Molecular Epidemiology and Evolution Research Programme
Project title:
MOLECULAR EPIDEMIOLOGY OF SPORADIC BREAST CANCER IN FINLAND
Project summary:
Background: Epidemiological studies have estimated that up to 80-90% of all cancers are related to environmental factors, tobacco smoke, diet and occupational exposures being the main attributable exposures. Majority of chemical carcinogens require metabolic activation before they interact with cellular macromolecules and can cause cancer initiation. A number of human genes involved in the activation and inactivation of evironmental agents have been shown to be polymorphic and majority of them have been suggested to modify the risk of environmentally induced cancers.
Objectives: The major objective of this study is to investigate whether environmental factors contribute to the growing incidence of breast cancer in Finland. This molecular epidemiological study uses various biomarkers to (1) evaluate whether widespread environmental carcinogens play a significant role in the etiology of breast cancer; (2) to determine which biomarkers have the greatest potential for identifying women at elevated risk; (3) to determine possible interactions between the polymorphic genotypes and external exposures.
Subjects: The study population consists of 508 breast cancer cases, 514 population controls and 689 women who were diagnosed healthy after examination for a suspected breast cancer. This study is an extension of the prospective Kuopio Breast Cancer Study aimed to find out, among others, the interaction between genetic and environmental factors in the development of breast cancer. Peripheral blood samples, formalin fixed and snap frozen breast tissue samples, questionaire data and pathology reports have been collected from the study subjects.
Methods: COMT, CYP1A1, CYP1B1, CYP2A6, GSTM1, GSTP1, GSTT1, NAT1, NAT2, and VDR genotyping analyses will be performed using polymerace chain reaction (PCR) based methods. The results will be interpretated by the help of traditional epidemiological methods and statistical analyses.
Significance: The research is valuable both in identifying environmental risk factors in breast cancer causation and creating tools to determine which women are at heightened risk in time to intervene to prevent the disease. Thus, the results of this study are expected to yield information on the interplay between environment, nutrition, hormonal status and modifying (risk) genes in the process of sporadic mammary cancer formation. If unequivocal biomarkers of genetic susceptibility to mammary cancer can be developed succesfully, then identification of subgroups (individuals with a particular genotype) at substantially increased risk could be particularly helpful in terms of public health and preventive medicine.
Keywords: breast cancer, genetic polymorphism, individual susceptibility, molecular biology, molecular genetics, molecular toxicology, xenobiotic metabolism
Project leader:
Ari Hirvonen, Finnish Institute of Occupational Health
Department of Industrial Hygiene and Toxicology
Topeliuksenkatu 41 a A, 00250 HELSINKI
Tel 358-9-4747-204, FAX: 358-9-4747-208
E-mail: Ari.Hirvonen@occuphealth.fi
Researchers:
Finnish Institute of Occupational Health
Katja Mitrunen, Timo Partanen, and Maria Reinikainen
University of Kuopio
Prof. Matti Uusitupa and the Kuopio Breast Cancer Study Research Group
National Institute of Public Health
Department of Nutrition
Pirjo Pietinen and Satu Männistö
University of Oulu
Department of Pharmacology and Toxicology
Hannu Raunio, Olavi Pelkonen and the research group
Collaborating parties:
International Agency for Research on Cancer
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