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Purpose Gastric cancer (GC) is aggressive cancer with a high mortality rate worldwide. N6-methyladenosine (m6A) RNA methylation is related to tumorigenesis, which is dynamically regulated by m6A modulators ("writer," "eraser," and "reader"). We conducted a comprehensive analysis of the m6A genes of GC patients in TCGA datasets to identify the potential diagnostic biomarkers. Materials and methods We analyzed the expression profile of m6A genes in the TCGA cohort and constructed a diagnostic-m6A-score (DMS) by the LASSO-logistic model. In addition, by consensus cluster analysis, we identified two different subgroups of GC risk individuals by the expression profile of m6A modulators, revealing that YTHDF1's expression variation profile in GC diagnosis. We also performed RT-qPCR and WB verification in 17 pairs of GC specimens and paired adjacent non-tumor tissues and GC cell lines, and verified the expression trend of YTHDF1 in five GEO GC datasets. YTHDF1 expression and clinical features of GC patients were assessed by the UALCAN. Results The DMS with high specificity and sensitivity (AUC = 0.986) is proven to distinguish cancer from normal controls better. Moreover, we found that the expression profile variation of YTHDF1 was significantly associated with the high-risk subtype of GC patients. RT-qPCR and Western blot results are consistent with silicon analysis, revealing that YTHDF1's potential oncogene role in GC tumor. Conclusion In conclusion, we developed the m6A gene-based diagnostic signature for GC and found that YTHDF1 was significantly correlated with the high-risk subtype of GC patients, suggesting that YTHDF1 might be a potential target in GC early diagnosis.

Cervical cancer (CC) is a malignant tumor that could seriously endanger women's life and health, of which cervical squamous cell carcinoma (CESC) accounts for more than 80%. High-risk human papillomavirus (HR-HPV) infection is the primary cause of CC. The 5-year survival rate is low due to poor prognosis. We need to explore the pathogenesis of CC and seek effective biomarkers to improve prognosis. The purpose of this research is to construct an HR-HPV-related long non-coding RNA (lncRNA) signature for predicting the survival and finding the biomarkers related to CC prognosis. First, we downloaded the CESC data from The Cancer Genome Atlas (TCGA) database to find HR-HPV-related lncRNAs in CC. Then, the differentially expressed lncRNAs were analyzed by univariate and multivariate Cox regression. Six lncRNAs were found to be associated with the prognosis and can be used as independent prognostic factors. Next, based on these prognostic genes, we established a risk score model, which showed that patients with higher score had poorer prognosis and higher mortality. Moreover, the Kaplan-Meier curve of the model indicated that the model was statistically significant (

Lung cancer is one of the deadliest cancers worldwide. To increase the survival rate of lung cancer, it is necessary to explore specific prognosis markers. More and more evidence finds that noncoding RNA is closely associated with the survival of lung cancer, and cancer stem cells (CSCs) also play a significant role in the progress of lung cancer. The objective of this study is to find CSLCs genes that affect the prognosis of lung cancer. The differential expression of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), messenger RNAs (mRNAs) in the Cancer Genome Atlas (TCGA) database and differential expression data from microarray of CD326+ and CD326- A549 cell are intersected to identify stable and consistent expression genes (2 lncRNAs, 15 miRNAs, and 134 mRNAs). The intersection of lncRNAs and miRNAs is analyzed by univariate and multivariate Cox regression to obtained prognostic genes. Two miRNAs (miR-30b-5p and miR-29c-3p) are significantly correlated with the overall survival rate. Then using these two miRNAs to construct a risk score model as a prognosis signature of lung cancer. Subsequently, we analyzed the association between two miRNAs and clinical information of lung cancer patients, of which T stage, Neoplasm cancer and risk score (P < .05) can be used as independent prognostic indicators of lung cancer. Finally, target genes of 2 miRNAs and 134 mRNAs were annotated with Gene Ontology and analyzed with Kyoto Encyclopedia of Genes and Genomes pathway, and verified with the GEO database. In summary, this study illustrates the role of miRNAs in the promotion of lung cancer by CSCs, which is important to find molecular biomarkers of lung cancer.

The digestive system cancers are aggressive cancers with the highest mortality worldwide. In this study, we undertook a systematic investigation of the tumor immune microenvironment to identify diagnostic and prognostic biomarkers. The fraction of 22 immune cell types of patients were estimated using CIBERSORT. The least absolute shrinkage and selection operator (LASSO) analysis was carried out to identify important immune predictors. By comparing immune cell compositions in 801 tumor samples and 46 normal samples, we constructed the diagnostic immune score (DIS), showing high specificity and sensitivity in the training (area under the receiver operating characteristic curve [AUC] = 0.929), validation (AUC = 0.935), and different cancer type cohorts (AUC > 0.70 for all). We also established the prognostic immune score (PIS), which was an effective prognostic factor for relapse‐free survival in training, validation, and entire cohorts (P, Our study comprehensively analyzed the utility of consideration of immune cells in the diagnosis and prognosis of digestive system cancers. The diagnostic immune score and prognostic immune score signature might serve as biomarkers for early diagnosis and predicting survival.

Genetic factors were identified to be associated with the development of idiopathic pulmonary fibrosis (IPF). We aimed to investigate associations between mucin 5B (MUC5B) and telomerase reverse transcriptase (TERT) polymorphisms and telomere length (TL) with honeycombing extent and survival in a Chinese IPF cohort. Seventy-nine patients diagnosed with IPF were enrolled. The honeycombing extents in high resolution CT scan (HRCT) were quantitatively scored and defined as mild (50%) upon the honeycombing extents involving the total lung. We tested five single-nucleotide polymorphisms [rs35705950, rs868903 in MUC5B, rs2736100, rs2853676 in TERT and rs1881984 in Telomerase RNA Gene (TERC) and TLs in peripheral blood leucocytes, and evaluated their associations with radiographic extent and survival in IPF. The minor allele frequencies (MAF) were significantly greater for MUC5B rs868903 (P = 0.042) and TERT rs2853676 (P = 0.041) in IPF than those in healthy controls. CT/CC genotype of MUC5B rs868903 (p = 0.045) and short TLs (p = 0.035) were correlated with the more extensive honeycombing opacities in HRCT. After adjustment for age, sex, and smoking status, MUC5B rs868903 polymorphism was the significant gene risk factors for reduced survival (p = 0.044) in IPF. MUC5B promoter rs868903 polymorphism and TLs were associated with radiographic extent and survival in a Chinese IPF cohort. These findings suggested a genetic clue for exploring the underlying molecular basis and pathogenesis of IPF.

