Andrzej Rozmiarek

Publications (4)24.19 Total impact

• Article: CDKN2A common variant and multi-organ cancer risk--a population-based study.

  Tadeusz Debniak, Rodney J Scott, Tomasz Huzarski, Tomasz Byrski, Andrzej Rozmiarek, Boguslaw Debniak, Bohdan Górski, Cezary Cybulski, Krzysztof Medrek, Marek Mierzejewski, [......], Dorota Oszutowska, Anna Szymańska, Jolanta Szymańska, Jennifer Castaneda, Thierry van de Wetering, Janina Suchy, Grzegorz Kurzawski, Oleg Oszurek, Steven Narod, Jan Lubinski
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  ABSTRACT: 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 = 0.0052). A similar trend, although nonsignificant after the Bonferroni correction, was observed for colorectal cancer (OR, 1.5; p = 0.5499). These results suggest that A148T variant may be associated with a multi-organ cancer risk in the Polish population.
  International Journal of Cancer 07/2006; 118(12):3180-2. · 5.44 Impact Factor
• Article: CDKN2A common variants and their association with melanoma risk: a population-based study.

  Tadeusz Debniak, Rodney J Scott, Tomasz Huzarski, Tomasz Byrski, Andrzej Rozmiarek, Bogusław Debniak, Elzbieta Załuga, Romuald Maleszka, Józef Kładny, Bohdan Górski, Cezary Cybulski, Jacek Gronwald, Grzegorz Kurzawski, Jan Lubinski
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  ABSTRACT: The population frequencies of the CDKN2A variants remain undetermined. In Poland there are three common variants of CDKN2A: an alanine to threonine substitution (A148T), Nt500c>g and Nt540c>t, which have been detected in other populations. To establish if they are associated with an increased malignant melanoma (MM) risk we did an association study based on genotyping 471 patients with MM and 1,210 random control subjects from the same Polish population. We found a significantly increased frequency of the A148T variant among patients with MM (7.0%) in comparison with the general population (2.9%). The incidence of the A148T variant remained greater in both unselected and familial melanoma subgroups. A statistically significant positive association was seen for unselected MM (odds ratio, 2.529; P = 0.0003), especially in patients diagnosed under 50 years of age (odds ratio, 3.4; P = 0.0002). The A148T carrier population (heterozygous G/A alleles) was more likely to have a relative with malignancy compared with the noncarrier population (57% versus 36%, respectively; P = 0.03). Further examination of the CDKN2A promoter sequence done in 20 melanoma patients with the A148T change (heterozygous G/A alleles) and 20 patients with MM without this alteration identified it was in linkage disequilibrium with a polymorphism in the promoter region at position P-493. We found no statistically significant overrepresentation of the Nt500c>g and the Nt540c>t polymorphisms in the Polish melanoma population. In conclusion, the A148T variant of the CDKN2A gene seems to be associated with an increased risk of development of MM. Additional studies are required to confirm whether this particular change is associated with increased risk of other nonmelanoma malignancies.
  Cancer Research 02/2005; 65(3):835-9. · 7.86 Impact Factor
• Source

  Available from: Hanna Janiszewska

  Article: A high proportion of founder BRCA1 mutations in Polish breast cancer families.

  Bohdan Górski, Anna Jakubowska, Tomasz Huzarski, Tomasz Byrski, Jacek Gronwald, Ewa Grzybowska, Andrzej Mackiewicz, Malgorzata Stawicka, Marek Bebenek, Dagmara Sorokin, [......], Cezary Cybulski, Elzbieta Kowalska, Aleksandra Tołoczko-Grabarek, Stanisław Zajaczek, Janusz Menkiszak, Krzysztof Medrek, Bartłomiej Masojć, Marek Mierzejewski, Steven Alexander Narod, Jan Lubiński
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  ABSTRACT: Three mutations in BRCA1 (5382insC, C61G and 4153delA) are common in Poland and account for the majority of mutations identified to date in Polish breast and breast-ovarian cancer families. It is not known, however, to what extent these 3 founder mutations account for all of the BRCA mutations distributed throughout the country. This question has important implications for health policy and the design of epidemiologic studies. To establish the relative contributions of founder and nonfounder BRCA mutations, we established the entire spectrum of BRCA1 and BRCA2 mutations in a large set of breast-ovarian cancer families with origins in all regions of Poland. We sequenced the entire coding regions of the BRCA1 and BRCA2 genes in 100 Polish families with 3 or more cases of breast cancer and in 100 families with cases of both breast and ovarian cancer. A mutation in BRCA1 or BRCA2 was detected in 66% of breast cancer families and in 63% of breast-ovarian cancer families. Of 129 mutations, 122 (94.6%) were in BRCA1 and 7 (5.4%) were in BRCA2. Of the 122 families with BRCA1 mutations, 119 (97.5%) had a recurrent mutation (i.e., one that was seen in at least 2 families). In particular, 111 families (91.0%) carried one of the 3 common founder mutations. The mutation spectrum was not different between families with and without ovarian cancer. These findings suggest that a rapid and inexpensive assay directed at identifying the 3 common founder mutations will have a sensitivity of 86% compared to a much more costly and labor-intensive full-sequence analysis of both genes. This rapid test will facilitate large-scale national epidemiologic and clinical studies of hereditary breast cancer, potentially including studies of chemoprevention.
  International Journal of Cancer 08/2004; 110(5):683-6. · 5.44 Impact Factor
• Article: Hereditary ovarian cancer in Poland.

  Janusz Menkiszak, Jacek Gronwald, Bohdan Górski, Anna Jakubowska, Tomasz Huzarski, Tomasz Byrski, Małgorzata Foszczyńska-Kłoda, Olga Haus, Hanna Janiszewska, Magdalena Perkowska, [......], Katarzyna Lamperska, Elwira Strózyk, Dariusz Godlewski, Małgorzata Stawicka, Bernard Waśko, Marek Bebenek, Andrzej Rozmiarek, Izabella Rzepka-Górska, Steven A Narod, Jan Lubiński
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  ABSTRACT: There is increasing evidence that hereditary factors play a greater role in ovarian cancer than in any of the other common cancers of adulthood. This is attributable, to a large extent, to a high frequency of mutations in the BRCA1 or BRCA2 genes. In Poland, 3 common founder mutations in BRCA1 account for the majority of families with identified BRCA mutations. Our study was conducted in order to estimate the prevalence of any of 3 founder BRCA1 mutations (5382insC, C61G and 4153delA) in 364 unselected women with ovarian cancer, and among 177 women with ovarian cancer and a family history of breast or ovarian cancer. A mutation was identified in 49 out of 364 unselected women with ovarian cancer (13.5%) and in 58 of 177 women with familial ovarian cancer (32.8%). The majority of women with ovarian cancer and a BRCA1 mutation have no family history of breast or ovarian cancer. The high frequency of BRCA1 mutations in Polish women with ovarian cancer supports the recommendation that all Polish women with ovarian cancer should be offered testing for genetic susceptibility, and that counseling services be made available to them and to their relatives. It is important that mutation surveys be conducted in other countries prior to the introduction of national genetic screening programs.
  International Journal of Cancer 11/2003; 106(6):942-5. · 5.44 Impact Factor