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RESEARCH PRODUCT
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
Virginia ValentiniMonica BarileMontagna MarcoSimonetta BianchiPiera RizzoloGiovanna MasalaLaura CortesiGiovanni ChillemiVeronica ZelliStefania TommasiAlessandra VielPeterlongo PaoloDomenico PalliSiranoush ManoukianLaura OttiniLiliana VarescoValentina SilvestriCalogero SaievaGiuseppe GianniniInes ZannaAntonio RussoRadice PaoloMarco ScarnòValeria PensottiAnna Sara Navaziosubject
MaleCancer ResearchPredictive Value of Test8q24.21; BRCA1/2; Clinical-pathologic characteristics; Low-penetrance BC alleles; Male breast cancer; SNPs; BRCA1 Protein; BRCA2 Protein; Biomarkers Tumor; Breast Neoplasms Male; Case-Control Studies; Chi-Square Distribution; Gene Frequency; Genetic Predisposition to Disease; Heterozygote; Homozygote; Humans; Italy; Linear Models; Logistic Models; Male; Multivariate Analysis; Mutation; Odds Ratio; Phenotype; Predictive Value of Tests; Risk Factors; Chromosomes Human Pair 11; Chromosomes Human Pair 14; Chromosomes Human Pair 8; Chromosomes Human Pair 9; Polymorphism Single Nucleotide; Oncology; Cancer ResearchGene FrequencyRisk FactorsGenotypeOdds RatioMedicineskin and connective tissue diseasesMultivariate AnalysiSettore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIAGeneticsClinical-pathologic characteristicsBRCA1 ProteinClinical-pathologic characteristicHomozygoteLow-penetrance BC allelesPhenotype8q24.21OncologyItalyMale breast cancer8q24.21; BRCA1/2; Clinical-pathologic characteristics; Low-penetrance BC alleles; Male breast cancer; SNPs; Cancer Research; OncologyLinear ModelCase-Control StudieChromosomes Human Pair 9HumanChromosomes Human Pair 8SNPsHeterozygoteLogistic ModelSNPSingle-nucleotide polymorphismPolymorphism Single NucleotideBreast Neoplasms MaleBreast cancerPredictive Value of TestsBRCA1/2Biomarkers TumorSNPHumansGenetic Predisposition to DiseaseAllele frequencyBRCA2 ProteinChromosomes Human Pair 14Chi-Square Distributionbusiness.industryRisk FactorChromosomes Human Pair 11Case-control studyOdds ratiomedicine.diseaseMale breast cancerLogistic ModelsCase-Control StudiesMultivariate AnalysisMutationLinear ModelsbusinessLow-penetrance BC alleledescription
Increasing 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 within BC-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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-01-01 |