Long noncoding RNA (lncRNA) has played the important function in regulation of various biological processes and in diagnostic value has been widely appreciated. In the present study, we have found that LOC101928316 was significantly downregulated in gastric cancer (GC) tissues specimen, GC cell lines, and associated with the GC patients tumor, node, and metastasis (TNM) stage and degree of differentiation (P ＜ 0.05). LOC101928316 overexpression can significantly inhibit SGC‐7901 cell migration, invasion, and proliferation (P＜0.05). LOC101928316 molecular mechanism investigates suggested that LOC101928316 can regulate PI3K‐Akt‐mTOR signaling pathway and change the GC development progression in vivo and in vitro. In vivo experiment also revealed that LOC101928316‐Overexpression can inhibit the tumorigenicity of GC cells in tumor‐burdened experimental nude mice (P ＜ 0.05). LOC101928316 may function as anti‐oncogene and also plays an important role in GC tumorigenesis. Collectively, our data provided the key role of LOC101928316 in the tumorigenesis of GC. In addition, the present study elucidates LOC101928316 potential regulatory network, which may help us to lead a better knowing of the pathogenesis of GC and probe the lncRNA as a novel biomarker to diagnosis and therapy for this malignant tumor.

Cutaneous malignant melanoma (hereafter called melanoma) is one of the most aggressive cancers with increasing incidence and mortality rates worldwide. In this study, we performed a systematic investigation of the tumor microenvironmental and genetic factors associated with melanoma to identify prognostic biomarkers for melanoma. We calculated the immune and stromal scores of melanoma patients from the Cancer Genome Atlas (TCGA) using the ESTIMATE algorithm and found that they were closely associated with patients' prognosis. Then the differentially expressed genes were obtained based on the immune and stromal scores, and prognostic immune-related genes further identified. Functional analysis and the protein-protein interaction network further revealed that these genes enriched in many immune-related biological processes. In addition, the abundance of six infiltrating immune cells was analyzed using prognostic immune-related genes by TIMER algorithm. The unsupervised clustering analysis using immune-cell proportions revealed eight clusters with distinct survival patterns, suggesting that dendritic cells were most abundant in the microenvironment and CD8+ T cells and neutrophils were significantly related to patients' prognosis. Finally, we validated these genes in three independent cohorts from the Gene Expression Omnibus database. In conclusion, this study comprehensively analyzed the tumor microenvironment and identified prognostic immune-related biomarkers for melanoma.

Objective: Gastric cancer is the most common gastrointestinal malignancy in China and results from a combination of genetic and environmental factors. The present study was conducted to investigate the relationship between long noncoding RNA (lncRNA) materally expressed gene 3 (MEG3) single nucleotide polymorphisms (SNPs) and the risk of gastric cancer and to construct a genetic-environmental risk assessment model. Methods: A case–control study was conducted to include 474 patients with gastric cancer diagnosed by clinical and pathological examination and 543 healthy physical examination subjects. Blood samples, general demographic data and behavioral lifestyle of the subjects were collected. The TaqMan real-time PCR method was used for testing the genotypes of MEG3 rs7158663 and rs10132552. Results: The A allele at the rs7158663 loci of MEG3 was found to be risk factor for gastric cancer (odds ratio (OR) = 1.41, 95% confidence interval (95% CI) = 1.14–1.74, P=0.002). Yet, no significant association between rs10132552 polymorphisms and gastric cancer was observed. Drinking, tea drinking and preserved food eating were risk factors for gastric cancer (P

Background Docetaxel (DTX) is a widely used anti-tumour drug, and its dosage is solely determined by body surface area (BSA). Adverse events, such as neutropenia or unsatisfied efficacy, likely occur because of differences in the pharmacokinetics (PK) and pharmacodynamics of patients. Thus, a feasible dosage adjustment method is needed. Methods A total of 209 eligible patients who provided consent were enrolled and randomised into two groups to receive the BSA- and PK-guided dosage adjustments of DTX-based chemotherapy (3 weeks per cycle). The AUC of DTX was detected, and the therapeutic window for Chinese patients was determined. The proportion of patients within the therapeutic window was evaluated. Neutropenia was examined in accordance with the toxicity grading standard suggested by the World Health Organisation. Tumour response was assessed in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. The primary endpoint was the incidence of neutropenia, and the secondary endpoints were disease control rate (DCR) and 3-year survival rate. Results The therapeutic window for Chinese patients was 1.7–2.5 mg·h/L. The proportion of patients within the therapeutic window was 63.89% versus 28.33% (P P = 0.001) in the experimental group versus the control group in the sixth cycle, respectively. DCR was 72% versus 85% (P = 0.018) in the control group versus the experimental group. The 3-year survival rate of the PK group was significantly higher than that of the BSA group (P = 0.034). Conclusions The PK-guided dosage adjustment of DTX could significantly increase the proportion of patients within the therapeutic window, decrease the incidence of neutropenia and increase the DCR and the 3-year survival rate. The PK-guided dosage adjustment based on the dynamic monitoring of AUC could be a useful method for oncologists to improve individualised treatment options, optimise drug efficacy and reduce drug toxicity.

