Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Hered Cancer Clin Pract ; 19(1): 6, 2021 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-33419454

RESUMEN

INTRODUCTION: The role of PALB2 in carcinogenesis remains to be clarified. Our main goal was to determine the prevalence of PALB2 (509_510delGA and 172_175delTTGT) mutations in bladder and kidney cancer patients from Polish population. MATERIALS AND METHODS: 1413 patients with bladder and 810 cases with kidney cancer and 4702 controls were genotyped for two PALB2 variants: 509_510delGA and 172_175delTTGT. RESULTS: Two mutations of PALB2 gene were detected in 5 of 1413 (0.35%) unselected bladder cases and in 10 of 4702 controls (odds ratio [OR], 1.7; 95% CI 0.56-4.88; p = 0.52). Among 810 unselected kidney cancer cases two PALB2 mutations were reported in two patients (0,24%) (odds ratio [OR], (OR = 1.2; 95% CI 0.25-5.13; p = 0.84). In cases with mutations in PALB2 gene cancer family history was negative. CONCLUSION: We found no difference in the prevalence of recurrent PALB2 mutations between cases and healthy controls. The mutations in PALB2 gene seem not to play a major role in bladder and kidney cancer development in Polish patients.

2.
Mol Biol Rep ; 42(3): 755-64, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25391773

RESUMEN

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.


Asunto(s)
Neoplasias Colorrectales/genética , Reparación del ADN/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Femenino , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Proteínas Nucleares/genética , Polonia , Factores Sexuales , Factores de Transcripción/genética , Proteína de la Xerodermia Pigmentosa del Grupo D/genética , Adulto Joven
3.
Int J Cancer ; 134(5): 1139-46, 2014 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-24037955

RESUMEN

Several single nucleotide polymorphisms (SNPs) have been associated with an elevated risk of prostate cancer risk. It is not established if they are useful in predicting the presence of prostate cancer at biopsy or if they can be used to define a low-risk group of men. In this study, 4,548 men underwent a prostate biopsy because of an elevated prostate specific antigen (PSA; ≥4 ng/mL) or an abnormal digital rectal examination (DRE). All men were genotyped for 11 selected SNPs. The effect of each SNP, alone and in combination, on prostate cancer prevalence was studied. Of 4,548 men: 1,834 (40.3%) were found to have cancer. A positive association with prostate cancer was seen for 5 of 11 SNPs studied (rs1800629, rs1859962, rs1447295, rs4430796, rs11228565). The cancer detection rate rose with the number of SNP risk alleles from 29% for men with no variant to 63% for men who carried seven or more risk alleles (OR = 4.2; p = 0.002). The SNP data did not improve the predictive power of clinical factors (age, PSA and DRE) for detecting prostate cancer (AUC: 0.726 vs. 0.735; p = 0.4). We were unable to define a group of men with a sufficiently low prevalence of prostate cancer that a biopsy might have been avoided. In conclusion, our data do not support the routine use of SNP polymorphisms as an adjunct test to be used on the context of prostate biopsy for Polish men with an abnormal screening test.


Asunto(s)
Polimorfismo de Nucleótido Simple , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Área Bajo la Curva , Biopsia , Tacto Rectal , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología
4.
Arch Med Sadowej Kryminol ; 73(4): 294-307, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38662482

RESUMEN

The purpose of this paper is to formulate recommendations for the disclosure of biological traces in the laboratory and the handling of forensic evidence submitted for identification tests, recommended by the Polish Speaking Working Group of the International Society for Forensic Genetics. The paper organizes the knowledge of the most relevant stages of preliminary analysis of biological traces based on both literature sources and those resulting from years of research practice. Recommendations formulated in the course of multi-stage expert consultations contained in this study should be used in the development of laboratory procedures applied during the execution. * The research is part of doctoral dissertation of Dagmara Lisman entitled "Genetic analysis of a skeleton site revealed during the works on the premises of the former German Forced Labor Camp Treblinka I."


Asunto(s)
Antropología Forense , Humanos , Polonia , Antropología Forense/métodos , Entierro , Filogenia , Genética Forense/métodos , Restos Mortales
5.
Hum Mutat ; 34(4): 636-43, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23520118

RESUMEN

Multiple genotyping techniques were developed on the basis of real-time PCR. In this article, we present a genotyping technique extending the induced Förster resonance energy transfer (iFRET) mechanism in conjunction with simultaneous mutation scanning. Rapid, asymmetric PCR was performed with SYTO9, polymerase lacking 5 → 3 exonuclease activity, two primers, and a probe labeled with 6-Carboxy-X-rhodamine. Six primers and probe sets were designed to detect germline mutations in BRCA1, a singular polymorphism in CCND1 and somatic mutations in KRAS and BRAF genes. The validation set consisted of 140 archival DNA samples from patients with previously confirmed BRCA1 mutation and 42 archival formalin-fixed and paraffin-embedded tissues from patients with colorectal cancer or malignant melanoma. BRCA1 and CCND1 genotyping by iFRET probe showed 100% agreement with Sanger sequencing and other validated methods. A combination of iFRET and high-resolution melting analysis (HRMA) detected a spectrum of six different mutations in the KRAS gene and three different mutations in the BRAF gene. Due to anallele enrichment effect, the sensitivity of mutation detection of iFRET­HRMA genotyping and sequencing of iFRET­HRMA PCR products was significant, increasing from 1.5% to 6.2%, respectively. The technique presented in this article is a useful and cost-effective method for the detection of both germline and somatic mutations.


Asunto(s)
Transferencia Resonante de Energía de Fluorescencia , Técnicas de Genotipaje , Alelos , Secuencia de Bases , Ciclina D1/genética , Análisis Mutacional de ADN , Genes ras , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas c-raf/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Temperatura de Transición
6.
Sci Rep ; 13(1): 21666, 2023 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-38066060

RESUMEN

DNA analysis-based identification is by far the gold standard in forensic genetics and it should be performed in every case involving human remains or unidentified bodies. Bones and teeth are the preferred source of human DNA for genetic analysis. However, there are cases where the nature of the proceedings and historical significance prevent the disruption of skeletal structure. The remains may also be heavily degraded. In such situations, forensic geneticists seek alternative sources of human DNA. Teeth calculus has proven to be a viable source of DNA for identification purposes. The aim of this study was to assess the concentration of human DNA in teeth calculus and evaluate the usefulness of teeth calculus as a DNA source in the identification process. Teeth calculus was collected from skeletons exhumed between 2021 and 2022 by the PBGOT (Polish Genetic Database of Victims of Totalitarianism) team from the former Stalag IID prisoner-of-war camp in Stargard. Genetic analyses included the determination of autosomal and Y-STR markers. The total concentration of human DNA was also evaluated in samples from teeth calculus and teeth taken from the same individuals. The pilot study included 22 skeletons with a sufficient amount of calculus for isolation (specified in the protocol). Samples were taken from the largest areas of calculus deposited on lingual surfaces of mandibular incisors. The prepared samples underwent DNA extraction. Our study demonstrated that teeth calculus is a source of human DNA for remains from the World War II period. The obtained DNA concentration allowed for the determination of STR markers. It was shown that teeth calculus contains human DNA in an amount suitable for preliminary identification analyses.


Asunto(s)
Dermatoglifia del ADN , Cálculos Dentales , Humanos , Cálculos Dentales/genética , Proyectos Piloto , Dermatoglifia del ADN/métodos , Repeticiones de Microsatélite , ADN/genética , Incisivo
7.
Sci Rep ; 13(1): 17118, 2023 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-37816715

RESUMEN

There is now substantial evidence that zinc-finger proteins are implicated in adiposity. Aims were to datamine for high-frequency (near-neutral selection) pretermination-codon (PTC) single-nucleotide polymorphisms (SNPs; n = 141) from a database with > 550,000 variants and analyze possible association with body mass index in a large Polish sample (n = 5757). BMI was regressed (males/females together or separately) against genetic models. Regression for rs67047829 uncovered an interaction-independent association with BMI with both sexes together: mean ± standard deviation, kg/m2: [G];[G], 25.4 ± 4.59 (n = 3650); [G](;)[A], 25.0 ± 4.28 (n = 731); [A];[A], 23.4 ± 3.60 (n = 44); additive model adjusted for age and sex: p = 4.08 × 10-5; beta: - 0.0458, 95% confidence interval (CI) - 0.0732 : - 0.0183; surviving Bonferroni correction; for males: [G];[G], 24.8 ± 4.94 (n = 1878); [G](;)[A], 24.2 ± 4.31 (n = 386); [A];[A], 22.4 ± 3.69 (n = 23); p = 4.20 × 10-4; beta: - 0.0573, CI - 0.0947 : - 0.0199. For average-height males the difference between [G];[G] and [A];[A] genotypes would correspond to ~ 6 kg, suggesting considerable protection against increased BMI. rs67047829 gives a pretermination codon in ERV3-1 which shares an exonic region and possibly promoter with ZNF117, previously associated with adiposity and type-2 diabetes. As this result occurs in a near-neutral Mendelian setting, a drug targetting ERV3-1/ZNF117 might potentially provide considerable benefits with minimal side-effects. This result needs to be replicated, followed by analyses of splice-variant mRNAs and protein expression.


Asunto(s)
Adiposidad , Obesidad , Humanos , Masculino , Femenino , Índice de Masa Corporal , Polonia , Genotipo , Obesidad/complicaciones , Adiposidad/genética , Pérdida de Peso/genética , Codón , Polimorfismo de Nucleótido Simple
8.
Oncotarget ; 13: 628-640, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35478773

RESUMEN

PURPOSE: The association between the NOD2 c.3020insC allele and CDKN2A missense variant c.442G>A (p.P.A148T) and survival of patients with bladder or kidney cancer remains controversial. MATERIALS AND METHODS: We compared the allele frequencies of NOD2 c.3020insC and CDKN2A p.A148T allele in 706 patients with bladder cancer, 410 cases with kidney cancer against two control groups. The Cox proportional hazards model was used to determine whether there were any survival differences between carriers of the NOD2 c.3020insC or the CDKN2A p.A148T variant. RESULTS: Among the three patient subgroups: patients under 60 years of age, non-smokers and a third with histological features of low grade noninvasive papillary bladder cancer, we observed that the c.3020insC allele had a nominal statistically significant effect on survival. We also observed that the NOD2 c.3020insC variant was more frequent in patients with bladder cancer aged between 51 and 60 years. There was some nominal evidence that the CDKN2A p.A148T polymorphism reduced survival in the subgroup of bladder cancer patients under 60 years of age. We observed that in kidney cancer patients, the incidence of the NOD2 variant appeared to be lower in the group aged between 60 and 70 years, however, this was not statistically significant. In addition, in patients with histological features of grade III chromophobic kidney cancer, the c.3020insC allele also appeared to be over-represented but this too was not statistically significant. CONCLUSION: We have shown that the NOD2 c.3020insC allele and the CDKN2A p.A148T polymorphism does not play a role in the survival of patients with bladder cancer.


Asunto(s)
Neoplasias Renales , Neoplasias de la Vejiga Urinaria , Anciano , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Proteína Adaptadora de Señalización NOD2/genética , Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética
9.
Sci Rep ; 12(1): 18923, 2022 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-36344606

RESUMEN

Number of children is an important human trait and studies have indicated associations with single-nucleotide polymorphisms (SNPs). Aim: to give further evidence for four associations using a large sample of Polish subjects. Data from the POPULOUS genetic database was provided from anonymous, healthy, unrelated, Polish volunteers of both sexes (N = 5760). SNPs (n = 173) studied: (a) 69 from the chromosome 17 H1/H2 inversion; (b) six from 1q21.3, 5q21.3 and 14q21.2; and (c) 98 random negative controls. Zero-inflated negative-binomial regression (z.i.) was performed (0-3 numbers of children per individual (NCI) set as non-events; adjustors: year of birth, sex). Significance level p = 0.05 with Bonferroni correction. Statistically-significant differences (with data from both sexes combined) were obtained from highly-linked inversion SNPs: representative rs12373123 gave means: homozygotes TT: 2.31 NCI (n = 1418); heterozygotes CT: 2.35 NCI (n = 554); homozygotes CC: 2.44 NCI (n = 43) (genotype p = 0.01; TTvs.CC p = 0.004; CTvs.CC p = 0.009). (Male data alone gave similar results.) Recessive modeling indicated that H2-homozygotes had 0.118 more children than H1-homozygotes + heterozygotes (z.i.-count estimates ± standard errors: CT, - 0.508 ± 0.194; TT, - 0.557 ± 0.191). The non-over-dispersed count model detected no interactions: of importance there was no significant interaction with age. No positive results were obtained from negative-control SNPs or (b). Conclusions: association between the H1/H2 inversion and numbers of children (previously reported in Iceland) has been confirmed, albeit using a different statistical model. One limitation is the small amount of data, despite initially ~ 6000 subjects. Causal studies require further investigation.


Asunto(s)
Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Femenino , Niño , Humanos , Masculino , Polonia , Estudios de Casos y Controles , Genotipo , Fenotipo
10.
PLoS One ; 16(9): e0257132, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34499690

RESUMEN

PURPOSE: The purpose of this study was to compare the clinical characteristics and the survival of CHEK2 mutation positive and CHEK2 mutation negative patients diagnosed with bladder or kidney cancer. MATERIALS AND METHODS: 1016 patients with bladder and 402 cases with kidney cancer and 8302 controls were genotyped for four CHEK2 variants: 1100delC, del5395, IVS2+1G>A and I157T. Predictors of survival were determined among CHEK2 pathogenic variant carriers using the Cox proportional hazards model. The median follow-up was 17.5 years. Covariates included age (≤60; >61 years), sex (female; male), clinical characteristics (stage: TNM, grade, histopathological type), smoking status (non-smoking; smoking) and cancer family history (negative; positive). RESULTS: We found no impact of CHEK2 mutations on bladder or kidney cancer survival. However, we observed a possible increased survival in the subgroup of patients with stage T1 bladder cancer with CHEK2 mutations but this did not meet statistical significance (HR = 0.14; 95% CI 0.02-1.04; p = 0.055). Moreover, we observed that the missense mutations were more frequent in the low grade invasive bladder cancer patient group (OR = 7.9; 95% CI 1.50-42.1; p = 0.04) and in patients with bladder cancer with stage Ta (OR = 2.4; 95% CI 1.30-4.55; p = 0.006). The different results where missense mutations occurs less often we observed among patients with high grade invasive bladder cancer (OR = 0.12; 95% CI 0.02-0.66; p = 0.04) and those with stage T1 disease (OR = 0.2; 95% CI 0.07-0.76; p = 0.01). Our investigations revealed that any mutation in CHEK2 occurs more often among patients with stage Ta bladder cancer (OR = 2.0; 95% CI 1.19-3.47; p = 0.01) and less often in patients with stage T1 disease (OR = 0.31; 95% CI 0.12-0.78; p = 0.01). In the kidney cancer patients, truncating mutations were present more often in the group with clear cell carcinoma GII (OR = 8.0; 95% CI 0.95-67.7; p = 0.05). The 10-year survival for all CHEK2 mutation carriers with bladder cancer was 33% and for non-carriers 11% (p = 0.15). The 10-year survival for CHEK2 mutation carriers with kidney cancer 34% and for non-carriers 20% (p = 0.5). CONCLUSION: CHEK2 mutations were not associated with any change in bladder or kidney cancer survival regardless of their age, sex, smoking status and family history. We observed a potentially protective effect of CHEK2 mutations on survival for patients with stage T1 bladder cancer. CHEK2 missense mutations were more common among patients with low grade invasive bladder cancer and in patients with stage Ta diease. The frequencies of the I157T CHEK2 pathogenic variant were less in patients with high grade invasive bladder cancer and those with stage T1 disease. Among patients with bladder cancer with stage Ta disease, the OR for any mutation in CHEK2 was 2.0 but for those with stage T1 disease, the OR was 0.3. We observed truncating CHEK2 mutations were associated with kidney cancer patients with GII clear cell carcinoma.


Asunto(s)
Quinasa de Punto de Control 2/genética , Neoplasias Renales/enzimología , Neoplasias Renales/genética , Mutación/genética , Neoplasias de la Vejiga Urinaria/enzimología , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis de Supervivencia
11.
Gut Microbes ; 11(6): 1518-1530, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32453670

RESUMEN

The link between gut microbiota and the development of colorectal cancer has been investigated. An imbalance in the gut microbiota promotes the progress of colorectal carcinogenesis via multiple mechanisms, including inflammation, activation of carcinogens, and tumorigenic pathways as well as damaging host DNA. Several therapeutic methods are available with which to alter the composition and the activity of gut microbiota, such as administration of prebiotics, probiotics, and synbiotics; these can confer various benefits for colorectal cancer patients. Nowadays, fecal microbiota transplantation is the most modern way of modulating the gut microbiota. Even though data regarding fecal microbiota transplantation in colorectal cancer patients are still rather limited, it has been approved as a clinical method of treatment-recurrent Clostridium difficile infection, which may also occur in these patients. The major benefits of fecal microbiota transplantation include modulation of immunotherapy efficacy, amelioration of bile acid metabolism, and restoration of intestinal microbial diversity. Nonetheless, more studies are needed to assess the long-term effects of fecal microbiota transplantation. In this review, the impact of gut microbiota on the efficiency of anti-cancer therapy and colorectal cancer patients' overall survival is also discussed.


Asunto(s)
Neoplasias Colorrectales/terapia , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Prebióticos/administración & dosificación , Probióticos/administración & dosificación , Simbióticos/administración & dosificación , Animales , Neoplasias Colorrectales/microbiología , Terapia Combinada , Humanos
12.
Int J Cancer ; 122(3): 583-6, 2008 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-17918154

RESUMEN

Germline mutations in CHEK2 have been associated with a range of cancer types but little is known about disease risks conveyed by CHEK2 mutations outside of the context of breast and prostate cancer. To investigate whether CHEK2 mutations confer an increased risk of bladder cancer, we genotyped 416 unselected cases of bladder cancer and 3,313 controls from Poland for 4 founder alleles in the CHEK2 gene, each of which has been associated with an increased risk of cancer at other sites. A CHEK2 mutation (all variants combined) was found in 10.6% of the cancer cases and in 5.9% of the controls (OR = 1.9; 95%CI 1.3-2.7; p = 0.0003). We conclude that CHEK2 mutations increase the risk of bladder cancer in the population.


Asunto(s)
Mutación de Línea Germinal , Proteínas Serina-Treonina Quinasas/genética , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Anciano de 80 o más Años , Quinasa de Punto de Control 2 , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Fumar , Neoplasias de la Vejiga Urinaria/enzimología
13.
Cancer Epidemiol ; 38(4): 382-5, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24947589

RESUMEN

Mutation in the BRCA1 gene increases the risk of the person developing breast and/or ovarian cancer. The prevalence and spectrum of large genomic rearrangements (LGRs) varies considerably among different tested populations. In our previous study we described three LGRs in BRCA1 (exons 13-19, exon 17 and exon 22) in Polish families at high risk of breast and ovarian cancer. In this study we analyzed a group of 550 unselected women with ovarian cancer for the three previously identified LGRs. We used a rapid, single-step and closed-tube method: high-resolution melting analysis (HRMA). In this group of unrelated patients diagnosed with ovarian cancer we found three cases with the same deletions of exon 22. This is the first recurrent large deletion in BRCA1 found in Poland. We conclude that screening for the exon 22 deletion in BRCA1 should be included in the Polish BRCA1 genetic testing panel and possibly extended into other Slavic populations.


Asunto(s)
Genes BRCA1 , Neoplasias Ováricas/genética , Exones/genética , Femenino , Eliminación de Gen , Reordenamiento Génico , Humanos , Persona de Mediana Edad , Linaje , Polonia , Reacción en Cadena de la Polimerasa
14.
Gene ; 546(2): 156-61, 2014 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-24933002

RESUMEN

The genetic basis of prostate cancer (PC) is complex and appears to involve multiple susceptibility genes. A number of studies have evaluated a possible correlation between several NER gene polymorphisms and PC risk, but most of them evaluated only single SNPs among XP genes and the results remain inconsistent. Out of 94 SNPs located in seven XP genes (XPA-XPG) a total of 15 SNPs were assayed in 720 unselected patients with PC and compared to 1121 healthy adults. An increased risk of disease was associated with the XPD SNP, rs1799793 (Asp312Asn) AG genotype (OR=2.60; p<0.001) and with the AA genotype (OR=531; p<0.0001) compared to the control population. Haplotype analysis of XPD revealed one protective haplotype and four associated with an increased disease risk, which showed that the A allele (XPD rs1799793) appeared to drive the main effect on promoting prostate cancer risk. Polymorphism in XPD gene appears to be associated with the risk of prostate cancer.


Asunto(s)
Alelos , Genotipo , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/genética , Proteína de la Xerodermia Pigmentosa del Grupo D/genética , Adulto , Anciano , Anciano de 80 o más Años , Proteínas de Unión al ADN/genética , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Proteína de la Xerodermia Pigmentosa del Grupo A/genética
15.
Gene ; 532(2): 173-6, 2013 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-24096176

RESUMEN

BACKGROUND: Germline mutations of BRCA2 and NBS1 genes cause inherited recessive chromosomal instability syndromes and predispose to prostate cancer of poor prognosis. Mutations of the BLM gene cause another chromosomal instability clinical syndrome, called Bloom syndrome. Recently, a recurrent truncating mutation of BLM (Q548X) has been associated with a 6-fold increased risk of breast cancer in Russia, Belarus and Ukraine, but its role in prostate cancer etiology and survival has not been investigated yet. METHODS: To establish whether the Q548X allele of the BLM gene is present in Poland, and whether this allele predisposes to poor prognosis prostate cancer, we genotyped 3337 men with prostate cancer and 2604 controls. RESULTS: Q548X was detected in 13 of 3337 (0.4%) men with prostate cancer compared to 15 of 2604 (0.6%) controls (OR=0.7; 95% CI 0.3-1.4). A positive family history of any cancer in a first- or second-degree relative was seen only in 4 of the 13 (30%) mutation positive families, compared to 49% (1485/3001) of the non-carrier families (p=0.3). The mean follow-up was 49months. Survival was similar among carriers of Q548X and non-carriers (HR=1.1; p=0.9). The 5-year survival for men with a BLM mutation was 83%, compared to 72% for mutation-negative cases. CONCLUSIONS: BLM Q548X is a common founder mutation in Poland. We found no evidence that this mutation predisposes one to prostate cancer or affect prostate cancer survival. However, based on the observed 0.6% population frequency of the Q548X allele, we estimate that one in 100,000 children should be affected by Bloom syndrome in Poland.


Asunto(s)
Codón sin Sentido , Neoplasias de la Próstata/genética , RecQ Helicasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Análisis Mutacional de ADN , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/mortalidad , Factores de Riesgo , Análisis de Supervivencia , Adulto Joven
16.
Eur J Cancer Prev ; 19(2): 167-71, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19952762

RESUMEN

Several recent association studies implicate three neighbouring regions of chromosome 8q24 as the site of prostate cancer susceptibility loci. One region contains both a microsatellite marker DG8S737 and a single nucleotide polymorphism rs1447295. Both have been consistently associated with prostate cancer risk in several populations. However, studies to date have not inquired whether the susceptibility associated with this particular region of 8q24 extends to other cancer sites. We genotyped 3822 cases of cancer of various sites and 1807 controls for rs1447295 polymorphism. A positive association was seen for prostate cancer, but not for any of the other sites studied [odds ratios (ORs) ranging from 0.8 to 1.1]. Prostate cancer cases and controls were genotyped for both rs1447285 and DG8S737. Significant ORs were observed for the A allele of rs1447285 (OR = 1.4; P = 0.01) and the -8 allele of DG8S737 (OR = 1.6; P = 0.006). The association was particularly strong for men with familial prostate cancer (OR = 2.0, P = 0.004 for the A allele; OR = 3.5, P<0.0001 for the -8 allele). The OR associated with the A allele of rs1447295 was slightly higher for aggressive tumours (Gleason score 8 or more) (OR = 1.5), than for tumours with Gleason score 7 and below (OR = 1.3). In conclusion, the relationship between the rs1447295 and DG8S737 polymorphic variants on chromosome 8q24 and prostate cancer risk is seen in the Polish population to a similar degree as it has been observed elsewhere. Although the carcinogenic mechanism associated with this particular locus of 8q24 is unclear it appears to be specific to prostate cancer.


Asunto(s)
Cromosomas Humanos Par 8/genética , Repeticiones de Microsatélite/genética , Neoplasias/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , ADN de Neoplasias/genética , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias/epidemiología , Neoplasias/patología , Polonia/epidemiología , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Factores de Riesgo , Adulto Joven
17.
Eur J Cancer Prev ; 17(5): 389-91, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18714178

RESUMEN

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.


Asunto(s)
Neoplasias de la Mama/genética , Genes p16 , Melanoma/genética , Neoplasias Pancreáticas/genética , Adulto , Edad de Inicio , Neoplasias de la Mama/epidemiología , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Pruebas Genéticas , Humanos , Masculino , Melanoma/epidemiología , Persona de Mediana Edad , Mutación , Neoplasias Pancreáticas/epidemiología , Polonia/epidemiología , Polimorfismo de Longitud del Fragmento de Restricción , Prevalencia
18.
Cancer Res ; 68(23): 9982-6, 2008 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-19047180

RESUMEN

Several genome-wide searches for common cancers have lead to the identification of a small number of loci that harbor low-risk cancer susceptibility markers. One marker, rs6983267 on chromosome 8q24, has been linked to both colon and prostate cancer, and is therefore a good candidate for a multicancer susceptibility marker. To determine the range of cancer sites associated with rs6983267, we genotyped 7,665 cases of cancer, representing 11 common cancer sites, and 1,910 controls. A significant odds ratio (OR) was observed for prostate cancer for carriers of genotype GG [OR, 1.77; 95% confidence interval (CI), 1.47-2.13]. The homozygote OR was higher for tumors with Gleason score 8 to 10 (OR, 1.94; 95% CI, 1.18-3.20) than for tumors with Gleason score 7 and below (OR, 1.65; 95% CI, 1.31-2.08). Significantly elevated (homozygote) ORs were observed for 4 other cancer sites, including colon (OR, 1.36; 95% CI, 1.08-1.72), kidney (OR, 1.52; 95% CI, 1.12-2.05), thyroid (OR, 1.37; 95% CI, 1.02-1.82), and larynx (OR, 1.39; 95% CI, 1.02-1.90). Information was available on family histories of cancer for eight sites. For six of the eight sites (prostate, breast, bladder, larynx, lung, and kidney), the homozygote ORs were higher for cases with a positive family history (at least one first-degree with any cancer) than for cases with unaffected first-degree relatives. Our results suggest that the range of cancers associated with the rs6983267 marker might be larger than previously thought.


Asunto(s)
Cromosomas Humanos Par 8 , Neoplasias/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Marcadores Genéticos/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Adulto Joven
19.
Breast Cancer Res Treat ; 102(1): 119-22, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16897426

RESUMEN

To investigate the contribution of a founder deletion in the CHEK2 gene to the burden of breast cancer in Poland we studied 4,454 women with breast cancer and 5,496 population controls. Cases and controls were genotyped for the presence of a 5,395 bp founder deletion that removes exons 9 and 10 of the CHEK2 gene. This deletion has recently been described in a Czech and Slovak population. The cases and controls had previously been tested for two protein-truncating (IVS2 + 1G > A and 1100delC) and one missense CHEK2 mutation (I157T) which are characteristic for the population. The exons 9 and 10 deletion was present in 0.4% of the controls, in 1.0% (19 of 1,978) of unselected breast cancer cases (OR=2.2; 95% CI: 1.2-4.0; p = 0.01) and in 0.9% (28 of 3,228) of the early-onset cases (OR=2.0; 95% CI: 1.3-1.8; p = 0.02). One of the three truncating CHEK2 mutations (del5395; 1100delC or IVS2 + 1G > A) was seen in 101 of 4,454 (2.3%) cases and in 58 of 5,496 controls (1.1%) (OR=2.2; 95% CI: 1.6-3.0 p < 0.0001). A 5,395 bp founder deletion contributes to the burden of breast cancer in Poland. The deletion was present in 0.9% of the women with breast cancer diagnosed under the age of 51 and in 0.9% of women with breast cancer over the age of 50. This is one of the most common protein-truncating CHEK2 variants in Poland. Overall, 2% of all breast cancers in Poland can be attributed to one of three protein-truncating mutations in CHEK2.


Asunto(s)
Neoplasias de la Mama/genética , Eliminación de Gen , Predisposición Genética a la Enfermedad , Proteínas Serina-Treonina Quinasas/genética , Quinasa de Punto de Control 2 , Femenino , Humanos , Mutación
20.
Breast Cancer Res Treat ; 99(1): 59-62, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16570116

RESUMEN

ARLTS1--a member of ADP-ribosylation factor family, is a newly described candidate tumour suppressor gene. Recent studies show that a nonsense polymorphism, G446A (Trp149Stop), in ARLTS1 gene is significantly more frequent in familial cancer cases than in sporadic cancer cases. This study presents analysis of the germ-line G446A polymorphism in the ARLTS1 gene among 1686 consecutively collected patients with breast cancer, prostate cancer, malignant melanoma, thyroid papillary cancer or laryngeal cancer in Poland. The G446A allele was present in 1.81% (9/497) breast cancer patients, 1.46% (5/343) prostate cancer patients, 1.76% (7/397) melanoma patients, 1.65% (3/182) thyroid papillary carcinoma patients and 2.68% (8/299) of laryngeal cancer patients. The frequency of this polymorphism in the control group was 1.45% (8/552). Differences in the frequency of the G446A polymorphism between case and control groups were not statistically significant. In addition, there was no significant difference in the number of Cancer Familial Aggregations (CFA) among breast, prostate, thyroid or laryngeal cancer cases harbouring the G446A polymorphism, when compared to the G446A negative cases. Interestingly out of the CFA melanoma cases, 4/6 (66.6%) were found to harbour the change compared to only 20.2% (69/341) sporadic melanoma cases. This difference was statistically significant (p = 0.02, OR = 7.8). The results of this study suggest that the G446A in ARLTS1 gene is probably not associated with an increased risk of sporadic breast cancer, prostate cancer, melanoma, thyroid papillary cancer or laryngeal cancer. Moreover, the G446A polymorphism is not significantly more frequent in CFA cases except for families in which the proband had melanoma. To confirm this result more cases of melanoma should be analysed.


Asunto(s)
Factores de Ribosilacion-ADP/genética , Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Neoplasias/genética , Neoplasias/metabolismo , Polimorfismo Genético , Alelos , Neoplasias de la Mama/metabolismo , Salud de la Familia , Femenino , Genes Supresores de Tumor , Humanos , Masculino , Melanoma/metabolismo , Oportunidad Relativa
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA