Chinese Case-control Study Research Articles

Reevaluating Adiponectin’s impact on obesity hypertension: a Chinese case-control study

BackgroundObesity and hypertension are major risk factors for cardiovascular diseases that affect millions of people worldwide. Both conditions are associated with chronic low-grade inflammation, which is mediated by adipokines such as adiponectin. Adiponectin is the most abundant adipokine that has a beneficial impact on metabolic and vascular biology, while high serum concentrations are associated with some syndromes. This “adiponectin paradox” still needs to be clarified in obesity-associated hypertension. The aim of this study was to investigate how adiponectin affects blood pressure, inflammation, and metabolic function in obesity hypertension using a Chinese adult case-control study.MethodsA case-control study that had finished recruiting 153 subjects divided as four characteristic groups. Adiponectin serum levels were tested by ELISA in these subjects among these four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Analyzation of correlations between the research index and differences between groups was done by SPSS.ResultsSerum adiponectin levels in the| normal healthy group (NH group) were significantly higher than those in the newly diagnosed untreated just-obesity group (JO group), and negatively correlated with the visceral adiposity index. With multiple linear egression analysis, it was found that, for serum adiponectin, gender, serum albumin (ALB), alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDLC) were the significant independent correlates, and for SB, age and HDLC were the significant independent correlates, and for DB, alkaline phosphatase (ALP) was the significant independent correlate. The other variables did not reach significance in the model.ConclusionsOur study reveals that adiponectin’s role in obesity-hypertension is multifaceted and is influenced by the systemic metabolic homeostasis signaling axis. In obesity-related hypertension, compensatory effects, adiponectin resistance, and reduced adiponectin clearance from impaired kidneys and liver all contribute to the “adiponectin paradox”.

Mediation of association between benzo[a]pyrene exposure and lung cancer risk by plasma microRNAs: A Chinese case-control study

Epidemiologic studies have reported the positive relationship of benzo[a]pyrene (BaP) exposure with the risk of lung cancer. However, the mechanisms underlying the relationship is still unclear. Plasma microRNA (miRNA) is a typical epigenetic biomarker that was linked to environment exposure and lung cancer development. We aimed to reveal the mediation effect of plasma miRNAs on BaP-related lung cancer. We designed a lung cancer case-control study including 136 lung cancer patients and 136 controls, and measured the adducts of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) and sequenced miRNA profiles in plasma. The relationships between BPDE-Alb adducts, normalized miRNA levels and the risk of lung cancer were assessed by linear regression models. The mediation effects of miRNAs on BaP-related lung cancer were investigated. A total of 190 plasma miRNAs were significantly related to lung cancer status at Bonferroni adjusted P < 0.05, among which 57 miRNAs showed different levels with |fold change| > 2 between plasma samples before and after tumor resection surgery at Bonferroni adjusted P < 0.05. Especially, among the 57 lung cancer-associated miRNAs, BPDE-Alb adducts were significantly related to miR-17–3p, miR-20a-3p, miR-135a-5p, miR-374a-5p, miR-374b-5p, miR-423–5p and miR-664a-5p, which could in turn mediate a separate 42.2%, 33.0%, 57.5%, 36.4%, 48.8%, 32.5% and 38.2% of the relationship of BPDE-Alb adducts with the risk of lung cancer. Our results provide non-invasion biomarker candidates for lung cancer, and highlight miRNAs dysregulation as a potential intermediate mechanism by which BaP exposure lead to lung tumorigenesis.

Association between Urinary BPA Substitutes and Precocious Puberty among Girls: A Single-Exposure and Mixed Exposure Approach from a Chinese Case-Control Study.

