title: Breast cancer genome-wide association studies: there is strength in numbers.
abstract: Breast cancer (BC) is a heterogeneous disease that exhibits familial aggregation. Family linkage studies have identified high-penetrance genes, BRCA1, BRCA2, PTEN and TP53, that are responsible for inherited BC syndromes. Moreover, a combination of family-based and population-based approaches indicated that genes involved in DNA repair, such as CHEK2, ATM, BRIP and PALB2, are associated with moderate risk. Therefore, all of these known genes account for only 25% of the familial aggregation cases. Recently, genome wide association studies (GWAS) in BC revealed single nucleotide polymorphisms (SNPs) in five novel genes associated to susceptibility: TNRC9, FGFR2, MAP3K1, H19 and lymphocyte-specific protein 1 (LSP1). The most strongly associated SNP was in intron 2 of the FGFR2 gene that is amplified and overexpressed in 5-10% of BC. rs3803662 of TNRC9 gene has been shown to be the SNP with the strongest association with BC, in particular, this polymorphism seems to be correlated with bone metastases and estrogen receptor positivity. Relevant data indicate that SNP rs889312 in MAP3K1 is correlated with BC susceptibility only in BRCA2 mutation carriers, but is not associated with an increased risk in BRCA1 carriers. Finally, different SNPs in LSP1 and H19 and in minor genes probably were associated with BC risk. New susceptibility allelic variants associated with BC risk were recently discovered including potential causative genes involved in regulation of cell cycle, apoptosis, metabolism and mitochondrial functions. In conclusion, the identification of disease susceptibility loci may lead to a better understanding of the biological mechanism for BC to improve prevention, early detection and treatment.
authors: Department of Surgical and Oncological Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors: D
authors: D
authors: Fanale
authors: V
authors: V
authors: Amodeo
authors: L R
authors: LR
authors: Corsini
authors: S
authors: S
authors: Rizzo
authors: V
authors: V
authors: Bazan
authors: A
authors: A
authors: Russo
mesh_terms: D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006609:High Mobility Group Proteins; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D015534:Trans-Activators
chemical_list: D051017:Apoptosis Regulatory Proteins; D006609:High Mobility Group Proteins; C489183:LSP1 protein, human; D008840:Microfilament Proteins; D011980:Receptors, Progesterone; C521752:TOX3 protein, human; D015534:Trans-Activators; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human