Influencia dos polimorfismos nos genes CYP1A1, CYP1B1 e CYP2C9 na suscetibidade ao adenocarcionama colorretal esporadico / Influence polymorphisms in the genes CYP1A1, CYP1B1 and CYP2C9 susceptibility to colorectal cancer

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

The colorectal cancer (CRC) characterizes a neoplasia which reaches the colon and the rectum tissues. It is classified as so, despites the biological and epidemiological differences between the colon and rectum cancer, because there is not a clear anatomical separation of these areas. The importance of external factors in the pathology of the sporadical CRC has been certified by epidemiological data. Thus, P450 polymorphisms might be associated to cancer due to the fact that these proteins play a role in transforming endogenous compounds during the process of differentiation of transformed cells, until its malignant stage. The objective of this work was to evaluate the prevalence of the polymorphisms M1 and M2 in CYP1A1 gene, 2C9*2 and 2C9*3 in CYP2C9 gene and 1B1*3 in CYP1B1 gene. Also, the correlation among the presence of these polymorphisms, the tobaccoism and the clinical stagnancy of the illness was performed. Polymerase chain reactions (PCRs) followed by specific enzymatic digestions were performed in order to analyze the polymorphisms. We evaluated 102 patients with sporadical CRC and 230 control individuals without familial history of CRC. Our results indicated that individuals that did not carry M1 and M2 variants of CYP1A1 gene presented a protective effect against CRC, while individuals who presented M1 or M2 variants had a 6 and almost 3 (2.89) times increasing of the risk, respectively, while patients with both M2 alleles had an almost 4 times (3.70) increasing risk. Analysis of CYP2C9 gene showed that genotype N/N (without * 2 and * 3 mutations) presented a protective effect, while individuals heterozygotes for * 3 mutation had an increase close to 6 times (5.90) of their risk. Homozygotes for the same mutation would present a 3 times increased risk. M1 and M2 alleles presence seems to be related to a worse prognostic of the illness, while the presence of * 3 mutation in CYP2C9 gene would result in a better prognostic. Other studies are necessary to confirm these findings. Polymorphism 1B1*3 of CYP1B1 gene does not seem to be related to CRC phenotype.

ASSUNTO(S)

fumo cytocrome enzime system sistema enzimatico do citocromo tabaco

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