ncreasing evidence indicates that common genetic variants may contribute to the heritable risk of breast cancer (BC). In this study, we investigated whether single nucleotide polymorphisms (SNPs), within the 8q24.21 multi-cancer susceptibility region and withinC-associated loci widespread in the genome, may influence the risk of BC in men, and whether they may be associated with specific clinical-pathologic characteristics of male BC (MBC). In the frame of the ongoing Italian Multicenter Study on MBC, we performed a case-control study on 386 MBC cases, including 50 BRCA1/2 mutation carriers, and 1105 healthy male controls, including 197 unaffected BRCA1/2 mutation carriers. All 1491 subjects were genotyped by Sequenom iPLEX technology for a total of 29 susceptibility SNPs. By logistic regression models, we found a significant association with MBC risk for five SNPs: rs1562430 ( p = 0.002) and rs445114 ( p = 0.026) both within the 8q24.21 region; rs1011970/9p21.3 ( p = 0.011), rs614367/11q13.3 ( p = 0.016) and rs1314913/14q24.1 ( p < 0.0001). Differences in the distribution of rs614367/11q13.3 genotypes according to oestrogen receptor (ER) status ( p = 0.006), and of rs1011970/9p21.3 genotypes according to human epidermal growth factor receptor 2 (HER2) status ( p = 0.002) emerged. Association of rs1011970/9p21.3 risk genotype with HER2+ MBC was confirmed by a multivariate analysis. rs1314913/14q24.1 was associated with increased MBC risk in analyses restricted to male BRCA1/2 mutation carriers ( p = 0.041). In conclusion, we provided the first evidence that the 8q24.21 region is associated with MBC risk. Furthermore, we showed that the SNPs rs1562430/8q24.21 and rs1314913/14q24.1 strongly influence BC risk in men and suggested that the SNP rs1314913/14q24.1 may act as a risk modifier locus in male BRCA1/2 mutation carriers

Novel and known genetic variants for male breast cancer risk at 8q24.21, 9p21.3, 11q13.3 and 14q24.1: Results from a multicenter study in Italy

zelli, veronica;
2015

Abstract

ncreasing evidence indicates that common genetic variants may contribute to the heritable risk of breast cancer (BC). In this study, we investigated whether single nucleotide polymorphisms (SNPs), within the 8q24.21 multi-cancer susceptibility region and withinC-associated loci widespread in the genome, may influence the risk of BC in men, and whether they may be associated with specific clinical-pathologic characteristics of male BC (MBC). In the frame of the ongoing Italian Multicenter Study on MBC, we performed a case-control study on 386 MBC cases, including 50 BRCA1/2 mutation carriers, and 1105 healthy male controls, including 197 unaffected BRCA1/2 mutation carriers. All 1491 subjects were genotyped by Sequenom iPLEX technology for a total of 29 susceptibility SNPs. By logistic regression models, we found a significant association with MBC risk for five SNPs: rs1562430 ( p = 0.002) and rs445114 ( p = 0.026) both within the 8q24.21 region; rs1011970/9p21.3 ( p = 0.011), rs614367/11q13.3 ( p = 0.016) and rs1314913/14q24.1 ( p < 0.0001). Differences in the distribution of rs614367/11q13.3 genotypes according to oestrogen receptor (ER) status ( p = 0.006), and of rs1011970/9p21.3 genotypes according to human epidermal growth factor receptor 2 (HER2) status ( p = 0.002) emerged. Association of rs1011970/9p21.3 risk genotype with HER2+ MBC was confirmed by a multivariate analysis. rs1314913/14q24.1 was associated with increased MBC risk in analyses restricted to male BRCA1/2 mutation carriers ( p = 0.041). In conclusion, we provided the first evidence that the 8q24.21 region is associated with MBC risk. Furthermore, we showed that the SNPs rs1562430/8q24.21 and rs1314913/14q24.1 strongly influence BC risk in men and suggested that the SNP rs1314913/14q24.1 may act as a risk modifier locus in male BRCA1/2 mutation carriers
File in questo prodotto:
File Dimensione Formato  
Silvestri_Novel_2015.pdf

non disponibili

Dimensione 401.11 kB
Formato Adobe PDF
401.11 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11697/159448
Citazioni
  • ???jsp.display-item.citation.pmc??? 12
  • Scopus 21
  • ???jsp.display-item.citation.isi??? 20
social impact