Few studies have examined the association between smoking status (including former smokers) at diagnosis and overall survival among cancer patients. We aimed to assess the benefits of quitting smoking on cancer prognosis in cohorts of cancer patient smokers obtained from the Cancer Genome Atlas (TCGA) database. Hazard ratios (HR) were calculated to evaluate smoking behavior at cancer diagnosis (reformed smokers vs. current smokers) in association with overall survival using multivariate‐adjusted Cox regressions analysis. According to our analyses, quitting smoking was the independent protective factor for overall survival in lung squamous cell carcinoma (LUSC) (HR = 0.67, 95% CI = 0.48–0.94). Comprehensive analysis of multicomponent data across reformed and current smokers identified a total of 85 differential expressed genes (DEGs) affected by different modes of genetic and epigenetic regulation, potentially representing cancer drivers in smokers. Moreover, we provided a smoking‐associated gene expression signature, which could evaluate the true effect on prognosis with high power (HR = 1.70, 95% CI = 1.19–2.43, AUC = 0.65, 0.67, and 0.70 for 2‐, 3‐, and 5‐year survival, respectively). This signature was also applicable in other smoking‐related cancers, including bladder urothelial carcinoma (HR = 1.70, 95% CI = 1.01–2.88), cervical carcinoma (HR = 5.69, 95% CI = 1.37–23.69), head and neck squamous cell carcinoma (HR = 1.97, 95% CI = 1.41–2.76), lung adenocarcinoma (HR = 1.73, 95% CI = 1.16–2.57), and pancreatic adenocarcinoma (HR = 4.28, 95% CI = 1.47–12.47). In conclusion, this study demonstrates that quitting smoking at diagnosis decreases risk of death in cancer patients. We also provide a smoking‐associated gene expression signature to evaluate the effect of smoking on survival. Lastly, we suggest that smoking cessation could comprise a part of cancer treatment to improve survival rates of cancer patients., Tobacco smoking is an established risk factor for many cancers' development. In the present study, we used the the Cancer Genome Atlas cohort to estimate the association between smoking cessation and overall survival, understand the genetic and immune microenvironment of smoking patients, and provide an effective smoking signature for evaluating the smoking level to predict prognosis.

Xin You,1,2,* Sheng Yang,3,* Jing Sui,3 Wenjuan Wu,3 Tong Liu,3 Siyi Xu,3 Yanping Cheng,3 Xiaoling Kong,3 Geyu Liang,3 Yongzhong Yao1,2 1Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China; 2Department of General Surgery, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this work Purpose: Papillary thyroid carcinoma (PTC), the most frequent type of malignant thyroid tumor, lacks novel and reliable biomarkers of patients’ prognosis. In the current study, we mined The Cancer Genome Atlas (TCGA) to develop lncRNA signature of PTC.Patients and methods: The intersection of PTC lncRNAs was obtained from the TCGA database using integrative computational method. By the univariate and multivariate Cox analysis, key lncRNAs were identified to construct the prognostic model. Then, all patients were divided into the high-risk group and low-risk group to perform the Kaplan–Meier (K–M) survival curves and time-dependent receiver operating characteristic (ROC) curve, estimating the prognostic power of the prognostic model. Functional enrichment analysis was also performed. Finally, we verified the results of the TCGA analysis by the Gene Expression Omnibus (GEO) databases and quantitative real-time PCR (qRT-PCR).Results: After the comprehensive analysis, a three-lncRNA signature (PRSS3P2, KRTAP5-AS1 and PWAR5) was obtained. Interestingly, patients with low-risk scores tended to gain obviously longer survival time, and the area under the time-dependent ROC curve was 0.739. Furthermore, gene ontology (GO) and pathway analysis revealed the tumorigenic and prognostic function of the three lncRNAs. We also found three potential transcription factors to help understand the mechanisms of the PTC-specific lncRNAs. Finally, the GEO databases and qRT-PCR validation were consistent with our TCGA bioinformatics results.Conclusion: We built a three-lncRNA signature by mining the TCGA database, which could effectively predict the prognosis of PTC. Keywords: The Cancer Genome Atlas, long noncoding RNAs, overall survival, risk score

4-tert-octylphenol (4t-OP) is a well-known xenoestrogen. Our objective was to explore the effects and molecular mechanisms of 4t-OP on human sperm. Sperm samples were exposed to 0, 0.1, or 0.3 mM 4t-OP for two hours. Results showed that both sperm viability and motility were significantly injured by 0.3 mM 4t-OP. We applied comparative proteomics to explore the molecular targets affected by 4t-OP. 81 differentially expressed (DE) proteins were identified. Bioinformatic analysis showed that these proteins were highly associated with motility and apoptosis, and were mostly enriched in cAMP-PKA/PKC-phosphorylation-associated pathway. We further verified that 0.1 mM and 0.3 mM 4t-OP significantly decreased cAMP activity of sperm. Expression of RACK1 and PRDX6 were detected by western blot (WB) to verify their tendencies in gels; antiapoptotic factor BCL2 was also detected by WB. The data indicated that 4-tert-octylphenol injures the motility and viability of human sperm probably by affecting cAMP-PKA/PKC-tyrosine phosphorylation signals.

Background Lung adenocarcinoma (LUAD), mainly originated in lung glandular cells, is the most frequent pathological type of lung cancer and the 5-year survival rate of LUAD patients is still very low. Therefore, we aim to identify a long noncoding RNA (lncRNA)-related signature as the sensitive and novel prognostic biomarkers. Methods The associations between survival outcome and the intersection of lncRNAs were obtained from The Cancer Genome Atlas (TCGA) database. By the univariate and multivariate Cox analyses, key lncRNAs were identified to construct the prognostic model. The model was estimated by survival analysis and receiver operating characteristic curve, and verified by the Kaplan-Meier (K-M) plotter and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Functional enrichment analysis was also performed. Results A four-lncRNA signature (CEBPA-AS1, GVINP1, MIR31HG, and RAET1K) was developed after Cox analysis. The power of the four-lncRNA prognostic signature was effective in the TCGA database. The results from by the K-M plotter and qRT-PCR validation were consistent with our TCGA bioinformatics results. Furthermore, Gene Ontology and pathway analysis revealed the tumorigenic and prognostic function of the four lncRNAs. Conclusions By mining the TCGA data, we built a four-lncRNA signature, which could effectively predict prognosis of LUAD. In the future, an independent cohort is needed to validate our findings. Impact The four-lncRNA signature could become potential prognostic indicator of LUAD in the future.

Accumulating evidence implies that long noncoding RNAs (lncRNAs) play a crucial role in predicting survival for Hepatocellular carcinoma (HCC) patients. This study aims to capture the current research hotspots of HCC, based on the analysis of publications related to HCC research from 2013 to 2017, and to identify a novel lncRNA signature for HCC prognosis through the data mining in The Cancer Genome Atlas (TCGA). “Prognosis” and “biomarker” were located in the core of the HCC research hotspot. Moreover, long noncoding RNA was the top one research frontier in HCC research. The associations between survival outcome and the expression of lncRNAs were evaluated by the univariate and multivariate Cox proportional hazards regression analyses. Four lncRNAs (LINC00261, TRELM3P, GBP1P1, and CDKN2B‐AS1) were identified as significantly correlated with overall survival (OS). These four lncRNAs were gathered as a single prognostic signature. There was a significant positive correlation between HCC patients with low‐risk scores and overall survival (HR = 1.802, 95%CI [1.224‐2.652], P = .003). Further analysis suggested that the prognostic value of this four‐lncRNA signature was independent in clinical features. The enrichment analysis of prognostic lncRNA‐related gene was performed to find out the related pathways. Our study indicates that this novel lncRNA expression signature may be a useful biomarker of the prognosis for HCC patients, based on bioinformatics analysis.

To investigate the clinical features, risk factors and outcomes of patients with interstitial pneumonia with autoimmune features (IPAF). A total of 1429 patients with idiopathic interstitial pneumonia (IIP) and undifferentiated connective tissue disease-associated interstitial lung disease (UCTD-ILD) were screened to identify patients who met IPAF criteria. Clinical, serological, and morphological features of patients with IPAF were characterized. Outcomes between patients with IPAF, UCTD-ILD, and IIP who were divided into idiopathic pulmonary fibrosis (IPF) and non-IPF groups were compared using survival as an endpoint. Patients with IPAF were much common in young female and had lower percentage of ever smoking and a significantly shorter survival than those with non-IPAF (P

This study investigated the role of microRNA(miRNA) in regulating the cytotoxicity of TiO2 nanoparticles (nano-TiO2) to RAW264.7 cells. RAW264.7 cells were treated with 0 and 100 μg/ml nano-TiO2 for 24 h (for miRNA analysis). The differentially expressed miRNAs were detected using Illumina HiSeq™ 2000 sequencing. Through the bio-informatics analysis, miR-350 was found to play an important role in multiple signaling pathways, including MAPK signaling pathway, NF-kappa B signaling pathway and Apoptosis. To characterize the miR-350 function, miR-350 mimic was transfected into RAW264.7 cells for 24 h. MTT and Flow Cytometry were performed to detect cell proliferation, apoptosis and cell cycle (repetition), respectively. QRT-PCR, Western Blot methods and Luciferase assays were applied to detect expression of putative target gene PIK3R3. The results showed that miRNA profiles were differentially dysregulated. The apoptosis rate of miR-350 mimic group was significantly higher than negative control group (p

// Yan Miao 1, * , Jing Sui 1, * , Si-Yi Xu 1 , Ge-Yu Liang 1 , Yue-Pu Pu 1 and Li-Hong Yin 1 1 Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, P.R. China * These authors have contributed equally to this work Correspondence to: Li-Hong Yin, email: lh.yin62@gmail.com Keywords: lncRNA, GC, prognostic biomarker, overall survival, TCGA Received: June 09, 2017 Accepted: July 26, 2017 Published: August 24, 2017 ABSTRACT Emerging evidence indicates that long non-coding RNAs (lncRNAs) play a crucial role in predicting survival for gastric cancer (GC) patients. This study aims to identify a lncRNA-related signature for evaluating the overall survival of 379 GC patients from The Cancer Genome Atlas (TCGA) database. The associations between survival outcome and the expression of lncRNAs were evaluated by the univariate and multivariate Cox proportional hazards regression analyses. Four lncRNAs (LINC01018, LOC553137, MIR4435-2HG, and TTTY14) were identified as significantly correlated with overall survival. These four lncRNAs were gathered as a single prognostic signature. There was a significant positive correlation between GC patients with low-risk scores and overall survival (P = 0.001). Further analysis suggested that the prognostic value of this four-lncRNA signature was independent in clinical features. Gene set enrichment analysis found that these four lncRNAs were correlated with several molecular pathways of the tumor. Our study indicates that this novel lncRNA expression signature may be a useful biomarker of the prognosis for GC patients, based on bioinformatics analysis.

The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated during disease occurrence and to play an important role in the progression of several cancers. However, the biological role and potential regulation mechanism of UCA1 in the carcinogenesis of gastric cancer remain unclear. In the present study, we found that UCA1 was aberrantly upregulated in gastric cancer tissues and gastric cancer cell lines, and was associated with TNM stage and metastasis. UCA1 silencing significantly inhibited gastric cancer BGC-823 cell proliferation and increased its apoptosis. We also found that UCA1 played an important role in the migration and invasion of gastric cancer cells in vitro and in vivo. The molecular mechanism of UCA1 suggested that UCA1 regulates the PI3K-Akt-mTOR signaling proteins and their downstream mediators, to alter gastric cancer progression in vitro and in vivo. Collectively, the results showed a pivotal role of UCA1 in the tumorigenesis of gastric cancer. In addition, the study characterized a novel lncRNA-mRNA regulatory network, which may lead to a better understanding of the pathogenesis of gastric cancer and assist in lncRNA-directed diagnosis and therapy for this malignancy.

