Complex cross-talk between EZH2 and miRNAs confers hallmark characteristics and shapes the tumor microenvironment.

Cancer epigenetic mechanisms support the acquisition of hallmark characteristics during oncogenesis. EZH2 - an important histone methyltransferase that writes histone H3 lysine 27 trimethylation marks - is known to be dysregulated in cancer cells. However, the interactions between EZH2 and miRNAs that form a complex network of cross-talk and reciprocal regulation that enable cancer cells to acquire hallmark characteristics have been relatively poorly appreciated.

Large-scale genotyping identifies a new locus at 22q13.2 associated with female breast size.

Background: Individual differences in breast size are a conspicuous feature of variation in human females and have been associated with fecundity and advantage in selection of mates. To identify common variants that are associated with breast size, we conducted a large-scale genotyping association meta-analysis in 7169 women of European descent across three independent sample collections with digital or screen film mammograms.

Methods: The samples consisted of the Swedish KARMA, LIBRO-1 and SASBAC studies genotyped on iCOGS, a custom illumina iSelect genotyping array comprising of 211 155 single nucleotide polymorphisms (SNPs) designed for replication and fine mapping of common and rare variants with relevance to breast, ovary and prostate cancer.

The heritability of mammographic breast density and circulating sex-hormone levels: two independent breast cancer risk factors.

Background: Mammographic breast density and endogenous sex-hormone levels are both strong risk factors for breast cancer. This study investigated whether there is evidence for a shared genetic basis between these risk factors.

Methods: Using data on 1,286 women from 617 families, we estimated the heritabilities of serum estradiol, testosterone, and sex-hormone binding globulin (SHBG) levels and of three measures of breast density (dense area, nondense area, and percentage density).

Identification of a novel percent mammographic density locus at 12q24.

Percent mammographic density adjusted for age and body mass index (BMI) is one of the strongest risk factors for breast cancer and has a heritable component that remains largely unidentified. We performed a three-stage genome-wide association study (GWAS) of percent mammographic density to identify novel genetic loci associated with this trait. In stage 1, we combined three GWASs of percent density comprised of 1241 women from studies at the Mayo Clinic and identified the top 48 loci (99 single nucleotide polymorphisms).

Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated with mammographic density measures that predict breast cancer risk.

Background: Mammographic density adjusted for age and body mass index (BMI) is a heritable marker of breast cancer susceptibility. Little is known about the biologic mechanisms underlying the association between mammographic density and breast cancer risk. We examined whether common low-penetrance breast cancer susceptibility variants contribute to interindividual differences in mammographic density measures.

Mammographic breast density and breast cancer: evidence of a shared genetic basis.

Percent mammographic breast density (PMD) is a strong heritable risk factor for breast cancer. However, the pathways through which this risk is mediated are still unclear. To explore whether PMD and breast cancer have a shared genetic basis, we identified genetic variants most strongly associated with PMD in a published meta-analysis of five genome-wide association studies (GWAS) and used these to construct risk scores for 3,628 breast cancer cases and 5,190 controls from the UK2 GWAS of breast cancer.

Genome-wide association studies in common cancers--what have we learnt?

Genome-wide association studies (GWAS) have led to the identification of more than 100 common, low-penetrance loci for cancer. At these loci, common genetic variants are associated with moderate increases in risk, typically <1.5-fold.