[show abstract][hide abstract] ABSTRACT: UBC9 protein (E2-conjugating enzyme) plays a key role in post-translation modification named sumoylation. Proteins, which are sumoylated take part in many cellular processes including cell growth, maintaining the genome integrity and stability and cancer development. The aim of this study was to investigate an association between three polymorphisms of the UBC9 gene: c.73G>A (rs11553473), c.430T>G (rs75020906) and g.1289209T>C (rs7187167) and a risk of ductal breast cancer occurrence. We performed a case-control study in 181 breast cancer cases and 277 controls using PCR-RLFP and ASO-PCR. In the case of the 430T>G polymorphism of the UBC9 gene lack of variability suggests that there is not a polymorphic site in polish population. We observed that a risk of breast cancer occurrence is elevated in patients with the G/A genotype (OR 5.03; 95 % Cl 3.05-8.28), the A/A genotype (OR 11.3; 95 % Cl 4.24-30.3) and the A allele (OR 6.86; 95 % Cl 4.43-10.6) of the c.73G>A polymorphism. In the case of the g.1289209T>C polymorphism we found a correlation between estrogen receptor (ER) expression and the T/T genotype (OR 0.22; 95 % Cl 0.07-0.64) and the T allele (OR 0.53; 95 % Cl 0.32-0.88). We also found a correlation between the T/T genotype (OR 4.13; 95 % Cl 1.21-14.1) and the T allele (OR 2.09; 95 % Cl 1.07-4.08) of the g.1289209T>C polymorphism with triple negative breast cancer. Our results suggest that the variability of the UBC9 gene can play a role in breast cancer occurrence.
Pathology & Oncology Research 07/2013; · 1.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: Tobacco smoking and alcohol drinking generate oxidative DNA damage and may contribute to larynx carcinogenesis. The X-ray repair cross complementing 1 (XRCC1) and excision repair cross-complementing rodent repair deficiency, complementation group 4 (ERCC4(XPF)) genes are important components of DNA excision repair systems, which repair DNA damage induced by various factors, including tobacco smoking and alcohol.
To investigate the association between the genotypes of the XRCC1-Arg399Gln (rs25487) and ERCC4-Arg415Gln (rs1800067) polymorphisms and smoking- and drinking-related larynx cancer in a Polish population.
The polymorphisms were determined by PCR-RFLP method in 253 patients with squamous cell carcinoma of the larynx and 253 sex- and age-matched controls.
We did not find any association between the investigated polymorphisms and larynx carcinoma, dependent on either smoking or drinking status. No association was found between these polymorphisms and larynx cancer grade, stage or age at diagnosis.
The results indicated that Arg399Gln polymorphism of XRCC1 gene and Arg415Gln polymorphism of ERCC4 gene may not be associated with smoking- and drinking-related larynx cancer in Polish population.
[show abstract][hide abstract] ABSTRACT: The cellular reaction to the DNA-damaging agents may modulate individual's cancer susceptibility. This reaction is mainly determined by the efficacy of DNA repair, which in turn, may be influenced by the variability of DNA repair genes, expressed by their polymorphism. The hOGG1 gene encodes a glycosylase of base excision repair and RAD51 specifies a key protein in homologues recombination repair. Both proteins can be involved in the repair of DNA lesions, which are known to contribute to endometrial cancer. In the present work we determined the extent of basal DNA damage and the efficacy of removal of DNA damage induced by hydrogen peroxide and N-methyl-N'-nitro N-nitrosoguanidyne (MNNG) in peripheral blood lymphocytes of 30 endometrial cancer patients and 30 individuals without cancer. The results from DNA damage and repair study were correlated with the genotypes of two common polymorphisms of the hOGG1 and RAD51 genes: a G>C transversion at 1245 position of the hOGG1 gene producing a Ser → Cys substitution at the codon 326 (the Ser326Cys polymorphism) and a G>C substitution at 135 position of the RAD51 gene (the 135G>C polymorphism). DNA damage and repair were evaluated by alkaline single cell gel electrophoresis and genotypes were determined by restriction fragment length polymorphism PCR. We observed a strong association between endometrial cancer and the C/C genotype of the 135G>C polymorphism of the RAD51 gene. Moreover, there was a strong correlation between that genotype and endometrial cancer occurrence in subjects with a high level of basal DNA damage. We did not observe any correlation between the Ser326Cys polymorphism of the hOGG1 gene and endometrial cancer. Our result suggest that the 135G>C polymorphism of the RAD51 gene may be linked to endometrial cancer and can be considered as an additional marker of this disease.
