Wojciech Kluźniak
A5050334362- BRCA gene mutations in cancer
- Genetic Associations and Epidemiology
- Prostate Cancer Treatment and Research
- Genetic factors in colorectal cancer
- DNA Repair Mechanisms
- Prostate Cancer Diagnosis and Treatment
- Nutrition, Genetics, and Disease
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Cancer-related Molecular Pathways
- Glutathione Transferases and Polymorphisms
- CRISPR and Genetic Engineering
- Microbial Inactivation Methods
- Cancer-related molecular mechanisms research
- Pancreatic and Hepatic Oncology Research
- Genomic variations and chromosomal abnormalities
- Male Breast Health Studies
- Bladder and Urothelial Cancer Treatments
- PARP inhibition in cancer therapy
- Gene expression and cancer classification
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Genomics and Chromatin Dynamics
- Immunodeficiency and Autoimmune Disorders
International Hereditary Cancer Center
2015-2025
Pomeranian Medical University
2015-2025
Hunter Medical Research Institute
2018
Greater Poland Cancer Center
2018
<h3>Abstract</h3> <h3>Objectives</h3> To develop and validate a genetic tool to predict age of onset aggressive prostate cancer (PCa) guide decisions who screen at what age. <h3>Design</h3> Analysis genotype, PCa status, select single nucleotide polymorphisms (SNPs) associated with diagnosis. These were incorporated into survival analysis estimate their effects on diagnosis (that is, not eligible for surveillance according National Comprehensive Cancer Network guidelines; any Gleason score...
Mutations in the cell cycle checkpoint kinase 2 (CHEK2) tumor suppressor gene are associated with multi-organ cancer susceptibility including cancers of breast and prostate. A genetic association between thyroid has been suggested, however little is known about determinants this association. To characterize CHEK2 mutations cancer, we genotyped 468 unselected patients papillary (matched) cancer-free controls for four founder (1100delC, IVS2 + 1G>A, del5395 I157T). We compared family histories...
To establish the contribution of eight founder alleles in three DNA damage repair genes (BRCA1, CHEK2 and NBS1) to prostate cancer Poland, measure impact these variants on survival among patients.Three thousand seven hundred fifty men with 3956 cancer-free controls were genotyped for BRCA1 (5382insC, 4153delA, C61G), four (1100delC, IVS2+1G>A, del5395, I157T), one allele NBS1 (657del5).The mutation was detected 53 3750 unselected cases compared 23 (0.6%) (odds ratio (OR)=2.5; P=0.0003). A...
Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We fine-mapped 64 GWAS regions known at the conclusion of iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases 26 274 controls European ancestry. detected evidence for multiple independent signals 16 regions, 12 which contained additional newly significant associations. A single signal comprising a spectrum correlated variation was observed 39 regions; 35...
BACKGROUND Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For cancer it is unknown if inclusion of genetic markers that so far not been associated with at a genome-wide significant level will improve disease prediction. METHODS We built polygenic in large training set over 25,000 individuals. Initially 65 were selected. After LD pruning additional prioritized based on their...
Abstract Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial for prostate cancer (PrCa), their functional effects on remain largely unknown. Here we use genotype data from 59,089 men European and African American ancestries combined with cell-type-specific epigenetic to build a genomic atlas single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences between variants prostate-relevant marks defined normal...
To optimize genetic testing, it is necessary to establish the spectrum of breast cancer‐predisposing mutations in particular ethnic groups. We studied 1,018 women with a strong family history for cancer (families hereditary cancer; HBC) from genetically homogenous population Poland, which populated by Slavs, 14 susceptibility genes. Additionally, we compared frequency candidate pathogenic variants cases and controls. Germline were detected 512 probands (50.3%), including BRCA1/2 420 families...
In designing national strategies for genetic testing, it is important to define the full spectrum of pathogenic mutations in prostate cancer (PCa) susceptibility genes. To investigate frequency PCa genes Polish familial cases and estimate gene-related risks probability aggressive disease, we analyzed coding regions 14 by exome sequencing 390 men with 308 cancer-free controls. We compared mutation frequencies between also clinical characteristics cancers carriers noncarriers. Of cases, 76...
A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and improved screening accuracy. Here, we assess potential impact PHS-informed screening.
