Joanna Trubicka - Academia.edu (original) (raw)

Papers by Joanna Trubicka

Hereditary Cancer in Clinical Practice, 2008

Hereditary Cancer in Clinical Practice, 2012

During the past decade many new molecular methods for DNA and RNA analysis have emerged. The most... more During the past decade many new molecular methods for DNA and RNA analysis have emerged. The most popular thus far have been SSCP, HET, CMC, DGGE, RFLP or ASA, which have now been replaced by methods that are more cost effective and less time consuming. Real-time amplification techniques and particularly those with the capacity of multiplexing have become commonly used in laboratory practice. Novel screening methods enable the very rapid examination of large patients series. Use of liquid handling robotics applied to the isolation of DNA or RNA, the normalisation of sample concentration, and standardization of target amplification by PCR have also contributed to a reduced risk of sample contamination and have resulted in laboratory analysis being easier and faster. The aim of this study is the introduction of a few modern techniques, most commonly used in detection of genetic predisposition to cancer.

The presence of multiple (5-100) colorectal adenomas suggests an inherited predisposition, but th... more The presence of multiple (5-100) colorectal adenomas suggests an inherited predisposition, but the genetic aetiology of this phenotype is undetermined if patients test negative for Mendelian polyposis syndromes such as familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). We investigated whether 18 common colorectal cancer (CRC) predisposition single-nucleotide polymorphisms (SNPs) could help to explain some cases with multiple adenomas who phenocopied FAP or MAP, but had no pathogenic APC or MUTYH variant. No multiple adenoma case had an outlying number of CRC SNP risk alleles, but multiple adenoma patients did have a significantly higher number of risk alleles than population controls (P ¼ 5.7 Â 10 À7). The association was stronger in those with Z10 adenomas. The CRC SNPs accounted for 4.3% of the variation in multiple adenoma risk, with three SNPs (rs6983267, rs10795668, rs3802842) explaining 3.0% of the variation. In FAP patients, the CRC risk score did not differ significantly from the controls, as we expected given the overwhelming effect of pathogenic germline APC variants on the phenotype of these cases. More unexpectedly, we found no evidence that the CRC SNPs act as modifier genes for the number of colorectal adenomas in FAP patients. In conclusion, common colorectal tumour risk alleles contribute to the development of multiple adenomas in patients without pathogenic germline APC or MUTYH variants. This phenotype may have 'polygenic' or monogenic origins. The risk of CRC in relatives of multiple adenoma cases is probably much lower for cases with polygenic disease, and this should be taken into account when counselling such patients.

Hereditary Cancer in Clinical Practice, 2006

H He er re ed di it ta ar ry y C Ca an nc ce er r i in n C Cl li in ni ic ca al l P Pr ra ac ct t... more H He er re ed di it ta ar ry y C Ca an nc ce er r i in n C Cl li in ni ic ca al l P Pr ra ac ct ti ic ce e 2006; 4(1) 52

Hereditary Cancer in Clinical Practice, 2005

H He er re ed di it ta ar ry y C Ca an nc ce er r i in n C Cl li in ni ic ca al l P Pr ra ac ct t... more H He er re ed di it ta ar ry y C Ca an nc ce er r i in n C Cl li in ni ic ca al l P Pr ra ac ct ti ic ce e 2005; 3(2) A Ab bs st tr ra ac ct t

Hereditary Cancer in Clinical Practice, 2004

H He er re ed di it ta ar ry y C Ca an nc ce er r i in n C Cl li in ni ic ca al l P Pr ra ac ct t... more H He er re ed di it ta ar ry y C Ca an nc ce er r i in n C Cl li in ni ic ca al l P Pr ra ac ct ti ic ce e 2004; 2(2) A Ab bs st tr ra ac ct t Central nervous system hemangioblastomas (cHAB) are rare tumours which most commonly arise in the cerebellum. Most tumours are sporadic, but as many as one third of cHABs occur in the course of the hereditary disorder -von Hippel-Lindau disease (VHL). In order to diagnose new VHL families in Poland we performed sequencing of the entire VHL gene in archival material (paraffin embedded hemangioblastoma tissues) in a large series of 203 unselected patients with cHAB. VHL gene mutations were detected in 70 (41%) of 171 tumour samples from which DNA of relatively good quality was isolated. We were able to obtain blood samples from 19 of mutation positive cases. Eight (42%) of these harboured germline mutations in persons from distinct undiagnosed VHL families.

PLoS Genetics, 2011

Genome-wide association studies (GWAS) have been successful in identifying common genetic variati... more Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p#5610 27 ). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1610 28 ) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2610 28 ) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls nonoverlapping samples presented here (rs1573496-ADH7, p = 5610 28 ; rs1229984-ADH1B, p = 7610 29 ; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

International Journal of Cancer, 2006

The population frequencies of the CDKN2A common variants remain undetermined. In Poland, there is... more The population frequencies of the CDKN2A common variants remain undetermined. In Poland, there is a common variant of the CDKN2A: an alanine to threonine substitution (A148T), which has been detected in other populations. We have recently showed that it is significantly overrepresented among Polish melanoma patients when compared to general population. Herein, we ascertained the prevalence of the A148T variant in 3,583 unselected cancer cases and 3,000 random control subjects from the same Polish population. We evaluated eleven different malignancies, representing the majority of all common cancer sites. Positive association with A148T variant was observed for lung cancer (OR, 2.0; p 5 0.0052). A similar trend, although nonsignificant after the Bonferroni correction, was observed for colorectal cancer (OR, 1.5; p 5 0.5499). These results suggest that A148T variant may be associated with a multi-organ cancer risk in the Polish population. ' 2006 Wiley-Liss, Inc.

