva; Ankill, Jørgen; Castro Mondragón, Jaime Abraham & Børresen-Dale, Anne-Lise [Show all 11 contributors for this article] (2021). Crosstalk between microRNA expression and DNA methylation drives the hormone-dependent phenotype of breast cancer. Genome Medicine. ISSN 1756-994X. 13:72, p. 1–21. doi: 10.1186/s13073-021-00880-4. Full text in Research Archive
• Svartdal Normann, Lisa Gregusson; Aure, Miriam Ragle; Leivonen, Suvi-Katri; Haugen, Mads Haugland; Hongisto, Vesa & Kristensen, Vessela N. [Show all 8 contributors for this article] (2021). MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro. Scientific Reports. ISSN 2045-2322. 11:10893, p. 1–11. doi: 10.1038/s41598-021-90385-2. Full text in Research Archive
• Graim, Kiley; Gorenshteyn, Dmitriy; Robinson, David G; Carriero, Nicholas J; Cahill, James A. & Chakrabarti, Rumela [Show all 14 contributors for this article] (2021). Modeling molecular development of breast cancer in canine mammary tumors. Genome Research. ISSN 1088-9051. 31(3), p. 337–347. doi: 10.1101/GR.256388.119.
• Zhang, Haoyu; Ahearn, Thomas U.; Lecarpentier, Julie; Barnes, Daniel; Beesley, Jonathan & Qi, Guanghao [Show all 272 contributors for this article] (2020). Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses. Nature Genetics. ISSN 1061-4036. 52(6), p. 572–581. doi: 10.1038/s41588-020-0609-2.
• Feng, Helian; Gusev, Alexander; Pasaniuc, Bogdan; Wu, Lang; Long, Jirong & Kristensen, Vessela N. [Show all 50 contributors for this article] (2020). Transcriptome‐wide association study of breast cancer risk by estrogen‐receptor status. Genetic Epidemiology. ISSN 0741-0395. 44(5), p. 442–468. doi: 10.1002/gepi.22288. Full text in Research Archive
• Fachal, Laura; Aschard, Hugues; Beesley, Jonathan; Barnes, Daniel R.; Allen, Jamie & Kristensen, Vessela N. [Show all 50 contributors for this article] (2020). Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes. Nature Genetics. ISSN 1061-4036. 52(1), p. 56–73. doi: 10.1038/s41588-019-0537-1. Full text in Research Archive
• Escala-Garcia, Maria; Abraham, Jean; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker & Børresen-Dale, Anne-Lise [Show all 51 contributors for this article] (2020). A network analysis to identify mediators of germline-driven differences in breast cancer prognosis. Nature Communications. ISSN 2041-1723. 11:312, p. 1–14. doi: 10.1038/s41467-019-14100-6. Full text in Research Archive
• Liu, Jingjing; van der Smissen, Wendy J. C. Prager; Collee, Margriet J.; Bolla, Manjeet K.; Wang, Qin & Kristensen, Vessela N. [Show all 82 contributors for this article] (2020). Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk. Scientific Reports. ISSN 2045-2322. 10:9688(1), p. 1–14. doi: 10.1038/s41598-020-65665-y. Full text in Research Archive
• Bergholtz, Helga; Kumar, Surendra; Wärnberg, Fredrik; Luders, Torben; Kristensen, Vessela N. & Sørlie, Therese (2020). Comparable cancer-relevant mutation profiles in synchronous ductal carcinoma in situ and invasive breast cancer. Cancer Reports. ISSN 2573-8348. 3:e1248(3), p. 1–7. doi: 10.1002/cnr2.1248. Full text in Research Archive
• Kramer, Iris; Hooning, Maartje J.; Mavaddat, Nasim; Hauptmann, Michael; Keeman, Renske & Steyerberg, Ewout W. [Show all 54 contributors for this article] (2020). Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk. American Journal of Human Genetics. ISSN 0002-9297. 107(5), p. 837–848. doi: 10.1016/j.ajhg.2020.09.001.
• Levy-Jurgenson, Alona; Tekpli, Xavier; Kristensen, Vessela N. & Yakhini, Zohar (2020). Spatial transcriptomics inferred from pathology whole-slide images links tumor heterogeneity to survival in breast and lung cancer. Scientific Reports. ISSN 2045-2322. 10:18802, p. 1–11. doi: 10.1038/s41598-020-75708-z. Full text in Research Archive
• Tinholt, Mari; Stavik, Benedicte; Tekpli, Xavier; Garred, Øystein; Borgen, Elin & Kristensen, Vessela N. [Show all 9 contributors for this article] (2020). Coagulation factor V is a marker of tumor-infiltrating immune cells in breast cancer. Oncoimmunology. ISSN 2162-4011. 9:e1824644(1), p. 1–12. doi: 10.1080/2162402X.2020.1824644. Full text in Research Archive
