Chunhua Song

Polymorphisms in lncRNA HOTAIR and susceptibility to breast cancer in a Chinese population.

Controversial data have emerged on the association between cancer risk and the single-nucleotide polymorphism (SNP, rs920778C>T) in Hox transcript antisense RNA (HOTAIR). No data on the association between HOTAIR polymorphism and breast cancer (BC) susceptibility and reproductive factors have been reported in China. In this study we investigated the association between HOTAIR polymorphisms and BC susceptibility in a population-based case-control study of 502 cases and 504 matched controls in China. Three haplotype tagging SNPs (rs1899663, rs4759314, rs920778) of HOTAIR were genotyped with polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and created-restriction-site PCR (CRS-RFLP) assays. False-positive report probability (FPRP) was calculated to test for false-positive associations. Interactions between the SNPs and reproductive factors were further evaluated by the multifactor dimensionality reduction (MDR) method. BC risk reduction was confined to subgroups of age at menarche >14 (OR: 0.42, 95%CI: 0.21, 0.82) and number of pregnancies >2 (OR: 0.65, 95%CI: 0.49, 0.95) for GT+TT rs1899663, and age at menopause ≤ 50 (OR: 0.97, 95%CI: 0.84, 0.99) for AG+GG rs4759314. Subjects with Trs920778 had a significantly increased risk of breast cancer (OR: 1.41, 95%CI: 1.13, 1.75). We observed a significant interaction between rs920778 and reproductive factors, including age at menopause, number of abortions, and family history. Our results were unlikely to be false positives according to FPRP calculation. In conclusion, genetic variant rs920778 in HOTAIR significantly increased the risk of BC, and it may have apparent interaction with reproductive factors in the progression on BC. These findings extend available data on the association between HOTAIR polymorphisms and BC susceptibility.

Genetic Polymorphisms in Long Noncoding RNA H19 Are Associated With Susceptibility to Breast Cancer in Chinese Population.

AbstractH19, a maternally expressed imprinted gene transcribing a long noncoding RNA, has previously been reported to be involved in tumorigenesis and cancer progression. However, the association between the H19 polymorphisms and breast cancer (BC) susceptibility has remained elusive. The aim of this study was to evaluate the associations between 2 H19 haplotype tagging SNPs (rs3741219 T>C, rs217727 C>T) and the risk of breast cancer.Our study comprised 464 BC patients and 467 cancer-free controls in China. rs3741219 and rs217727 were genotyped with polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and created restriction site PCR (CRS-RFLP) assays, respectively. False-positive report probability (FPRP) was calculated to test the false-positive association.On performing univariate analysis, no significant association between H19 polymorphisms (rs3741219 and rs217727) and BC was observed. However, in further stratified analyses, CT+TT genotypes of rs217727 had a significantly lower risk of breast cancer among women with number of pregnancy >2 (OR = 0.79; 95% CI = 0.55–0.97). CT genotype of rs217727 was associated with ER positivity (OR = 2.19; 95 % CI = 1.07–4.45) and HER-2 positivity (OR = 1.34; 95 % CI = 1.05–2.12). It was proved that our results were less likely to be false positives according to false-positive report probability calculation.Our findings extend available data on the association of H19 polymorphisms and BC susceptibility. Further validation in large population or cohort studies is needed.

Comparison of visceral and body fat indices and anthropometric measures in relation to untreated hypertension by age and gender among Chinese