There is an argument that BPA substitutes may have the same or more deleterious health effects as BPA due to their structural similarity. This study explored the association between urinary BPA substitutes and precocious puberty among girls by including 120 girls with precocious puberty (cases) aged 2-10 years enrolled at Nanjing Children's Hospital Department of Endocrinology in China between April 2021 to September 2021 and 145 healthy girls (controls) recruited from a primary school. Logistic regression was used to evaluate the effect of single exposures, and Bayesian kernel machine regression (BKMR) and quantile-based g-computation were used for the mixed effect. In the multivariate logistic regression, BPS (bisphenol S), TBBPA (tetrabromobisphenol A), and BPFL (bisphenol-FL) were significantly associated with increased risk of precocious puberty (odds ratio (OR) = 1.75, 95% confidence interval (CI): 1.13, 2.76, p = 0.014), (OR = 1.46, CI: 1.06, 2.05; p = 0.023), and (OR = 1.47, CI: 1.01, 2.18; p = 0.047), respectively. The BMKR and quantile-based g-computation models revealed consistent associations for single exposures and there was insufficient evidence for the associations of the mixed exposure of bisphenols with precocious puberty. In conclusion, BPA substitutes such as BPS, TBBPA, and BPFL may be associated with an increased risk of precocious puberty in girls.

HOGG1 rs1052133 Polymorphism and Prostate Cancer Risk: A Chinese Case-Control Study and Meta-Analysis.

BACKGROUND We performed a case-control study and an updated meta-analysis to assess the relationship between the hOGG1 rs1052133 polymorphism and prostate cancer (PCa) risk. MATERIAL AND METHODS We recruited 160 PCa cases and 243 healthy controls. For the meta-analysis, relevant studies were recruited from diverse databases up to April 2022. Genetic risk was evaluated by using an odds ratio (OR) with a corresponding 95% confidence interval (95% CI). The genotypes of this polymorphism were genotyped via the SNaPshot genotyping method. RESULTS In the case-control study, we failed to identify any association between the hOGG1 rs1052133 polymorphism and PCa risk. Negative results were also obtained when stratified analyses were performed based on the patient's prostatic-specific antigen (PSA) level and Gleason score, as well as tumor, node, and metastasis (TNM) stage. To enlarge the sample size, we performed a restricted updated meta-analysis by recruiting 10 case-control studies (including the current one), and the results suggested that genotypes of rs1052133 polymorphism were significantly associated with an elevated risk of PCa in 2 genetic models - the heterozygote and dominant models. In the stratification analysis by population ethnicity, a significant association of this polymorphism with susceptibility to PCa was found both in the Asian populations and White populations. CONCLUSIONS Our case-control and updated meta-analysis study suggest that the hOGG1 rs1052133 polymorphism is a susceptibility factor for PCa, but still needs to be further verified in the Chinese population.

Is intestinal metaplasia the point of no return in the progression of gastric carcinogenesis?

Is intestinal metaplasia the point of no return in the progression of gastric carcinogenesis?

Association of serum vaspin, apelin, and visfatin levels and stroke risk in a Chinese case-control study.

Adipose tissue acts as an active endocrine organ secreting a number of adipokines and may be involved in biological mechanism of stroke. Vaspin, apelin, and visfatin play important roles in the regulation of vascular disorders.Our aim was to evaluate whether the concentrations of vaspin, apelin, and visfatin were associated with stroke risk.A total of 235 patients with stroke (156 patients with ischemic stroke and 79 patients with hemorrhagic stroke) and 235 age- and gender-matched healthy controls were included in this study. A sandwich ELISA was developed to measure the serum vaspin, apelin, and visfatin levels.There was a statistically significant difference in the median levels of serum vaspin, apelin, and visfatin levels between stroke cases and controls (vaspin: 1.50 vs 1.07 ng/ml; apelin: 1.56 vs 1.32 pg/ml; visfatin: 23.40 vs 19.65 ng/ml; all P values <.001). Multiple logistic regression analysis showed that, serum vaspin and visfatin levels were significantly inversely associated with increased risk of stroke, and the odds ratios (ORs) in the highest tertile were 2.25 [95% confidence interval (CI) 1.38–3.67; P for trend <.001] for vaspin and 2.56 (95% CI 1.46–4.47; P for trend <.001) for visfatin, respectively, compared with the lowest tertile. Higher apelin levels were marginally associated with lower stroke risk (P for trend =.060).Our study indicated that higher vaspin, apelin, and visfatin levels might be associated with increased stroke risk. Necessary prospective cohort studies should be conducted to confirm this association in the future.

Lymphocyte-to-monocyte ratio in predicting the calcific aortic valve stenosis in a Chinese case-control study.

Aim: This study examined the role of lymphocyte-to-monocyte ratio (LMR), an inflammatory biomarker, in predicting the severity of calcific aortic valve stenosis (CAVS) in a Chinese case-control study. Results: The LMR significantly decreased in the patients with CAVS compared with healthy controls. An inverse correlation was observed between the severity of stenosis and LMR in the patients. Additionally, the LMR was identified in the multivariate analysis as an independent predictor of severe CAVS. Conclusion: This study provides evidence of an inverse correlation between the severity of CAVS and LMR. LMR could potentially be applied as an independent predictor of severe CAVS and could be incorporated into a novel predictive model.

Association between Dietary Zinc and Selenium Intake, Oxidative Stress-Related Gene Polymorphism, and Colorectal Cancer Risk in Chinese Population - A Case-Control Study

Zinc and selenium may protect against colorectal cancer (CRC) progression through their anti-oxidative effects. This study examined the independent and combined effect of dietary zinc and selenium intake, and polymorphisms of the oxidative stress-related genes (superoxide dismutase 1, superoxide dismutase 2, glutathione peroxidase, and catalase) on CRC risk in a Chinese case-control study. A total of 493 cases and 498 sex and age-matched controls were randomly selected from an ongoing case-control study. Dietary information was assessed through face-to-face interviews using a validated food frequency questionnaire. Multiplex PCR-ligase detection reaction was used for genotyping the target SNPs. Multivariable logistic regression was used to estimate the odds ratios (ORs) and 95% confidence interval (CI). Intake of selenium was found to be inversely associated with CRC risk, while zinc was not associated with CRC risk. The ORs (95% CI) for the highest vs. the lowest quartile were 0.42 (95% CI 0.28, 0.64, P trend < 0.001) for selenium and 0.96 (95% CI 0.63, 1.47, P trend = 0.505) for zinc. Combined effect was observed between zinc and SOD1 rs4998557 on CRC risk (P interaction < 0.05). This study identified a novel diet-gene interaction in the oxidative stress pathway on CRC risk in Chinese population.

SAT497 - High rate of hepatitis B virus S-integrated human extra spindle pole bodies like 1 fusion gene is detected in hepatitis B virus-related liver cancer patients: a Chinese case-control study

SAT497 - High rate of hepatitis B virus S-integrated human extra spindle pole bodies like 1 fusion gene is detected in hepatitis B virus-related liver cancer patients: a Chinese case-control study

Interaction between common variants of MDM2 and PPP1R13L and CD3EAP and TP53 SNPs in relation to lung cancer risk among Chinese.