• Tahiri, Andliena; Tekpli, Xavier; Somisetty, Venkata Satheesh; DeWijn, Rik; Luders, Torben & Bukholm, Ida Rashida Khan [Show all 9 contributors for this article] (2020). Loss of progesterone receptor is associated with distinct tyrosine kinase profiles in breast cancer. Breast Cancer Research and Treatment. ISSN 0167-6806. 183, p. 585–598. doi: 10.1007/s10549-020-05763-7. Full text in Research Archive
• Pladsen, Arne Valebjørg; Nilsen, Gro; Rueda, Oscar M.; Aure, Miriam Ragle; Borgan, Ørnulf & Liestøl, Knut [Show all 18 contributors for this article] (2020). DNA copy number motifs are strong and independent predictors of survival in breast cancer. Communications Biology. ISSN 2399-3642. 3. doi: 10.1038/s42003-020-0884-6. Full text in Research Archive
• Egeland, Nina Gran; Jonsdottir, Kristin; Aure, Miriam Ragle; Sahlberg, Kristine Kleivi; Kristensen, Vessela N. & Cronin-Fenton, Deirdre [Show all 10 contributors for this article] (2020). MiR-18a and miR-18b are expressed in the stroma of oestrogen receptor alpha negative breast cancers. BMC Cancer. ISSN 1471-2407. 20. doi: 10.1186/s12885-020-06857-7. Full text in Research Archive
• Gythfeldt, Hedda von der Lippe; Lien, Tonje Gulbrandsen; Tekpli, Xavier; Silwal-Pandit, Laxmi; Borgen, Elin & Garred, Øystein [Show all 15 contributors for this article] (2020). Immune phenotype of tumor microenvironment predicts response to bevacizumab in neoadjuvant treatment of ER-positive breast cancer. International Journal of Cancer. ISSN 0020-7136. 147(9), p. 2515–2525. doi: 10.1002/ijc.33108. Full text in Research Archive
• Ree, Anne Hansen; Nygaard, Vigdis; Pedersen, Kjetil Boye; Heinrich, Daniel; Dueland, Svein & Bergheim, Inger Riise [Show all 25 contributors for this article] (2020). Molecularly matched therapy in the context of sensitivity, resistance, and safety; patient outcomes in end-stage cancer?the MetAction study. Acta Oncologica. ISSN 0284-186X. p. 1–10. doi: 10.1080/0284186X.2020.1742377. Full text in Research Archive
• Zhu, Qian; Tekpli, Xavier; Troyanskaya, Olga G. & Kristensen, Vessela N. (2020). Subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations. Bioinformatics. ISSN 1367-4803. 36(4), p. 994–999. doi: 10.1093/bioinformatics/btz709. Full text in Research Archive
• Shu, Xiang; Wu, Lang; Khankari, Nikhil K.; Shu, Xiao-Ou; Wang, Thomas J & Michailidou, Kyriaki [Show all 51 contributors for this article] (2019). Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis. International Journal of Epidemiology. ISSN 0300-5771. 48(3), p. 795––806. doi: 10.1093/ije/dyy201.
• Tekpli, Xavier; Lien, Tonje Gulbrandsen; Røssevold, Andreas Hagen; Nebdal, Daniel J.H.; Borgen, Elin & Ohnstad, Hege Oma [Show all 19 contributors for this article] (2019). An independent poor-prognosis subtype of breast cancer defined by a distinct tumor immune microenvironment. Nature Communications. ISSN 2041-1723. 10:5499, p. 1–14. doi: 10.1038/s41467-019-13329-5. Full text in Research Archive
• Nome, Marianne Eikhom; Euceda, Leslie R.; Jabeen, Shakila; Debik, Julia; Bathen, Tone Frost & Giskeødegård, Guro F. [Show all 17 contributors for this article] (2019). Serum levels of inflammation-related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers. International Journal of Cancer. ISSN 0020-7136. 146(1), p. 223–235. doi: 10.1002/ijc.32638. Full text in Research Archive
• Parashar, Deepak; Geethadevi, Anjali; Aure, Miriam Ragle; Mishra, Jyotsna; George, Jasmine & Chen, Changliang [Show all 24 contributors for this article] (2019). miRNA551b-3p Activates an Oncostatin Signaling Module for the Progression of Triple-Negative Breast Cancer. Cell reports. ISSN 2211-1247. 29(13), p. 4389–4406.e10. doi: 10.1016/j.celrep.2019.11.085.
• Levy-Jurgenson, Alona; Tekpli, Xavier; Kristensen, Vessela N. & Yakhini, Zohar (2019). Predicting Methylation from Sequence and Gene Expression Using Deep Learning with Attention. Lecture Notes in Computer Science (LNCS). ISSN 0302-9743. 11488 LNBI, p. 179–190. doi: 10.1007/978-3-030-18174-1_13.
• Dörk, Thilo; Peterlongo, Paolo; Mannermaa, Arto; Bolla, Manjeet K.; Wang, Qin & Dennis, Joe [Show all 170 contributors for this article] (2019). Two truncating variants in FANCC and breast cancer risk. Scientific Reports. ISSN 2045-2322. 9, p. 1–14. doi: 10.1038/s41598-019-48804-y. Full text in Research Archive