In addition to several well-established breast cancer (BC) susceptibility genes, the contribution of other candidate genes BC risk remains mostly undefined. BARD1 is a potentially predisposing gene, however, rarity its mutations and an insufficient family/study size have hampered corroboration estimation associated risks. To clarify role in predisposition, comprehensive case-control association study recurring nonsense mutation c.1690C>T (p.Q564X) was performed, comprising ~14,000...
Abstract BACKGROUND The G84E mutation in the HOXB13 gene has been associated with a high lifetime risk of prostate cancer North America (about 20‐fold). geographical and ethnic extent this recurrent allele not yet determined. METHODS We assayed for presence 3,515 patients 2,604 controls from Poland estimated odds ratio allele. RESULTS was detected 3 (0.1%) individuals general population 20 (0.6%) men (Odds [OR] = 5.0; 95% CI: 1.5–16.7; P 0.008). present 4 416 (1.0%) familial (OR 8.4,...
Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management prostate cancer. Improved tools to distinguish lethal from critical.
APOBEC3B, in addition to other members of the APOBEC3 gene family, has recently been intensively studied due its identification as a whose activation cancer is responsible for specific pattern massively occurring somatic mutations. It was shown that common large deletion cluster (the APOBEC3B deletion) may increase risk breast cancer. However, conflicting evidence regarding this association also reported. In first step our study, using different approaches, including an in-house designed...
Background/Objectives: Ductal carcinoma in situ (DCIS) is the most common non-invasive form of breast cancer. It not clear to what extent DCIS a part hereditary breast/ovarian cancer syndrome caused by BRCA1/2 mutations. Therefore, we investigated association mutations patients with and assessed their impact on survival. Methods: We studied 564 Polish women for six alleles BRCA1 (c.181T>G, c.5266dupC, c.4035delA, c.3700_3704del5, c.68_69del c.5251C>T) four BRCA2 (c.658_659del,...
Familial pancreatic cancer describes families with at least two first-degree relatives that do not fulfil the criteria of other inherited tumor syndromes increased risks cancer. Although much has been learned regarding aggregation in some families, genetic basis for this familial is poorly understood. This study evaluated prevalence 10 Polish founder mutations four genes among individuals from diagnosed syndrome and assessed their possible association (FPC) risk Poland.In study, 400 FPC...
Purpose The purpose of this study was to establish the contribution four founder alleles NBN prostate cancer risk and survival. Materials Methods Five thousand one hundred eighty-nine men with 6,152 controls were genotyped for recurrent variants (657del5, R215W, I171V, E185Q). Results 657del5 mutation detected in 74 5,189 unselected cases 35 (odds ratio [OR], 2.5; p < 0.001). In carriers deletion, restricted GG genotype E185Q variant same gene. Among genotype, OR associated 4.4 (95%...
Bloom Syndrome is a rare recessive disease which includes susceptibility to various cancers. It caused by homozygous mutations of the BLM gene. To investigate whether heterozygous carriers mutation are predisposed breast cancer, we sequenced in 617 patients from Polish families with strong family history cancer. We detected founder (c.1642C>T, p.Gln548Ter) 3 cancer (0.49%) who were sequenced. Then, genotyped 14,804 unselected cases and 4698 cancer-free women for mutation. was identified...
The aim of the study was to analyze frequency and magnitude association 21 recurrent founder germline mutations in BRCA1, BRCA2, PALB2, RAD51C, CHEK2 genes with ovarian cancer risk among unselected patients Poland. We genotyped BRCA1 (9 mutations), BRCA2 (4 RAD51C (3 PALB2 (2 mutations) 2270 Polish 1743 healthy controls, assessed odds ratios (OR) for developing each gene. Mutations were detected 369 out 2095 (17.6%) cases 117 (6.7%) unaffected controls. associated (OR = 40.79, 95% CI:...
The goal of this study was to estimate the risk thyroid cancer following breast and identify therapeutic genetic factors for development after cancer. We followed 10,832 patients a mean 14 years new cases All women were genotyped three Polish founder mutations in BRCA1 (C61G, 4153delA, 5382insC) four CHEK2 (1100delC, IVS2 + 1G/A, del5395, I157T). Information collected on chemotherapy, radiotherapy, hormonal therapies, oophorectomy. Of women, 53 (0.49%) developed second primary Based...