Epidemiology and molecular biology of thyroid microcarcinomas according to iodine uptake. Oxidative DNA damage in tyroid carcinomas.

-Summary of "OTKA" supported project-

1.Epidemiological studies show different geographical distribution patterns of thyroid diseases which could be due to enviromental factors. The trace element iodine is an important environmental factor exerting significant effect on thyroid hormone homeostasis. The Carpathian basin - located in East-Central Europe, mostly Hungary - has a specific situation. According to our previous studies the Hungarian Lowland is an iodine abundant area (median urinary excretion: 200-500 μg/g creatinine), due to water supply from the very deep artesian wells. The northern part of the Carpathian basin ( central and northern Hungary ) is iodine deficient, the median urinary iodine excretion being about 70 μg/g creatinine. Microcarcinomas of the thyroid gland ( the tumor less than 1 cm ) are found with a frequency of 8-35% in autopsy series. Similar iodine intake-dependent distribution of microcarcinomas in autopsy series may be supposed but has not been systematically studied so far. The age specific distribution of the microcarcinomas is also unknown. The genetic background of individuals with thyroid microcarcinomas without clinical manifestation during life as well as the acquired somatic mutations may be different from those seen in patients with clinical thyroid cancer and may be influenced by nutrition, environmental factors, radiation and differences in iodine intake. Comparative epidemiological investigations on the prevalence of clinically and post mortem detected thyroid cancer have been started in Hungarian regions of different iodine intake. Thyroid glands from serial autopsies will be obtained in two pathological departments located in areas with different iodine intake. Area "A": Budapest (iodine deficient), area "B": Hungarian Lowland (iodine abundant). The prposed sample number is 400.This project aims to study of presence and distribution of microcarcinomas in autopsy series in areas of different iodine intake and to investigate somatic RAS codon 12,13 mutations in the microcarcinomas, using laser capture microdissection and PCR and direct sequencing analysis. It is a cooperation between Charitee Institut Berlin (Prof Joseph Köhrle) and National Medical Center (Prof. Istvan Szabolcs).2. Former epidemiologicl investigations suggested that iodine and selenium and free oxide remnants influent the occurrence of thyroid tumors. Our marker of DNA damage is 8-hydroxy-deoxyguanosine (a DNA adduct). Our investigation aims to base a specific anti 8-hydroxyguanosine antibody method in cell culture and in paraffine embedded thyroid carcinoma tissues from different iodine uptake areas (planned number is 50-50) and 20-20 benign from abundant and poor iodine intake areas. Main attention is payed for the border of normal and tumorous region, where DNA adduct formation was most intensive according to studies on non-thyroid carcinoma tissues.OTKA number: T0378012002-2004.