RESUMO
BACKGROUND: Colorectal cancer incidence and prognosis are influenced by vitamin D intake and expression of the vitamin D receptor (VDR). Polymorphisms of the VDR are linked to several diseases. This study was aimed to investigate whether variants of the VDR poly(A) microsatellite are associated with colorectal cancer incidence. MATERIALS AND METHODS: The poly(A) polymorphism was analyzed in a series of 255 colorectal cancer patients and 255 controls of Caucasian origin (case-control study) by a combination of GeneScan and sequencing. RESULTS: There was a distinct separation between long and short alleles. We found 19, 20, 21, and 22 A-repeats for the long variant and 14 and 15 A-repeats for the short variant. Frequencies of long and short alleles did not differ between cases and controls, nor did frequencies of any single variant. CONCLUSION: Our findings do not support an association between VDR poly(A) variants and the incidence of colorectal cancer.
Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Repetições de Microssatélites/genética , Poli A/genética , Receptores de Calcitriol/genética , População Branca/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The multidrug resistance gene 1 (MDR1) seems to play a role in the carcinogenesis of colorectal tumors. The importance of MDR1 SNPs 2677G > T/A in exon 21 and 3435C > T in exon 26 for cancer susceptibility, however, has not yet been clearly defined. METHODS: Two hundred and eighty-five colorectal cancer patients and 275 controls from five hospitals in the European part of Russia were genotyped for the polymorphisms -129T > C (rs3213619) in exon 1b, 2677G > T/A (rs2032582), and 3435C > T (rs1045642) in this population-based case-control study. Genotype-phenotype analysis was performed with simultaneous consideration of lifestyle risk factors. RESULTS: Our analysis confirmed the preponderate impact of smoking on colorectal cancer development. The risk of heavy smokers (>/=60 pack years) to develop colorectal cancer by far exceeded that of lifelong non-smokers (OR = 3.9, 95% CI: 1.4 to 10.6). Smoking is a more potent risk factor than is the genetic influence of MDR1 in our study. However, a smoking and age-stratified analysis, revealed a statistically significant association between MDR1 genotypes and colorectal cancer in life-long non-smokers with an age > or =63 years (the median age in our sample). The association was stronger for rectal cancer than for colon cancer. Patients who carried the genotypes (-129TT; 2677GG; 3435CC) or (-129TT; 2677TT; 3435TT) developed more frequently colorectal cancer than others (OR = 3.9; 95% CI: 2.0 to 7.7). CONCLUSIONS: Our results show that the interaction of genetic and lifestyle risk factors should be taken into account to elucidate the genetic influence of MDR1 variability on cancer susceptibility.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Fumar/efeitos adversos , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adulto , Idoso , Envelhecimento , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/patologia , Feminino , Genótipo , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco , Federação RussaRESUMO
Pharmacogenetics, one of the fields of clinical pharmacology, studies how genetic factors influence drug response. If hereditary traits are taken into account appropriately before starting drug treatment, the type of drug and its dosage can be tailored to the individual patient's needs. Pharmacogenetics adds a considerable amount of stringency to the doctor's therapeutic approach. Today, it is the relationship between dosage requirements and genetic variations in drug metabolizing enzymes like cytochrome P450 (CYP) 2D6 and CYP2C19, or in drug transporters like p-glycoprotein, that is substantiated best. A standard dose will bring about more adverse effects than usual if enzymatic activity is lacking or feeble. Sometimes, however, therapeutic response might be better due to higher concentrations: proton pump inhibitors for eradication of Helicobacter pylori are more efficacious in carriers of a deficient CYP2C19 variant. The drug's interaction with its target (e.g. receptor) also depends on genetic factors. In some cases genetic tests can help distinguish between responders and non-responders of a specific drug treatment. The first pharmacogenetic tests are already on the market.