Study of the role of genes involved in estrogen metabolism in Graves disease and differentiated thyroid cancer

Abstract

Graves' disease and differentiated thyroid cancer are both multifactorial pathologies. Both present high prevalence in Brazil likewise all over the world and a notorious predominance in women. Moreover, there are evidences that these diseases have gender-related differences in their outcome. Variations in hormone metabolism may be responsible for these differences since hormone metabolites may cause genetic damage. Germline polymorphisms associated to xeno- and endobiotics metabolism are related to the susceptibility to many diseases. Because the inheritance of their profile is related to ethnicity, we settled collaboration with Prof. Wilmar M. Wiersinga (Amsterdam, Netherlands), who sent us 300 European Graves' disease DNA samples that we aim to compare to our population. The objective of the present project is to analyze polymorphisms of genes related to the synthesis and excretion of estrogen in 195 differentiated thyroid cancer patients; 300 Brazilian Graves' disease patients; 300 European Graves' disease patients, compared to 300 Brazilian control individuals paired for gender, age and environmental exposure. We will analyze the role of the inheritance of CYP17, HSD17 ²1, CYP1A1 m1, CYP1A2*1F, CYP1B1 codon 432 and 119, CYP19A1, COMT, UGT1A1*28, SULT1A1 and SULT1E1 genes in the susceptibility and outcome of both diseases and their association to other genes previously studied by our groups in these same patients. (AU)