[Show abstract][Hide abstract] ABSTRACT: Publication is summarization of existing data being results of literature review and our experience on usefulness of selenium as a diagnostic marker selection for control examinations in surveillance and as a marker of patients with high risk of cancers.
[Show abstract][Hide abstract] ABSTRACT: Xeroderma pigmentosum (XP) is a rare autosomal recessive disease that is associated with a severe deficiency in nucleotide excision repair. Genetic polymorphisms in XP genes may be associated with a change in DNA repair capacity, which could be associated with colorectal cancer development. We assessed the association between 94 single nucleotide polymorphisms (SNPs) within seven XP genes (XPA-XPG) and the colorectal cancer risk in the Polish population. We genotyped 758 unselected patients with colorectal cancer and 1,841 healthy adults. We found that a significantly decreased risk of colorectal cancer was associated with XPC polymorphism rs2228000_CT genotype (OR 0.59; p < 0.0001) and the rs2228000_TT genotype (OR 0.29; p < 0.0001) compared to the reference genotype (CC). And an increased disease risk was associated with the XPD SNP, rs1799793_AG genotype (OR 1.44, p = 0.018) and rs1799793_AA genotype (OR 3.31, p < 0.0001) compared to the reference genotype. Haplotype analysis within XPC, XPD and XPG revealed haplotypes associated with an altered colorectal cancer risk. Stratified analysis by gender showed differences between the association of three SNPs: XPC rs2228000, XPD rs1799793 and XPD rs238406 in females and males. Association analysis between age of disease onset and polymorphisms in XPD (rs1799793) and XPC (rs2228000) revealed differences in the prevalence of these variants in patients under and over 50 years of age. Our results confirmed that polymorphisms in XPC and XPD may be associated with the risk of colorectal cancer.
[Show abstract][Hide abstract] ABSTRACT: The E318K mutation in the MITF gene has been associated with a high risk of melanoma, renal cell carcinoma, and pancreatic cancer; the risk of other cancers has not been evaluated so far. Herein, we examined the possible association of E318K and a novel variant of the MITF gene, V320I, with the risk of cancers of different sites of origin in a Polish population. We assayed for the presence of the E318K and V320I missense mutations in 4,226 patients with one of six various cancers (melanoma or cancer of the kidney, lung, prostate, colon, or breast) and 2,114 controls from Poland. The E318K mutation was detected in 4 of 2,114 participants (0.19%) in the Polish control population, the V320I in 3 of 2,114 participants (0.14%) in the control group. We found no statistically significant differences in the prevalence of the E318K and V320I variants among cases and controls. We found two carriers of the E318K variant among melanoma patients (P = 0.95), one carrier among breast cancer patients (P = 0.77), one carrier among colorectal cancer patients (P = 0.82), and one carrier among kidney cancer patients (P = 0.64). Our study demonstrates a lack of strong association of E318K and V320I with increased risk of melanoma or cancers of the kidney, breast, prostate, lung, or colon.
[Show abstract][Hide abstract] ABSTRACT: Parasitic protozoans of the Cryptosporidium genus are intracellular intestinal parasites of mammals, causing cryptosporidiosis. Clinically, cryptosporidiosis manifests as chronic diarrhoea. Individuals with immune disorders, including those with neoplasms, are at risk of symptomatic invasion.
Was the evaluation of Cryptosporidium sp. prevalence in patients with diagnosed colorectal cancer.
The studied group encompassed 87 patients with diagnosed colorectal cancer, undergoing surgery at the Department of General and Oncological Surgery, Pomeranian Medical University, in the years 2009-2010. Immunoenzymatic tests for Cryptosporidium sp. on faeces samples were performed with the use of commercial test kit, ProSpecT(®)Cryptosporidium Microplate Assay (Remel Inc).
The presence of Cryptosporidium sp. was found in 12.6% of studied patients with colorectal cancer. The performed statistical analysis did not reveal any correlation between Cryptosporidium sp. infection and gender, age, neoplasm advancement stage as per Astler-Coller scale, neoplasm differentiation grade, or neoplastic tumour localisation in relation to the splenic flexure.
There was found high prevalence of Cryptosporidium sp. in patients with colorectal cancer. It was comparable to the prevalence reported for patients with immune deficiency.
[Show abstract][Hide abstract] ABSTRACT: Effective treatment is the primary objective of surgeon in the treatment of advanced gastric cancer. Poor prognosis and significant advancement of gastric cancer at the time of diagnosis are decisive factors for the only possible surgical management method being palliative procedures.
was the evaluation of the value of palliative resection procedures in patients with advanced gastric cancer.
The subject in the study was a group of 105 patients with gastric adenocarcinoma at stage 4 of advancement, in whom curative treatment was not possible. The group constituted 44.5% of patients operated on due to gastric cancer at the Department of General and Oncological Surgery, PUM, in the years 1998-2009. The patients were divided into two groups: the first one comprised 44 patients post palliative resections, the second - 61 patients post non-resection procedures. The subject of analysis were early and late treatment results post palliative resections, and they were compared with the treatment results post non-resection procedures.
Palliative resections were performed in 44 patients (19 females and 25 males), while in 61 patients (38 males and 23 females) non-resection procedures were performed. Postoperative complications were observed in 25% of patients in the group post palliative resections and in 11.5% in the group of patients without the resection of primary focus. In-hospital mortality stood at 4.5% in the group post palliative resections and 4.8% in the group post non-resection procedures. The percentage of 1-year and 4-year survival post palliative resections stood at 43% and 8.8%, respectively. In the group without the resection of primary focus, 16% survived 1 year and nobody survived 2 years.
Palliative resections improve the survival of patients with incurable gastric cancer and should be considered if only the loco-regional conditions are favourable.
[Show abstract][Hide abstract] ABSTRACT: Optimal management of asymptomatic generalized rectal cancer is still the matter of debate. The aim of the study was to review stage IV rectal cancer patients who were treated in our clinic since 2000 till 2008 in order to evaluate the effectiveness of surgery.
Fifty-two generalized rectal cancer patients treated with elective resection of primary tumor were identified. Patients' age, sex, duration of hospital stay, modality of surgery, complications, postoperative mortality rate and survival rate were assessed.
Median survival was 16.3 months. Postoperative complications occurred in 29% patients. Postoperative mortality rate was 1.9%.
In properly selected group of patients elective resection of primary tumor may cause low mortality rate and acceptable morbidity rate. This surgical modality allows to avoid potential complications of tumor local growth.
[Show abstract][Hide abstract] ABSTRACT: Evidence to date that germline mutations in the tumor suppressor gene BRCA1 increase the incidence of colorectal cancer is mixed, and both positive and negative results have been reported. To establish whether or not inherited variation in BRCA1 influences the risk of colorectal cancer, we genotyped 2,398 unselected patients with colorectal cancer and 4,570 controls from Poland for three BRCA1 founder mutations (C61G, 4153delA and 5382insC). A BRCA1 mutation was present in 0.42% of unselected cases of colorectal cancer and in 0.48% of controls (OR = 0.8; P = 0.8). The mutation frequency was slightly higher (0.93%) in 321 cases who reported a family history of colon cancer in a first- or second-degree relative (OR = 1.9; P = 0.5). A BRCA1 mutation was also seen in excess (0.82%) in 851 cases who were diagnosed with colorectal cancer at age 60 or earlier (OR = 1.7; P = 0.3). The mean age at onset in carriers was 7 years younger than in non-carriers (57.0 years vs. 64.0) and the difference was significant (P = 0.05). This study suggests that BRCA1 mutations may be associated with early-onset of colorectal cancer.
Familial Cancer 12/2010; 9(4):541-4. · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility.
We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls.
The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect.
Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations.
BMC Cancer 08/2010; 10:420. · 3.32 Impact Factor
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[Show abstract][Hide abstract] ABSTRACT: Mutations of genes associated with the mismatch repair mechanism and mutations of the APC gene are the most frequent causes of hereditary colorectal cancer. An iPLEX test combined with TaqMan genotyping assays was therefore developed to identify common recurrent mutations of those genes in the Polish population. We analyzed 349 DNA samples from 95 positive controls previously identified by sequencing and 254 unexamined individuals. The iPLEX test included two plexes, which comprised seven mutations of the APC gene and 29 mutations of three of the mismatch repair genes. TaqMan assays were designed for nine mutations not covered by the iPLEX assays: one mutation in the APC gene and eight mutations in the mismatch repair genes. Results were then verified independently by sequencing. Our combination method allowed detection of all recurrent mutations occurring in group of patients, followed by full analysis by DNA sequencing. With the exception of one false positive in the iPLEX test in the positive control group that could be assigned to contamination from neighboring wells rather than a detection error, given sufficient DNA concentration and quality, the designed iPLEX/TaqMan test had an accuracy of 100% for the designed assays. These results suggest that the combined iPLEX/TaqMan test is an outstanding tool for identification of recurrent mutations among hereditary colorectal cancer patients.
The Journal of molecular diagnostics: JMD 12/2009; 12(1):82-90. · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recently, the 1100delC variant of cell cycle checkpoint kinase 2 (CHEK2) has been reported to confer a colorectal cancer risk in hereditary non-polyposis-colorectal cancer (HNPCC) and HNPCC-related families in the Netherlands. To investigate whether CHEK2 mutations confer increased cancer risk in HNPCC and HNPCC-related families in Poland, we genotyped 463 probands from HNPCC and HNPCC-related families, and 5,496 controls for 4 CHEK2 alleles (1100delC, IVS2+1G>A, del5395, I157T). All 463 probands were screened for mutations in the HNPCC-related genes MSH2, MLH1 and MSH6. A positive association was observed for HNPCC-related cancer and the I157T missense CHEK2 mutation (OR = 1.7; p = 0.007), but not for the truncating alleles (OR = 1.0; p = 1.0). The association with the I157T was seen both for the 117 cases who fulfill Amsterdam criteria (OR = 1.9; p = 0.1) and for the 346 cases who do not fulfill the criteria (OR = 1.6; p = 0.03). One hundred forty-five of the 463 families had a mutation in MSH2, MLH1 or MSH6 (MMR-positive families). A positive association between the CHEK2 I157T mutation and HNPCC-related cancer was observed only for MMR-negative cases (OR = 2.1; p = 0.0004), but not for MMR-positive cases (OR = 0.8; p = 0.9). The association with I157T was particularly strong for MMR-negative cases with familial colorectal cancer (2 or more first-degree relatives affected) (OR = 2.5; p < 0.0001). We conclude that the I157T variant of CHEK2 increases the risk of colorectal cancer among MMR-negative, HNPCC/HNPCC-related families in Poland.
International Journal of Cancer 10/2009; 126(12):3005-9. · 6.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Genetic predispositions to disease have focused on highly penetrant causative changes in tumor suppressor genes or genes associated with DNA mismatch repair. New investigations are revealing new genetic associations with disease that are more subtle in their association with disease and require characterization.
In this report we have examined the tumor characteristics in a group of patients who have been shown to harbor two polymorphisms in two genes that are associated with the immune system NOD2 and TNFalpha.
Colorectal cancers from patients with NOD2 3020insC and TNFalpha-1031T/T constitutional changes are mostly right-sided disease (OR=2.21, p=0.03) with a tendency to higher stages (OR=2.41, p=0.06), increased number of associated polyps (OR=1.77, p=0.16) and later age of average age of disease onset (p=0.039).
The results reveal that there appear to be specific characteristics associated with the tumors that may aid in determining management strategies to reduce the risk of disease.
[Show abstract][Hide abstract] ABSTRACT: In this report the contribution of CDKN2A/ARF germline mutations to early-onset cancers of the breast, pancreas and malignant melanoma was examined. We screened 66 women with breast cancer diagnosed at age 30 and below, 72 melanoma patients with the median age at diagnosis < or = 40 years and 51 pancreatic cancer patients diagnosed under the age of 50 years. In the total set of 189 patients we found a novel change Pro48Arg (nt 143 c > g), a novel intronic change IVS1+36 g>c and two common variants A148T and IVS3+29 c>g. The results of this study revealed a paucity of mutations in CDKN2A/ARF suggesting that in the Polish population this gene does not contribute significantly to early-onset breast cancer, pancreatic cancer and malignant melanoma.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 11/2008; 17(5):389-91. · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to determine whether four VDR gene single nucleotide polymorphisms (SNPs: rs1544410, rs731236, rs10735810 and rs4516035) are associated with breast cancer risk in Polish population. Two independent series of female patients were employed: 960 consecutive breast cancer cases, and 800 unselected early onset cases diagnosed under the age of 51. The control group for the consecutive breast cancer cases consisted of 960 healthy, age-matched women with a negative cancer family history. 550 healthy women, aged 51 or less, with negative cancer family history were selected as the independent controls for the early onset breast cancer cases. The frequencies of the VDR polymorphisms in the unselected cases when compared to the respective control population failed to reveal any association between the individual SNPs and disease. Examination of the group of early-onset patients, revealed an association between rs10735810 and increased breast cancer risk. Heterozygous carriers for the change had an OR = 1.73 (95% CI 1.33-2.26, P < 0.0001) and homozygous carriers OR = 2.34 (95% CI 1.71-3.21, P < 0.0001). The remaining three examined SNPs failed to show any association with disease risk. In summary, this study has identified an association between the VDR gene and early onset breast cancer risk in the Polish population.
Breast Cancer Research and Treatment 06/2008; 115(3):629-33. · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study is to verify the hypothesis that genetic polymorphisms are associated with the predisposition to all malignancies. Using as a model breast cancers from the homogenous Polish population (West Pomeranian region) after stratification of 977 patients by age at diagnosis (under 51 years and above 50 years) and by tumour pathology (ductal cancers--low and high grade, lobular cancers, ER-positive/negative) we tested this hypothesis. Altogether 20 different groups of breast cancer cases have been analyzed. The results were compared to a group of unaffected controls that were matched by age, sex, ethnicity and geographical location and originated from families without cancers of any site among relatives. Molecular alterations selected for analyses included those which have been previously recognized as being associated with breast cancer predisposition. Statistically significant differences between the breast cancer cases and controls were observed in 19 of the 20 analyzed groups. Genetic changes were present in more than 90% of the breast cancer patients in 18 of 20 groups. The highest proportion of cases with constitutional changes-99.3% (139/140) was observed for lobular cancers. The number and type of genetic marker and/or the level of their association with the specific cancer predisposition was different between groups. Markers associated with majority of groups included: BRCA1, CHEK2, p53, TNRnTT, FGFRnAA, XPD CC/AA and XPD GG. Some markers appeared to be group specific and included polymorphisms in CDKN2A, CYP1B1, M3K nAA, and RS67.
Breast Cancer Research and Treatment 05/2008; 114(1):121-6. · 4.47 Impact Factor