IntroductionMature microRNAs (miRNAs) are naturally occurring small noncoding RNAs that act as negative regulators of gene expression through messenger RNA interference. These molecules were described for the first time in 1993 by Ambros and colleagues in Caenorhabditis elegans (Lee et al 1 ), and to date, hundreds of miRNAs have been identified in other species, including viruses. 2,3 miRNAs are encoded by intronic or intergenic DNA regions, primarily as large molecules that can exceed 1 Kb, and are cleaved by an RNase complex into fragments with characteristic stem-loop structures. In the cytoplasm, a RNase called Dicer further cleaves miRNA to generate a duplex molecule of 21 to 25 nucleotides in length. 4 One of the 2 chains is the mature miRNA that binds a protein complex called the RNA-induced silencing complex (RISC). When a miRNA and a messenger RNA exhibit total complementarities, RISC is capable of degrading target messenger RNA, 4 whereas if an incomplete base pairing complementarity takes place, translational silencing of the target occurs. Through these mechanisms, miRNAs decrease translation of human genes. 5,6 miRNAs play an important role in cellular proliferation and differentiation and embryonic development, and they also act as oncogenes or tumor suppressor genes. 7-10 Notably, the majority of miRNAs are found in cancer-associated genomic regions or in chromosome-fragile sites, 11 suggesting an important role for miRNAs in human tumorigenesis. There is also evidence that the influence of miRNAs in oncogenesis might be indirectly driven. For example, the presence of some viruses in a cell may change the host miRNA pattern. 12 Viruses may participate in the origin of some tumors, such as the Epstein-Barr virus (EBV) in Hodgkin lymphoma (HL).HL is a neoplasm characterized by the presence of relatively few tumoral cells (Hodgkin and Reed-Sternberg cells) in a nonneoplastic microenvironment. 13 Hodgkin and Reed-Sternberg cells arise from germinal center B cells. 14 Classic HL (cHL) is subclassified according to the morphology of Reed-Sternberg cells and the composition of the cellular background into nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte depletion. 15 The 2 former subtypes are the most frequent forms of cHL and contain a variable proportion of neoplastic cells.EBV is present in the malignant cells of 40% to 60% of cHL patients. However, the precise role of the EBV in the pathogenesis of cHL is unknown. It has been reported that viruses have their own miRNA set, 16 and that there is an interaction between the host miRNAs and virus miRNAs. 17,18 The interaction between the virus and the malignant cells in cHL might be mediated in part by miRNAs.To investigate whether a specific expression signature of miRNAs is associated with cHL, we assessed the expression of 156 miRNAs, the majority of which are related to hematopoiesis or tumorigenesis, 7,8,11 in lymph nodes from patients with nodular sclerosis and mixed cellularity cHL and compared the expression patterns with tho...

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BackgroundThe biological mechanisms involved in non-contact musculoskeletal soft tissue injuries (NCMSTI) are poorly understood. Genetic risk factors may be associated with susceptibility to injuries, and may exert marked influence on recovery times.MethodsData on type and degree of injury and recovery time were collected in 73 male professional soccer players (43 White, 11 Black Africans and 19 Hispanics) who suffered total of 242 injuries (203 muscle, 24 ligament, and 15 tendon injuries). One single nucleotide polymorphism (SNPs) in the following genes were analyzed: Elastin (ELN); Titin (TTN); SRY-related HMG-box (SOX15); Insulin-like growth factor 2 (IGF2); Chemokine, CC motif, ligand 2 (CCL2); Collagen type 1 alpha 1(COL1A1); Collagen type 5 alpha 1 (COL5A1), and Tenascin C (TNC).ResultsThere was evidence of a statistically significant association between the degree of injury and the IGF2 genotype (P = 0.034). In addition, there was evidence of a statistically significant association between the degree of muscle injury and CCL2 (P = 0.026) Finally, there was evidence of a statistically significant association between ELN and degree of injury (p = 0.009) and recovery time (P = 0.043). There was no evidence of a statistically significant association between any of the genes studied and degree of injury or recovery time for tendon injuries.ConclusionSNPs in the IGF2, CCL2, and ELN genes may be associated to the degree and recovery time of NCMSTI.

