title: Concomitance of oncogenic HPV types, CHEK2 gene mutations, and CYP1B1 gene polymorphism as an increased risk factor for malignancy.
abstract: BACKGROUND
  Urinary bladder carcinoma ranks the fourth position in malignancy incidence rates in men (6.1%) and the 17th position in women (1.6%). In general, neoplastic diseases should be approached from two perspectives: prevention with implementation of prophylactic measures and early diagnostics. Prophylactics is possible in the preclinical phase of neoplasm, being both justified and plausible in patients from high-risk groups. Thus, it is particularly important to select such groups, not only by referring to environmental carcinogenic factors (occupational and extra-occupational) but also from genetic predisposition, which may be conductive for neoplasm formation. The mutations / polymorphisms of CHEK2 and CYP1B1 genes predispose to neoplasm via multiorgan mechanisms, while the human papilloma virus (HPV) may participate in the neoplastic transformation as an environmental factor.
  
  
  METHODS
  131 patients with diagnosed urinary bladder cancer were qualified to the study. Mutations/polymorphisms of CHEK2 (IVS2 + 1G > A gene, 1100delC, del5395, I157T) and CYP1B1- 355T/T were identified by the PCR in DNA isolated directly from the tumor and from peripheral blood. The ELISA test was used for the studies of 37 HPV genotypes in DNA, isolated tumour tissue.
  
  
  RESULTS
  11 mutations of CHEK2 gene were found, 355T/T polymorphism if CYP1B1 gene occurred in 18 patients (12.9%). Oncogenic HPV was found in 36 (29.3%), out of 123 examined patients.
  
  
  CONCLUSIONS
  The concomitance of CHEK2 gene mutations or 355T/T polymorphism of CYP1B1 gene and the presence of oncogenic HPV types statistically significantly correlates with histological malignancy grades of urinary bladder carcinoma.
authors.affiliation: Chair of Clinical and Laboratory Genetics, Department of Clinical Genetics, Medical University of Łódź, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Banaszkiewicz
authors.affiliation: Chair of Clinical and Laboratory Genetics, Department of Clinical Genetics, Medical University of Łódź, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Constantinou
authors.affiliation: Chair of Clinical and Laboratory Genetics, Department of Clinical Genetics, Medical University of Łódź, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Pietrusiński
authors.affiliation: Chair of Clinical and Laboratory Genetics, Department of Clinical Genetics, Medical University of Łódź, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kępczyński
authors.affiliation: 2nd Department of Urology, Medical University of Łódź, Poland Department of Urology, The John Paul II District Hospital in Bełchatów, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Jędrzejczyk
authors.affiliation: Non-Public Outpatient Clinic of Urology - "Lekarze Urolodzy Marek Rożniecki i Partnerzy", Łask, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Rożniecki
authors.affiliation: Department of Urology, The John Paul II District Hospital in Bełchatów, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Marks
authors.affiliation: Chair of Clinical and Laboratory Genetics, Department of Clinical Genetics, Medical University of Łódź, Poland.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Kałużewski
keywords: CHEK2; CYP1B1; HPV; histological malignancy grade; urinary bladder cancer