BackgroundGermline mutations of the CHEK2 gene have been reported to be associated with breast cancer. In this study, we analyzed the association of CHEK2 mutations with the risk of development of breast cancer in women of North-Central Poland.Methods420 women with breast cancer and 435 controls were tested for three protein truncating (IVS2 + 1G > A, 1100delC, del5395) and one missense (I157T) CHEK2 mutation. IVS2 + 1G > A and I157T mutations were identified by RFLP-PCR, 1100delC variant was analyzed using an ASO-PCR and del5395 mutation by multiplex-PCR. The statistical tests: the odds ratio (OR) and Fisher’s exact test were used.ResultsIn 33 out of 420 (7.9%) women consecutively diagnosed with breast cancer, we detected one of four analyzed CHEK2 mutations: I157T, 1100delC, IVS2 + 1G > A or del5395. Together they were not associated with the increased risk of breast cancer (North-Central control group: OR = 1.6, p = 0.124; the general Polish population: OR = 1.4, p = 0.109). This association was only seen for IVS2 + 1G > A mutation (OR = 3.0; p = 0.039). One of the three truncating CHEK2 mutations (IVS2 + 1G > A, 1100delC, del5395) was present in 9 of 420 women diagnosed with breast cancer (2.1%) and in 4 of 121 women (3.3%) with a history of breast cancer in a first- and/or second- degree relatives. Together they were associated with the increased risk of disease in these groups, compared to the general Polish population (OR = 2.1, p = 0.053 and OR = 3.2; p = 0.044, respectively). I157T mutation was detected in 25 of 420 women diagnosed with breast cancer (6.0%) and in 8 of 121 women (6.6%) with a history of breast cancer in first- and/or second- degree relatives. The prevalance of I157T mutation was 4.1% (18/435) in North-Central control group and 4.8% (265/5.496) in the general Polish population. However it was not associated with an increased risk of breast cancer.ConclusionObtained results suggest that CHEK2 mutations could potentially contribute to the susceptibility to breast cancer. The germline mutations of CHEK2, especially the truncating ones confer low-penetrance breast cancer predisposition that contribute significantly to familial clustering of breast cancer at the population level.

Background: Ehlers-Danlos syndrome (EDS) is a common non-inflammatory, congenital connective tissue disorder. Classical type (cEDS) EDS is one of the more common forms, typically caused by mutations in the COL5A1 and COL5A2 genes, though causative mutations in the COL1A1 gene have also been described. Material and methods: The study group included 59 patients of Polish origin, diagnosed with cEDS. The analysis was performed on genomic DNA (gDNA) with NGS technology, using an Illumina sequencer. Thirty-five genes related to connective tissue were investigated. The pathogenicity of the detected variants was assessed by VarSome. Results: The NGS of 35 genes revealed variants within the COL5A1, COL5A2, COL1A1, and COL1A2 genes for 30 of the 59 patients investigated. Our panel detected no sequence variations for the remaining 29 patients. Discussion: Next-generation sequencing, with an appropriate multigene panel, showed great potential to assist in the diagnosis of EDS and other connective tissue disorders. Our data also show that not all causative genes giving rise to cEDS have been elucidated yet.

IntroductionThe Ehlers-Danlos syndrome (EDS) is a non-inflammatory, heritable connective tissue disorder divided into 13 types according to the 2017 International Classification of the Ehlers-Danlos syndromes. One of the subtypes of EDS, classical (cEDS), is characterized by joint hypermobility, skin hyperextensibility and atrophic scars, which are major criteria of cEDS.AimIn this study, the first in Central Eastern Europe, 44 patients were investigated. All of them were tested for COL5A1 mutations with direct DNA sequencing.Material and methodsThe study group included 44 patients of Polish origin, all of whom fulfilled criteria for the classical type of Ehlers-Danlos syndrome. Direct sequencing of the COL5A1, COL5A2 and COL1A1 c.934C>T genes was performed for all of them. Evaluation of potential pathogenicity of detected missense mutation was conducted using SIFT (Sorting Intolerant from Tolerant), PolyPhen-2, AlignGVGD (Align Grantham Variance/Grantham Difference). The effect of the splice site mutations was predicted by Human Splicing Finder and NetGene2 tools.ResultsAmong all tested patients, nine mutations of COL5A1 gene were detected (8 missense mutations and 1 splice site). The alterations identified by us are new, hitherto not described in other reports. Evaluation of the mutations by in silico tools indicate their pathogenicity.ConclusionsOur study is the first COL5A1 gene molecular investigation conducted among cEDS patients from Central Eastern Europe. Besides new COL5A1 variant findings, we gained molecular confirmation of clinical diagnosis of cEDS. In some cases, specific and adequate evaluation and classification of EDS patients based only on clinical features, may be difficult.

We tested the association between PON1 L55M, Q192R and I102V polymorphic variants and PC risk in Polish men. DNA from 110 consecutive, newly diagnosed patients hospitalized because of PC and DNA from 110 men -volunteers, healthy at the time of the study. PCR-RFLP method. In our study the average age at PC diagnosis of 55MM genotype carriers from families fulfilling Hereditary Prostate Criteria (HPC) was statistically significantly lower (by 7 years) than the average age at the disease diagnosis of 55MM carriers from families without HPC (54.6 ±6.7 vs. 61.9 ±5.4, respectively, p = 0.03). The probability of 5-year survival for the 55MM carriers was 81.3%, compared to 95.7% for non-carriers (p = 0.08, tendency). This is the first study in Polish men evaluating the impact of PON1 genetic polymorphisms on prostate cancer development and its clinical course. PON1 55MM variant may be probably associated with younger age at PC onset in men from families with HPC and with a shorter survival. However, more extensive studies on a larger number of PC patients, possibly from various populations, are necessary to confirm, and extend our findings.