[show abstract][hide abstract] ABSTRACT: UBC9 (E2) SUMO conjugating enzyme plays an important role in the maintenance of genome stability and integrity. In the present work we examined the association between the c.73G>A (Val25Met) polymorphism of the UBC9 gene (rs11553473) and efficacy of DNA double-strand breaks (DSBs) repair (DRE) in breast cancer patients. We determined the level of endogenous (basal) and exogenous (induced by γ-irradiation) DSBs and efficacy of their repair in peripheral blood lymphocytes of 57 breast cancer patients and 70 healthy individuals. DNA damage and repair were studied by neutral comet assay. Genotypes were determined in DNA from peripheral blood lymphocytes by allele-specific PCR (ASO-PCR). We also correlated genotypes with the clinical characteristics of breast cancer patients. We observed a strong association between breast cancer occurrence and the variant allele carried genotypes in patients with elevated level of basal as well as induced DNA damage (OR 6.74, 95% CI 2.27-20.0 and OR 5.33, 95% CI 1.81-15.7, respectively). We also found statistically significant (p<0.05) difference in DRE related to the c.73G>A polymorphism of the UBC9 gene in breast cancer patients. Carriers of variant allele have decreased DNA DRE as compared to wild type genotype carriers. We did not find any association with the UBC9 gene polymorphism and estrogen and progesterone receptor status. The variant allele of the UBC9 gene polymorphism was strongly inversely related to HER negative breast cancer patients (OR 0.03, 95% CI 0.00-0.23). Our results suggest that the c.73G>A polymorphism of the UBC9 gene may affect DNA DSBs repair efficacy in breast cancer patients.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 12/2010; 694(1-2):31-8. · 3.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: Dental composite materials contain polymers of methacrylates, which, due to mechanical abrasion and enzymatic action of saliva, may release their monomers into oral cavity and the pulp. Moreover, polymerization is always incomplete and leaves usually considerable fraction of free monomers. Mechanisms of the genotoxicity of methacrylate monomers have been rarely explored. As the polymerization of a monomer is catalyzed by a co-monomer, their combined action should be considered. In the present work, we investigated cytotoxic and genotoxic effects of urethane dimethacrylate (UDMA), often used as a monomer, at 1 mM, and triethylene glycol dimethacrylate (TEGDMA), a typical co-monomer, at 5 mM singly and in combination. Experiments were conducted on Chinese hamster ovary cells. Cell viability, apoptosis and cell cycle were assessed by flow cytometry, whereas DNA damage was evaluated by plasmid conformation test and comet assay. Both compounds decreased the viability of the cells, but did not induce strand breaks in an isolated plasmid DNA. However, both substances, either singly or in combination, damaged DNA in CHO cells as evaluated by comet assay. Both compounds induced apoptosis, but a combined action of them led to a decrease in the number of apoptotic cells. The combined action of UDMA and TEGDMA in the disturbance of cell cycle was lesser compared to the action of each compound individually. Individually, though UDMA and TEGDMA may induce cytotoxic and genotoxic, however, a combination of both does not produce a significant increase in these effects.