Nature genetics, 2011

We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 aff... more We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r² = 0.99 in controls), rs11894252 (P = 1.8 × 10⁻⁸) and rs7579899 (P = 2.3 × 10⁻⁹), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 × 10⁻¹⁴). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 × 10⁻⁸). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.

PLoS genetics, 2011

PloS one, 2011

Genetic factors associated with the risk of smoking related cancers have until recently remained ... more Genetic factors associated with the risk of smoking related cancers have until recently remained elusive. Since the publication of a genome-wide association study (GWAS) on lung cancer new genetic loci have been identified that appear to be associated with disease risk. In this replication study we genotyped 14 single nucleotide polymorphisms (SNPs) located at the 5p12.3-p15.33, 6p21.3-p22.1, 6q23-q27 and 15q25.1 loci in 874 lung, 450 bladder, 418 laryngeal cancer cases and cancer-free controls, matched by year of birth and sex to the cases. Our results revealed that loci in the chromosome region 15q25.1 (rs16969968[A], rs8034191[G]) and 5p15 (rs402710[T]) are associated with lung cancer risk in the Polish population (smoking status adjusted OR = 1.45, 1.35, 0.77; p ≤ 0.0001, 0.0005, 0.002; 95%CI 1.23-1.72, 1.14-1.59, 0.66-0.91 respectively). None of the other regions analyzed herein were implicated in the risk of lung, bladder or laryngeal cancer. This study supports previous findi...

European Journal of Human Genetics, 2006

Germline mutations in the fumarate hydratase (FH) gene were recently shown to predispose to the d... more Germline mutations in the fumarate hydratase (FH) gene were recently shown to predispose to the dominantly inherited syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is characterized by benign leiomyomas of the skin and the uterus, renal cell carcinoma, and uterine leiomyosarcoma. The aim of this study was to identify new families with FH mutations, and to further examine the tumor spectrum associated with FH mutations. FH germline mutations were screened from 89 patients with RCC, skin leiomyomas or ovarian tumors. Subsequently, 13 ovarian and 48 bladder carcinomas were analyzed for somatic FH mutations. Two patients diagnosed with ovarian mucinous cystadenoma (two out of 33, 6%) were found to be FH germline mutation carriers. One of the changes was a novel mutation (Ala231Thr) and the other one (435insAAA) was previously described in FH deficiency families. These results suggest that benign ovarian tumors may be associated with HLRCC.

Cancer Epidemiology, Biomarkers & Prevention, 2011

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensi... more Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35). Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case–control studies. Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08–1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95–1.09, P = 0.66; P-heterogeneity (Phet) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was obser...

Breast Cancer Research and Treatment, 2007

The CYP1B1 gene is a polymorphic member of the P450 gene family and is considered to be a candida... more The CYP1B1 gene is a polymorphic member of the P450 gene family and is considered to be a candidate gene for cancers of various types. We inquired whether four SNPs in the CYP1B1 gene, alone or in combination, might be associated with breast cancer risk in Poland. We genotyped 2017 cases of breast cancer and 876 controls, for four SNPs in the CYP1B1 gene. Genotype and haplotype frequencies were compared in cases and controls. In combinations of the R48G, A119S and L432V SNPs, four of the eight CYP1B1 haplotypes were more common in controls than in cases and each of these appeared to have a significant protective effect. A large reduction in risk was observed for women who were homozygous for one of these four haplotypes (OR = 0.2; 95%; CI = 0.05-0.5; P = 0.001) compared to women who were homozygous for the most common haplotype. In contrast, women who were homozygous for the GTC haplotype were at increased risk (OR = 1.5; 95%; CI = 1.0-2.1; P = 0.03) compared to women with the most common haplotype. The CYP1B1 gene appears to influence breast cancer susceptibility in Poland.

BMC Cancer, 2010

Background: CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to car... more Background: CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility.

The American Journal of Human Genetics, 2004

A single founder allele of the CHEK2 gene has been associated with predisposition to breast and p... more A single founder allele of the CHEK2 gene has been associated with predisposition to breast and prostate cancer in North America and Europe. The CHEK2 protein participates in the DNA damage response in many cell types and is therefore a good candidate for a multisite cancer susceptibility gene. Three founder alleles are present in Poland. Two of these result in a truncated CHEK2 protein, and the other is a missense substitution of an isoleucine for a threonine. We ascertained the prevalence of each of these alleles in 4,008 cancer cases and 4,000 controls, all from Poland. The majority of the common cancer sites were represented. Positive associations with proteintruncating alleles were seen for cancers of the thyroid (odds ratio [OR] 4.9;

PLoS Genetics, 2012

Phospho-and sphingolipids are crucial cellular and intracellular compounds. These lipids are requ... more Phospho-and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57 phosphatidylcholines (PC), 20 lysophosphatidylcholines (LPC), 27 phosphatidylethanolamines (PE), and 16 PE-based plasmalogens (PLPE), as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88610 2204) and 10 loci for sphingolipids (smallest P-value = 3.10610 257). After a correction for multiple comparisons (P-value,2.2610 29), we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1) and two with sphingolipids (PLD2 and APOE) explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3) suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms.