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Association between the BRCA2N372H variant and male breast cancer risk: a population-based case-control study in Tuscany, Central Italy

Authors: Palli, D.; Falchetti, M.; Masala, G.; Lupi, R.; Sera, F.; Saieva, C.; D'Amico, C.; +5 Authors

Association between the BRCA2N372H variant and male breast cancer risk: a population-based case-control study in Tuscany, Central Italy

Abstract

Abstract Background Male breast cancer (MBC) is a rare disease and little is known about its aetiology. Germ-line mutations of BRCA2 and, at lower frequency, of BRCA1 are implicated in a relatively small proportion of MBC cases. Common polymorphic variants in BRCA1 and BRCA2 genes may represent breast cancer (BC) susceptibility alleles and could be associated with a modestly increased risk of MBC at population level. Considering the relevant role of BRCA2 in MBC, we investigated whether the BRCA2 N372H variant, representing the only common non-synonymous polymorphism in BRCA2, might modulate the risk of BC in male populations. Methods A case-control study was performed comparing a population-based series of 99 MBC cases, characterized for BRCA1 and BRCA2 mutations, with 261 male population controls, all residing in Tuscany, Central Italy. All MBC cases and controls were genotyped for the BRCA2 N372H allele by TaqMan allelic discrimination assays. To evaluate the genotype specific risk of the BRCA2 N372H variant, MBC carriers of germ-line BRCA1/2 mutations were excluded from the analyses. Results No association emerged in univariate and age-adjusted analyses. Age-specific analyses suggested an increased risk for the HH homozygous genotype in subjects younger than 60 years. A statistically significant interaction emerged between this genotype and age (p = 0.032). When analyses were restricted to MBC cases enrolled in the first 4 years following diagnosis, a recessive model showed a significantly increased risk of MBC in HH subjects younger than 60 years (OR = 5.63; 95% CI = 1.70;18.61). Conclusion Overall, our findings, although based on a relatively small series, suggest that the BRCA2 HH homozygous genotype might be positively associated with an increased risk of MBC in men younger than 60 years.

Keywords

Male, Cancer Research, Genes, BRCA2, GENE POLYMORPHISMS, Polymorphism, Single Nucleotide, Breast Neoplasms, Male, Risk Factors, EPITHELIAL OVARIAN-CANCER, Genetics, Humans, Genetic Predisposition to Disease, BRCA2, male, breast cancer, RC254-282, Aged, MUTATIONS, Reverse Transcriptase Polymerase Chain Reaction, Age Factors, WOMEN, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, MEN, Middle Aged, COMMON VARIANT, Oncology, Italy, Case-Control Studies, GASTRIC-CANCER, Research Article

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
29
Top 10%
Top 10%
Top 10%
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