Protein is important to the human body, and different sources of protein may have different effects on the risk of breast cancer. Thus, we conducted a meta-analysis to investigate the association between different dietary protein sources and breast cancer risk. PubMed and several databases were searched until December 2015. Relevant articles were retrieved according to specific searching criteria. Forty-six prospective studies were included. The summary relative risk (RR) for highest versus lowest intake was 1.07 (95% confidence interval (CI) 1.01–1.14, I2 = 34.6%) for processed meat, 0.92 (95% CI 0.84–1.00, I2 = 0%) for soy food, 0.93 (95% CI 0.85–1.00, I2 = 40.1%) for skim milk, and 0.90 (95% CI 0.82–1.00, I2 = 0%) for yogurt. Similar conclusions were obtained in dose-response association for each serving increase: total red meat (RR: 1.07; 95% CI 1.01–1.14, I2 = 7.1%), fresh red meat (RR: 1.13; 95% CI 1.01–1.26, I2 = 56.4%), processed meat (RR: 1.09; 95% CI 1.02–1.17, I2 = 11.8%), soy food (RR: 0.91; 95% CI 0.84–1.00, I2 = 0%), and skim milk (RR: 0.96; 95% CI 0.92–1.00, I2 = 11.9%). There was a null association between poultry, fish, egg, nuts, total milk, and whole milk intake and breast cancer risk. Higher total red meat, fresh red meat, and processed meat intake may be risk factors for breast cancer, whereas higher soy food and skim milk intake may reduce the risk of breast cancer.

DNA methylation is a critical epigenetic mechanism involved in key cellular processes. Its deregulation has been linked to many human cancers including esophageal squamous cell carcinoma (ESCC). This study was designed to explore the whole methylation status of ESCC and to identify potential plasma biomarkers for early diagnosis. We used Infinium Methylation 450k array to analyze ESCC tissues (n = 4), paired normal surrounding tissues (n = 4) and normal mucosa from healthy individuals (n = 4), and combined these with gene expression data from the GEO database. One hundred and sixty eight genes had differentially methylated CpG sites in their promoter region and a gene expression pattern inverse to the direction of change in DNA methylation. These genes were involved in several cancer-related pathways. Three genes were validated in additional 42 ESCC tissues and paired normal surrounding tissues. The methylation frequency of EPB41L3, GPX3, and COL14A1 were higher in tumor tissues than in normal surrounding tissues (P<0.017). The higher methylation frequency of EPB41l3 was correlated with large tumor size (P = 0.044) and advanced pT tumor stage (P = 0.001). The higher methylation frequency of GPX3 and COL14A1 were correlated with advanced pN tumor stage (P = 0.001 and P<0.001). The methylation of EPB41L3, GPX3, and COL14A1 genes were only found in ESCC patients' plasma, but not in normal individuals upon testing 42 ESCC patients and 50 healthy individuals. Diagnostic sensitivity was increased when methylation of any of the 3 genes were counted (64.3% sensitivity and 100% specificity). These differentially methylated genes in plasma may be used as biomarkers for early diagnosis of ESCC.

Binding of 30S ribosomal subunits to mRNA during the initiation of prokaryotic translation is known to be influenced by the initiation codon and the Shine-Dalgarno sequence. Site-directed mutagenesis ofrnd, the Escherichia cofi gene encoding RNase D, has now shown that a Us sequence upstream of the Shine-Dalgarno region is also essential for expression of this mRNA. Alteration of two to five uridine residues within this sequence has no effect on mRNA levels but decreases RNase D protein and activity by as much as 95%, indicating that the U-rich sequence acts as an enhancer of translation. Moreover, mutant transcripts bind to 30S ribosomes in vitro with lower affinity than their wild-type counterparts, suggesting that the role of the Us sequence is in the initial binding of ribosomes to the translation initiation region of the message. These data demonstrate that sequences other than those previously recognized can be essential for translation initiation.Selection of the correct initiation codon by 30S ribosomal subunits is a primary determinant of accurate translation of mRNA in prokaryotic cells. However, despite extensive study, it is still not understood how this sequence of three nucleotides is distinguished from other residues in a message (1, 2). Factors known to influence the efficiency of binding of ribosomes to the translation initiation region of a mRNA include the initiation codon itself, a run of three to seven nucleotides upstream ofthe initiation codon termed the ShineDalgarno sequence, the spacing between these two segments, and the secondary structure of the initiation region (3,4). However, statistical analyses (5) and isolation of functional translation initiation regions (6) have shown that other sequences in these regions are nonrandom and may also play a role in the initiation process. Several possibilities for sequences upstream of the Shine-Dalgarno region that might function as translational enhancers have been proposed (7,8), although their significance is unclear. In addition to the RNA-RNA interactions between mRNA and ribosomes, it is likely that ribosomal proteins also participate in the selection of translation start sites, and protein S1 of the 30S subunit, in particular, has been implicated in this process (9). Based on UV crosslinking of protein S1 to phage and bacterial messages in vitro, it was suggested recently that pyrimidine-rich regions upstream of the Shine-Dalgarno sequence might interact with protein S1 and serve as ribosome recognition sites (10).During the course of studying the Escherichia coli rnd gene, which encodes the tRNA-processing enzyme RNase D, we identified (11, 12) a potential stem-loop structure followed by eight uridine residues located upstream of the initiator UUG codon and the Shine-Dalgarno sequence in the mRNA (Fig. 1). Although such a structure has features of a transcription terminator, when the stem-loop and uridine residues were deleted neither the rnd mRNA level nor the transcription start site was altered, but RNase D expression was el...