[show abstract][hide abstract] ABSTRACT: The interaction between a chemical and a cell may strongly depend on whether this cell is normal or pathological. Side effects of anticancer drugs may sometimes overcome their benefit action, so it is important to investigate their effect in both the target and normal cells. Capecitabine (Xeloda, CAP), a prodrug of 5-fluorouracil, is mainly used in colon cancer, but little is known about its action in head and neck cancer. We compared the cyto- and genotoxicity of CAP in head and neck HTB-43 cells and normal human lymphocytes by comet assay and flow cytometry. CAP at concentration up to 50 μM significantly decreased the viability of the cancer cells, whereas it did not affect normal lymphocytes. The drug did not interact with isolated plasmid DNA, but it damaged DNA in both cancer and normal cells. However, the extent of the damage in the former was much higher than in the latter. CAP induced apoptosis in the cancer cells, but not in normal lymphocytes. Pre-treatment of the cells with the nitrone spin traps α-(4-pyridil-1-oxide)-N-tert-butylnitrone and N-tert-butyl-α-phenylnitrone decreased the extent of CAP induced DNA damage, suggesting that free radicals may be involved in the formation of DNA lesions induced by CAP. The drug evoked an increase in the G0/G1 cell population accompanied by a decrease in the S cell population. CAP may evoke a pronounced cyto- and genotoxic effects in head and neck cancer cells, whereas it may or may not induce such effects in normal cells to far lesser extent.
[show abstract][hide abstract] ABSTRACT: XRCC2 and XRCC3 proteins are structurally and functionally related to RAD51 which play an important role in the homologous recombination, the process frequently involved in cancer transformation. In our previous work we show that the 135G>C polymorphism (rs1801320) of the RAD51 gene can modify the effect of the Thr241Met polymorphism (rs861539) of the XRCC3 gene. We tested the association between the 135G>C polymorphism of the RAD51 gene, the Thr241Met polymorphism of the XRCC3 gene and the Arg188His polymorphism (rs3218536) of the XRCC2 gene and colorectal cancer risk and clinicopathological parameters. Polymorphisms were evaluated by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) in 100 patients with invasive adenocarcinoma of the colon and in 100 sex, age and ethnicity matched cancer-free controls. We stratified the patients by genotypes, tumour Duke's and TNM stage and calculated the linkage of each genotype with each stratum. Carriers of Arg188Arg/Me241tMet, His188His/Thr241Thr and His188His/G135G genotypes had an increased risk of colorectal cancer occurrence (OR 5.70, 95% CI 1.10-29.5; OR 12.4, 95% CI 1.63-94.9; OR 5.88, 95% CI 1.21-28.5, respectively). The C135C genotype decreased the risk of colorectal cancer singly (OR 0.06, 95% CI 0.02-0.22) as well as in combination with other two polymorphisms. TNM and Duke's staging were not related to any of these polymorphisms. Our results suggest that the 135G>C polymorphism of the RAD51 gene can be an independent marker of colorectal cancer risk. The Thr241Met polymorphism of the XRCC3 gene and the Arg188His polymorphism of the XRCC2 gene can modify the risk of colorectal cancer.
[show abstract][hide abstract] ABSTRACT: Bisphenol A-glycidyl methacrylate (BisGMA) is monomer of dental filling composites, which can be released from these materials and cause adverse biologic effects in human cells. In the present work, we investigated genotoxic effect of BisGMA on human lymphocytes and human acute lymphoblastic leukemia cell line (CCRF-CEM) cells. Our results indicate that BisGMA is genotoxic for human lymphocytes. The compound induced DNA damage evaluated by the alkaline, neutral, and pH 12.1 version of the comet assay. This damage included oxidative modifications of the DNA bases, as checked by DNA repair enzymes EndoIII and Fpg, alkali-labile sites and DNA double-strand breaks. BisGMA induced DNA-strand breaks in the isolated plasmid. Lymphocytes incubated with BisGMA at 1 mM were able to remove about 50% of DNA damage during 120-min repair incubation. The monomer at 1 mM evoked a delay of the cell cycle in the S phase in CCRF-CEM cells. The experiment with spin trap-DMPO demonstrated that BisGMA induced reactive oxygen species, which were able to damage DNA. BisGMA is able to induce a broad spectrum of DNA damage including severe DNA double-strand breaks, which can be responsible for a delay of the cell cycle in the S phase.
