RESUMEN
BACKGROUND: E-cadherin (CDH1) plays an important role in intercellular adhesion, cell signaling, and cellular differentiation. Association of single-nucleotide polymorphisms (SNPs) of CDH1 has been identified in a number of epithelial malignancies; however, studies related to breast cancer are very few. AIM: To investigate the association between CDH1 SNPs and breast cancer risk in south Indian women. METHODS: Genotyping of CDH1 functional SNPs (-347G/GA, -160C/A, and +54C/T) was carried out on genomic DNA of blood from breast cancer patients (n=202) and controls (n=250) of south Indian origin by PCR-sequencing and PCR-restriction fragment length polymorphism techniques. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D') for pairwise linkage disequilibrium (LD) were assessed by Haploview Software. RESULTS: The frequencies of -160A/A genotypes (p=0.038) and -160A alleles (p=0.046) were significantly higher in patients compared to controls. In addition, the frequency of the -347GA/-160A/+54C haplotype was also significantly elevated in patients (p=0.0238). Strong LD was observed between -347G/GA and +54C/T loci (D'=0.44) in patients compared to controls. CONCLUSION: The CDH1 -160C/A polymorphism may constitute an inheritable risk factor for breast cancer in south Indian women.
Asunto(s)
Neoplasias de la Mama/genética , Cadherinas/genética , Polimorfismo de Nucleótido Simple , Antígenos CD , Pueblo Asiatico , Neoplasias de la Mama/etnología , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , India , Desequilibrio de Ligamiento , Reacción en Cadena de la Polimerasa , Factores de RiesgoRESUMEN
Uterine leiomyomas/fibroids are the most common pelvic tumors of the female genital tract. The initiators remaining unknown, estrogens and progesterone are considered as promoters of fibroid growth. Fibroids are monoclonal tumors showing 40-50% karyo-typically detectable chromosomal abnormalities. Cytogenetic aberrations involving chromosomes 6, 7, 12 and 14 constitute the major chromosome abnormalities seen in leiomyomata. This has led to the discovery that disruptions or dysregulations of HMGIC and HMGIY genes contribute to the development of these tumors. Genes such as RAD51L1 act as translocation partners to HMGIC and lead to disruption of gene structure leading to the pathogenesis of uterine fibroids. The mechanism underlying this disease is yet to be identified. The occurrence of PCOLCE amid a cluster of at least eight Alu sequences is potentially relevant to the possible involvement of PCOLCE in the 7q22 rearrangements that occur in many leiomyomata. PCOLCE is implicated in cell growth processes. Involvement of Alu sequences in rearrangements can lead to the disruption of this gene and, hence, loss of control for gene expression leading to uncontrolled cell growth. This can also lead to the formation of fibroids. Though, cytogenetics provides a broad perspective on uterine fibroid formation, further molecular analysis is required to understand the etiopathogenesis of uterine fibroids.