个人简介

BSc. Biochemistry (Co-op), Simon Fraser University, MSc. Medical Biophysics, University of Toronto, PhD. Genetics, University of British Columbia

研究领域

Cancer Genetics, genetics of healthy aging, lymphoma, human genetics

Genetics of Non-Hodgkin Lymphoma Collaborators: John Spinelli (Cancer Control Research, BCCA), Randy Gascoyne (Hematopathologist, BCCA), Joseph Connors (Medical Oncologist, BCCA) Cancer is considered a complex genetic trait in which genetic susceptibility, environmental exposures and lifestyle factors all play a role. Our laboratory group investigates the genetic basis of cancer susceptibility at the population level. One of our primary interests is Lymphoma. We are using single nucleotide polymorphism (SNP) and haplotype-based case / control studies in candidate genes to discover novel genetic factors underlying susceptibility to Non-Hodgkin Lymphoma (NHL). These association studies will allow us to identify genetic factors underlying cancer susceptibility in the presence of genetic heterogeneity (when multiple genes contribute to a disease) and incomplete penetrance (when not all individuals who have the susceptibility factor are affected). Through collaboration with members of the Cancer Control Research group at the BCCA, particularly Dr. John Spinelli, we will also study the interaction between genetic susceptibility and environmental triggers in causing NHL. This work was initially funded by the Canadian Cancer Society through a grant from the National Cancer Institute of Canada, and is currently funded by CIHR. We also collaborate with InterLymph, an international consortium of researchers collaborating on epidemiological studies of the genetic and environmental basis of NHL. People: Johanna Schuetz, Karla Bretherick Lymphoma Families Study Lymphoma Families Study: We have also recently undertaken a family-based study to identify genetic factors contributing to lymphoid Cancers including lymphoma, leukemia and myeloma. Although most lymphoid cancers are sporadic in origin, the diagnosis of lymphoproliferative disorders within the same family may indicate the existence of genetic susceptibility factors. In this study, we hope to identify genes involved in susceptibility to lymphoma and/or lymphocytic leukemia by using both linkage and positional cloning, as well as sib-pair based methods. People: Amy English Healthy Aging Collaborators: Nhu Le (Cancer Control Research, BCCA), Ken Madden (Gerontologists, Vancouver General Hospital and UBC), Steven Jones (Bioinformatics, Genome Sciences Centre, BCCA), Joseph Connors (Medical Oncologist, BCCA), Denise Daley (iCapture, St. Paul's Hospital) Living to the advanced age of eighty-five and beyond without developing age-related diseases is strived for by many but achieved by few. Fortunate individuals who achieve this goal may either lack susceptibility factors that contribute to age-related diseases in the majority of people, or may possess resistance factors that enhance their ability to resist disease and prolong lifespan. Healthy aging is considered to be a complex phenotype that is determined intrinsically by genes for which expression and physiological consequences are modified by extrinsic factors such as lifestyle and environment. Variation in such genes may contribute to a variety of processes that result in long-term good health. A multidisciplinary team of researchers with expertise in genomics, genetics, gerontology, biostatistics, bioinformatics and cancer research has been formed to study healthy aging. Our objective is to identify "healthy aging" genes that contribute to exceptional health in old age. We will assess whether genetic variation including single nucleotide polymorphisms (SNPs) and haplotypes in these genes are associated with healthy aging by performing case/control based genetic association tests comparing exceptionally healthy seniors to ordinary middle-aged controls. The cases are healthy seniors over eighty-five chosen for freedom from cancer, cardiovascular disease, pulmonary disease, diabetes and Alzheimer disease who have a good quality of life. People: Julius Halaschek-Wiener, Dan Fornika, Maziar Rahmani, Madalene Earp Cervical Cancer and the Human Papillomavirus Collaborators: Gina Ogilvie (BC Cervical Cancer Screening Program) In collaboration with the BC Centre for Disease Control and supported by Merck Frosst Canada Ltd., we have just completed a study of the prevalence of different types of human papillomavirus (HPV) in British Columbia. People:Richard Moore Pharmacogenetics Collaborators: Fawziah Marra Pulmonary tuberculosis (TB) is among the most serious public health problems in both developing and developed countries. Incidence rates are increasing in high-risk populations within Canada. The current treatment of latent TB generally includes the administration of isoniazid (INH), a drug known to cause hepatotoxicity as a potentially serious side effect. In collaboration with the BC Centre for Disease Control, this pilot study analyzes a group of 67 case(who developed hepatotoxicity upon INH treatment) and 111 controls (who did not develop hepatotoxicity) to test for strong genetic effects on the development of toxicity in the Vancouver TB-exposed population. 178 patients treated for latent TB at the BC Centre for Disease Control TB Clinic in 2004-05 were enrolled with informed consent. People: So Yamada

