Professor Angela Cox
One of the great success stories in human genetics in the last decade has been the identification of hundreds of low-penetrance genetic variants associated with risk in common diseases, including cancer. Professor Cox aims to translate such findings into an improved understanding of disease mechanism, and consequent development of better therapeutic approaches and risk estimation. Since 2000, she has been examining the impacts of both inherited and somatic genetic variants in cancer, with a particular interest in genes whose proteins are involved in the DNA damage response and apoptosis pathways.
Research in my laboratory centres on three main themes of cancer genetics:
- Apoptosis and DNA damage response genes in cancer susceptibility
The group bring together epidemiology, tumour genetics and molecular biology to elucidate the mechanisms of action of cancer-associated variants, and to do this collaborations are in place with colleagues Drs. Bryant and Collis for their expertise in genomic instability and the DNA damage response pathways. Professor Cox’s group was one of the first to link the apoptosis gene CASP8 with breast cancer susceptibility, and subsequent fine-mapping demonstrated a number of variants in and around CASP8 involved in breast cancer susceptibility. The group have begun to identify the causal variants behind these associations and link them to cancer phenotypes.
- Identification of novel cancer susceptibility alleles
It was not until the first genome-wide association studies were carried out in 2007 that the group began to characterise the genetic basis of common cancers. This work has not only revolutionized understanding of cancer genetics, but has also changed the way researchers work together, engendering a much more collaborative approach. Professor Cox and her group are involved in a number of cancer genetics consortia including the BCAC (breast cancer), PRACTICAL (prostate cancer), Interlymph (haematological malignancies), ILCCO (lung cancer) and COGS (Collaborative Oncological Gene-Environment Study). These consortia, with access to large sample sizes, have also enabled us to begin to identify how inherited factors relate to cancer subtypes and outcome, leading to the development of prognostic tools.
- The use of circulating tumour DNA as a source of biomarkers.
With the advent of new technologies such as highly parallel sequencing, it has become feasible to quantitatively detect tumour-specific genetic aberrations in circulating cell-free DNA (“liquid biopsies”). This may revolutionize our ability to detect and monitor cancer in patients. The group are currently developing biomarkers for lung cancer and melanoma in collaboration with Cancer Bioinformatics Fellow Dr. Bradford, colleagues in the Sheffield Genetics Diagnostic Service at Sheffield Children’s Hospital and in the Cancer Clinical Trials Centre at Weston Park Hospital.
A full list of my publications can be found at:
- Camp NJ, Lin W-Y, Bigelow A, Burghel GJ, Mosbruger TL, Parry MA, Waller RG, Rigas SH, Tai P-Y, Berrett K, Rajamanickam V, Cosby R, Brock IW, Jones B, Connley D, Sargent R, Wang G, Factor RE, Bernard PS, Cannon-Albright LA, Knight S, Abo R, Werner TL, Reed MWR, Gertz J, Cox A. Discordant Haplotype Sequencing Id entifies Functional Variants at the 2q33 Breast Cancer Risk Locus. Cancer Res. 2016 Jan 21. pii: canres.1629.2015. [Epub ahead of print]
- Lin WY*, Camp NJ*, et al. and Cox A. (2015) Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk. Hum Mol Genet. 24, 285-98. doi: 10.1093/hmg/ddu431.
- Michailidou K., et al. (2015) Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer. Nat Genet 47, 373-380 doi:10.1038/ng.3242
- Mavaddat, N. et al. (2015) Prediction of breast cancer risk based on profiling with common genetic variants. J Natl Cancer Inst. 107, doi: 10.1093/jnci/djv036
- Patil AA, Sayal P, Depondt ML, Beveridge RD, Roylance A, Krinlani DH, Myers KN, Cox A, Jelinek D, Fernando M, Carroll TA & Collis SJ (2014) FANCD2 expression correlates with glioma grade and chemical inhibition of the Fanconi Anaemia pathway sensitises gliomas to chemotherapeutic agents. Oncotarget 2014 5, 6414-6424 doi: 10.18632/oncotarget.2225
- Burghel G, Lin W-Y, Whitehouse H, Brock IW, Hammond D, Bury J, Stephenson Y, George R and Cox A. (2013) Identification of candidate driver genes in common focal chromosomal aberrations of microsatellite stable colorectal cancer PLoS One 8, e83859, doi: 10.1371/journal.pone.0083859
- Berndt SI, et al (2013) Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. Nat Genet. 45, 868-76 doi: 10.1038/ng.2652.
- Michailidou K, et al (2013) Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet 45, 353–361 doi: 10.1038/ng.3242
- Camp NJ*, Parry P*, Knight S, Abo R, Elliott G, Rigas S, Balasubramanian SP, Reed MWR, McBurney H, Latif A, Newman WG, Cannon-Albright LA, Evans DG, Cox A. Fine-mapping CASP8 risk variants in Breast Cancer. (2012) Cancer Epidemiology, Biomarkers Prev 21, 176-81 doi: 10.1158/1055-9965.EPI-11-0845
- Lin, W-Y., Camp, N.J., Cannon-Albright, L.A., Allen-Brady, K., Balasubramanian, S.P., Reed, M.W., Hopper, J.L., Apicella, C., Giles, G.G., Southey, M.C., Milne, R.L., Perez, J.I.A., Rodríguez, P.M., Benítez, J., Grundmann, M., Dubrowinskaja, N., Park-Simon, T-W., Dörk, T., Garcia-Closas, M., Figueroa, J., Sherman, M., Lissowska, J., Easton, D.F., Dunning, A.M., Rajaraman, P., Sigurdson, A.J., Doody, M.M., Linet, M.S., Paul D. Pharoah, P.D., Schmidt, M.K., and Cox, A. (2011). A role for XRCC2 gene polymorphisms in breast cancer risk and survival. J Med Genet 48, 477-484 doi: 10.1136/jmedgenet-2011-100018
- Fasching, PA*, Pharoah, PDP*, Cox, A*, et al and Schmidt, MK.* (2012) The role of genetic breast cancer susceptibility loci as prognostic factors. Hum Mol Genet 21, 3926-39 doi: 10.1093/hmg/dds159
- Wishart GC Bajdik CD, Dicks E, Provenzano E, Schmidt MK, Sherman M, Greenberg DC, Green AR, Gelmon KA, Kosma V-M, Olson JE, Beckmann MW, Winqvist R, Cross SS, Severi G, Huntsman D, Pylkäs K, Ellis I, Nielsen TO, Giles G, Blomqvist C, Fasching PA, Couch FJ, Rakha E, Foulkes WD, Blows FM, Bégin LR, van’t Veer LJ, Southey M, Nevanlinna H, Mannermaa A, Cox A, Cheang M, Baglietto L, Caldas C, Garcia-Closas M, Pharoah PD (2012) PPREDICT Plus: development and validation of a prognostic model for early breast cancer that includes HER2 Br J Cancer 107, 800-807