Research Group Genomic Epidemiology
Dr. Federico Canzian
Our main focus is to investigate the relation between human genetic variability and susceptibility to cancer. Cancer risk is most likely influenced by inherited genetic variants conferring small to moderate risk of disease. Nevertheless, addition of small risks determined by single genetic variants can concur to increase or decrease significantly cancer susceptibility. We aim at identifying genetic variants that alter cancer risk, alone or in interaction with common environmental and lifestyle exposures, with the long-term goal of elaborating predictive models and adopting screening strategies for cancer prevention.
Genetic variability is thought to be also responsible for the inter-individual differences observed in responses to drugs and in the onset of side effects, as well as long term outcomes (i.e. overall survival or event-free survival) of patients. Therefore, our objective is also to perform studies on pharmacogenetics and survival.
To achieve the needed power to detect each small contribution to cancer risk we operate in the context of large-scale population-based studies (i.e. international cohorts and/or consortia). Our studies are mainly performed through the candidate gene (i.e. hypothesis driven exhaustive study of genetic variants in key genes) and the genome-wide (i.e. screening of thousand of variants in genome-wide association studies (GWAS)) approaches, including the following investigations to further characterize the best hits emerging from GWAS.
In the short and mid-term we plan to continue the expansion of the consortia on pancreatic cancer and multiple myeloma we created. We are actively trying to recruit new clinical collaborators and also to include cases and controls from prospective cohorts. So far our collections of cases and controls are almost exclusively including subjects of Caucasian origin, but we plan to expand the consortia to other ethnicities as well. In parallel with the focus on genetic factors influencing risk, response to treatment and survival, we plan to characterize our cancer cases and controls for other biomarkers or intermediate endpoints, which could affect cancer etiology as well. In particular, we are interested in somatic genetic alterations, telomere length, gene expression, methylation, mitochondrial copy number, as well as metabolomics. The techniques to measure these markers are either being set up in our lab or implemented in collaborating groups at DKFZ, or commercially available. The long-term goal of this approach is to generate rich, multi-dimensional dataset on cancer cases and controls, in order to have a more complete picture of genetic, epigenetic and environmental risk factors, which will provide useful insight in mechanisms of cancerogenesis.
Campa D, Kaaks R, Le Marchand L, Haiman CA, Travis RC, Berg CD, Buring JE, Chanock SJ, Diver WR, Dostal L, Fournier A, Hankinson SE, Henderson BE, Hoover RN, Isaacs C, Johansson M, Kolonel LN, Kraft P, Lee IM, McCarty CA, Overvad K, Panico S, Peeters PH, Riboli E, Sanchez MJ, Schumacher FR, Skeie G, Stram DO, Thun MJ, Trichopoulos D, Zhang S, Ziegler RG, Hunter DJ, Lindström S, Canzian F. (2011). Interactions between genetic variants and breast cancer risk factors in the breast and prostate cancer cohort consortium. J. Natl. Cancer Inst. ,103(16), 1252-63
Rizzato C, Campa D, Giese N, Werner J, Rachakonda PS, Kumar R, Schanné M, Greenhalf W, Costello E, Khaw KT, Key TJ, Siddiq A, Lorenzo-Bermejo J, Burwinkel B, Neoptolemos JP, Büchler MW, Hoheisel JD, Bauer A, Canzian F. (2011). Pancreatic cancer susceptibility loci and their role in survival. PLoS One, 6(11), e27921
Martino A, Sainz J, Buda G, Jamroziak K, Reis RM, García-Sanz R, Jurado M, Ríos R, Szemraj-Rogucka Z, Marques H, Lesueur F, Moreno V, Orciuolo E, Gemignani F, Landi S, Rossi AM, Dumontet C, Petrini M, Campa D, Canzian F. (2012). Genetics and molecular epidemiology of multiple myeloma: the rationale for the IMMEnSE consortium. Int. J. Oncol., 40(3), 625-38
Rizzato C, Torres J, Plummer M, Muñoz N, Franceschi S, Camorlinga-Ponce M, Fuentes-Pananá EM, Canzian F, Kato I. (2012). Variations in Helicobacter pylori cytotoxin-associated genes and their influence in progression to gastric cancer: implications for prevention. PLoS One, 7(1), e29605