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Moore RA, Ogilvie G, Fornika D, Moravan V, Brisson M, Amirabbasi-Beik M, Kollar A, Burgess T, Hsu R, Towers L, Lo J, Matisic J and Brooks-Wilson A. Prevalence and type distribution of human papillomavirus in 5,000 British Columbia women – Implications for vaccination. Cancer Causes and Control. 2009 Oct;20(8):1387-96. Halaschek-Wiener J, Amirabbasi-Beik M, Monfared N, Pieczyk M, Sailer C, Kollar A, Thomas R, Agalaridis G, Yamada S, Oliveira L, Collins JA, Meneilly G, Marra MA, Madden KM, Le ND, Connors JM and Brooks-Wilson AR. Genetic variation in healthy oldest old. PLoS One. 2009 Aug 14;4(8):e6641. Schuetz JM, MaCarthur AC, Leach S, Lai AS, Gallagher RP, Connors JM, Gascoyne RD, Spinelli JJ, Brooks-Wilson AR. Genetic Variation in the NBS1, MRE11, RAD50 and BLM Genes and Susceptibility to non-Hodgkin Lymphoma (NHL). BMC Medical Genetics 2009, Nov 16; 10:117. Yamada S, Richardson K, Tang M, Halaschek-Wiener J, Cook VJ, Fitzgerald JM, Elwood K, Marra F and Brooks-Wilson A. Genetic Variation in Carboxylesterase Genes and Susceptibility to Isoniazid-induced Hepatotoxicity. Pharmacogenomics J. 2010 Dec;10(6):524-36. Bretherick KL, Bu R, Gascoyne RD, Connors JM, Spinelli JJ and Brooks-Wilson AR. Elevated circulating t(14;18) translocation levels prior to diagnosis of Follicular Lymphoma. Blood 2010 Dec 23;116(26):6146-7. Earp MA, Rahmani M, Chew K and Brooks-Wilson A. Estimates of array and pool-construction variance for planning efficient DNA-pooling genome wide association studies. BMC Medical Genomics 2011 Nov 28;4:81. Schuetz JM¥, Johnson NA¥, Morin RD, Scott DW, Tan K, Ben-Nierah S, Boyle M, Slack GW, Marra MA, Connors JM, Brooks-Wilson AR and Gascoyne RD. BCL2 Mutations in Diffuse Large B-Cell Lymphoma. Leukemia 2012 Jun;26(6):1383-90. Schuetz JM, Daley D, Graham J, Berry BR, Gallagher RP,Connors JM, Gascoyne RD, Spinelli JJ and AR Brooks-Wilson.Genetic variation in cell death genes and risk of non-Hodgkin lymphoma. PLoS ONE February 2012, Vol 7, Issue 2, e31560. Schuetz JM, Leach S, Kaurah P, Jeyes J,Butterfield Y, Huntsman D and Brooks-Wilson A. Catenin Family Genes are not Commonly Mutated in Hereditary Diffuse Gastric Cancer.Equal contribution. Cancer Epidemiol Biomarkers Prev. 2012 Dec;21(12):2272-4. Bashash M, Shah A, Hislop G, Treml M, Bretherick K, Janoo-Gilani R, Leach S, Le N, Bajdik C and Brooks-Wilson A. Genetic polymorphisms at TIMP3 are associated with survival of adenocarcinoma of the gastroesophageal junction. PLoS One. 2013;8(3):e59157. Bretherick KL, Schuetz JM, Morton LM, Purdue MP, Conde L, Gallagher RP, Connors JM, Gascoyne RD, Berry BR, Armstrong B, Kricker A, Vajdic CM, Grulich A, Hjalgrim H, Smedby KE, Skibola CF, Rothman N, Spinelli JJ and Brooks-Wilson AR. Sex- and subtype-specific analysis of HAFX polymorphisms in non-Hodgkin lymphoma. PLoS ONE. 2013 Sep 17; 8(9):e74619. Schuetz JM, Daley D, Leach S, Conde L, Berry BR, Gallagher RP, Connors JM, Gascoyne RD, Bracci PM, Skibola CF, Spinelli JJ and Brooks-Wilson AR. Non-Hodgkin lymphoma risk and variants in genes controlling lymphocyte development. PLoS ONE. 2013 Sep 30; 8(9):e75170. Tindale LC, Leach S, Ushey K, Daley D and Brooks-Wilson AR. Rare and common variants in the Apolipoprotein E gene in healthy oldest-old. Neurobiology of Aging 2014 Mar; 35(3):727.e1-3. Earp MA, 131 other authors, Brooks-Wilson A; Ovarian Cancer Association Consortium. Genome-wide Association Study of Subtype-Specific Epithelial Ovarian Cancer Risk Alleles Using Pooled DNA. Human Genetics 2014 May;133(5):481-97. Bretherick KL, Leach S and AR Brooks-Wilson. Functional characterization of genetic polymorphisms in the H2AFX distal promoter. Mutation Research 2014 Aug-Sept; 766-767:37-43. Cerhan JR, Sonja I Berndt, 12 other authors, Angela R Brooks-Wilson, et al. Genome-wide association study identifies multiple susceptibility loci for diffuse large B-cell lymphoma. Nat Genet. 2014 Nov; 46 (11): 1233-8. Tindale LC, Zeng A, Bretherick KL, Leach S, Thiessen N and Brooks-Wilson AR. Burden of common complex disease variants in the exomes of two healthy centenarian brothers. Gerontology. 2015 Dec;62(1):58-62. doi: 10.1159/000430462.