Significance of CDKN2A gene A148T variant in patients with bladder cancer
نویسندگان
چکیده
OBJECTIVES The A148T polymorphism of CDKN2A gene is observed in various neoplasms with the incidence rate of 3-35%, however, rather little is known either about the frequency of its occurrence or of its significance in urinary bladder carcinoma. MATERIALS AND METHODS DNA was isolated from blood of 156 patients with urinary bladder carcinoma (130 men). In histopathology, 84 cases were classified as G1, 42 as G2, and 30 as G3. The clinical stage was in 81 cases estimated at Ta and in 75 cases at T1-T4. A148T polymorphism was detected by the MSSCP technique and by sequencing. RESULTS A148T polymorphism was identified in 9/156 urinary bladder carcinoma cases (only in men). The obtained results were compared with the polymorphism incidence for the Polish population, estimated by Debniak et al. The occurrence in the group of the bladder cancer patients turned out higher (5.77%) from that in the control group (2.89%) (G test, table 2×2: NBLADDER CANCER = 156, NCONTROL = 1210, G = 4.298, p <0.05). CONCLUSION Summing up and taking into account the analysis of clinical parameters and the age of the disease occurrence, the A148T polymorphism of CDKN2A gene was identified in the study group only in men, in whom the disease was diagnosed above the age of 60, while the diagnosed neoplasms were in the majority of cases characterized by higher clinical stages and higher grades of malignancy. This has been the first study that attempted to show a potential association between A148T alterations and an increased risk for bladder cancer development.
منابع مشابه
The A148T variant of CDKN2A gene in bladder cancer
Results We found common polymorphic variants reported in the literature at codon 148 in exon 2 (Arg148Thr) and at nucleotides 500 and 540 in the 3’untranslated region which were not considered to be functional variants. We compared the obtained frequencies for the particular CDKN2A variants with the control group for the Polish population examined by Debniak and colleagues (Cancer Research 2005...
متن کاملCDKN2A common variants and their association with melanoma risk: a population-based study.
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...
متن کاملA common variant of CDKN2A (p16) predisposes to breast cancer.
BACKGROUND A common missense variant of the CDKN2A gene (A148T) predisposes to malignant melanoma in Poland. An association between malignant melanoma and breast cancer has been reported in several families with CDKN2A mutations, OBJECTIVE To determine whether this variant also predisposes to breast cancer. METHODS Genotyping was undertaken in 4209 cases of breast cancer, unselected for fam...
متن کاملEffect of tumor suppressor gene cyclin-dependent kinase inhibitor 2A wild-type and A148T mutant on the cell cycle of human ovarian cancer cells
Single-base substitution may affect the function of genes. This study identified a single-base substitution of G for A in codon 148 of cyclin-dependent kinase inhibitor 2A (CDKN2A/p16) by sequencing human ovarian cancer cell line UACC-1598. As a tumor suppressor gene, the expression of CDKN2A/p16 should be strictly controlled. In order to control CDKN2A/p16 gene expression, an inducible pTUNE v...
متن کاملمتیلاسیون اگزون 1، ژن CDKN2A در نمونههای بلوک پارافینه سرطان روده بزرگ
Background: The molecular studies indicate some of the genes in the promoter region itself, will undergo methylation. Methylation of CpG islands in the promoter region of that cause silence or reduced expression of genes involved in cell growth pathways, which are colorectal cancer causing agents. Detection of methylation status can be used as a marker for cancer diagnosis and prediction of dis...
متن کامل