Paweł Domagała

Publications (3)6.08 Total impact

• Article: The risk of gastric cancer in carriers of CHEK2 mutations.

  Urszula Teodorczyk, Cezary Cybulski, Dominika Wokołorczyk, Anna Jakubowska, Teresa Starzyńska, Małgorzata Lawniczak, Paweł Domagała, Katarzyna Ferenc, Krzysztof Marlicz, Zbigniew Banaszkiewicz, Rafał Wiśniowski, Steven A Narod, Jan Lubiński
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  ABSTRACT: CHEK2 is a tumor suppressor gene whose functions are central to the induction of cell cycle arrest and apoptosis following DNA damage. Mutations in CHEK2 have been associated with cancers at many sites, including breast and prostate cancers, but the relationship between CHEK2 and gastric cancer has not been extensively studied. In Poland, there are four known founder alleles of CHEK2; three alleles are protein truncating (1100delC, IVS2G>A, del5395) and the other is a missense variant (I157T). We examined the frequencies of four Polish founder mutations in the CHEK2 gene in 658 unselected gastric cancer patients, in 154 familial gastric cancer patients and in 8,302 controls. A CHEK2 mutation was seen in 57 of 658 (8.7 %) unselected patients with gastric cancer compared to 480 of 8,302 (5.8 %) controls (OR 1.6, p = 0.004). A CHEK2 mutation was present in 19 of 154 (12.3 %) familial cases (OR = 2.3, p = 0.001). The odds ratio for early onset (<50 years) gastric cancer was higher (2.1, p = 0.01), than for cases diagnosed at age of 50 or above (OR 1.4, p = 0.05). Truncating mutations of CHEK2 were associated with higher risk (OR = 2.1, p = 0.02) than the missense mutation I157T (OR = 1.4, p = 0.04). CHEK2 mutations predispose to gastric cancer, in particular to young-onset cases.
  Familial Cancer 01/2013; · 1.30 Impact Factor
• Article: KRAS mutation testing in colorectal cancer as an example of the pathologist's role in personalized targeted therapy: a practical approach.

  Paweł Domagała, Jolanta Hybiak, Violetta Sulżyc-Bielicka, Cezary Cybulski, Janusz Ryś, Wenancjusz Domagała
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  ABSTRACT: Identifying targets for personalized targeted therapy is the pathologist's domain and a treasure. For decades, pathologists have had to learn, understand, adopt and implement many new laboratory techniques as they arrived on the scene. Pathologists successfully integrate the results of those tests into final pathology reports that were, and still are, the basis of clinical therapeutic decisions. The molecular methods are different but no more difficult to comprehend in the era of "kit procedures". In recent years, the development of targeted therapies has influenced routine practices in pathology laboratories because the use of molecular techniques is required to include clinically useful predictive information in the pathology report. Pathologists have the knowledge and expertise to identify particular gene mutations using the appropriate molecular tests currently available. This review focuses on the most important recent developments in KRAS mutation testing in metastatic colorectal cancer (CRC), and shows that a pathologist is involved in 10 stages of this procedure. Recent studies have shown that highly sensitive, simple, reliable and rapid assays may significantly improve the identification of CRC patients resistant to anti-EGFR therapy. Thus, direct sequencing does not seem to be an optimal procedure of KRAS testing for clinical purposes. Twelve currently available high-sensitivity diagnostic assays (with the CE-IVD mark) for KRAS mutation testing are briefly described and compared. The suggested pathology report content for somatic mutation tests is described. In conclusion, evidence is presented that sending away paraffin blocks with tumor tissue for KRAS mutation testing may not be in the best interest of patients. Instead, an evidence-based approach indicates that KRAS mutation testing should be performed in pathology departments, only with the use of CE-IVD/FDA-approved KRAS tests, and with the obligatory, periodic participation in the KRAS EQA scheme organized by the European Society of Pathology as an independent international body.
  Polish journal of pathology: official journal of the Polish Society of Pathologists 01/2012; 63(3):145-64. · 0.35 Impact Factor
• Source

  Available from: Joanna Trubicka

  Article: Genetic contribution to all cancers: the first demonstration using the model of breast cancers from Poland stratified by age at diagnosis and tumour pathology.

  Jan Lubiński, Marcin Korzeń, Bohdan Górski, Cezary Cybulski, Tadeusz Debniak, Anna Jakubowska, Katarzyna Jaworska, Dominika Wokołorczyk, Krzysztof Medrek, Joanna Matyjasik, [......], Pablo Serrano-Fernàndez, Andrzej Piegat, Rafał Uciński, Paweł Domagała, Wenancjusz Domagała, Maria Chosia, Józef Kładny, Barbara Górecka, Steven Narod, Rodney Scott
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  ABSTRACT: The aim of the study is to verify the hypothesis that genetic polymorphisms are associated with the predisposition to all malignancies. Using as a model breast cancers from the homogenous Polish population (West Pomeranian region) after stratification of 977 patients by age at diagnosis (under 51 years and above 50 years) and by tumour pathology (ductal cancers--low and high grade, lobular cancers, ER-positive/negative) we tested this hypothesis. Altogether 20 different groups of breast cancer cases have been analyzed. The results were compared to a group of unaffected controls that were matched by age, sex, ethnicity and geographical location and originated from families without cancers of any site among relatives. Molecular alterations selected for analyses included those which have been previously recognized as being associated with breast cancer predisposition. Statistically significant differences between the breast cancer cases and controls were observed in 19 of the 20 analyzed groups. Genetic changes were present in more than 90% of the breast cancer patients in 18 of 20 groups. The highest proportion of cases with constitutional changes-99.3% (139/140) was observed for lobular cancers. The number and type of genetic marker and/or the level of their association with the specific cancer predisposition was different between groups. Markers associated with majority of groups included: BRCA1, CHEK2, p53, TNRnTT, FGFRnAA, XPD CC/AA and XPD GG. Some markers appeared to be group specific and included polymorphisms in CDKN2A, CYP1B1, M3K nAA, and RS67.
  Breast Cancer Research and Treatment 05/2008; 114(1):121-6. · 4.43 Impact Factor