Duration-specific association between plasma IGFBP7 levels and diabetic complications in patients with type 2 diabetes mellitus.

OBJECTIVE: Insulin-like growth factor binding protein 7 (IGFBP7) has a strong affinity to insulin. This study aimed to evaluate the relationship between IGFBP7 and complications among type 2 diabetes mellitus (T2DM) patients. DESIGN: A total of 1449 T2DM patients were selected from a cross-sectional study for disease management registered in the National Basic Public Health Service in Changshu, China, and further tested for their plasma IGFBP7 levels. Logistic regressions and Spearman's rank correlation analyses were used to explore the associations of IGFBP7 with diabetic complications and clinical characteristics, respectively. RESULTS: Among the 1449 included T2DM patients, 403 (27.81%) had complications. In patients with shorter duration (less than five years), the base 10 logarithms of IGFBP7 concentration were associated with T2DM complications, with an adjusted odds ratio (OR) of 2.41 [95% confidence interval (95%CI) = 1.06-5.48]; while in patients with longer duration (more than five years), plasma IGFBP7 levels were not associated with T2DM complications. Furthermore, in T2DM patients with shorter duration, those with two or more types of complications were more likely to have higher levels of IGFBP7. CONCLUSION: IGFBP7 is positively associated with the risk of complication in T2DM patients with shorter duration.

[Relationship between dairy and product consumption and the high-risk of cardiovascular diseases of 35-75 years old residents in 6 districts of Jiangsu Province from 2015 to 2017].

OBJECTIVE: To explore the effect of intake of milk and milk products on high risk of cardiovascular disease. METHODS: Six districts in Jiangsu Province were selected as project sites by using cluster sampling method. The residents aged 35-75 years old in the districts were screened at early stage for high risk population of cardiovascular diseases from June 2015 to September 2017, and the risk of cardiovascular diseases was assessed, a total of 40 234 subjects were classified as high-risk subjects of cardiovascular disease((57.30±9.44) years old, 24 608 female(61.15%), 20 412 rural residents(50.72%)). Through questionnaire, physical examination, laboratory test, and propensity score matching, 35 104 subjects were finally included in this study. The t test, χ~2 test, multivariate Logistic regression and additive interaction analysis were used to analyze the data with software of SPSS 23.0. RESULTS: There were 67.30%(n=23 607) of subjects with milk and product consumption<1 d/week. With the frequency as a reference, adjusted urban and rural areas, educational level, occupation, annual family income, drinking, BMI, abdominal obesity, and intake of vegetables and fruits, multiple Logistic regression analysis showed that the risk of cardiovascular disease decreased with the increase of intake frequency of milk and milk products(P<0.001), the frequency of 4-6 d/week was the lowest(OR=0.608, 95% CI 0.546-0.677). Additive interaction analysis found that combination with vegetable consumption significantly reduced the high risk of cardiovascular diseases(P<0.05). While the high risk of cardiovascular disease was reduced by increasing fruit intake frequency at the same intake frequency of milk and products. CONCLUSION: More intake milk and product can reduce the high-risk of cardiovascular diseases. Combination with vegetables or fruits could synergistically reduce the high risk, the effect is stronger with vegetables than that with fruits.

Snoring frequency and risk of type 2 diabetes mellitus: a prospective cohort study.

OBJECTIVE: To evaluate the association between snoring frequency and type 2 diabetes mellitus (T2DM) according to age and gender in Chinese population. DESIGN: A cohort study was performed in Suzhou site of the China Kadoorie Biobank. Residents who didn't suffer from T2DM at baseline survey (2004-2008) and in half a year after baseline were enrolled in this study and followed cause-specific morbidity until 31 December 2013. All participants were requested to complete a detailed questionnaire and undergo anthropometric measurements. Cox regression models were used to estimate HRs and 95% CIs for the snoring and T2DM association. SETTING: Wuzhong district, Suzhou, China. PARTICIPANTS: A total of 49 453 participants (men: 41.8%; mean age: 51.14±10.28 years) were enrolled in this study. OUTCOME MEASURES: T2DM cases were defined as International Classification of Diseases 10th Revision code of E11 and were identified through disease registries and health insurance databases. RESULTS: During a media of 7.18 years follow-up, 1120 T2DM cases were identified. Higher T2DM incidence was observed in participants with frequent and occasional snoring compared with those without (4.80 and 2.87 vs 2.39 per 1000 person-years). The multivariable-adjusted model found snoring was independently associated with T2DM (HR 1.28, 95% CI 1.20 to 1.38), both in men (HR 1.25, 95% CI 1.10 to 1.41) and women (HR 1.28, 95% CI 1.17 to 1.39). Moreover, a significant multiplicative interaction effect between snoring and age was detected on T2DM risk (p=0.015). CONCLUSIONS: Snoring was independently associated with an increased risk of T2DM in Chinese population, both in men and women. Meanwhile, there was an interaction effect between snoring and age on T2DM risk.

Internal fat mediates the impact of age on diabetes onset in chinese people between 30 and 44 years old / La grasa interna media en el impacto de la edad sobre la aparición de diabetes en personas chinas de entre 30 y 44 años de edad

AIMS: We sought to measure the effect of controlling body fat indexes on decreasing the incidence of type 2 diabetes mellitus (T2DM) mathematically. METHODS: Study samples were selected from a well-established cohort in Suzhou, China between 2004 and 2008, comprising 6364 males and 9678 females. The questionnaire contained socio-demographic characteristics, smoking, alcohol consumption, diet, physical activity, personal and family medical history and current medication. Multiple linear regression, Cox regression and mediation analyses were performed to determine the relationship among age, body fat indexes and T2DM onset. RESULTS: All the three body fat indexes [the body mass index (BMI), waist-to-hip ratio (WHR) and body fat percentage] showed a significant positive association (P<0.05) with age and T2DM. Significant indirect effects (IE) were detected for age, which were mediated respectively through WHR [IE=1.10, 95%CI: 1.07-1.13; P<0.001], the BMI (IE=1.15, 95%CI: 1.11-1.18; P<0.001), and body fat percentage (IE=1.09, 95%CI: 1.07-1.12; P<0.001). The combined body fat index score demonstrated a significant association with age (P<0.001) and a stronger relationship with the onset of diabetes (P<0.001) along with a significant mediating effect (IE=1.17; 95%CI: 1.13-1.22; P<0.001). The total effect of age on T2DM was 1.60 (95%CI: 1.21-2.10; P=0.0008). As a result, the three body fat indexes jointly mediated 33.97% of the age impact on diabetes onset. CONCLUSIONS: This pilot study revealed important roles for body fat indexes in mediating the age pathway to the onset of diabetes. Controling body fat in the appropriate range could reduce 33.97% of the risk of T2DM onset with increasing age

OBJETIVOS: Medir matemáticamente el efecto del control de los índices de grasa corporal en la reducción de la incidencia de diabetes mellitus del tipo 2 (DMT2). MÉTODOS: Se obtuvieron durante 2004-2008 muestras para estudio de una cohorte bien establecida de Suzhou, China, formada por 6.364 varones y 9.678 mujeres. Mediante un cuestionario se recogieron los datos de las características sociodemográficas, el tabaquismo, el consumo de alcohol, la dieta, la actividad física, los antecedentes médicos personales y familiares y la medicación en curso. Se realizaron regresión lineal múltiple, regresión de Cox y análisis de mediación para determinar la relación entre edad, índices de grasa corporal y comienzo de la DMT2. RESULTADOS: Se halló una asociación positiva significativa (p < 0,05) de 3 índices de grasa corporal (índice de masa corporal [IMC], índice cintura-cadera [ICC] y porcentaje de grasa corporal) con la edad y la DMT2. Se detectaron efectos causales indirectos (EI) significativos de la edad, mediados respectivamente por el ICC (EI: 1,10; IC al 95%: 1,07-1,13; p < 0,001], el IMC (EI: 1,15; IC al 95%: 1,11-1,18; p < 0,001) y el porcentaje de grasa corporal (EI: 1,09; IC al 95%: 1,07-1,12; p < 0,001). La puntuación combinada de los índices de grasa corporal seguía mostrando una asociación significativa con la edad (p < 0,001) y una relación más intensa con el comienzo de la diabetes (p < 0,001), junto con un efecto mediador significativo (EI: 1,17; IC al 95%: 1,13-1,22; p < 0,001). El efecto total de la edad en la DMT2 era 1,60 (IC: 1,21-2,10; p = 0,0008). Como resultado, los 3 índices de grasa corporal fueron los mediadores del 33,97% de los efectos de la edad en el comienzo de la diabetes. CONCLUSIONES: Este estudio piloto reveló las importantes funciones de los índices de grasa corporal como mediadores del efecto de la edad en la aparición de la diabetes. El control de la grasa corporal dentro de límites apropiados podría reducir el 33,97% de riesgo de comienzo de la DMT2 con el paso de la edad

Internal fat mediates the impact of age on diabetes onset in chinese people between 30 and 44 years old.