BACKGROUND The aim of the study was to compare the efficiency of bioelectrical indices (percentage body fat, PBF; visceral fat index, VFI) and various anthropometric measures (body mass index, BMI; waist circumference, WC; waist-to-height ratio, WHtR) on determining hypertension in Chinese. METHODS We conducted the community-based cross-sectional survey during August of 2013 to August of 2015 in 66 sample sites selected by multistage random sampling method from Henan province. 14,364 residents were included in the study. RESULTS In both genders, VFI and PBF tended to rise with age. However, for each age-specific group, men consistently had significantly greater VFI than women (all P<0.0001) and women had considerably higher PBF (all P<0.0001). The odds ratios and area under the ROC curves (AUCs) for hypertension associated with adiposity indices decreased with age. In younger (15~34year) men and women, VFI had the highest crude (2.43-7.95) and adjusted (2.40-11.63) odds ratio for hypertension. The AUCs for PBF, VFI and WHtR were significantly larger than those for BMI and WC (all P<0.01). Whereas no statistically significant difference were found in AUCs among PBF, VFI and WHtR (all P>0.10). Additionally, VFI and PBF yielded the greatest Youden index in identifying hypertension in men (0.27) and women (0.34), respectively. Optimal cutoffs for VFI/PBF were 11.70/24.45 and 7.55/33.65 in men and women, respectively. CONCLUSIONS VFI and PBF could be better candidates for identifying hypertension in men and women, respectively. Adolescents and young adults should be highlighted in preventing hypertension by control of excess body and visceral fat.

Tumour-Associated Autoantibodies as Diagnostic Biomarkers for Breast Cancer: A Systematic Review and Meta-Analysis.

Tumour‐associated autoantibodies may be promising biomarkers that could facilitate breast cancer (BC) diagnosis and improve patient outcomes. This review aims to identify the tumour‐associated autoantibodies with the greatest diagnostic potential. Systematic searches were conducted using PubMed and Web of Science. The most studied tumour‐associated autoantibody was included in a meta‐analysis, and its clinical value was determined using Fagans nomogram. The analysis included 84 studies regarding tumour‐associated autoantibodies with the diagnostic value. Anti‐p53 antibody was the most frequently studied autoantibody, followed by autoantibodies against MUC1, HER2 and cyclin B1. Although individual tumour‐associated autoantibodies showed low diagnostic sensitivity, combinations of autoantibodies offered relatively high sensitivity. Enzyme‐linked immunosorbent assay (ELISA) was the most common detection method, and nucleic acid programmable protein microarrays appeared preferable to common protein microarrays. As the most commonly studied autoantibody, anti‐p53 antibody was included in a meta‐analysis. When it had been detected using ELISA and cut‐off values were defined as the mean +2 or 3 standard deviations, the summary area under the receiver operating characteristic curve for the presence of BC was 0.78. Fagans nomogram showed post‐test probabilities of 32% and 6% for positive and negative results, respectively. Mammography might be supplemented by the use of tumour‐associated autoantibodies as biomarkers for BC diagnosis in younger women with increased risks of BC. Even though several studies have investigated the diagnostic use of tumour‐associated autoantibodies as biomarkers for BC detection, a high‐quality prospective study is needed to validate their diagnostic value in practice.

Genetic variants in lncRNA SRA and risk of breast cancer

Long non-coding RNA (lncRNA) steroid receptor RNA activator (SRA) has been identified to activate steroid receptor transcriptional activity and participate in tumor pathogenesis. This case-control study evaluated the association between two haplotype tagging SNPs (htSNPs) (rs10463297, rs801460) of the whole SRA sequence and breast cancer risk. We found that rs10463297 TC genotype significantly increased BC risk compared with CC genotype in both the codominant (TC vs. TT: OR=1.43, 95 % CI=1.02–2.00) and recessive (TC+CC vs. TT: OR=1.39, 95 % CI=1.01–1.92) genetic models. Both TC, TC + CC genotypes of rs10463297 and GA, AA, GA+AA genotypes of rs801460 were significantly associated with estrogen receptor (ER) positivity status. rs10463297 TC (2.09 ± 0.41), CC (2.42 ± 0.51) and TC + CC (2.20 ± 0.47) genotypes were associated with higher blood plasma SRA mRNA levels compared with the TT genotype(1.45 ± 0.34). Gene–reproductive interaction analysis presented a best model consisted of four factors (rs10463297, age, post-menopausal, No. of pregnancy), which could increase the BC risk with 1.58-fold (OR=1.58, 95 % CI=1.23–2.03). These findings suggest that SRA genetic variants may contribute to BC risk and have apparent interaction with reproductive factors in BC progression.

