The Epidemiological Investigation on the Risk Factors of Hepatocellular Carcinoma: A Case–Control Study in Southeast China

Incidence of hepatocellular carcinoma (HCC) ranked the fifth in male and ninth in the female counterparts, and 50% of incidence HCC cases were occurred in China with high hepatitis B virus (HBV) prevalence. HCC has seriously compromised the health status of general population in China. A case–control study of 314 HCC cases and 346 controls was conducted in Xiamen, which is an epidemic area in China for both hepatitis B infection and HCC. Face-to-face interview was conducted to gather information on demographic characteristics as well as exposure of environmental factors. Commercial enzyme-linked immunosorbent assay kits were used to determine the status of serological markers of HBV infection. Odds ratios and 95% confidence intervals were estimated by using unconditional logistic regression. Multivariate unconditional logistic regression analysis was applied to evaluate the potential interactions of variables or confounders.As expected, HBV and alcohol intake still are the major risk factors of HCC. Liver disease history and passive smoking are also associated with elevated HCC risk. Indoor air pollution and pesticide exposure have newly identified as risk factors of HCC. Fruit and tea intake can significantly lower the HCC risk.The application of HBV vaccine and reduction on alcohol intake should be further promoted in high-risk population. Fruit and tea can be served as chemoprevention in daily life due to their high accessibility.     

Association Between SLCO1B1 Gene T521C Polymorphism and Statin-Related Myopathy Risk: A Meta-Analysis of Case–Control Studies

Statin-related myopathy is an important adverse effect of statin which is classically unpredictable. The evidence of association between solute carrier organic anion transporter 1B1 (SLCO1B1) gene T521C polymorphism and statin-related myopathy risk remained controversial. This study aimed to investigate this genetic association.Databases of PubMed, EMBASE, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database, and Wanfang Data were searched till June 17, 2015. Case-control studies investigating the association between SLCO1B1 gene T521C polymorphism and statin-related myopathy risk were included. The Newcastle–Ottawa Scale (NOS) was used for assessing the quality of included studies. Data were pooled by odds ratios (ORs) and their 95% confidence intervals (CIs).Nine studies with 1360 cases and 3082 controls were included. Cases of statin-related myopathy were found to be significantly associated with the variant C allele (TC + CC vs TT: OR = 2.09, 95% CI = 1.27–3.43, P = 0.003; C vs T: OR = 2.10, 95% CI = 1.43–3.09, P < 0.001), especially when statin-related myopathy was defined as an elevation of creatine kinase (CK) >10 times the upper limit of normal (ULN) or rhabdomyolysis (TC + CC vs TT: OR = 3.83, 95% CI = 1.41–10.39, P = 0.008; C vs T: OR = 2.94, 95% CI = 1.47–5.89, P = 0.002). When stratified by statin type, the association was significant in individuals receiving simvastatin (TC + CC vs TT: OR = 3.09, 95% CI = 1.64–5.85, P = 0.001; C vs T: OR = 3.00, 95% CI = 1.38–6.49, P = 0.005), but not in those receiving atorvastatin (TC + CC vs TT: OR = 1.31, 95% CI = 0.74–2.30, P = 0.35; C vs T: OR = 1.33, 95% CI = 0.57–3.12, P = 0.52).The available evidence suggests that SLCO1B1 gene T521C polymorphism is associated with an increased risk of statin-related myopathy, especially in individuals receiving simvastatin. Thus, a genetic test before initiation of statins may be meaningful for personalizing the treatment.     

eNOS Genetic Polymorphisms and Cancer Risk: A Meta-Analysis and a Case–Control Study of Breast Cancer

The association between endothelial nitric oxide synthase (eNOS) polymorphisms (intron 4a/b, -786T>C and 894G>T) and cancer risk remains elusive. In addition, no studies focused on their associations with the risk of breast cancer in Chinese Han population. Thus, a meta-analysis was conducted to determine the relationship between eNOS polymorphisms and cancer risk, and then a case–control study in Chinese Han population was performed to assess their associations with breast cancer susceptibility.Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The pooled analysis indicated that eNOS intron 4a/b and -786T>C polymorphisms were significantly associated with an increased risk of overall cancer. In subgroup analyses based on cancer type, the significant association was found between eNOS intron 4a/b polymorphism and prostate cancer risk, eNOS -786T>C polymorphism and risk of prostate, bladder and breast cancers, and eNOS 894G>T polymorphism and breast cancer risk. In subgroup analyses based on ethnicity, eNOS intron 4a/b and -786T>C polymorphisms were associated with an increased risk of cancer in Caucasians. In consistent with our meta-analysis results, a case–control study in Chinese Han population showed significant associations of eNOS -786T>C and 894G>T polymorphisms with the increased risk of breast cancer. In addition, stratified analyses based on pathological type showed that eNOS 894G>T polymorphism was only associated with the risk of infiltrative ductal carcinoma. Stratified analyses by tumor stage showed that eNOS -786T>C polymorphism was only associated with the risk of tumor stage III and IV.In conclusion, our meta-analysis and case–control study suggest that eNOS -786T>C and 894G>T polymorphisms are associated with the increased risk of breast cancer.     