Lung adenocarcinoma (LUAD) is a complex disease that poses challenges for diagnosis and treatment. The aim of the present study is to investigate LUAD-specific key microRNAs (miRNAs) from large-scale samples in The Cancer Genome Atlas (TCGA) database. We used an integrative computational method to identify LUAD-specific key miRNAs related to TNM stage and lymphatic metastasis from the TCGA database. Twenty-five LUAD-specific key miRNAs (fold change >2, p

Although increasing evidence suggests a potential beneficial effect of nut consumption on various diseases, no epidemiologic study has yet examined the association between nut consumption and risk of hepatocellular carcinoma (HCC). We prospectively examined this association in 88,783 women from the Nurses’ Health Study and 51,492 men from the Health Professionals Follow-up Study. Nut consumption was assessed every 4 years using validated food frequency questionnaires. Multivariable HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression models after adjusting for HCC risk factors. After an average of 27.9 years of follow-up, we identified a total of 162 incident HCC cases. Higher total nut consumption was not significantly associated with HCC risk (the highest vs. lowest tertile intake, HR, 0.84; 95% CI, 0.56–1.26). For the same comparison, higher tree nut consumption was associated with a lower HCC risk (HR, 0.64; 95% CI, 0.43–0.95). We found nonsignificant inverse associations with consumption of walnuts, peanuts, and peanut butter. Overall, nut consumption was not strongly associated with HCC risk. There was a suggestive inverse association with tree nut consumption. Future studies should carefully consider hepatitis B or C virus infections and examine these associations in other racial/ethnic groups.

Accumulating evidence implies that N6-methyladenosine (m6A) methylation participated in the tumorigenesis of gastric cancer (GC). Here we synthetically analyzing the prognostic value and expression profile of seven m6A methylation-relevant genes through silico analysis of sequencing data downloaded from The Cancer Genome Atlas, Kaplan-Meier plotter, and Gene Expression Omnibus database. We explored the methyltransferase-like 3 (METTL3) expression in GC cell line and tumor tissues by reverse transcription quantitative polymerase chain reaction and western blot analysis. The m6A methylation status of total RNA was measured by m6A RNA methylation quantification kit. Small interfering RNA was used to establish METTL3 knockdown cell lines. We also measure the proliferation and migration capability GC cell. Furthermore, we detect the epithelial cell mesenchymal transition marker and m6A methylation level after METTL3 knock down. Our result revealed that METTL3 was significantly increased in GC tissues compared with control in big crowd data sets. Survival analysis showed that METTL3 serve as a poor prognostic factor for GC patients. The expression level of METTL3 gradually increased with the progress of tumor stage and grade. GFI1 is an important transcription factor associated with METTL3. We verified the up-trend of METTL3 in messenger RNA and protein expression and observed a significant increase in the m6A methylation status of total RNA in the GC cells and tissues. METTL3 knockdown inhibited total RNA m6A methylation level, as well as cell proliferation and migration capacity. Moreover, METTL3 knockdown decreased α-smooth muscle actin. Taken together, our finding revealed that m6A methylation writer METTL3 serve as an oncogene in tumorigenesis of GC.

Accumulating evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor biology. However, the roles of cancer specific lncRNAs in lncRNA-related ceRNA network of lung adenocarcinoma (LUAD) are still unclear. In the present study, the 465 RNA sequencing profiles in LUAD patients were obtained from the cancer genome atlas (TCGA) database, which provides large sample RNA sequencing data free of charge, and 41 cancer specific lncRNAs, 25 miRNAs and 1053 mRNAs (fold change >2, p

// Shasha Meng 1 , Shaowei Wu 2 , Liming Liang 1 , Geyu Liang 4 , Edward Giovannucci 1, 3, 5 , Immaculata De Vivo 1, 3, * , Hongmei Nan 6, 7, * 1 Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA 2 Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA 3 Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA 4 Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, China 5 Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA 6 Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA 7 Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA * Co-senior authors Correspondence to: Immaculata De Vivo, email: nhidv@channing.harvard.edu Hongmei Nan, email: hnan@iu.edu Keywords: mitochondrial DNA copy number, anthropometric indices, weight change, telemere length Received: May 09, 2016 Accepted: June 09, 2016 Published: June 29, 2016 ABSTRACT Objectives: To examine the association between leukocyte mitochondrial DNA copy number (mtCN) and different anthropometric indices as well as weight changes; and to compare mtCN and telomere length with respect to their associations with BMI and age. Design: Population based cohort study. Setting: Nurses’ Health Study, an ongoing prospective cohort study of 121,700 nurses enrolled in 1976; in 1989-1990 a subset of 32,826 women provided blood samples. Participants: 1,700 disease-free US women from case-control studies nested within the Nurses’ Health Study with mtCN and telomere length measured who also have anthropometric measurements. Main outcome measure: Relative mtCN and telomere lengths in peripheral blood leukocytes measured by quantitative real time polymerase chain reaction and various anthropometric measurements data from initial questionnaire. Results: Leukocyte mtCN was inversely associated with current weight (LS means Q1-Q4: 0.07, 0.04, 0.03, -0.17; P trend =0.002), waist size (LS means Q1-Q4: 0.06, 0.05, -0.04, -0.06; P trend = 0.04), BMI (LS means normal light, normal heavy, overweight, pre-obese, obese: 0.11, -0.01, -0.04, 0.04, -0.25; P trend

Abnormal expression of long non-coding RNAs (lncRNAs) have been shown to play an important role in tumor biology. The Cancer Genome Atlas (TCGA) platform is a large sample sequencing database of lncRNAs, and further analysis of the associations between these data and patients' clinical related information can provide new approaches to find the functions of lncRNA. In the present study, 361 RNA sequencing profiles of gastric cancer (GC) patients were selected from TCGA. Then, we constructed the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network of GC. There were 25 GC specific lncRNAs (fold change >2, p

Non-small cell lung cancer (NSCLC) is a major type of lung cancer with high morbidity and mortality. Long non-coding RNAs (lncRNAs) have been reported to be important in development and progression of NSCLC. However, the role of lncRNA SFTA1P remains unclear. This study aims to explore the clinical roles, biological function, and mechanism of SFTA1P in NSCLC. SFTA1P expression was estimated by the quantitative real-time polymerase chain reaction (qRT-PCR) of 90 pairs of tissue samples, the Cancer Genome Atlas (TCGA) database and microarray. After overexpressing SFTA1P, NSCLC cell proliferation, cycle, and apoptosis were detected. We found that the expression of SFTA1P was significantly downregulated in NSCLC tissues with high diagnostic value (AUC = 0.87), which was consistent with the results of TCGA and microarray data. For the analysis of clinical features, the results revealed that SFTA1P expression was closely related to the pathological type (P 0.01). Furthermore, the cell function results suggested that the overexpression of SFTA1P triggered cell cycle arrest in the S-phase (P 0.05). From a mechanistic perspective, the results showed that the PI3K-AKT signaling pathway was inhibited after overexpression of SFTA1P in NSCLC. Taken together, this work supported that SFTA1P may play a suppressing role in the tumorigenesis of NSCLC by modulating PI3K-AKT signaling pathway to influence cell cycle, which provides a potential and prospective biomarker for NSCLC.