• Lindholm, Evita Maria; Aure, Miriam Ragle; Haugen, Mads Haugland; Sahlberg, Kristine Kleivi; Kristensen, Vessela N. & Nebdal, Daniel J.H. [Show all 9 contributors for this article] (2019). miRNA expression changes during the course of neoadjuvant bevacizumab and chemotherapy treatment in breast cancer. Molecular Oncology. ISSN 1574-7891. 13(10), p. 2278–2296. doi: 10.1002/1878-0261.12561. Full text in Research Archive
• Václavíková, Radka; Klajic, Jovana; Brynychová, Veronika; Elsnerova, Katerina; Grenaker, Grethe Irene & Tost, Jörg [Show all 12 contributors for this article] (2019). Development of high-resolution melting analysis for ABCB1 promoter methylation: Clinical consequences in breast and ovarian carcinoma. Oncology Reports. ISSN 1021-335X. 42(2), p. 763–774. doi: 10.3892/or.2019.7186.
• Bahrami, Nazli; Sauer, Torill; Engebretsen, Siri Strøm; Aljabri, Mohammad Belal; Bemanian, Vahid & Lindstrøm, Jonas Christoffer [Show all 17 contributors for this article] (2019). The NEOLETEXE trial: a neoadjuvant cross-over study exploring the lack of cross resistance between aromatase inhibitors. Future Oncology. ISSN 1479-6694. 15(32), p. 3675–3682. doi: 10.2217/fon-2019-0258. Full text in Research Archive
• Escala-Garcia, Maria; Guo, Qi; Dörk, Thilo; Canisius, Sander; Keeman, Renske & Dennis, Joe [Show all 236 contributors for this article] (2019). Genome-wide association study of germline variants and breast cancer-specific mortality. British Journal of Cancer. ISSN 0007-0920. 120(6), p. 647–657. doi: 10.1038/s41416-019-0393-x. Full text in Research Archive
• Ferreira, Manuel A.; Gamazon, Eric R.; Al-Ejeh, Fares; Aittomäki, Kristiina; Andrulis, Irene L. & Anton-Culver, Hoda [Show all 210 contributors for this article] (2019). Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer. Nature Communications. ISSN 2041-1723. 10(1741). doi: 10.1038/s41467-018-08053-5. Full text in Research Archive
• Lai, Xiaoran; Geier, Oliver; Fleischer, Thomas; Garred, Øystein; Borgen, Elin & Funke, Simon Wolfgang [Show all 14 contributors for this article] (2019). Towards personalized computer simulation of breast cancer treatment: a multi-scale pharmacokinetic and pharmacodynamic model informed by multi-type patient data. Cancer Research. ISSN 0008-5472. 79(16), p. 4293–4304. doi: 10.1158/0008-5472.CAN-18-1804. Full text in Research Archive
• Johansson, Henrik J.; Socciarelli, Fabio; Vacanti, Nathaniel M.; Haugen, Mads Haugland; Zhu, Yafeng & Siavelis, Ioannis [Show all 36 contributors for this article] (2019). Breast cancer quantitative proteome and proteogenomic landscape. Nature Communications. ISSN 2041-1723. 10:1600, p. 1–14. doi: 10.1038/s41467-019-09018-y. Full text in Research Archive
• Brinkman, Arie B.; Nik-Zainal, Serena; Simmer, Femke; Rodríguez-González, F. Germán; Smid, Marcel & Alexandrov, Ludmil B. [Show all 29 contributors for this article] (2019). Partially methylated domains are hypervariable in breast cancer and fuel widespread CpG island hypermethylation. Nature Communications. ISSN 2041-1723. 10. doi: 10.1038/s41467-019-09828-0. Full text in Research Archive
• Lee, Young-suk; Krishnan, Arjun; Oughtred, Rose; Rust, Jennifer; Chang, Christie S. & Ryu, Joseph [Show all 10 contributors for this article] (2019). A Computational Framework for Genome-wide Characterization of the Human Disease Landscape. Cell Systems. ISSN 2405-4712. 8(2), p. 152–162.e6. doi: 10.1016/j.cels.2018.12.010.
• Jiang, Xia; Finucane, Hilary K.; Schumacher, Fredrick R.; Schmit, Stephanie L.; Tyrer, Jonathan P. & Han, Younghun [Show all 333 contributors for this article] (2019). Shared heritability and functional enrichment across six solid cancers. Nature Communications. ISSN 2041-1723. 10:431, p. 1–23. doi: 10.1038/s41467-018-08054-4. Full text in Research Archive
• Nguyen, Chinh BKrong; Kumar, Surendra; Zucknick, Manuela; Kristensen, Vessela N.; Gjerstad, Johannes & Nilsen, Hilde Loge [Show all 7 contributors for this article] (2019). Associations between clinical symptoms, plasma norepinephrine and deregulated immune gene networks in subgroups of adolescent with Chronic Fatigue Syndrome. Brain, Behavior, and Immunity. ISSN 0889-1591. 76, p. 82–96. doi: 10.1016/j.bbi.2018.11.008. Full text in Research Archive
• Tahiri, Andliena; Aure, Miriam Ragle & Kristensen, Vessela N. (2018). MicroRNA Networks in Breast Cancer Cells. Methods in molecular biology. ISSN 1064-3745. 1711, p. 55–81. doi: 10.1007/978-1-4939-7493-1_4.