BackgroundLung cancer is a complex disease that diagnosed the most common cancer and led cause of cancer death. MDM2 (MDM2 proto-oncogene) encodes a nuclear-localized E3 ubiquitin ligase. The encoded protein can promote tumor formation by targeting tumor suppressor proteins, such as TP53, for proteasomal degradation. Epidemiology studies have investigated the association of MDM2 single nucleotide polymorphisms (SNP) and interaction between genetic and environmental factors with lung cancer.MethodsThis Chinese case-control study comprised 627 cases and 633 controls explored the role of MDM2 five htSNPs (rs1690924, rs1846402, rs2291857, rs3730581 and rs3730635, haplotype-tagging SNP) tagging 95% of the common haplotypes across the gene and the interactions of MDM2, PPP1R13L, CD3EAP and TP53 in the same pathological pathway on lung cancer risk, together with smoking-duration.ResultsNone of the htSNPs in MDM2 were associated with lung cancer risk in co-dominant, dominant, recessive, and log-additive models (adjusted for smoking-duration). Haplotype analysis showed that global haplotype association was statistically significant (P=0.0036, adjusted for smoking-duration) and haplotype5 (rs1690924A-rs1846402G-rs2291857C-rs3730581G-rs3730635A) was associated with reduced risk of lung cancer [OR (95%) =0.52 (0.33–0.82), P=0.0053, adjusted for smoking-duration]. MDR interaction analysis showed that two the best significant models and strong synergy between MDM2 and TP53.ConclusionsMDM2 five-htSNPs haplotype exhibited association with lung cancer susceptibility, interaction of MDM2 and TP53 htSNPs and smoking-duration contributed to lung cancer risk and strong synergy between MDM2 and TP53 htSNPs influenced lung cancer predisposition. Our results suggest that MDM2, TP53 and smoking-duration interact in relation to lung carcinogenesis.

Circulating metabolites from the choline pathway and acute coronary syndromes in a Chinese case-control study

BackgroundAccumulating evidence shows that circulating levels of trimethylamine N-oxide, which is generated from the metabolism of dietary choline, may predict cardiovascular disease among Caucasians. Acute coronary syndrome (ACS), one common presentation of cardiovascular disease, is a spectrum of signs and symptoms due to acute decreased blood flow in the coronary arteries. The relationship between the metabolites from choline pathway and ACS remains unclear. We aimed to assess the associations of circulating metabolites from the choline pathway with ACS among a Chinese population, who consume a different dietary pattern than their Western counterparts.MethodsWe recruited 501 participants who were admitted to the Department of Cardiology, Zhongshan Hospital,Shanghai China between March 2017 and June 2018, including 254 ACS cases and 247 controls. Liquid chromatography-tandem mass spectrometry was used to measure circulating concentrations of metabolites in the choline pathway, including betaine, choline, trimethylamine, and trimethylamine N-oxide. A composite metabolite score using a weighted sum of these four metabolites, and the betaine/choline ratio were calculated. Multivariable logistic regressions were applied to estimate the association of metabolites with ACS, with adjustment of age, sex, body mass index, smoking index, history of diseases, and kidney function.ResultsAfter adjusting for traditional risk factors, per 1-standard deviation (SD) increment in choline was positively associated with the odds of ACS [odds ratio (OR), 95% confidence interval (CI), 1.77(1.44–2.18)], and the other metabolites were not associated with ACS at a statistical significance level. Compared with participants in the lowest quartile of the metabolite score, those in the highest quartile had higher odds of ACS [OR (95% CI), 3.18(1.85–5.54), p < 0.001 for trend]. Per 1-SD increment in metabolite score was positively associated with higher odds of ACS [OR (95% CI), 1.80 (1.37–2.40)], and per 1-SD increment in the betaine/choline ratio was inversely associated with the odds of ACS [OR (95% CI), 0.49 (0.39–0.60)].ConclusionsAmong our Chinese participants, trimethylamine N-oxide was not associated with ACS, while a composite metabolite score of metabolites from the choline pathway was associated with increased odds of ACS. The choline pathway metabolites may be related to the pathophysiology of ACS among Chinese.

The Dietary Inflammatory Index Is Positively Associated with Colorectal Cancer Risk in a Chinese Case-Control Study.

Diet may modulate chronic inflammation. The aim of this study is to investigate whether the dietary inflammatory index (DII®) was associated with the risk of colorectal cancer in a Chinese population. A case-control study was conducted from July 2010 to April 2019, in Guangzhou, China. A total of 2502 eligible cases were recruited along with 2538 age- (5-year interval) and sex-matched controls. Dietary data derived from a validated food frequency questionnaire were used to calculate the energy-adjusted DII (E-DII) scores. Odds ratios (ORs) and 95% confidence intervals (CIs) for colorectal cancer risk were estimated using unconditional logistic regression models. In this study, E-DII scores ranged from −5.96 (the most anti-inflammatory score) to +6.01 (the most pro-inflammatory score). A positive association was found between the E-DII and colorectal cancer risk, with the OR = 1.40 (95% CI 1.16, 1.68; Ptrend < 0.01) for the highest E-DII quartile compared with the lowest quartile after adjusting for potential confounders. When stratified based on cancer subsite, sex, body mass index, and smoking status, significant associations were not observed in women or underweight individuals. Results from this study confirmed that a higher E-DII score was associated with an increased risk of colorectal cancer in a Chinese population.

High Rate of Detection of Human ESPL1-HBV S Fusion Gene in Patients With HBV-related Liver Cancer: A Chinese Case-Control Study.

It has been shown that the integration of hepatitis B virus (HBV) gene into the host genome is a high-risk factor for development of hepatocellular carcinoma (HCC). However, the relationship between HBV S-integrated human extra spindle pole bodies-like 1 (ESPL1) gene and HCC is unknown. This study was designed to detect HBV S-integrated human ESPL1 fusion gene in patients with HCC for potentially using this fusion gene as a biomarker for HCC diagnosis. Nineteen and 70 patients with chronic hepatitis B (CHB) were recruited to the experimental and control groups, respectively, and both groups underwent an effective nucleoside/nucleotide analog therapy and follow-up for HCC occurrence for up to 11 years. HCC tissues were obtained by surgical resection from the experimental group, while liver tissues were collected by liver biopsy in the control group prior to treatment with nucleoside/nucleotide analogs. Alu polymerase chain reaction was used to assess HBV S gene integration in the liver tissues from both groups. HBV S-integrated human ESPL1 fusion gene was then detected in patients with HBV S gene integration using a gene database. All patients in the experimental group developed HCC, whereas no HCC was diagnosed in the control group. HBV S gene integration was identified in 12 out of 19 HCC tissues in the experimental group, giving a detection rate of 63.2%, which was significantly greater than that of 15.7% (11/70) in the control group (p<0.001). We further showed that HBV S-integrated human ESPL1 fusion gene was detected in eight patients (rate of 66.7%) among the 12 patients with HCC with HBV S gene integration in the experimental group, whereas the fusion gene was not detectable in any of the patients in the control group (p=0.001). This research demonstrates a high detection rate of HBV S-integrated human ESPL1 fusion gene in patients with HBV-related HCC and shows that this fusion gene appears to be associated with HCC development in patients with CHB. These findings suggest that HBV S-integrated human ESPL1 fusion gene may potentially serve as a biomarker for early detection of HCC in HBV-infected populations.

Riding behavior and electric bike traffic crashes: A Chinese case-control study

Objective: The present case-control study sought to explore at-risk riding behaviors associated with e-bike related traffic crashes among e-bike riders in China.Methods: Cases were recruited from residents aged 16 years and over in communities which stated “selected e-bikes as travel tools and experienced traffic crashes in the last year”. Two controls for each case were randomly selected from a population of e-bike riders who had not experienced a traffic crash in the past year. The cases and controls were matched by gender, age (within 5 years) and school education level. Data were collected using questionnaires and face-to-face interviews from July 2015 to September 2015 in China. After conducting univariate logistic analysis on study variables, a conditional logistic regression model based on the 1:2 matched case-control study design was developed.Results: Multiple-factor conditional logistic regression analysis of e-bike related traffic crashes showed that running red lights (always vs. never, AOR = 3.094, 95% CI, 1.077-8.891, P < .05), riding after drinking (yes vs. no, AOR = 1.578, 95% CI, 1.102-2.259, P < .05), carrying adults while riding (always vs. never, AOR = 2.140, 95% CI, 1.273-3.595, P < .05), turning without signaling (sometimes vs. never, AOR = 1.446, 95% CI, 1.805-1.928, P < .05), riding in the motor vehicle lane (always vs. never, AOR = 2.413, 95% CI, 1.576-3.695, P < .01), prior crash history (yes vs. no, AOR = 1.670, 95% CI, 1.257-2.220, P < .05), and type of e-bikes (scooter-style e-bikes vs. bicycle-style e-bikes, AOR = 1.471, 95% CI, 1.068-2.026, P < .05) were identified as possible risk factors for e-bike traffic crashes.Conclusion: The findings of this research provide evidence about specific risky behaviors related to road traffic crashes involving e-bikes and indicated that behavioral intervention and education need to be strengthened to reduce dangerous riding behaviors. These results will be helpful for design of e-bike road risk prevention programs.

Abstract 132: Predictive Value of Inflammation Markers With Stroke Recurrence and Cardiovascular Mortality

Background: Inflammation markers are associated with the risk of cardiovascular events, however, the relationships of inflammation markers with risk of post-stroke remain controversial. Objects: To investigated association of two clinical recorded inflammation markers, white blood cell count (WBC) and platelet count (PLTC) with first-onset stroke and long-term prognosis of stroke. Methods: A Chinese case-control study was conducted, comprising 2002 stroke cased (885 atherothrombosis, 565 lacunar stroke, 552 hemorrhagic stroke) and 1996 controls. Stroke patients were prospectively followed-up for a median of 4.5 years (range, 0.1-6.0). Results: The WBC and PLTS were higher in stroke patients than controls, however, the ratio of PLTS to WBC was lower in stroke patients than controls. During the follow-up, 369 recurrent strokes and 343 cardiovascular mortality were documented. Adjusted for cardiovascular disease, the increased ration of PLTC to WBC was negatively correlated with stroke recurrence (HR, 0.60, 95%CI 0.44 to 0.81, P =0.001), with no associations for PLTC and WBC. Compared with stroke patients with WBC in the first quartile (2.1-5.6х10 9 /L) , subjects in the fourth quartile (7.8-19.8х10 9 /L) had 2.10-fold risk for cardiovascular mortality (hazard ration [HR],2.10, 95% confidence interval [CI], 1.20 to 2.48, P =0.004), with no associations for PLTC. However, the increased ratio of PLTC to WBC decreased risk of cardiovascular mortality HR was 0.61 in the second quartile (2.09-17.60х10 9 /L), HR was 0.58 in the third quartile (17.61-24.04х10 9 /L) and HR was 0.48 in the fourth quartile (24.05-34.54х10 9 /L) (all P &lt;0.01). Conclusion: Higher WBC and PLTC are associated with poorer prognosis of stroke, and the ration of WBC to PLTC improved the predictive value for cardiovascular mortality and stroke recurrence.

Effect of gene–gene and gene–environment interaction on the risk of first‐ever stroke and poststroke death

BackgroundMultiple genetic and environmental factors contribute to the individual‐level heterogeneity in stroke. This study aimed to assess how the genetic interactions confer risk of stroke.MethodsIn a Chinese case‐control study including 1,405 strokes and 1,263 controls who were followed up (range, 0.1–6.0 years), eight genes, including apolipoprotein(a) (APOA1), methylenetetrahydrofolate reductase (MTHFR), vitamin K epoxide reductase complex subunit 1 (VKORC1), arachidonate 5‐lipoxygenase‐activating protein (ALOX5AP), NOTCH3, chromosome 9p21.3(Chr.9p21.3), vascular endothelial growth factor (VEGFA), and kinase insert domain‐containing receptor (KDR), were analyzed for interactions by the generalized multifactor dimensionality reduction method and validated by the multivariate logistic regression models. The genetic associations with carotid artery intima‐media thickness (IMT) were examined.ResultsThe interaction of VKORC1 and Chr.9p21.3 was identified for stroke and its worse prognosis, and subjects having the VKORC1 rs2359612C and Chr.9p21.3 rs10757274G alleles had higher risks for stroke (OR = 1.83, 95% CI = 1.32–2.52) as well as for stroke recurrence (HR = 1.84, 95% CI = 1.24–2.73), cardiovascular events (HR = 1.65, 95% CI = 1.15–2.38), and cardiovascular mortality (HR = 2.16, 95% CI = 1.24–3.79). Supporting, they were associated with higher IMT. Hypertension or physical inactivity increased the risk effect. The interaction of VEGFA rs833061C and KDR rs2305948T was identified for hemorrhagic stroke.ConclusionsOur findings identified two novel genetic interactions of VKORC1 and Chr.9p21.3 and of VEGFA and KDR for risk of stroke and subtypes as well as future stroke prognosis.

Cytokine fibroblast growth factor 10 (FGF10) polymorphisms are associated with risk of myopia in young children.

Myopia has become a major public health issue worldwide. Identification of genetic loci related to myopia in young children may advance our knowledge of the pathogenesis of myopia. Fibroblast growth factor 10 (FGF10) plays essential roles for the development of myopia through modulating extracellular matrix-associated genes. Studies revealed that genetic variants of FGF10 were associated with extreme myopia in adults. However, their associations with susceptibility of myopia in young children, which are less affected by confounding factors and more suitable for studying genetic factors of myopia, have not been explored. In the current study, we evaluated 13 tagSNPs that captured 100% of genetic variation in the FGF10 gene region for their associations with myopia in a large Chinese case-control study with 900 myopia children and 900 nonmyopia children. We found rs2973644 was significantly associated with increased risk of myopia (odds ratio [OR]: 1.26; 95% confidence intervals [CI]: 1.06-1.49; P = 0.009). furthermore, rs339501 (OR: 1.73; 95% CI: 1.18-2.53; P = 0.005), rs2973644 (OR: 1.57; 95% CI: 1.13-2.19; P = 0.007), and rs79002828 (OR: 1.83; 95% CI: 1.20-2.77; P = 0.005) were significantly associated with increased risk of high myopia in young children. Functional assessment of rs2973644 by luciferase assays revealed the risk G allele causes a higher expression level of FGF10 than the protective A allele. Our results do support that genetic variants of cytokine FGF10 are associated with susceptibility of myopia (as well as high myopia) in young children and further exploration are needed for myopia in children.

The association of POLR2E rs3787016 polymorphism and cancer risk: a Chinese case-control study and meta-analysis.

How single nucleotide polymorphisms in long non-coding RNAs are involved in cancer susceptibility remains poorly understood. We hypothesized that polymerase II polypeptide E (POLR2E) rs3787016 polymorphism, identified in a genome-wide association study of prostate cancer, might be a common genetic risk factor for cancer risk. To address this issue, we here conducted a case–control study to investigate the association of POLR2E rs3787016 polymorphism with risk of liver and lung cancer (including 800 normal controls, 480 liver cancer patients, and 550 lung cancer patients), followed by a meta-analysis. The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by sequencing. Although no significant association was found for rs3787016 with risk of liver or lung cancer, the further stratified analysis identified that rs3787016 contributed to liver cancer risk particularly for over than 60 years individuals who drink. Moreover, the meta-analysis demonstrated that rs3787016 was associated with overall cancer risk and prostate cancer risk. Collectively, the POLR2E rs3787016 polymorphism may be a valuable biomarker for cancer predisposition.