Archives of Toxicology 09/2010; 85(11):1453-61. · 5.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: A C/T transition - rs4987117 (the Thr1915Met polymorphism) and an A/G transition - rs11571653 (the Met784Val polymorphism) in the BRCA2 gene were linked to breast cancer risk in Polish and Japanese populations, respectively.
To study the association between polymorphisms of the BRCA2 gene and clinical parameters in breast cancer.
Both polymorphisms were evaluated by RFLP - PCR in blood samples obtained from 117 women with sporadic breast cancer. Patients were stratified by genotype, Bloom - Richardson grade, TNM stage, estrogene and progesterone receptors (PR) status and the linkages of each genotype with each stratum were calculated by logistic regression.
Variant genotypes and alleles of both polymorphisms of the BRCA2 gene were inversely related to hormone receptor status for a group of patients with at least one positive receptor status as compared to a group with both receptors negative status (OR 0.27, 95% CI 0.07 - 0.95, p = 0.043 and OR 0.39, 95% CI 0.19 - 0.82, p = 0.013 for Met1915Met homozygote and 1915Met allele, respectively and OR 0.02, 95% CI 0.00 - 0.13, p = 0.0005 and OR 0.43, 95% CI 0.21 - 0.88, p = 0.021, for Val784Val homozygote and the 784Val allele. No association was found between both polymorphisms and Bloom - Richardson grading and TNM staging.
Our results suggest that variant genotypes of the Thr1915Met and Met784Val polymorphisms of the BRCA2 gene may be indicative factors in therapy of ductal breast cancer.
[show abstract][hide abstract] ABSTRACT: Mutations in the DNA repair genes may contribute to the increased risk of cancer, including colorectal cancer. Xeroderma pigmentosum group D (XPD) protein and human homolog of the 8-oxoguanine glycosylase 1 (hOGG1) are involved in nucleotide excision repair and base excision repair, respectively. The XPD and the hOGG1 genes are highly polymorphic, and some of their polymorphisms are associated with several types of cancers. However, there is controversy as to the relationship between their polymorphisms and the risk of colorectal cancer. In the present study, we therefore searched for the association in a Polish population between colorectal cancer and two common polymorphisms: an A --> C transversion in the XPD gene that produces a Lys-to-Gln substitution at codon 751 (the Lys751Gln polymorphism; rs28365048) and a C --> G transversion in the hOGG1 gene resulting in a Ser-to-Cys change at codon 326 (the Ser326Cys polymorphism; rs1052133). Genotypes were determined using peripheral blood lymphocytes of 100 colorectal cancer patients and 100 age-, sex- and ethnicity-matched cancer-free controls by PCR and restriction fragment-length polymorphism analysis. We did not find statistically significant association between each polymorphism and the occurrence of colorectal cancer, and did not observe any relationship between each polymorphism and colorectal cancer progression assessed by node metastasis, tumor size and Duke's stage. Moreover, there was no correlation between combined genotypes of the two polymorphisms and colorectal cancer. Therefore, the Lys751Gln polymorphism of the XPD gene and the Ser326Cys polymorphism of the hOGG1 gene are not associated with colorectal cancer in a Polish population.
The Tohoku Journal of Experimental Medicine 08/2009; 218(3):185-91. · 1.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: DNA repair processes assure genomic integrity and play the crucial role in protecting against carcinogenic factors. Mutations in DNA repair genes, which code proteins engaged in repair processes, may lead to carcinogenesis and among others also to colorectal cancer development. RAD51 gene encodes a protein of DNA homologues recombination repair.
To evaluate the role of RAD51 gene polymorphism in patients with colorectal cancer in Polish subpopulation Materials and methods. The studied group comprised 100 colorectal cancer patients (aged 57-75) and 236 age, sex-, age- and ethnicity-matched cancer-free controls. Genotypes were determined in DNA from peripheral blood lymphocytes by PCR-RFLP.
