Prevalence of ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms in Brazilian breast cancer-unaffected women

Abstract

Polymorphisms of hormone receptor genes have been linked to modifications in reproductive factors and to an increased risk of breast cancer (BC). In the present study, we have determined the allelic and genotypic frequencies of the ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms and investigated their relationship with mammographic density, body mass index (BMI) and other risk factors for BC. A consecutive and unselected sample of 750 Brazilian BC-unaffected women enrolled in a mammography screening program was recruited. The distribution of PGR PROGINS genotypic frequencies was 72.5, 25.5 and 2.0% for A1A1, A1A2 and A2A2, respectively, which was equivalent to that encountered in other studies with healthy women. The distribution of ERα genotypes was: ERα-397 PvuII C/T: 32.3% TT, 47.5% TC, and 20.2% CC; ERα-351 XbaI A/G: 46.3% AA, 41.7% AG and 12.0% GG. ERα haplotypes were 53.5% PX, 14.3% Px, 0.3% pX, and 32.0% px. These were significantly different from most previously published reports worldwide (P < 0.05). Overall, the PGR PROGINS genotypes A2A2 and A1A2 were associated with fatty and moderately fatty breast tissue. The same genotypes were also associated with a high BMI in postmenopausal women. In addition, the ERα-351 XbaI GG genotype was associated with menarche ≥12 years (P = 0.02). ERα and PGR polymorphisms have a phenotypic effect and may play an important role in BC risk determination. Finally, if confirmed in BC patients, these associations could have important implications for mammographic screening and strategies and may be helpful to identify women at higher risk for the disease.

Hormone-related pathways and risk of breast cancer subtypes in African American women

“…These three SNPs were not associated with breast cancer in the present study. Several studies have reported evidence that PGR variants modify the effect of hormone replacement therapy on breast cancer risk [74–76], and a few studies have reported PGR associations with mammographic density [77, 78]. Still, the role of PGR variants in breast cancer development remains uncertain.…”

A aplicação do mapeamento genético na identificação dos polimorfismos do câncer de mama e o direcionamento da terapia alvo

“…A aplicação clínica do MG foca na identificação dos polimorfismos genéticos que são variações genéticas na sequência de DNA de ocorrência habitual na população, que quando encontrado com frequência superior a 1% poderá promover alteração no funcionamento, por exemplo, de um determinado receptor ou a mudança no mecanismo de ação do hormônio estrogênico (Souza et al, 2012). A literatura atual mostra que, em certas populações, polimorfismos específicos em hormônios genes receptores podem estar associados a um risco aumentado de câncer de mama em desenvolvimento (Giacomazzi et al, 2012).…”

Does circulating progesterone mediate the associations of single nucleotide polymorphisms in progesterone receptor (PGR)-related genes with mammographic breast density in premenopausal women?

“…Single nucleotide polymorphisms (SNPs) in the PGR gene modulate changes in MD in response to menopausal hormone therapy. However, there are conflicting results on the associations of genetic variations in progesterone-related pathways with MD [18][19][20]. In addition, there are limited data in premenopausal women [19], where hormonal variation during menstrual cycle makes it challenging to evaluate these associations.…”