Endocrine Abstracts

Introduction: CHEK2 gene is one of the genes in the DNA repair complex. Dysfunction of genes in this complex leads to genomic instability and is regarded as a cause of tumorigenesis. CHEK2 mutations spectrum was assessed in many populations, including polish one. The most common are mutations truncating CHEK2 protein (1100delC, IVS2+1G>A, del5395) and a missense I157T CHEK2 mutation. Literature data indicate that mutations truncating CHEK2 protein lead to a five-fold increased risk of papillary thyroid cancer.

Aim: The aim of the study was to evaluate the relation between CHEK2 protein truncating mutations and prevalence of nodular goiter and thyroid cancer.

Material and methods: 62 women, aged 25–60 years (average 42.5 years), with 1100delC, IVS2+1G>A and del5395 mutations of CHEK 2 gene were enrolled into the study. Thyroid ultrasound was performed with Aloka equipment with 7.5 MHz probe and blood sample was drawn to perform genetic tests. RFLP-PCR technique was used to detect IVS2+1G>A mutation, PCR to detect del5395 mutation and ASO-PCR using specific starter for an allele with single nucleotide deletion to detect 1100delC. Positive results of RFLP-PCR and ASO-PCR were subsequently verified by DNA sequencing.

Results: Among 62 women, 37 (59.7%) were diagnosed with nodular goiter and 25 (40.3%) had no thyroid lesions. In the group with nodular goiter 25 subjects (67.6%) underwent fine-needle aspiration biopsy (FNAB), 5 are planned for FNAB and 7 (18.9%) have not been qualified to FNAB because of too small dimensions of thyroid lesions and no sonographically suspicious features. Analyzing the group of 32 subjects (25 with FNAB and 7 without FNAB because of no indications), in 4 (12.5%) papillary thyroid cancer was initially diagnosed and afterwards confirmed with postoperative histopathological examination, 27 (84.4%) had benign lesions (20 had group II in The Bethesda System and in 7 basing on ultrasound features) and 1 (3.1%) the result was undetermined (group III).

Conclusions: 1. Prevalence of nodular goiter in the study group was comparable to the general population.

2. Prevalence of papillary thyroid cancer in patients with nodular goiter carrying CHEK2 gene mutations was three-fold higher than prevalence of this cancer in general population.

Our preliminary conclusions may be redefined after performing thyroid diagnostics in more women carrying CHEK2 gene mutations.