An association between colorectal cancer occurrence and the G/C variant of the 135 G/C RAD51 polymorphism was found (OR 2.45; 95% CI 1,45-4,14) (p > 0.05).
The G/C variant of the 135 G/C RAD51 polymorphism may be associated with the increased risk of colorectal cancer development.
Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 05/2009; 26(155):455-7.
[show abstract][hide abstract] ABSTRACT: The RAD51 protein and its paralog, XRCC3, play an important role in the repair of DNA double-strand breaks (DSBs) by homologous recombination. Since DSBs may contribute to the pathogenesis of breast cancer and variability in DNA repair genes may be linked with some cancers, we performed a case-control study (135 cases and 175 controls) to check the association between the genotypes of the Thr241Met polymorphism of the XRCC3 gene and the 135G>C polymorphism of the RAD51 gene and breast cancer occurrence and progression. Genotypes were determined in peripheral blood lymphocytes by RFLP-PCR. We did not find any association between either polymorphism singly and breast cancer occurrence. Both polymorphisms were not related to tumor size, estrogen and progesterone receptors status, cancer type and grade. However, the Thr241Met genotype of the XRCC3 polymorphism slightly increased the risk of local metastasis in breast cancer patients (OR 2.56, 95% CI 1.27-5.17). The combined Thr241Met/135G>C genotype decreased the risk of breast cancer occurrence (OR 0.22, 95% CI 0.08-0.59). Our results suggest that the variability of the DNA homologous recombination repair genes RAD51 and XRCC3 may play a role in breast cancer occurrence and progression, but this role may be underlined by a mutual interaction between these genes.
Experimental and Molecular Pathology 05/2009; 87(1):32-5. · 2.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: Elevated oxidative stress in type 2 diabetic patients leads to the accumulation of DNA damage and possibly acceleration of diabetic complications. Numerous studies indicate that diabetic patients may display impaired DNA repair compared to healthy subjects.
The aim of the study was to compare the distribution of genotypes of DNA repair genes between type 2 diabetic patients and non-diabetic subjects.
Polymerase chain reaction-based restriction fragment length polymorphism was used to determine the distribution of genotypes and frequency of alleles of polymorphisms of base excision repair genes, including the Arg399Gln polymorphism of the XRCC1 gene and Ser326Cys in the hOGG1 gene. The study population included 195 subjects, including 94 with type 2 diabetes mellitus and 101 with normal glucose metabolism. All study participants were Caucasian and inhabited the city of Łódź, Poland.
The frequency of the Gln allele in XRCC1 gene (41% vs. 47%, odds ratio [OR] 0.80, CI 0.54-1.19) and Cys allele in hOGG1 gene (19% vs. 18%, OR 1.09, CI 0.65-1.82) did not differ significantly between diabetic patients and subjects with normal glucose metabolism. Linkage analysis revealed that the Arg/Gln-Ser/Ser combination of genotypes of XRCC1 and hOGG1, respectively (not associated with a decreased activity of both genes) occurs more commonly in type 2 diabetic patients.
The results of our study suggest no association between decreased activity of the examined DNA repair genes and type 2 diabetes mellitus in the studied population.
Polskie archiwum medycyny wewnȩtrznej 04/2009; 119(3):122-8. · 1.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: The risk of sporadic colorectal cancer can be associated with environmental and lifestyle factors that may be sources of physical and chemical carcinogens, modulated by products of many low penetrance genes. Polymorphisms of DNA repair genes may influence variation in individual DNA repair capacity, which is crucial for preventing genomic instability, which, in turn, may be associated with risk of cancer. XRCC1 is an essential protein for the base excision repair pathway which primarily deals with DNA base modifications, arisen spontaneously or as a consequence of the action of environmental factors.