Purpose: To evaluate the efficacy of treatment with the aromatase inhibitor letrozole in breast cancer patients segregated with respect to DNA polymorphisms of the aromatase gene CYP19. Patients and Methods: Postmenopausal patients (n = 67) with hormone receptor^positive metastatic breast cancer were treated with the aromatase inhibitor letrozole. PCR allelic discrimination was used to examine three single-nucleotide polymorphisms (SNP) in DNA obtained from breast carcinoma tissue. Two SNPs analyzed (rs10046 and rs4646) were located in the 3 ¶ untranslated region and one (rs727479) was in the intron of the aromatase CYP19 gene. The primary end point of treatment efficacy was time to progression (TTP). Results: Median age was 62 years and median number of metastatic sites was 2. Observed allelic SNP frequencies were rs10046, 71%; rs4646, 46%; and rs727479, 63%. Of the 67 patients, 65 were evaluable for efficacy. Median TTP was 12.1 months. We observed no relationship between TTP and the rs10046 or rs727479 variants. In contrast, we found that TTP was significantly improved in patients with the rs4646 variant, compared with the wild-type gene (17.2 versus 6.4 months; P = 0.02). Conclusion: In patients with hormone receptor^positive metastatic breast cancer treated with the aromatase inhibitor letrozole, the presence of a SNP in the 3 ¶ untranslated region of the CYP19 aromatase gene is associated with improved treatment efficacy. Testing for the CYP19 rs4646 SNP as a predictive tool for breast cancer patients on antiaromatase therapy deserves prospective evaluation.Aromatase inhibitors, when administered to postmenopausal women, prevent the conversion of androgens to estrogens via inhibition of the aromatase enzyme. The antiaromatase compounds have emerged as a family of potent target-directed agents in the hormonal treatment of breast cancer. Third-generation aromatase inhibitors are used in the treatment of metastatic breast carcinoma (1, 2) and in the adjuvant setting (3 -5).Currently, the clinical indication for the use of aromatase inhibitors in breast cancer patients is guided by two criteria: a postmenopausal status and a positive hormone receptor status. Menopause is the critical criterion because functioning ovaries synthesize estrogen in an amount that would preclude aromatase inhibitors from being active. Positivity of estrogen or progesterone receptors in breast carcinomas has been related to the efficacy of tamoxifen as well as aromatase inhibitors. A recent review concluded that, when using anastrozole or letrozole as first-line treatment of patients with metastatic breast cancer, positive hormone receptor status is of prime importance in improving the time to disease progression (6). However, the clinical relevance of hormone receptors when using aromatase inhibitors is moderate because only f30% of the patients exhibit an objective clinical response (7 -9) and, therefore, the power to discriminate potentially responding from nonresponding patients is low. Additional biomarkers that could h...

Genetic profile could explain why some elite soccer players are predisposed to suffer more injuries than others and why they need more time to recover from a particular injury. SNPs in HGF genes have an important role as biomarkers of biological processes fragility within muscle injuries related to injury rate, severity, and long recovery time.

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Purpose Muscle injuries are common in professional football, even though prevention protocols are being implemented. Genetics constitutes a novel ield for studying intrinsic injury risks and performance. Since previous studies involving single nucleotide polymorphisms (SNPs) have shown that SNPs inluence muscle injury rate, injury severity and recovery time, the aim was to study the association the SNP of ACTN3 has with those parameters in professional football players. Methods The medical staf team recorded non-contact musculoskeletal soft-tissue injuries in 43 professional football players in 7 diferent seasons (2007-2012 and 2015-2016). Injury rate, injury severity and injury recovery times were established. Players were genotyped by extracting DNA from a blood sample and using a polymerase chain reaction. Results Injury rate was associated with the SNP of ACTN3 (p = 0.003). The 577R allele was more frequent in subjects than in a normal population by showing presence in 93% of the subjects and suggesting that it could inluence football performance. No statistically signiicant diferences in injury severity and recovery time were associated with the SNP of ACTN3. Conclusions Genetics is gaining in importance when assessing injury risk and performance in professional football. ACTN3 can be regarded as a biomarker of injury susceptibility in this discipline. Identifying those players with the highest injury susceptibility through genetics could lead football teams to individualise workloads and prevention protocols. Level of evidence III. Keywords Single nucleotide polymorphism • Football • Muscle injuries • GeneticsEnric Clos and Ricard Pruna contributed equally to the study.

miR-200a, miR-200c, miR-141, and miR-429 expression levels may identify CRC patients, including those with stage II disease, who are most likely to benefit from adjuvant chemotherapy.