Discovery and replication of microRNAs for breast cancer risk using genome-wide profiling

Genome-wide miRNA expression may be useful for predicting breast cancer risk and/or for the early detection of breast cancer

Racial differences in genome-wide methylation profiling and gene expression in breast tissues from healthy women

<p>Breast cancer is more common in European Americans (EAs) than in African Americans (AAs) but mortality from breast cancer is higher among AAs. While there are racial differences in DNA methylation and gene expression in breast tumors, little is known whether such racial differences exist in breast tissues of healthy women. Genome-wide DNA methylation and gene expression profiling was performed in histologically normal breast tissues of healthy women. Linear regression models were used to identify differentially-methylated CpG sites (CpGs) between EAs (n = 61) and AAs (n = 22). Correlations for methylation and expression were assessed. Biological functions of the differentially-methylated genes were assigned using the Ingenuity Pathway Analysis. Among 485 differentially-methylated CpGs by race, 203 were hypermethylated in EAs, and 282 were hypermethylated in AAs. Promoter-related differentially-methylated CpGs were more frequently hypermethylated in EAs (52%) than AAs (27%) while gene body and intergenic CpGs were more frequently hypermethylated in AAs. The differentially-methylated CpGs were enriched for cancer-associated genes with roles in cell death and survival, cellular development, and cell-to-cell signaling. In a separate analysis for correlation in EAs and AAs, different patterns of correlation were found between EAs and AAs. The correlated genes showed different biological networks between EAs and AAs; networks were connected by Ubiquitin C. To our knowledge, this is the first comprehensive genome-wide study to identify differences in methylation and gene expression between EAs and AAs in breast tissues from healthy women. These findings may provide further insights regarding the contribution of epigenetic differences to racial disparities in breast cancer.</p

Plasma IGF-1 and IGFBP-3 may be imprecise surrogates for breast concentrations: an analysis of healthy women.

We investigated insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 concentrations in histologically normal breast tissues and assessed their association with plasma concentrations, and breast cancer risk factors. IGF-1 and IGFBP-3 were assessed in plasma and breast tissues of 90 women with no history of any cancer and undergoing reduction mammoplasty. Pearson correlations and ANOVAs were used to describe plasma-breast associations and biomarker differences by breast cancer risk factors, respectively. Multivariable regression models were used to determine associations between risk factors, and breast IGF-1 and IGFBP-3. The mean age of the study sample was 37.3 years, 58 % were white, and generally these women were obese (mean BMI = 30.8 kg/m(2)). We observed no plasma-breast correlation for IGF-1, IGFBP-3, or IGF-1/IGFBP-3 (r = −0.08, r = 0.14, and r = 0.03, respectively; p-values >0.05). Through age- and BMI-adjusted analysis, BMI and years of oral contraceptive (OC) use were inversely associated with breast IGF-1 (p-values = 0.02 and 0.003, respectively) and age was associated with breast IGFBP-3 (p = 0.01), while breast IGF-1/IGFBP-3 was higher in blacks than whites (1.08 vs. 0.68, p = 0.04) and associated with age and BMI (p-values = 0.03 and 0.002, respectively). In multivariable-adjusted models, some breast cancer risk factors studied herein explained 24, 10, and 15 % of the variation in breast IGF-1, IGFBP-3, and IGF-1/IGFBP-3, respectively. While reasons for the lack of plasma-breast hormone correlations in these cancer-free women are unknown, several factors were shown to be associated with breast concentrations. The lack of correlation between blood and tissue IGF-1 and IGFBP-3 suggests that studies of breast cancer risk assessing blood IGF-1 and IGFBP-3 may have important limitations in understanding their role in breast carcinogenesis

Four representative somatic mutation sequences at different mtDNA regions in smokers

() Heteroplasmic to homoplasmic insertion of cytidine at np7466–7471 transfer RNA (tRNA) serine 1; () HM to HM change of T10034C at tRNA glycine; () Heteroplasmic to homoplasmic deletion C at poly-(C) tract D310 of D-loop region and () HM to HM transversion change of C7409A at cytochrome c oxidase subunit I of messenger RNA coding region.<p><b>Copyright information:</b></p><p>Taken from "Associations between cigarette smoking and mitochondrial DNA abnormalities in buccal cells"</p><p></p><p>Carcinogenesis 2008;29(6):1170-1177.</p><p>Published online 14 Feb 2008</p><p>PMCID:PMC2443276.</p><p></p

Correlations between ratio of buccal cells/lymphocytes mtDNA content and smoking status

Pearson’s correlation test (two tailed) after data log transformation.<p><b>Copyright information:</b></p><p>Taken from "Associations between cigarette smoking and mitochondrial DNA abnormalities in buccal cells"</p><p></p><p>Carcinogenesis 2008;29(6):1170-1177.</p><p>Published online 14 Feb 2008</p><p>PMCID:PMC2443276.</p><p></p