Inherited Genetic Susceptibility to Breast Cancer

Abstract

Genome-wide association studies have identified 72 loci associated with breast cancer susceptibility. Seventeen of these are known to predispose to other cancers. High-penetrance susceptibility loci for breast cancer usually result from coding alterations, principally in genes involved in DNA repair, whereas almost all of the associations identified through genome-wide association studies are found in noncoding regions of the genome and are likely to involve regulation of genes in multiple pathways. However, the genes underlying most associations are not yet known. In this review, we summarize the findings from genome-wide association studies in breast cancer and describe the genes and mechanisms that are likely to be involved in the tumorigenesis process. We also discuss approaches to fine-scale mapping of susceptibility regions used to identify the likely causal variant(s) underlying the associations, a major challenge in genetic epidemiology. Finally, we discuss the potential impact of such findings on personalized medicine and future avenues for screening, prediction, and prevention programs.

In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci

“…Combining the results with a previously published summary of human BrCa risk loci (Ghoussaini et al 2013) revealed that 5 of the 20 Mdq were syntenic with previously detected BrCa risk loci (Figure 7, Table 4). The potential significance of these loci as well as the remaining QTL will be addressed further below.…”

“…Most recently, the use of genome-wide association studies (GWAS) in human populations has identified 72 loci associated with a modest (relative risk <1.5) increase in BrCa risk (Ghoussaini et al 2013). The identification of these loci represent an enormous opportunity to further our understanding of BrCa, but this work also points to the complexity of the disease, since all of these common alleles have only modest effects and likely interact in complex ways.…”

“…The identification of these loci represent an enormous opportunity to further our understanding of BrCa, but this work also points to the complexity of the disease, since all of these common alleles have only modest effects and likely interact in complex ways. Even with all of the loci identified to date, a majority of the heritability for BrCa still remains to be identified (Ghoussaini et al 2013). This highlights the need for novel approaches to identifying genetic loci that could contribute to BrCa risk.…”

Frecuencia de las mutaciones en los genes BRCA en mujeres con agregación familiar de cáncer de glándula mamaria/ovario

“…El metaanálisis realizado por Ghoussaini y colaboradores muestra evidencias de que la presencia de un familiar en primer grado con CGM incrementa el riesgo relativo en 2,1 y que este incremento es inversamente proporcional a la edad de inicio en el familiar afectado (Ghoussaini et al, 2013). En general, se considera que el riesgo de herencia es mayor según el número de familiares afectados y la cercanía del parentesco.…”

Sleep and circadian disruption and incident breast cancer risk: An evidence-based and theoretical review

“…Many of the identified risk factors are non-modifiable, however, and thus far, only a small percentage of breast cancer risk has been successfully linked to genetic inheritance (Oldenburg et al, 2007; Ghoussaini et al, 2013). Considerable research has investigated the associations between daytime behaviors, such as alcohol consumption (Smith-Warner et al, 1998), smoking (Xue et al, 2011), diet (Boyd, 2003), and physical activity (Vainio et al, 2002), and individual risk for breast cancer.…”