Lung squamous cell carcinoma (LUSC) is one of the main histological types of lung cancer with high mortality. The role of microRNA-486-5p in LUSC remains unclear. In the current study, the aim was to explore miR-486-5p expression and its role in LUSC. The miR-486-5p expression was significantly low-expressed in patients with LUSC from The Cancer Genome Atlas database, which was further confirmed in the Gene Expression Omnibus database, patients' tissues, different cell lines by quantitative real-time polymerase chain reaction, and the high-throughput gene sequencing data of lung tissues of mice after a long-term B(a)P exposure. The meta-analysis was performed to evaluate the expression and diagnosis power of miR-486-5p (standard mean difference = -2.25; 95% confidence interval: -3.47 to -1.03; P = 0.0003; area under curve = 0.9082). Functional enrichment analysis revealed the potential function of miR-486-5p in LUSC using gene set enrichment analysis and clusterProfiler package in R software. At last, the hub genes (PTEN, TEK, PIK3R1, PPM1B, SMAD2, and SPTA1) of miR-486-5p were verified. In conclusion, miR-486-5p may be a LUSC antioncogene, playing an important role to serve as a biomarker in LUSC.

The aim of this work was to determine the expression of the ERβ (estrogen receptor β) and multidrug resistance, namely MDR1 (P-glycoprotein, P-gp), in 152 samples of non-small cell lung cancer. The expression pattern of ERβ and MDR1 were assessed by the quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry. We also analyzed the correlation between ERβ and MDR1 with clinical and pathological data. The co-expression pattern of ERβ and individual MDR1 proteins was assessed by correspondence analysis and chi-squared tests. In the present study, we found that patients with tumor stage I-II showed higher ERβ mRNA expression levels and decreased expression of ERβ protein with increasing tumor grade, which is opposite to MDR1 expression. In addition, an opposite co-expression pattern of ERβ and individual MDR1 proteins was also observed. In conclusion, the results can be used to better understand the expression control of MDR1 and may allow for the establishment of new cancer chemistry strategies that will control P-gp expression in NSCLC.

Background Recent scientific evidence has suggested that microRNAs (miRNAs) play an important role in papillary thyroid cancer (PTC). In the current study, we aim to identify a miRNA-related signature as the sensitive and novel prognostic biomarkers. Methods We performed a comprehensive analysis of the data downloaded from the Cancer Genome Atlas (TCGA) database. The association between survival outcome and miRNA was assessed by the univariate and multivariate Cox proportional hazards model. The risk score model was built to evaluate the predicting value of miRNA signature. The potential biofunctions and transcription factors of target miRNAs were investigated through bioinformatic analysis. The result was verified by the quantitative real-time polymerase chain reaction (qRT-PCR) in 32 pairs of PTC and adjacent nontumor tissues. In addition, the results were verified by other cohorts from gene expression omnibus (GEO) as detected by microarrays. Results A total of 1030 miRNAs were identified from the TCGA database. Thirty-six key intersection miRNAs were obtained. The associations between clinical features and key miRNAs were evaluated. Eventually, a two-miRNA signature (hsa-miR-181a-2-3p and hsa-miR-138-1-3p) was identified. The power of the miRNA prognostic signature was effective. In total, we identified 202 genes that were associated with 2 miRNAs above, and the top 10 enriched transcript factors that highly related with the target miRNAs were explored. The qRT-PCR and GEO data validation were consistent with bioinformatics results. Conclusions A tumor-specific miRNA signature was identified, and the joint prognostic power was evaluated, which may be potential biomarkers for prognosis of PTC. Impact The two-miRNA signature could become the potential prognostic indicator of PTC in the future.

BACKGROUND: Mitochondrial dysfunction is an important component of the aging process and has been implicated in the development of many human diseases. Mitochondrial DNA copy number (mtDNAcn), an indirect biomarker of mitochondrial function, is sensitive to oxidative damage. Few population-based studies have investigated the impact of fruit and vegetable consumption and cigarette smoke (2 major sources of exogenous antioxidants and oxidants) on leukocyte mtDNAcn. OBJECTIVES: We investigated the association between fruit and vegetable consumption, cigarette smoke, and leukocyte mtDNAcn based on data from the Nurses’ Health Study (NHS). METHODS: Data from 2769 disease-free women in the NHS were used to examine the cross-sectional associations between dietary sources of antioxidants, cigarette smoke, and leukocyte mtDNAcn. In vitro cell-based experiments were conducted to support the findings from the population-based study. RESULTS: In the multivariable-adjusted model, both whole-fruit consumption and intake of flavanones (a group of antioxidants abundant in fruit) were positively associated with leukocyte mtDNAcn (P-trend = 0.005 and 0.02, respectively), whereas pack-years of smoking and smoking duration were inversely associated with leukocyte mtDNAcn (P-trend = 0.01 and 0.007, respectively). These findings are supported by in vitro cell-based experiments showing that the administration of naringin, a major flavanone in fruit, led to a substantial increase in mtDNAcn in human leukocytes, whereas exposure to nicotine-derived nitrosamine ketone, a key carcinogenic ingredient of cigarette smoke, resulted in a significant decrease in mtDNAcn of cells (all P < 0.05). Further in vitro studies showed that alterations in leukocyte mtDNAcn were functionally linked to the modulation of mitochondrial biogenesis and function. CONCLUSIONS: Fruit consumption and intake of dietary flavanones were associated with increased leukocyte mtDNAcn, whereas cigarette smoking was associated with decreased leukocyte mtDNAcn, which is a promising biomarker for oxidative stress–related health outcomes.

Background Lung cancer is considered as one of the most frequent and deadly cancers with high mortality all around the world. It is critical to find new biomarkers for early diagnosis of lung cancer, especially lung squamous cell carcinoma (LUSC). The Cancer Genome Atlas (TCGA) is a database which provides both cancer and clinical information. This study is a comprehensive analysis of a novel diagnostic biomarker for LUSC, based on TCGA. Methods and Results The present study investigated LUSC-specific key microRNAs (miRNAs) from large-scale samples in TCGA. According to exclusion criteria and inclusion criteria, the expression profiles of miRNAs with related clinical information of 332 LUSC patients were obtained. Most aberrantly expressed miRNAs were identified between tumor and normal samples. Forty-two LUSC-specific intersection miRNAs (fold change >2, p < 0.05) were obtained by an integrative computational method, among them six miRNAs were found to be aberrantly expressed concerning characteristics of patients (gender, lymphatic metastasis, patient outcome assessment) through Student t-test. Five miRNAs correlated with overall survival (log-rank p < 0.05) were obtained through the univariate Cox proportional hazards regression model and Mantel–Haenszel test. Then, five miRNAs were randomly selected to validate the expression in 47 LUSC patient tissues using quantitative real-time polymerase chain reaction. The results showed that the test findings were consistent with the TCGA findings. Also, the diagnostic value of the specific key miRNAs was determined by areas under receiver operating characteristic curves. Finally, 577 interaction mRNAs as the targets of 42 LUSC-specific intersection miRNAs were selected for further bioinformatics analysis. Conclusion This study indicates that this novel microRNA expression signature may be a useful biomarker of the diagnosis for LUSC patients, based on bioinformatics analysis.

Cutaneous melanoma (CM) is the most malignant tumor of skin cancers because of its rapid development and high mortality rate. Long noncoding RNAs (lncRNAs), which play essential roles in the tumorigenesis and metastasis of CM and interplay with microRNAs (miRNAs) and mRNAs, are hopefully considered to be efficient biomarkers to detect deterioration during the progression of CM to improve the prognosis. Bioinformatics analysis was fully applied to predict the vital lncRNAs and the associated miRNAs and mRNAs, which eventually constructed the competing endogenous RNA (ceRNA) network to explain the RNA expression patterns in the progression of CM. Further statistical analysis emphasized the importance of these key genes, which were statistically significantly related to one or few clinical features from the ceRNA network. The results showed the lncRNAs MGC12926 and LINC00937 were verified to be strongly connected with the prognosis of CM patients.

Background Cervical cancer (CC) is a common gynecological malignancy in women worldwide. Evidence suggests that long non-coding RNAs (lncRNAs) can be used as biomarkers in patients with CC. However, prognostic biomarkers for CC are still lacking. The aim of our study was to find lncRNA biomarkers which are able to predict prognosis in CC based on the data from The Cancer Genome Atlas (TCGA). Methods The patients were divided into three groups according to FIGO stage. Differentially expressed lncRNAs were identified in CC tissue compared to adjacent normal tissues based on a fold change >2 and P < 0.05 for up- and downregulated lncRNA, respectively. The relationship between survival outcome and lncRNA expression was assessed with univariate and multivariate Cox proportional hazards regression analysis. We constructed a risk score as a method to evaluate prognosis. We used receiver operating characteristic (ROC) curve and the area under curve (AUC) analyses to assess the diagnostic value of a two-lncRNA signature. We detected the expression levels of the two lncRNAs in 31 pairs of newly diagnosed CC specimens and paired adjacent non-cancerous tissue specimens, and also in CC cell lines. Finally, the results were statistically compared using t-tests. Results In total, 289 RNA sequencing profiles and accompanying clinical data were obtained. We identified 49 differentially expressed lncRNAs, of which two related to overall survival (OS) in CC patients. These two lncRNAs (ILF3-AS1 and RASA4CP) were found together as a single prognostic signature. Meanwhile, the prognosis of patients with low-risk CC was better and positively correlated with OS (P < 0.001). Further analysis showed that the combined two-lncRNA expression signature could be used as an independent biomarker to evaluate the prognosis in CC. qRT-PCR results were consistent with TCGA, confirming downregulated expression of both lncRNAs. Furthermore, upon ROC curve analysis, the AUC of the combined lncRNAs was greater than that of the single lncRNAs alone (0.723 vs 0.704 and 0.685), respectively; P < 0.05. Conclusions Our study showed that the two-lncRNA signature of ILF3-AS1 and RASA4CP can be used as an independent biomarker for the prognosis of CC, based on bioinformatic analysis.

Lung cancer is one of the most lethal malignancies worldwide. To reduce the high morbidity and mortality of the disease, sensitive and specific biomarkers for early detection are urgently needed. Tumor-specific microRNAs (miRNAs) seem to be potential biomarkers for the early diagnosis and treatment of cancer. In this study, the microarray of miRNAs and mRNAs on the same samples was performed and the intersection taken with The Cancer Genome Atlas (TCGA) lung cancer miRNA/RNAseq dataset. Then, miRNA-mRNA regulatory network was constructed to identify miRNA candidates associated with lung cancer through integrating gene expression and miRNA-target prediction. Furthermore, the expression levels of miRNA candidates were validated by stem-loop real-time reverse transcription PCR (qRT-PCR) in larger lung cancer population. The relationship between signature miRNAs and the risk of lung cancer were assessed by conditional logistic regression analysis. Diagnostic value of these miRNAs was determined by areas under receiver operating characteristic curves (ROC). The Affymetrix microarray analysis identified a total of 116 miRNAs and 502 mRNAs that could distinguish lung tumor tissues from adjacent non-tumor tissues, of which 70 miRNAs and 136 mRNAs were upregulated, while 46 miRNAs and 366 mRNAs were downregulated, respectively. In combination with TCGA analysis, we identified 32 miRNAs and 377 mRNAs related to lung cancer. Then, 28 key miRNAs related to 61 inter-section mRNAs were identified by miRNA-mRNA network analysis. The miRNA function analysis was indicative of that 18 upregulated and 10 downregulated miRNAs involved in signaling pathways related to Environmental Information Processing and Human Diseases. Population result showed that the expression of 7 miRNAs (miR-205-5p, miR-3917, miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p and miR-27a-5p) was consistent with the analysis result of microarray and TCGA. In addition, upregulation of miR-205-5p, miR-3917 and downregulation of miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p, miR-27a-5p increased the risk of lung cancer by conditional logistic regression analysis. The diagnostic accuracy of miR-205-5p, miR-3917, miR-27a-5p, miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p showed that their corresponding AUCs were 0.728, 0.661, 0.637, 0.758, 0.772, 0.734, 0.776, respectively. Therefore, there are a set of signature miRNAs which may be promising biomarkers for the early screening of high-risk populations and early diagnosis of lung cancer.