Quality Control and Validation of Oscillometric Blood Pressure Measurements Taken During an Epidemiological Investigation

Abstract This study aims to validate blood pressure (BP) values measured by an oscillometric BP monitor and seek possible calibration methods if discrepancies exist. Noninvasive BP measurement outcomes were determined using an oscillometric BP monitor (Omron HBP-1300) versus a mercury sphygmomanometer (standard device). Two percent of subjects enrolled in an epidemiological investigation were systematically sampled in this study. Intraclass correlation coefficient (ICC) was used to evaluate measurement reliability, paired t-test was used to evaluate trueness, and linear regression was used for calibration. The Association for the Advancement of Medical Instrumentation (AAMI) standards and British Hypertension Society (BHS) protocols were used for validation quality assessment. Both mercury sphygmomanometer (standard device) and oscillometric BP monitor (test device) displayed high reliability. A significant difference in systolic blood pressure (SBP) was observed between devices. SBP calibration was achieved by using an effective linear regression model (B = 0.803 and constant = 19.592, P < 0.001). The calibrated model was corroborated by verification samples (P = 0.120) and was found to pass AAMI standards and BHS protocol requirements. Calibrated SBP measurements from the Omron HBP-1300 device were valid. Use of a combination of statistical methods, such as ICC for reliability assessment as well as paired t-test for trueness evaluation can be used to validate data from the oscillometric BP monitors.

Association analyses of genetic variants in long non-coding RNA MALAT1 with breast cancer susceptibility and mRNA expression of MALAT1 in Chinese Han population

The long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1(MALAT1) has been implicated in breast cancer (BC). Polymorphisms in MALAT1 may play a vital role in the progress of breast cancer by its regulation function. However, potential genetic variants in MALAT1 affecting the development of BC is rarely explored. In our current molecular epidemiology study, all three tagging SNPs (rs3200401, rs619586 and rs7927113) in lncRNA MALAT1 were selected for genotyping in 487BCE patients and 489 cancer-free controls in Chinese Han population, and futher experiment of quantitative real-time (qRT) PCR was conducted to examine the relative expression of MALAT1. The results showed that individuals with genotype AG of rs619586 has a decreased risk of BC in codominant model (OR: 0.684, 95%CI: 0.478-0.979), dominant mode (OR: 0.675, 95%CI: 0.479-0.951) and over-dominant model (OR: 0.692, 95%CI: 0484-0.989). Also, qRT-PCR results revealed that the expression for MALAT1 with AG (0.827±0.490), GG (0.511±0.149) and AG+GG genotypes (0.743±0.447) of rs619586 was significantly lower than that with genotype AA (1.511±0.737). In addition, females with genotype CT of rs3200401 had a lower risk of BC in the codominant model (OR: 0.75, 95%CI: 0.559-1.007) and over-dominant model (OR: 0.741, 95%CI: 0.552-0.993). In summary, our results implied that the genetic variants of lncRNA MALAT1 were associated with the susceptibility of BC, and meaningful genetic alteration might affect the corresponding mRNA expression of lncRNA MALAT1.

Systematic evaluation of cancer risk associated with rs2292832 in miR‑149 and rs895819 in miR‑27a: a comprehensive and updated meta‑analysis.

The aim of this study is to provide a precise quantification for the association between miR-149 T > C (rs2292832) and miR-27a A > G (rs895819) and the risk of cancer. We conducted a systematic literature review and evaluated the quality of included studies based on Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to assess the strengths of the associations. We identified 40 studies for pooled analyses. Overall, the results demonstrated that the rs2292832 polymorphism was subtly decrease the risk of breast cancer (CT + CC vs TT: OR = 0.83, 95% CI: 0.70–0.98, P = 0.03; CC vs CT + TT: OR = 0.80, 95% CI: 0.68–0.93, P = 0.00), and the rs895819 polymorphism wasassociated with significantly increased cancer risk in the Asian population (AG + GG vs AA: OR = 1.24, 95% CI: 1.03–1.50, P = 0.02) and in colorectal cancer subgroup (GG vs AA: OR = 1.45, 95% CI: 1.10–1.92, P = 0.00; AG + GG vs AA: OR = 1.35, 95% CI: 1.15–1.58, P = 0.00; GG vs AG + AA: OR = 1.36, 95% CI: 1.04–1.77, P = 0.02). In addition, a subtly decreased risk was observed in the Caucasian population and in breast cancer subgroup. In conclusion, the rs2292832 polymorphism was significantly associated with increased breast cancer risk, and the rs895819 polymorphism contributes to the susceptibility of colorectal and breast cancer.

Prognostic significance of low microRNA-218 expression in patients with different types of cancer: Evidence from published studies.

Background: Mounting evidence showed that microRNAs may be useful as prognostic biomarkers of cancer. Therefore, we summarize the predictive role of microRNA-218 (miR-218) for survival in patients with various cancers. Methods: We performed a systematic literature review and assessed the quality of included studies based on Meta-analysis of Observational Studies in Epidemiology group (MOOSE). Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated to assess the correlation between miR-218 expression and prognosis of different cancers. Results: We identified 10 studies for pooled analyses. For overall survival, a lower expression levels of miR-218 significantly predicted poorer survival, with the pooled HR of 2.61 (95% CI: 2.11–3.22, P < 0.001). For disease-free survival/progressive-free survival/recurrence-free survival (DFS/PFS/RFS), a lower expression level of miR-218 significantly predicted worse DFS/PFS/RFS in various carcinomas, with the pooled HR of 2.73 (95% CI: 2.08–3.58, P < 0.001). Similarly, subgroup analysis by detection method, ethnicity and cancer subtype analysis suggested that lower expression of miR-218 correlated with. Conclusion: Our data demonstrated that lower miR-218 expression is significantly associated with poorer overall survival (OS) and DFS/PFS/RFS and may be a novel prognostic biomarker in some cancer types.

Functional long non-coding RNAs associated with gastric cancer susceptibility and evaluation of the epidemiological efficacy in a central Chinese population

AIM To screen and validate the gastric cancer-associated long non-coding RNAs (lncRNAs) and their functional single nucleotide polymorphisms (SNPs). METHODS Based on case-control design, we select the differentially expressed lncRNAs by bioinformation tools and validate SNPs in lncRNAs genes in population. Attributable risk percentage (ARP) and population attributable risk percentage (PARP) were used to assess the effect of epidemiology. RESULTS Four lncRNAs with SNPs (lnc-EVX1-3:3 (rs1859168), lnc-MACC1-1:7 (rs3815254), lnc-AMFR-1:1 (rs4784659) and lnc-ZNF33B-2:1 (rs579501)) were selected to be validated in population. The unconditional multiple logistic regression based on the dominant (odds ratio, OR=0.64, 95%confidence interval, 95%CI: 0.47-0.86) and recessive genetic model (OR=1.77, 95%CI: 1.34-2.35) showed rs1859168 was significantly associated with lower risk of gastric cancer. The dominant (OR=0.42, 95%CI:0.31-0.57) and additive (OR=0.52, 95%CI:0.40-0.67) genetic model revealed that rs4784659 decreased the risk of gastric cancer. Similarly, the dominant (OR=0.72, 95%CI: 0.52-0.98) and additive (OR=0.73, 95%CI: 0.56-0.97) genetic model showed the individuals with rs579501 had reduced risk of gastric cancer. Whereas no statistical association between rs3815254 and gastric cancer. ARP and PARP for gastric cancer associated with rs1859168 in dominant model (56.25%, 33.05%), and in recessive model (43.50% and 29.37%). For rs4784659, ARP and PARP were 138.09% and 10.39% in dominant model, 92.31% and 8.76% in additive model. For rs579501, ARP and PARP were 38.89% and 4.03% in dominant model, 36.99% and 3.88% in additive model. CONCLUSION Our findings showed rs4784659, rs579501 and rs1859168 reduced the susceptibility of gastric cancer. From epidemiological perspective, the lncRNAs with SNPs attenuate the development of gastric cancer.