RESUMO
MDR1, which is encoded by the ABCB1 gene, is involved in multidrug resistance (hydrophobic), as well as the elimination of xenotoxic agents. The association between ABCB1 gene polymorphisms and breast cancer risk in different populations has been described previously; however, the results have been inconclusive. In this study, we examined the association between polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene and breast cancer development in Mexican women according to their menopausal status and molecular classification. Molecular subtypes as well as allele and genotype frequencies were analyzed. A total of 248 women with initial breast cancer diagnosis and 180 ethnically matched, healthy, unrelated individuals were enrolled. Polymerase chain reaction-restriction fragment length polymorphism was performed to detect polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene. Premenopausal T allele carriers of the 3435 C/T polymorphism showed a 2-fold increased risk of breast cancer with respect to the reference and postmenopausal groups, as well as triple-negative expression regarding the luminal A/B molecular subrogated subtypes. In contrast, the CT genotype of the 1236 polymorphism was a protective factor against breast cancer. We conclude that the T allele carrier of the 3435 C/T polymorphism in the ABCB1 gene in combination with an estrogen receptor-negative status may be an important risk factor for breast cancer development in premenopausal women.
Assuntos
Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Polimorfismo de Nucleotídeo Único , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Etnicidade , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , México , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Pós-Menopausa , Pré-Menopausa , Fatores de RiscoRESUMO
Breast cancer (BC) is the leading cause of cancer-related deaths among women in Mexico. Two single-nucleotide polymorphisms (SNPs) in the thymidylate synthase (TS) gene, the 28-base pair (bp) tandem repeat in the TS 5'-untranslated enhanced region (TSER) and the 6-bp insertion/deletion in the TS 3'-untranslated region (TS 3'-UTR), increase the rate of misincorporation of uridylate into DNA and may lead to chromosomal damage. We examined the association between these polymorphisms and BC risk in Mexican women according to menopause status. Mexican patients with initial BC diagnosis (N = 230) and 145 individuals from a reference general population group (RGP) were included. For statistical analysis, the BC group was divided into pre- and post-menopause groups (PRE and POST groups, respectively). We analyzed both TS polymorphisms (TSER and TS 3'-UTR) using polymerase chain reaction. Finetti analysis was used to evaluate inter-and intra-group differences. The results showed a high frequency for the 3R and ins6 alleles in the BC, RGP, PRE, and POST groups. No significant differences were observed for the TS and TSER genotype and allele frequency distributions between groups. We found that the TSER and TS 3'-UTR SNPs are not associated with BC risk in Mexican patients.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético , Timidilato Sintase/genética , Regiões 3' não Traduzidas/genética , Regiões 5' não Traduzidas/genética , Adulto , Alelos , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Mutação INDEL , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Pós-Menopausa/genética , Pré-Menopausa/genética , Fatores de Risco , Sequências de Repetição em Tandem/genética , Adulto JovemRESUMO
In a previous study we reported a direct correlation between the degree of total proteolytic activity and the natural history of cervical carcinoma. The present work examined whether an increase in the urokinase-type plasminogen activator (uPA) and the plasminogen activator inhibitors (PAIs) is correlated with the natural history of cervical carcinoma. We measured uPA and PAI-1 activities and uPA, PAI-1 and PAI-2 antigen concentrations in cervical extracts from normal, squamous intraepithelial lesions (SIL) or invasive carcinoma patients. The uPA activity in invasive carcinoma extracts was 8.46 times that of normal extracts and 4.9 times that of SIL extracts. The PAI-1 activity in invasive carcinoma extracts was 1.3 times that of normal extracts and 1.24 times that of SIL extracts. uPA, PAI-1 and PAI-2 amounts were 25.7-, 12.1- and 7.9-fold higher, respectively, in invasive carcinoma than in SIL, and 39.1-, 21.38- and 27.3-fold higher, respectively, than in normal extracts. uPA and PAI-1 activities were 2.02- and 1.42-fold higher in extracts from patients with stages II-IV than those from stage I extracts, respectively. uPA, PAI-1 and PAI-2 amounts were 3.06-, 4.2- and 1.4-fold higher in extracts from patients with stages II-IV than those from stage I extracts, respectively. The increase in uPA activity and the antigen levels of uPA and PAIs (PAI-1 and PAI-2) in stages II-IV of invasive carcinoma of the cervix suggests that these components play an important role in invasion and metastasis in advanced stages of this tumour.