To perform a case-control study and test the association between two polymorphisms in the XRCC1 gene: Arg194Trp and Arg399Gln and colorectal cancer risk and progression.
Genotypes were determined in DNA from peripheral blood lymphocytes of 100 colorectal cancer patients and 100 age, sex and ethnic-matched cancer-free controls by PCR RFLP.
We found that both polymorphisms of the XRCC1 gene were not associated with risk and progession of colorectal cancer in a Polish population. Moreover, there was not such association form the Arg194Trp/Arg399Gln haplotypes.
The Arg194Trp and Arg399Gln polymorphisms of the XRCC1 gene may not be associated with colorectal cancer in Polish population.
[show abstract][hide abstract] ABSTRACT: We performed a case-control study (150 cases and 150 controls) to test the association between three polymorphisms in BRCA2 and RAD51 genes and breast cancer risk. Genotypes were determined in DNA from blood cells by PCR-RFLP. Cancer occurrence was strongly associated with the BRCA2 Met/1915Thr homozygous polymorphic variants, whereas heterozygous variant was associated with significant reduction in breast cancer risk. Gene-gene interaction between the BRCA2-Met1915Thr Thr/Thr and BRCA2-Met784Val Met/Met homozygous variants increased the risk. Therefore, the Met1915Thr polymorphism in the BRCA2 gene may be considered as an independent marker of breast cancer.
Breast Cancer Research and Treatment 12/2005; 94(2):105-9. · 4.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: DNA damage may be associated with type 2 diabetes mellitus (T2DM) and its complications mainly through oxidative stress. Little is known about DNA repair disturbances potentially contributing to the overall extent of DNA damage in T2DM, which, in turn, may be linked with genomic instability resulting in cancer. To assess whether DNA repair may be perturbed in 2DM we determined: (1) the level of endogenous basal DNA damage, this means damage recognized in the alkaline comet assay (DNA strand breaks and alkali labile sites) as well as endogenous oxidative and alkylative DNA damage (2) the sensitivity to DNA-damaging agents hydrogen peroxide and doxorubicin and the efficacy of removing of DNA damage induced by these agents in peripheral blood lymphocytes of T2DM patients and healthy individuals. The level of DNA damage and the kinetics of DNA repair was evaluated by the alkaline single cell gel electrophoresis (comet assay). Oxidative and alkylative DNA damage were assayed with the use of DNA repair enzymes endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg), recognizing oxidized DNA bases and 3-methyladenine-DNA glycosylase II (AlkA) recognizing alkylated bases. The levels of basal endogenous and oxidative DNA damage in diabetes patients were higher than in control subjects. There was no difference between the level of alkylative DNA in the patients and the controls. Diabetes patients displayed higher susceptibility to hydrogen peroxide and doxorubicin and decreased efficacy of repairing DNA damage induced by these agents than healthy controls. Our results suggest that type 2 diabetes mellitus may be associated not only with the elevated level of oxidative DNA damage but also with the increased susceptibility to mutagens and the decreased efficacy of DNA repair. These features may contribute to a link between diabetes and cancer and metrics of DNA damage and repair, measured by the comet assay, may be markers of risk of cancer in diabetes.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 11/2004; 554(1-2):297-304. · 3.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: Impaired DNA repair may fuel up malignant transformation of breast cells due to the accumulation of spontaneous mutations in target genes and increasing susceptibility to exogenous carcinogens. Moreover, the effectiveness of DNA repair may contribute to failure of chemotherapy and resistance of breast cancer cells to drugs and radiation. The breast cancer susceptibility genes BRCA1 and BRCA2 are involved in DNA repair. To evaluate further the role of DNA repair in breast cancer we determined: (1) the kinetics of removal of DNA damage induced by hydrogen peroxide and the anticancer drug doxorubicin, and (2) the level of basal, oxidative and alkylative DNA damage before and during/after chemotherapy in the peripheral blood