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Concomitance of oncogenic HPV types, CHEK2 gene mutations, and CYP1B1 gene polymorphism as an increased risk factor for malignancy.

Banaszkiewicz M, Constantinou M, Pietrusiński M, Kępczyński L, Jędrzejczyk A, Rożniecki M, Marks P, Kałużewski B - Cent European J Urol (2013)

Bottom Line: The ELISA test was used for the studies of 37 HPV genotypes in DNA, isolated tumour tissue. 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.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.

View Article: PubMed Central - PubMed

Affiliation: Chair of Clinical and Laboratory Genetics, Department of Clinical Genetics, Medical University of Łódź, Poland.

ABSTRACT

Introduction: 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.

Material and 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.

No MeSH data available.


Related in: MedlinePlus

Model of response to DNA damage in early carcinogenesis based on ATM/ATR path activation – modified.
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Figure 0002: Model of response to DNA damage in early carcinogenesis based on ATM/ATR path activation – modified.

Mentions: The transformation of a normal cell into a neoplastic cell is a multi–stage process. One of the factors that may play some role in this process is the integration of HPV DNA with DNA of the infected cell, a process that disturbs the E2 reading frame and causes an overexpression of E6 and E7 oncoproteins. Respective of published literature data [12, 15], E6 and E7 oncoproteins produced by oncogenic HPV types come into interactions with endogenous proteins, which are responsible for cellular cycle control: p53 and Rb proteins. These interactions lead to a loss of cellular cycle control by degrading p53 and Rb proteins and dysconfiguration of intracellular control points (Figure 2). The presence of HPV in the cell is an additional biological factor, which may favor a deeper penetration of the already existing mutation of DNA in the infected cell. The 1100del mutation of the CHEK2 gene entirely impairs protein functions while the missense mutation encodes a protein that seems to have the potential of CDC25C phosphorylation and inactivation that leads to G2 control point. This reveals a decreased catalytic ability with regards to CDC25A and an impaired ability of binding p53 and BRCA1 [16]. Literature data quote a model of response to DNA damage in early carcinogenesis based on activation of the ATM/ATR pathway in which the CHEK2 protein plays a big role. A mutation, which either completely switches off protein activity or disturbs its course, may lead to pathway disorders that normally suppress the growth of cells with damaged genetic material [17].


Concomitance of oncogenic HPV types, CHEK2 gene mutations, and CYP1B1 gene polymorphism as an increased risk factor for malignancy.

Banaszkiewicz M, Constantinou M, Pietrusiński M, Kępczyński L, Jędrzejczyk A, Rożniecki M, Marks P, Kałużewski B - Cent European J Urol (2013)

Model of response to DNA damage in early carcinogenesis based on ATM/ATR path activation – modified.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921859&req=5

Figure 0002: Model of response to DNA damage in early carcinogenesis based on ATM/ATR path activation – modified.
Mentions: The transformation of a normal cell into a neoplastic cell is a multi–stage process. One of the factors that may play some role in this process is the integration of HPV DNA with DNA of the infected cell, a process that disturbs the E2 reading frame and causes an overexpression of E6 and E7 oncoproteins. Respective of published literature data [12, 15], E6 and E7 oncoproteins produced by oncogenic HPV types come into interactions with endogenous proteins, which are responsible for cellular cycle control: p53 and Rb proteins. These interactions lead to a loss of cellular cycle control by degrading p53 and Rb proteins and dysconfiguration of intracellular control points (Figure 2). The presence of HPV in the cell is an additional biological factor, which may favor a deeper penetration of the already existing mutation of DNA in the infected cell. The 1100del mutation of the CHEK2 gene entirely impairs protein functions while the missense mutation encodes a protein that seems to have the potential of CDC25C phosphorylation and inactivation that leads to G2 control point. This reveals a decreased catalytic ability with regards to CDC25A and an impaired ability of binding p53 and BRCA1 [16]. Literature data quote a model of response to DNA damage in early carcinogenesis based on activation of the ATM/ATR pathway in which the CHEK2 protein plays a big role. A mutation, which either completely switches off protein activity or disturbs its course, may lead to pathway disorders that normally suppress the growth of cells with damaged genetic material [17].

Bottom Line: The ELISA test was used for the studies of 37 HPV genotypes in DNA, isolated tumour tissue. 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.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.

View Article: PubMed Central - PubMed

Affiliation: Chair of Clinical and Laboratory Genetics, Department of Clinical Genetics, Medical University of Łódź, Poland.

ABSTRACT

Introduction: 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.

Material and 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.

No MeSH data available.


Related in: MedlinePlus