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1.
Cancer Epidemiol ; 33(2): 161-3, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19679065

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.


Assuntos
Neoplasias Colorretais/genética , Proteína Adaptadora de Sinalização NOD2/genética , Polimorfismo Genético/genética , Fator de Necrose Tumoral alfa/genética , Idoso , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
2.
BMC Cancer ; 8: 112, 2008 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-18433468

RESUMO

BACKGROUND: Patients with chronic inflammatory bowel disease (IBD) are at an increased risk of colorectal cancer (CRC) and it is estimated that one in six persons diagnosed with IBD will develop CRC. This fact suggests that genetic variations in inflammatory response genes may act as CRC disease risk modifiers. METHODS: In order to test this hypothesis we investigated a series of polymorphisms in 6 genes (NOD2, DLG5, OCTN1, OCTN2, IL4, TNFalpha) associated with the inflammatory response on a group of 607 consecutive newly diagnosed colorectal cancer patients and compared the results to controls (350 consecutive newborns and 607 age, sex and geographically matched controls). RESULTS: Of the six genes only one polymorphism in TNFalpha(-1031T/T) showed any tendency to be associated with disease risk (64.9% for controls and 71.4% for CRC) which we further characterized on a larger cohort of CRC patients and found a more profound relationship between the TNFalpha -1031T/T genotype and disease (64.5% for controls vs 74.7% for CRC cases above 70 yrs). Then, we investigated this result and identified a suggestive tendency, linking the TNFalpha -1031T/T genotype and a previously identified change in the CARD15/NOD2 gene (OR = 1.87; p = 0,02 for CRC cases above 60 yrs). CONCLUSION: The association of polymorphisms in genes involved in the inflammatory response and CRC onset suggest that there are genetic changes capable of influencing disease risk in older persons.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Doenças Inflamatórias Intestinais/genética , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias Colorretais/etiologia , Feminino , Testes Genéticos , Humanos , Doenças Inflamatórias Intestinais/complicações , Interleucina-4/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteína Adaptadora de Sinalização NOD2/genética , Proteínas de Transporte de Cátions Orgânicos/genética , Fatores de Risco , Membro 5 da Família 22 de Carreadores de Soluto , Simportadores , Proteínas Supressoras de Tumor/genética
3.
Int J Cancer ; 118(12): 3180-2, 2006 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-16395703

RESUMO

The population frequencies of the CDKN2A common variants remain undetermined. In Poland, there is a common variant of the CDKN2A: an alanine to threonine substitution (A148T), which has been detected in other populations. We have recently showed that it is significantly overrepresented among Polish melanoma patients when compared to general population. Herein, we ascertained the prevalence of the A148T variant in 3,583 unselected cancer cases and 3,000 random control subjects from the same Polish population. We evaluated eleven different malignancies, representing the majority of all common cancer sites. Positive association with A148T variant was observed for lung cancer (OR, 2.0; p = 0.0052). A similar trend, although nonsignificant after the Bonferroni correction, was observed for colorectal cancer (OR, 1.5; p = 0.5499). These results suggest that A148T variant may be associated with a multi-organ cancer risk in the Polish population.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Genes p16 , Neoplasias/epidemiologia , Neoplasias/genética , Adulto , Idoso , Alanina , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Feminino , Variação Genética , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polônia/epidemiologia , Prevalência , Medição de Risco , Fatores de Risco , Treonina
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