• Mavaddat, Nasim; Michailidou, Kyriaki; Dennis, Joe; Lush, Michael; Fachal, Laura & Lee, Andrew [Show all 56 contributors for this article] (2018). Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes. American Journal of Human Genetics. ISSN 0002-9297. 104(1), p. 21–34. doi: 10.1016/j.ajhg.2018.11.002.
• Møller, Elen Kristine; Nord, Silje; Wedge, David C; Lingjærde, Ole Christian; Silwal-Pandit, Laxmi & Gythfeldt, Hedda [Show all 19 contributors for this article] (2018). Time series analysis of neoadjuvant chemotherapy and bevacizumab-treated breast carcinomas reveals a systemic shift in genomic aberrations. Genome Medicine. ISSN 1756-994X. 10:92. doi: 10.1186/s13073-018-0601-y. Full text in Research Archive
• Jabeen, Shakila; Espinoza, Jaime; Torland, Lilly Anne; Zucknick, Manuela; Kumar, Surendra & Haakensen, Vilde Drageset [Show all 15 contributors for this article] (2018). Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics. Oncoimmunology. ISSN 2162-4011. :e1537691. doi: 10.1080/2162402X.2018.1537691. Full text in Research Archive
• Tinholt, Mari; Garred, Øystein; Borgen, Elin; Beraki, Else; Schlichting, Ellen & Kristensen, Vessela N. [Show all 8 contributors for this article] (2018). Subtype-specific clinical and prognostic relevance of tumor-expressed F5 and regulatory F5 variants in breast cancer: the CoCaV study. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 16(7), p. 1347–1356. doi: 10.1111/jth.14151.
• Jabeen, Shakila; Zucknick, Manuela; Nome, Marianne Eikhom; dannenfelser, ruth; Fleischer, Thomas & Kumar, Surendra [Show all 15 contributors for this article] (2018). Serum cytokine levels in breast cancer patients during neoadjuvant treatment with bevacizumab. Oncoimmunology. ISSN 2162-4011. 7(11), p. e1457598-1–e1457598-15. doi: 10.1080/2162402X.2018.1457598.
• Prasmickaite, Lina; Tenstad, Ellen; Pettersen, Solveig; Jabeen, Shakila; Egeland, Eivind Valen & Nord, Silje [Show all 12 contributors for this article] (2018). Basal-like breast cancer engages tumor-supportive macrophages via secreted factors induced by extracellular S100A4. Molecular Oncology. ISSN 1574-7891. 12(9), p. 1540–1558. doi: 10.1002/1878-0261.12319. Full text in Research Archive
• O'Mara, Tracy A.; Glubb, Dylan M.; Amant, Frédéric; Annibali, Daniela; Ashton, Katie & Attia, John [Show all 125 contributors for this article] (2018). Identification of nine new susceptibility loci for endometrial cancer. Nature Communications. ISSN 2041-1723. 9:3166, p. 1–12. doi: 10.1038/s41467-018-05427-7. Full text in Research Archive
• Bemanian, Vahid; Noone, John Christopher; Sauer, Torill; Touma, Joel Joul; Vetvik, Katja K & Söderberg-Naucler, Cecilia [Show all 10 contributors for this article] (2018). Somatic EP300-G211S mutations are associated with overall somatic mutational patterns and breast cancer specific survival in triple-negative breast cancer. Breast Cancer Research and Treatment. ISSN 0167-6806. 2, p. 339–351. doi: 10.1007/s10549-018-4927-3.
• Wu, Lang; Shi, Wei; Long, Jirong; Guo, Xingyi; Michailidou, Kyriaki & Beesley, Jonathan [Show all 210 contributors for this article] (2018). A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer. Nature Genetics. ISSN 1061-4036. 50(7), p. 968–978. doi: 10.1038/s41588-018-0132-x.
• Mauger, Florence; Kernaleguen, Magali; Lallemand, Céline; Kristensen, Vessela N.; Deleuze, Jean-François & Tost, Jörg (2018). Enrichment of methylated molecules using enhanced-ice-co-amplification at lower denaturation temperature-PCR (E-ice-COLD-PCR) for the sensitive detection of disease-related hypermethylation. Epigenomics. ISSN 1750-1911. 10(5), p. 525–537. doi: 10.2217/epi-2017-0166.
• Painter, Jodie N.; O'Mara, Tracy A.; Morris, Andrew P.; Cheng, Timothy H.T.; Gorman, Maggie & Martin, Lynn [Show all 76 contributors for this article] (2018). Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses. Cancer Medicine. ISSN 2045-7634. 7(5), p. 1978–1987. doi: 10.1002/cam4.1445.
• Milne, Roger L; Kuchenbaecker, Karoline B; Michailidou, Kyriaki; Beesley, Jonathan; Kar, Siddhartha & Lindström, Sara [Show all 20 contributors for this article] (2017). Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nature Genetics. ISSN 1061-4036. 49(12), p. 1767–1778. doi: 10.1038/ng.3785. Show summary

  Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10−8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

• Jiao, Xiang; Aravidis, Christos; Marikkannu, Rajeshwari; Rantala, Johanna; Picelli, Simone & Adamovic, Tatjana [Show all 104 contributors for this article] (2017). PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1. OncoTarget. ISSN 1949-2553. 8(61), p. 102769–102782. doi: 10.18632/oncotarget.21800. Full text in Research Archive Show summary

  Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD >2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.

• Guo, Qi; Burgess, Stephen; Turman, Constance; Bolla, Manjeet K; Wang, Qin & Lush, Michael [Show all 52 contributors for this article] (2017). Body mass index and breast cancer survival: a Mendelian randomization analysis. International Journal of Epidemiology. ISSN 0300-5771. 46(6), p. 1814–1822. doi: 10.1093/ije/dyx131. Full text in Research Archive Show summary

  Background<br/> There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.<br/><br/> Methods<br/> We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis.<br/><br/> Results<br/> BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01–1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89–1.13, P = 0.95).<br/><br/> Conclusions<br/> Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.

• Clancy, Trevor; dannenfelser, ruth; Troyanskaya, Olga G.; Malmberg, Karl-Johan; Hovig, Eivind & Kristensen, Vessela N. (2017). Bioinformatics approaches to profile the tumor microenvironment for immunotherapeutic discovery. Current pharmaceutical design. ISSN 1381-6128. 23(32), p. 4716–4725. doi: 10.2174/1381612823666170710154936. Full text in Research Archive Show summary

  In the microenvironment of a malignancy, tumor cells do not exist in isolation, but rather in a diverse ecosystem consisting not only of heterogeneous tumor-cell clones, but also normal cell types such as fibroblasts, vasculature, and an extensive pool of immune cells at numerous possible stages of activation and differentiation. This results in a complex interplay of diverse cellular signaling systems, where the immune cell component is now established to influence cancer progression and therapeutic response. It is experimentally difficult and laborious to comprehensively and systematically profile these distinct cell types from heterogeneous tumor samples in order to capitalize on potential therapeutic and biomarker discoveries. One emerging solution to address this challenge is to computationally extract cell-type specific information directly from bulk tumors. Such in silico approaches are advantageous because they can capture both the cell-type specific profiles and the tissue systems level of cell-cell interactions. Accurately and comprehensively predicting these patterns in tumors is an important challenge to overcome, not least given the success of immunotherapeutic drug treatment of several human cancers. This is especially challenging for subsets of closely related immune cell phenotypes with relatively small gene expression differences, which have critical functional distinctions. Here, we outline the existing and emerging novel bioinformatics strategies that can be used to profile the tumor immune landscape.

• Helland, Thomas; Henne, Nina; Bifulco, Ersilia; Naume, Bjørn; Borgen, Elin & Kristensen, Vessela N. [Show all 15 contributors for this article] (2017). Serum concentrations of active tamoxifen metabolites predict long-term survival in adjuvantly treated breast cancer patients. Breast Cancer Research. ISSN 1465-5411. 19(1). doi: 10.1186/s13058-017-0916-4. Full text in Research Archive Show summary

  Background Controversies exist as to whether the genetic polymorphisms of the enzymes responsible for the metabolism of tamoxifen can predict breast cancer outcome in patients using adjuvant tamoxifen. Direct measurement of concentrations of active tamoxifen metabolites in serum may be a more biological plausible and robust approach. We have investigated the association between CYP2D6 genotypes, serum concentrations of active tamoxifen metabolites, and long-term outcome in tamoxifen treated breast cancer patients. Methods From an original observational study comprising 817 breast cancer patients, 99 women with operable breast cancer were retrospectively included in the present study. This cohort of patients were adjuvantly treated with tamoxifen, had provided serum samples suitable for measuring tamoxifen metabolites, and were relapse-free at 3 years after the primary treatment commenced. The median follow-up time from this entry point to breast cancer death was 13.9 years. Patients were CYP2D6 genotyped and grouped into four CYP2D6 phenotype groups (Ultra rapid, extensive, intermediate, and poor metabolizers). Tamoxifen and nine metabolites were quantified in serum (n = 86) and compared with CYP2D6 phenotype groups and outcome. Results Breast cancer patients with low concentrations of Z-4-hydroxy-tamoxifen (Z-4OHtam; ≤ 3.26 nM) had a breast cancer-specific survival (BCSS) of 60% compared to 84% in patients with Z-4OHtam concentrations > 3.26 nM (p = 0.020, log-rank hazard ratio (HR) = 3.56, 95% confidence interval (CI) = 1.14–11.07). For patients with Z-4-hydroxy-N-desmethyl-tamoxifen (Z-endoxifen) levels ≤ 9.00 nM BCSS was 57% compared to 84% for patients with concentrations > 9.00 nM (p = 0.029, HR = 3.73, 95% CI = 1.05–13.22). Low concentrations of Z-4OHtam and Z-endoxifen were associated with poorer survival also after adjusting for clinically relevant variables (HR = 4.27, 95% CI = 1.35–13.58, and HR = 3.70, 95% CI = 1.03–13.25, respectively). Overall survival analysis showed similar survival differences for both active metabolites. The Antiestrogen Activity Score showed comparable effects, but did not improve the prognostic information. Conclusions Patients with Z-4OHtam and Z-endoxifen concentrations lower than 3.26 nM or 9.00 nM, respectively, showed an adverse outcome. Our results suggest that direct measurement of active tamoxifen metabolite concentrations could be of clinical value. Validation in larger study cohorts is warranted.

• Michailidou, Kyriaki; Lindström, Sara; Dennis, Joe; Beesley, Jonathan; Hui, Shirley & Kar, Siddhartha [Show all 359 contributors for this article] (2017). Association analysis identifies 65 new breast cancer risk loci. Nature. ISSN 0028-0836. 551(7678), p. 92–94. doi: 10.1038/nature24284. Show summary

  Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry1. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10−8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2–5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

• Ohnstad, Hege Oma; Borgen, Elin; Falk, Ragnhild Sørum; Lien, Tonje Gulbrandsen; Aaserud, Marit & Sveli, My Anh Tu [Show all 14 contributors for this article] (2017). Prognostic value of PAM50 and risk of recurrence score in patients with early-stage breast cancer with long-term follow-up. Breast Cancer Research. ISSN 1465-5411. 19(120). doi: 10.1186/s13058-017-0911-9. Full text in Research Archive
• Fleischer, Thomas; Tekpli, Xavier; Mathelier, Anthony; Wang, Shixiong; Nebdal, Daniel J.H. & Dhakal, Hari Prasad [Show all 16 contributors for this article] (2017). DNA methylation at enhancers identifies distinct breast cancer lineages. Nature Communications. ISSN 2041-1723. 8(1379). doi: 10.1038/s41467-017-00510-x. Full text in Research Archive
• Cheng, Jiqiu; Demeulemeester, Jonas; Wedge, David C.; Vollan, Hans Kristian Moen; Pitt, Jason & Russnes, Hege Elisabeth Giercksky [Show all 18 contributors for this article] (2017). Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors. Nature Communications. ISSN 2041-1723. 8:1221, p. 1–14. doi: 10.1038/s41467-017-01355-0. Full text in Research Archive
• Shimelis, Hermela; Mesman, Romy L.S.; Von Nicolai, Catharina; Ehlen, Asa; Guidugli, Lucia & Martin, Charlotte [Show all 133 contributors for this article] (2017). BRCA2 hypomorphic missense variants confer moderate risks of breast cancer. Cancer Research. ISSN 0008-5472. 77(11), p. 2789–2799. doi: 10.1158/0008-5472.CAN-16-2568.
• Bjørklund, Sunniva Maria Stordal; Panda, Anshuman; Kumar, Surendra; Seiler, Michael; Robinson, Doug & Gheeya, Jinesh [Show all 15 contributors for this article] (2017). Widespread alternative exon usage in clinically distinct subtypes of Invasive Ductal Carcinoma. Scientific Reports. ISSN 2045-2322. 7(1). doi: 10.1038/s41598-017-05537-0. Full text in Research Archive
• dannenfelser, ruth; Nome, Marianne Eikhom; Tahiri, Andliena; Ursini-Siegel, Josie; Vollan, Hans Kristian Moen & Haakensen, Vilde Drageset [Show all 12 contributors for this article] (2017). Data-driven analysis of immune infiltrate in a large cohort of breast cancer and its association with disease progression, ER activity, and genomic complexity. OncoTarget. ISSN 1949-2553. 8(34), p. 57121–57133. doi: 10.18632/oncotarget.19078. Full text in Research Archive Show summary

  The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry. Herein we utilize a machine learning based approach to identify lymphocyte markers with which we can quantify the presence of B cells, cytotoxic T-lymphocytes, T-helper 1, and T-helper 2 cells in any gene expression data set and apply it to studies of breast tissue. By leveraging over 2,100 samples from existing large scale studies, we are able to find an inherent cell heterogeneity in clinically characterized immune infiltrates, a strong link between estrogen receptor activity and infiltration in normal and tumor tissues, changes with genomic complexity, and identify characteristic differences in lymphocyte expression among molecular groupings. With our extendable methodology for capturing cell type specific signal we systematically studied immune infiltration in breast cancer, finding an inverse correlation between beneficial lymphocyte infiltration and estrogen receptor activity in normal breast tissue and reduced infiltration in estrogen receptor negative tumors with high genomic complexity.

• Quigley, David; Tahiri, Andliena; Luders, Torben; Riis, Margit; Balmain, Allan & Børresen-Dale, Anne-Lise [Show all 8 contributors for this article] (2017). Age, estrogen, and immune response in breast adenocarcinoma and adjacent normal tissue. Oncoimmunology. ISSN 2162-4011. 6(11). doi: 10.1080/2162402X.2017.1356142. Full text in Research Archive Show summary

  Chronic inflammation promotes breast tumor growth and invasion by accelerating angiogenesis and tissue remodeling in the tumor microenvironment. There is a complex relationship between inflammation and estrogen, which drives the growth of 70 percent of breast tumors. While low levels of estrogen exposure stimulate macrophages and other inflammatory cell populations, very high levels are immune suppressive. Breast tumor incidence is increased by obesity and age, which interact to influence inflammatory cell populations in normal breast tissue. To characterize the impact of these factors on tumors and the tumor microenvironment, we measured gene expression in 195 breast adenocarcinomas and matched adjacent normal breast tissue samples collected at Akershus University Hospital (AHUS). Age and Body Mass Index (BMI) were independently associated with inflammation in adjacent normal tissue but not tumors. Estrogen Receptor (ER)-negative tumors had elevated macrophage expression compared with matched normal tissue, but ER-positive tumors showed an unexpected decrease in macrophage expression. We found an inverse relationship between the increase in tumor estrogen pathway expression compared with adjacent normal tissue and tumor macrophage score. We validated this finding in 126 breast tumor-normal pairs from the previously published METABRIC cohort. We developed a novel statistic, the Rewiring Coefficient, to quantify the rewiring of gene co-expression networks at the level of individual genes. Differential correlation analysis demonstrated distinct pathways were rewired during tumorigenesis. Our data support an immune suppressive effect of high doses of estrogen signaling in breast tumor microenvironment, suggesting that this effect contributes to the greater presence of prognostic and therapeutically relevant immune cells in ER-negative tumors.

• Muranen, Taru A.; Greco, Dario; Blomqvist, Carl; Aittomäki, Kristiina; Khan, Sofia & Hogervorst, Frans [Show all 74 contributors for this article] (2017). Genetic modifiers of CHEK2*1100delC-associated breast cancer risk. Genetics in Medicine. ISSN 1098-3600. 19(5), p. 599–603. doi: 10.1038/gim.2016.147.
• Silwal-Pandit, Laxmi; Nord, Silje; Gythfeldt, Hedda; Møller, Elen Kristine; Fleischer, Thomas & Rødland, Einar Andreas [Show all 25 contributors for this article] (2017). The longitudinal transcriptional response to neoadjuvant chemotherapy with and without bevacizumab in breast cancer. Clinical Cancer Research. ISSN 1078-0432. 23(16), p. 4662–4670. doi: 10.1158/1078-0432.CCR-17-0160. Full text in Research Archive
• Aure, Miriam Ragle; Vitelli, Valeria; Jernström, Sandra Johanna; Kumar, Surendra; Krohn, Marit & Due, Eldri Undlien [Show all 34 contributors for this article] (2017). Integrative clustering reveals a novel split in the luminal A subtype of breast cancer with impact on outcome. Breast Cancer Research. ISSN 1465-5411. 19. doi: 10.1186/s13058-017-0812-y. Full text in Research Archive Show summary

  Background Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. Methods Tumor tissue from 425 patients with primary breast cancer from the Oslo2 study was cut and blended, and divided into fractions for DNA, RNA and protein isolation and metabolomics, allowing the acquisition of representative and comparable molecular data. Patients were stratified into groups based on their tumor characteristics from five different molecular levels, using various clustering methods. Finally, all previously identified and newly determined subgroups were combined in a multilevel classification using a “cluster-of-clusters” approach with consensus clustering. Results Based on DNA copy number data, tumors were categorized into three groups according to the complex arm aberration index. mRNA expression profiles divided tumors into five molecular subgroups according to PAM50 subtyping, and clustering based on microRNA expression revealed four subgroups. Reverse-phase protein array data divided tumors into five subgroups. Hierarchical clustering of tumor metabolic profiles revealed three clusters. Combining DNA copy number and mRNA expression classified tumors into seven clusters based on pathway activity levels, and tumors were classified into ten subtypes using integrative clustering. The final consensus clustering that incorporated all aforementioned subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype; these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between the luminal A clusters were important for cancer cell survival. These microRNAs were used to validate the split in luminal A tumors in four independent breast cancer cohorts. In two cohorts the microRNAs divided tumors into subgroups with significantly different outcomes, and in another a trend was observed. Conclusions The six integrated subtypes identified confirm the heterogeneity of breast cancer and show that finer subdivisions of subtypes are evident. Increasing knowledge of the heterogeneity of the luminal A subtype may add pivotal information to guide therapeutic choices, evidently bringing us closer to improved treatment for this largest subgroup of breast cancer.

• Jaime A, Espinoza; Jabeen, Shakila; Batra, Richa; Papaleo, Elena; Haakensen, Vilde Drageset & Wielenga, Vera Timmermans [Show all 13 contributors for this article] (2016). Cytokine profiling of tumor interstitial fluid of the breast and its relationship with lymphocyte infiltration and clinicopathological characteristics. Oncoimmunology. ISSN 2162-4011. 5(12). doi: 10.1080/2162402X.2016.1248015.
• Wyszynski, Asaf; Hong, Chi-Chen; Lam, Kristin; Michailidou, Kyriaki; Lytle, Christian & Yao, Song [Show all 110 contributors for this article] (2016). An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression. Human Molecular Genetics. ISSN 0964-6906. 25(17), p. 3863–3876. doi: 10.1093/hmg/ddw223. Show summary

  Breast cancer is the most diagnosed malignancy and the second leading cause of cancer mortality in females. Previous association studies have identified variants on 2q35 associated with the risk of breast cancer. To identify functional susceptibility loci for breast cancer, we interrogated the 2q35 gene desert for chromatin architecture and functional variation correlated with gene expression. We report a novel intergenic breast cancer risk locus containing an enhancer copy number variation (enCNV; deletion) located approximately 400Kb upstream to IGFBP5, which overlaps an intergenic ERα-bound enhancer that loops to the IGFBP5 promoter. The enCNV is correlated with modified ERα binding and monoallelic-repression of IGFBP5 following oestrogen treatment. We investigated the association of enCNV genotype with breast cancer in 1,182 cases and 1,362 controls, and replicate our findings in an independent set of 62,533 cases and 60,966 controls from 41 case control studies and 11 GWAS. We report a dose-dependent inverse association of 2q35 enCNV genotype (percopy OR = 0.68 95%CI 0.55–0.83, P = 0.0002; replication OR = 0.77 95% CI 0.73-0.82, P = 2.1 × 10−19) and identify 13 additional linked variants (r2 > 0.8) in the 20Kb linkage block containing the enCNV (P = 3.2 × 10−15 − 5.6 × 10−17). These associations were independent of previously reported 2q35 variants, rs13387042/rs4442975 and rs16857609, and were stronger for ER-positive than ER-negative disease. Together, these results suggest that 2q35 breast cancer risk loci may be mediating their effect through IGFBP5.

• Demeulemeester, Jonas; Kumar, Parveen; Møller, Elen Kristine; Nord, Silje; Wedge, David C. & Peterson, April [Show all 20 contributors for this article] (2016). Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing. Genome Biology. ISSN 1465-6906. 17(1). doi: 10.1186/s13059-016-1109-7.
• Southey, Melissa C; Goldgar, David E; Winqvist, Robert; Pylkäs, Katri; Couch, Fergus & Tischkowitz, Marc [Show all 326 contributors for this article] (2016). PALB2, CHEK2 and ATM rare variants and cancer risk: Data from COGS. Journal of Medical Genetics. ISSN 0022-2593. 53(12), p. 800–811. doi: 10.1136/jmedgenet-2016-103839. Show summary

  Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.

• Hamdi, Yosr; Soucy, Penny; Adoue, Veronique; Michailidou, Kyriaki; Canisius, Sander & Lemacon, Audrey [Show all 94 contributors for this article] (2016). Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21. OncoTarget. ISSN 1949-2553. 7(49), p. 80140–80163. doi: 10.18632/oncotarget.12818.

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• Frigessi Di Rattalma, Arnoldo; Köhn-Luque, Alvaro; Kristensen, Vessela N.; Gørbitz, Carl Henrik & Engebråten, Olav (2020). Kan statistikk og matematikk redde like mange liv som nye medisiner? Aftenposten (morgenutg. : trykt utg.). ISSN 0804-3116.
• Jiang, Xia; Finucane, Hilary K.; Schumacher, Fredrick; Schmit, Stephanie L.; Tyrer, Jonathan P. & Han, Younghun [Show all 333 contributors for this article] (2019). Publisher Correction: Shared heritability and functional enrichment across six solid cancers (Nature Communications, (2019), 10, 1, (431), 10.1038/s41467-018-08054-4). Nature Communications. ISSN 2041-1723. 10(1). doi: 10.1038/s41467-019-12095-8.
• Cheng, Jiqiu; Demeulemeester, Jonas; Wedge, David C.; Vollan, Hans Kristian Moen; Pitt, Jason J. & Russnes, Hege Elisabeth Giercksky [Show all 18 contributors for this article] (2019). Correction to: Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors (Nature Communications, (2017), 8, 1, (1221), 10.1038/s41467-017-01355-0). Nature Communications. ISSN 2041-1723. 10(1). doi: 10.1038/s41467-019-08512-7.
• Tinholt, Mari; Stavik, Benedicte; Sletten, Marit; Garred, Øystein; Tekpli, Xavier & Kristensen, Vessela N. [Show all 9 contributors for this article] (2019). Coagulation factor V is associated with immune response and tumor lymphocyte recruitment in breast cancer.
• Vaske, Charlie; Parulkar, R.; Bahrami, Nazli; Sauer, Torill; Lüders, Torben & Lorentzen, Annika [Show all 9 contributors for this article] (2019). Time-course DNA and RNA profiling reveals down-regulation of all members of the sulfotransferase 1A subfamily during neoadjuvant therapy with aromatase inhibitors.
• Bahrami, Nazli; Jabeen, Shakila; Sauer, Torill; Kristensen, Vessela N.; Gundersen, Joanna M. & Geisler, Jürgen (2019). The aromatase inactivator exemestane suppresses serum leptin levels significantly in vivo - in contrast to the aromatase inhibitor letrozole.
• Vaske, Charlie; Bahrami, Nazli; Parulkar, R.; Newton, Y.; Sauer, Torill & Loeng, Marie [Show all 11 contributors for this article] (2018). Time-course DNA and RNA profiling of tumors from intra-patient cross-over trial of sequential use of aromatase inhibitors.
• Bahrami, Nazli; Sauer, Torill; Loeng, Marie; Gravdehaug, Berit; Engebretsen, Siri & Aljabri, Belal [Show all 11 contributors for this article] (2018). The NEO-LET-EXE trial: an intra-patient cross-over study to explore the lack of cross-resistance between steroidal and nonsteroidal aromatase inhibitors .
• Kaveh, Fatemeh; Baumbusch, Lars Oliver; Nebdal, Daniel J.H.; Børresen-Dale, Anne-Lise; Lingjærde, Ole Christian & Edvardsen, Hege [Show all 8 contributors for this article] (2018). Correction: A systematic comparison of copy number alterations in four types of female cancer. BMC Cancer. ISSN 1471-2407. 18(80). doi: 10.1186/s12885-017-3766-7.
• Bemanian, Vahid; Sauer, Torill; Touma, Joel Joul; Vetvik, Katja K; Noone, John Christopher & Kristensen, Vessela N. [Show all 8 contributors for this article] (2017). The EP300.G211S mutation is highly associated with low overall mutational burden in triple-negative breast cancer patients.
• Kristensen, Vessela N. (2017). The Antigenicity of the Tumor Cell — Context Matters. New England Journal of Medicine. ISSN 0028-4793. 376, p. 491–493. doi: 10.1056/NEJMcibr1613793.
• Jabeen, Shakila & Kristensen, Vessela N. (2018). Non-invasive biomarkers of metabolic and immune profiles: clinical presentation, and treatment response in cancer. Det medisinske fakultet, Universitetet i Oslo. ISSN 978-82-8377-305-7. Full text in Research Archive

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