AIMS: We sought to measure the effect of controlling body fat indexes on decreasing the incidence of type 2 diabetes mellitus (T2DM) mathematically. METHODS: Study samples were selected from a well-established cohort in Suzhou, China between 2004 and 2008, comprising 6364 males and 9678 females. The questionnaire contained socio-demographic characteristics, smoking, alcohol consumption, diet, physical activity, personal and family medical history and current medication. Multiple linear regression, Cox regression and mediation analyses were performed to determine the relationship among age, body fat indexes and T2DM onset. RESULTS: All the three body fat indexes [the body mass index (BMI), waist-to-hip ratio (WHR) and body fat percentage] showed a significant positive association (P<0.05) with age and T2DM. Significant indirect effects (IE) were detected for age, which were mediated respectively through WHR [IE=1.10, 95%CI: 1.07-1.13; P<0.001], the BMI (IE=1.15, 95%CI: 1.11-1.18; P<0.001), and body fat percentage (IE=1.09, 95%CI: 1.07-1.12; P<0.001). The combined body fat index score demonstrated a significant association with age (P<0.001) and a stronger relationship with the onset of diabetes (P<0.001) along with a significant mediating effect (IE=1.17; 95%CI: 1.13-1.22; P<0.001). The total effect of age on T2DM was 1.60 (95%CI: 1.21-2.10; P=0.0008). As a result, the three body fat indexes jointly mediated 33.97% of the age impact on diabetes onset. CONCLUSIONS: This pilot study revealed important roles for body fat indexes in mediating the age pathway to the onset of diabetes. Controling body fat in the appropriate range could reduce 33.97% of the risk of T2DM onset with increasing age.

Systematic identification of genes with a cancer-testis expression pattern in 19 cancer types.

Cancer-testis (CT) genes represent the similarity between the processes of spermatogenesis and tumorigenesis. It is possible that their selective expression pattern can help identify driver genes in cancer. In this study, we integrate transcriptomics data from multiple databases and systematically identify 876 new CT genes in 19 cancer types. We explore their relationship with testis-specific regulatory elements. We propose that extremely highly expressed CT genes (EECTGs) are potential drivers activated through epigenetic mechanisms. We find mutually exclusive associations between EECTGs and somatic mutations in mutated genes, such as PIK3CA in breast cancer. We also provide evidence that promoter demethylation and close non-coding RNAs (namely, CT-ncRNAs) may be two mechanisms to reactivate EECTG gene expression. We show that the meiosis-related EECTG (MEIOB) and its nearby CT-ncRNA have a role in tumorigenesis in lung adenocarcinoma. Our findings provide methods for identifying epigenetic-driver genes of cancer, which could serve as targets of future cancer therapies.

A functional variant in miR-155 regulation region contributes to lung cancer risk and survival.

Emerging evidence suggested that upregulation of miR-155 could serve as a promising marker for the diagnosis and prognosis of non-small cell lung cancer (NSCLC). In the present study, we genotyped rs767649 (A > T) located in miR-155 regulation region in 1341 cases and 1982 controls, and analyzed the associations of rs767649 with NSCLC risk and survival. Consequently, rs767649 exhibited the significant associations with the risk (adjusted OR = 1.12, 95% CI = 1.01-1.24, P = 0.031) and prognosis of NSCLC (adjusted HR = 1.17, 95% CI = 1.03-1.32, P = 0.014). Meanwhile, rs767649 specifically interacted with radio-chemotherapy (P(int) = 0.013), and patients with both the rs767649-TT genotype and radio-chemotherapy had the highest hazard ratio (adjusted HR = 1.65, 95% CI = 1.26-2.16, P < 0.001). Furthermore, using functional assays and The Cancer Genome Atlas (TCGA) Lung Adenocarcinoma (LUAD) dataset, we found that rs767649 variant allele could increase the transcriptional activity of miR-155, which in turn facilitated tumor growth and metastasis by inhibiting HBP1, TJP1, SMAD5 and PRKAR1A expression. Our findings suggested that rs767649 A > T might contribute to the increased risk and poor prognosis of NSCLC, highlighting the importance of rs767649 in the prevention and therapy of NSCLC.

Genetic Variation in the 3'-Untranslated Region of NBN Gene Is Associated with Gastric Cancer Risk in a Chinese Population.

NBN plays a crucial role in carcinogenesis as a core component for both homologous recombination (HR) and non-homologous end-joining (NHEJ) DNA double-strand breaks (DSBs) repair pathways. Genetic variants in the NBN gene have been associated with multiple cancers risk, suggesting pleiotropic effect on cancer. We hypothesized that genetic variants in the NBN gene may modify the risk of gastric cancer. To test this hypothesis, we evaluated the association between four potentially functional single nucleotide polymorphisms in NBN and gastric cancer risk in a case-control study of 1,140 gastric cancer cases and 1,547 controls in a Chinese population. We found that the A allele of rs10464867 (G>A) was significantly associated with a decreased risk of gastric cancer (odds ratio [OR] = 0.81, 95% confidence interval [95% CI] = 0.71-0.94; P = 4.71×10-3). Furthermore, the association between A allele of rs10464867 and decreased risk of gastric cancer was more significantly in elder individuals (per-allele OR = 0.72[0.59-0.88], P = 1.07×10-3), and male individuals (per-allele OR = 0.73[0.62-0.87], P = 3.68×10-4). We further conducted a haplotype analysis and identified that the NBN Ars10464867Grs14448Grs1063053 haplotype conferred stronger protective effect on gastric cancer (OR = 0.76[0.65-0.89], P = 6.39×10-4). In summary, these findings indicate that genetic variants at NBN gene may contribute to gastric cancer susceptibility and may further advance our understanding of NBN gene in cancer development.

Telomere length, genetic variants and gastric cancer risk in a Chinese population.

Telomeres maintain chromosomal stability and integrity and are crucial in carcinogenesis. Telomere length is implicated in multiple cancer risk, but the results are conflicting. Genome-wide association studies have identified several genetic loci associated with telomere length in Caucasians. However, the roles of telomere length and related variants on gastric cancer development are largely unknown. We conducted a case-control study including 1136 gastric cancer cases and 1012 controls to evaluate the associations between telomere length, eight telomere length-related variants identified in Caucasians and gastric cancer risk in Chinese population. We observed an obvious U-shaped association between telomere length and gastric cancer risk (P < 0.001), with odds ratios (95% confidence intervals) being 3.81 (2.82-5.13), 1.65 (1.21-2.26), 1.28 (0.93-1.77) and 1.78 (1.30-2.44) for individuals in the first (the shortest), second, third and fifth (the longest) quintile as compared with those in the fourth quintile as reference group. The weighted genetic score (WGS) of eight variants was significantly associated with telomere length (P < 0.001), and in particular, the G allele of rs2736100 in TERT at 5p15.33 exhibited a significant association with long telomeres (P = 0.047). However, we did not observe significant associations between these genetic variants and gastric cancer risk for both single-variant and WGS analyses. These findings suggest that either short or extreme long telomeres may be risk factor for gastric cancer. Genetic variants identified in Caucasians may also contribute to the variation of telomere length in Chinese but seems not to gastric cancer susceptibility.

Genetic variants at 8q24 are associated with risk of esophageal squamous cell carcinoma in a Chinese population.

Esophageal cancer and gastric cancer have shared risk factors and inherited susceptibility. Recent genome-wide association studies have identified multiple genetic loci associated with gastric cancer risk, which may also involve in the development of esophageal cancer. Herein, we evaluated the relationship of gastric cancer risk-related variants at 1q22, 3q13.3, 5p13.1, and 8q24 with the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese population with a case-control study (2139 cases and 2273 controls). We found that the T allele of rs2294008, an intronic variant of the PSCA gene at 8q24 that was previously associated with an increased risk of gastric cancer, was inversely associated with a decreased risk of ESCC (odds ratio = 0.90; 95% confidence interval, 0.81-0.99; P = 0.034). Of interest, the association of rs2294008 with ESCC was consistent with that observed in esophageal adenocarcinoma and ESCC in Caucasian populations. However, no significant associations were observed for the other three variants at 1q22 (rs4072037), 3q13.31 (rs9841504), and 5p13.1 (rs13361707). Our findings suggest that the susceptibility locus of PSCA at 8q24 may be a double-edged sword, as modulator between the carcinogenesis processes of stomach and esophagus.

Genetic variants at 5p15 are associated with risk and early onset of gastric cancer in Chinese populations.

Genetic variants at 5p15 have been associated with multiple cancers risk, suggesting pleiotropic effect on cancer. We hypothesized that genetic variants at 5p15 are important in the development of gastric cancer. To test this hypothesis, we evaluated the associations of genetic variants at 5p15 with gastric cancer based on our existing genome-wide association study (GWAS) data set of gastric cancer (1006 cases and 2273 controls), and replicated two promising loci in an independent case-control study with 1681 gastric cancer cases and 1705 controls in a Chinese population. We found that rs10052016 was consistently associated with gastric cancer risk in GWAS discovery stage (odds ratio [OR] = 0.69, 95% confidence interval [95% CI] = 0.55-0.87) and replication stage (OR = 0.80, 95% CI = 0.68-0.94). After combining these two studies, we found that the G allele of rs10052016 (at 132 kb upstream of TERT) was significantly associated with a decreased risk of gastric cancer (OR = 0.76, 95% CI = 0.67-0.87, P = 5.35 × 10(-5)). Moreover, the protective allele of rs10052016-G was also significantly associated with late onset of gastric cancer (P = 0.013). In summary, these findings indicate that genetic variants at 5p15 may contribute to gastric cancer susceptibility and may further advance our understanding of 5p15 locus in cancer development.