// Xin Li 1 , Geyu Liang 2 , Mengmeng Du 3 , Immaculata De Vivo 1, 4 , Hongmei Nan 5 1 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA 2 Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, China 3 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA 4 Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA 5 Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, and Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA Correspondence to: Hongmei Nan, email: hnan@iu.edu Keywords: telomere length-related loci, melanoma, nevus count, genome-wide association study, genetic score Received: July 14, 2016 Accepted: September 07, 2016 Published: September 14, 2016 ABSTRACT Background: Longer telomeres have been associated both with increased melanoma risk and increased nevus counts. Nevus count is one of the strongest risk factors for melanoma. Recent data showed that a genetic score derived by telomere length-related single nucleotide polymorphisms (SNPs) was strongly associated with melanoma risk; however, the relationships between these SNPs and number of cutaneous nevi have not been investigated. Methods: We evaluated the associations between telomere length-related SNPs reported by previous genome-wide association study (GWAS) and nevus counts among 15,955 participants of European Ancestry in the Nurses’ Health Study and Health Professionals Follow-up Study. Results: None of the SNPs was associated with nevus counts, nor was the genetic score combining the dosage of alleles related to increased telomere length. Conclusions: The telomere length-related SNPs identified by published GWAS do not appear to play an important role in nevus formation. Genetic determinants of telomere length reported by GWAS do not explain the observed epidemiologic association between telomere length and nevus counts.

To investigate the potential candidate microRNA (miRNA) biomarkers for the clinical diagnosis, classification, and prognosis of gastric cancer (GC). We use bioinformatics overlapping subclasses analysis to find the tumor grade and lymphatic metastasis-related GC specific miRNAs from the Cancer Genome Atlas (TCGA) database. Then, we further investigated these GC specific miRNAs distributions in different GC clinical features and their correlations overall survival on the basis of GC patients’ information and their related RNA sequencing profile from TCGA. Finally, we randomly selected some of key miRNAs use qRT-PCR to confirm the reliability and validity. 22 GC specific key miRNAs were identified (Fold-change >2, P

Gastric cancer (GC) is one of the most lethal malignancies worldwide. To reduce its high mortality, sensitive and specific biomarkers for early detection are urgently needed. Recent studies have reported that tumor-specific long non-coding RNAs (lncRNAs) seem to be potential biomarkers for the early diagnosis and treatment of cancer. In the present study, lncRNA and mRNA expression profiling of GC specimens and their paired adjacent non-cancerous tissues was performed. Differentially expressed lncRNAs and mRNAs were identified through microarray analysis. The function of differential mRNA was determined by gene ontology and pathway analysis and the functions of lncRNAs were studied by constructing a co-expression network to find the relationships with corresponding mRNAs. We connected the co-expression network, mRNA functions, and the results of the microarray profile differential expression and selected 14 significantly differentially expressed key lncRNAs and 21 key mRNAs. Quantitative RT-PCR (qRT-PCR) was conducted to verify these key RNAs in 50 newly diagnosed GC patients. The data showed that RP5-919F19, CTD-2541M15 and UCA1 was significantly higher expressed. AP000459, LOC101928316, RP11-167N4 and LINC01071 expression was significantly lower in 30 advanced GC tumor tissues than adjacent non-tumor tissues P

Background Recent reports have shown that vitamin D status was inversely associated with the risk of various cancers. However, few studies examined the association between vitamin D levels and risk of skin cancer. Methods We prospectively evaluated the association between baseline plasma 25(OH)D levels and the risk of incident squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) among 4,641 women from the Nurses’ Health Study (NHS) and the NHS II with 510 incident BCC cases and 75 incident SCC cases. We used multivariate logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results Plasma 25(OH)D levels were positively associated with risk of BCC after adjusting for age at blood draw, season of blood draw, lab batch, hair color, burning tendency, the number of sunburns, and ultra-violet B flux of residence at blood collection. Women in the highest quartile of 25(OH)D had more than 2-fold increased risk of BCC compared with women in the lowest quartile (OR = 2.07, 95% CI = 1.52–2.80, P for trend

Background Telomere length has been proposed as a marker of aging. However, our knowledge of lifestyle risk factors determining telomere length is limited. Methods We evaluated the associations between years of rotating night shifts, self-reported sleep duration, and telomere length in 4,117 female participants from the Nurses' Health Study. Telomere length in peripheral blood leukocytes was determined by Real-Time PCR assay. Information on rotating night shifts and sleep duration was collected via questionnaires prior to blood collection. We used multivariable linear regression to investigate the associations between rotating night shifts, sleep duration, and telomere length. Results Compared with women in the category (9 hours), those in the lowest category of sleep duration (≤6 hours) had a 0.12 unit decrease in z score after adjustment for age, BMI and cigarette smoking (equivalent to 9-year telomere attrition, P for trend = 0.05). Significant positive association between sleep duration and telomere length was seen among women under age of 50 (P for trend = 0.004), but not among those over 50 (P for trend = 0.33) (P for interaction = 0.005). In addition, we observed that women with a longer history of rotating night shifts tended to have shorter telomere length, but this relation was not statistically significant (P for trend = 0.36). Conclusion We found that sleep duration was positively associated with telomere length among women under 50 years old. Further research is needed to confirm the observed associations.