RESUMO
The presence of activating somatic mutations in codons 542 and 545 of exon 9 (p.E542K c.1624G>A and p.E545K c.1633G>A) and in codon 1047 of exon 20 (p.H1047R c.3140A>G and p.H1047L c.3140A>T) of PIK3CA gene encoding catalytic p110α-subunit of phosphatidylinositol-3-kinase was studied in tumors of 473 breast cancer patients by multiplex allele-specific real-time PCR. Fifty-eight (12.3%) different mutations were found. An increase in the frequency of PIK3CA gene mutations with disease progression (from 2.4 to 28.7% with tumor progression from I-IIa to III-IV stage; p=0.0001) and a trend towards its increase in the tumors with unfavorable prognostic characteristics (high histological grade, triple negative phenotype) were demonstrated. The presence of the studied PIK3CA gene mutations in tumors significantly reduces relapse-free survival in the total group and in stage III cancer patients.
Assuntos
Neoplasias da Mama/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Mutação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Neoplasias da Mama/patologia , Éxons/genética , Humanos , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Compelling evidence demonstrates chromosome 8q24 as a prostate cancer susceptibility locus. In present work we studied whether the common variants of 8q24 region, rs6983267 and rs1447295, were associated with the sporadic prostate cancer risk in the Russian population. Polymorphisms were genotyped in 393 case and 384 control Russian Caucasian men from Siberia region. The A allele of rs1447295 was significantly associated with the risk of prostate cancer (OR[CI 95%] = 1.74 [1.26-2.4], p = 7.8 x 10(-4)). A common G-A haplotype for rs6983267 - rs1447295 also showed an association with prostate cancer risk in Russian population (OR[CI 95%] = 2.03 [1.1 - 3.75], p = 0.02). We performed a meta-analysis combining our results with previous studies to evaluate the association between studied SNPs and prostate cancer risk. Meta-analysis has strongly supported the association for these SNPs (p < 10(-6)). Accordingly our study confirms the association between chromosome 8q24 and prostate cancer risk.