Impact of interaction between CYP1A1 genetic polymorphisms and smoking on coronary artery disease in the Han of China

ABSTRACTAims: To investigate the association of CYP1A1 genotype and additional gene–smoking interaction with coronary artery disease (CAD) risk based on a Chinese case-control study. Methods: A total of 1862 participants (1134 men, 728 women) were selected, including 620 CAD patients and 1242 normal controls. Logistic regression was performed to investigate association of CYP1A1 genotype, gene–gene, and gene–smoking interaction with CAD. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best gene–gene and gene–smoking interaction combination, cross-validation consistency, the testing balanced accuracy, and the sign test, to assess if each selected interaction was calculated. Results: The carriers of homozygous mutant of rs4886605 polymorphism and heterozygous of rs4646903 are associated with increased CAD risk than those with wild-type homozygotes; OR (95% CI) was 1.98 (1.53–2.61) and 1.58 (1.24–1.96), respectively. The carriers of homozygous mutant of rs1048943 polymorphism is associated with decreased CAD risk than those with wild-type homozygotes, OR (95% CI) = 0.75 (0.60–0.93). GMDR model indicated a potential gene–gene interaction between rs4886605 and rs4646903 and a potential gene–smoking interaction between rs4886605 and smoking. Participants with rs4886605-CT or TT and rs4646903-TC or CC genotype have the highest CAD risk, compared to participants with rs4886605-CC and rs4646903-TT genotype; OR (95% CI) was 2.72 (2.03–3.61). In addition, we also found that smokers with rs4886605-CT or TT genotype have the highest CAD risk, compared to nonsmokers with rs4886605-CC genotype; OR (95% CI) was 3.07 (2.23–3.96). Conclusions: rs4886605 and rs4646903 are associated with increased CAD risk, but rs1048943 is associated with decreased CAD risk; we also found gene–gene interaction between rs4886605 and rs4646903 and gene–environment interaction between rs4886605 and smoking.

Fibroids and IVF: retrospective studies or randomised clinical trials?

The opening statement in the manuscript by Christopoulos et al. cannot be misunderstood. “Uterine fibroids are the commonest benign tumours in women of reproductive age etc”. Clearly, uterine fibroids are a serious health issue. The obvious follow-up question is whether fibroids negatively impact reproduction and, if so, what the most effective and safe intervention is to treat fibroids. Given this serious issue, one would expect ample research generating high-level evidence on the clinical significance of fibroids and interventions. However, this is not the case. The authors review of the literature including multiple systematic reviews clearly indicates that research to date has been limited to retrospective cohort studies or case–control studies, fraught with their intrinsic biases, confounding and clinical heterogeneity. So, it comes as no surprise that these reviews, that represent the highest level of evidence presently available, provide no evidence-based recommendations on clinical management of fibroids to improve reproductive outcomes. The aim of the present study is to assess the impact of non-cavity-distorting fibroids on in vitro fertilisation (IVF) pregnancy outcomes. Unfortunately this study will also not provide us the definitive answer, as once again we are presented with yet another observational study. This is a retrospective, matched, single-centre cohort study in 194 women. In addition, the authors missed the opportunity to explore the impact of fibroid diameter, as they used a predetermined cut-off based upon one Chinese case–control study. The authors correctly point out that “the negative impact of uterine fibroids on pregnancy rates after IVF does not de facto suggest that surgical management in the form of open or laparoscopic myomectomy could alleviate this effect and that to date randomised controlled trials on the surgical management of such fibroids are lacking”. The reason for this is then – to a certain extent – attributed to short- and long-term complications after surgery. This means that myomectomy is offered to these patients in routine care, but not as part of randomised controlled trials (RCTs) out of fear for complications. Does that make sense and, more importantly, is it ethical? The authors then present as their final conclusion that “given the expected morbidity associated with surgical management of fibroids, data from RCTs on the use of medical agents to treat fibroids prior to assisted conception treatment may currently be preferable”. This seems reasonable at first sight, but the data on effectiveness of the drug Ulipristal acetate in reference to reproductive outcomes consist of only a few case reports, and data on safety are non-existent and, as such, RCTs are premature. So, we as gynaecologists have been and still are practicing myomectomies in women of reproductive age without the underpinning evidence and without even trying to provide the evidence. On the other hand, as soon as a new drug enters the market of which we know very little, we start randomising immediately. It is a strange world. None declared. Completed disclosure of interests form available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.