lymphocytes of breast cancer patients and healthy individuals. The level of DNA damage and the kinetics of DNA repair were evaluated by alkaline single cell gel electrophoresis (comet assay). Oxidative and alkylative DNA damage were assayed with the use of DNA repair enzymes endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg), recognizing oxidized DNA bases and 3-methyladenine-DNA glycosylase II (AlkA) recognizing alkylated bases. We observed slower kinetics of DNA repair after treatment with hydrogen peroxide and doxorubicin in lymphocytes of breast cancer patients compared to control individuals. The level of basal, oxidative and alkylative DNA damage was higher in breast cancer patients than in the control and the difference was more pronounced when patients after chemotherapy were engaged, but usually the level of DNA damage in these patients was too high to be measured with our system. Our results indicate that peripheral blood lymphocytes of breast cancer patients have more damaged DNA and display decreased DNA repair efficacy. Therefore, these features can be considered as risk markers for breast cancer, but the question whether they are the cause or a consequence of the illness remains open. Nevertheless, our results suggest that research on the mutagen sensitivity and efficacy of DNA repair could impact the development of new diagnostic and screening strategies as well as indicate new targets to prevent and cure cancer. Moreover, the comet assay may be applied to evaluate the suitability of a particular mode of chemotherapy to a particular cancer patient.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 11/2004; 554(1-2):139-48. · 3.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: Variability in DNA repair genes may contribute to human cancer risk. We performed a case-control study (51 cases and 100 controls) to test the association between two polymorphisms: Arg399Gln in the XRCC1 gene and Thr241Met in the XRCC3 gene and colorectal cancer risk. Genotypes were determined in tumour tissue and distant mucosa samples by PCR RFLP with the NciI restriction enzyme for XRCC1 and NcoI for XRCC3. Cancer occurrence was strongly associated with the XRCC3 Met/Met polymorphic variant (OR = 9.45; (95% CI 8.77-11.65)), whereas Thr/Thr and Thr/Met variants were associated with significant reduction in colorectal cancer risk (OR = 0.16; 95% CI 0-0.26 and OR = 0.26; 95% CI 0.25-0.27, respectively). Weak association was found between the XRCC1 Arg/Arg and Gln/Gln variants and the risk of colorectal cancer (OR = 1.28; 95% CI 1.00-1.84 and OR = 1.13; 95% CI 0.85-2.34, respectively). Gene-gene interaction between the XRCC1 Arg/Arg and XRCC3 Met/Met homozygous variants slightly increased the risk (OR = 10.50; 95% CI 5.67-14.79). Both polymorphisms were not associated with colorectal cancer progression.
Journal of experimental & clinical cancer research: CR 07/2004; 23(2):285-94. · 1.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study describes the distribution of GSTT1 and GSTM1 polymorphisms in a normal population of central Poland. A homozygous inherited deletion of either gene leads to absence of enzyme activity in affected individuals, and those lacking more than one detoxifying gene are at the highest risk for diseases caused by environmental factors. The prevalence of the "null" genotype of the GSTM1 and GSTT1 genes was determined by using a multiplex polymerase chain reaction methodology in a group of 233 healthy individuals. We found the following frequencies of individuals with mutated alleles: 47.6% were homozygously deficient for GSTM1 (51.1% males, 42.4% females) and 16.3% for GSTT1 (17.7% males, 15.2% females). The combined analyses GSTM1/GSTT1 revealed the following genotypes: +/+, 44.2% (42.6% males, 46.7% females); "null"/+, 39.1% (39.7% males, 38.0% females); +/"null," 8.6% (7.1% males, 10.9% females); "null"/"null," 8.1% (10.6% males, 4.4% females). Of interest is the small number of women lacking both genes. Significant differences occurred between men and women in some age groups, which could suggest that sex differences in susceptibility to diseases may be caused by genotype differences in detoxifying enzymes such as glutathione S-transferase. The data obtained may prove to be useful for epidemiological studies.
Human Biology 05/2003; 75(2):301-7. · 1.52 Impact Factor