Association Between Benzodiazepine Use and Epilepsy Occurrence: A Nationwide Population-Based Case–Control Study

We conducted a retrospective case–control study to evaluate the association between the risk of benzodiazepine (BZD) use and epilepsy occurrence by using data from the Taiwan National Health Insurance Research Database.We recruited 1065 participants who ages 20 years or older and newly diagnosed with epilepsy (International Classification of Diseases, Ninth Revision, Clinical Modification 345) between 2004 and 2011 and assigned them to the epilepsy group. We subsequently frequency-matched them with participants in a control group (n = 4260) according to sex, age, and index year at a 1:4 ratio. A logistic regression model was employed to calculate the odds ratio (OR) for association of epilepsy with BZD exposure. Multivariate logistic regression was conducted to estimate the dose–response relationship between BZD levels and epilepsy risk.The adjusted OR (aOR) for the association of epilepsy with BZD exposure was 2.02 (95% confidence interval [CI] = 1.68–2.42). The aOR for an average BZD dose increased to 1.26 for the participants on <0.01 defined daily dose (DDD), and increased to 4.32 for those on ≥1.50 DDD. On average, when the DDD of BZD exposure increased by 100 units, the epilepsy risk increase by 1.03-fold (95% CI = 1.01–1.04, P = 0.003). The annual BZD exposure day ranges were significantly associated with epilepsy (2–7 days: aOR = 1.67; 8–35 days: aOR = 3.16; and ≥35 days: aOR = 5.60). Whenever the annual BZD exposure increased by 30 days, the risk of epilepsy notably increased by 1.03-fold (95% CI = 1.01–1.04, P < 0.001). In addition, users who quit BZD for more than 6 months still exhibited a higher risk of epilepsy than did the non-BZD users.A considerable increase in epilepsy occurrence was observed in ones with BZD use, particularly in those with prolonged use, multiple exposure, and high-dose consumption.     

Association Between Vitamin D Metabolism Gene Polymorphisms and Risk of Tunisian Adults’ Asthma

Introduction

Several studies have shown a strong correlation between the serum vitamin D level and asthma severity and deficits in lung function.

Objective

Study the relationship between vitamin D and the severity of asthma by targeting five SNPs of vitamin D metabolism gene pathway in a Tunisian adult asthmatics population.

Methods

Our case–control study includes 154 adult asthmatic patients and 154 healthy Tunisian subjects. We genotyped many variants in three human genes encoding key components of the vitamin D metabolism, CYP2R1, CYP27B1, GC. The GC gene rs4588 and rs7041 polymorphisms were analysed using the PCR-RFLP method, while rs10741657 and rs12794714 for CYP2R1 gene and rs10877012 of CYP27B1 gene were investigated using TaqMan PCR genotyping techniques.

Results

We found that the presence of at least one copy of the rs12794714 A, allele was associated with lower risk of developing asthma (OR 0.61). Further, the rs12794714 is a protector factor against asthma severity (OR 0.5). However, the presence of rs10877012 TG genotype is a risk factor related to asthma severity (OR 1.89). When we classified the population according to sex, our results showed that rs10877012 TT genotype was a risk factor for women subjects (OR 6.7). Moreover, the expression of TT genotype was associated with a higher risk of asthma in non-smoker patients (OR 7.13). We found a significant lower VD serum levels in asthmatics than controls but no impact of the polymorphisms on VD levels.

Conclusions

We found that rs12794714 and rs10877012 SNPs were associated with asthma risk.

     

Correlation Between Blood Lipid Levels and Chronic Pancreatitis: A Retrospective Case–Control Study of 48 Cases

The incidence of chronic pancreatitis (CP) is increasing, and dyslipidemia severely affects the health of middle-aged and elderly people. We investigated the association between blood lipid levels and CP.The serum lipid metabolic indices of 48 patients with CP (CP group) were summarized retrospectively. The physical examination results of 40 randomly selected healthy individuals were used as the normal control (NC) group. Statistical analyses of the blood lipid data were performed between the 2 groups using the case–control study method.High-density lipoprotein-cholesterol (HDL-c) levels decreased and fasting blood glucose (GLU) levels increased in the CP group compared with those in the NC group (P < 0.01). Pearson correlation analysis results showed that serum amylase (AMY) was positively correlated with low-density lipoprotein-cholesterol (LDL-c; r = 0.414, P < 0.05), and urine AMY (UAMY) was positively correlated with total cholesterol (TC; r = 0.614, P < 0.01) and LDL-c (r = 0.678, P < 0.01). A binary logistic regression analysis showed that GLU (odds ratio [OR], 5.052; P < 0.01) and TC (OR, 1.074; P < 0.01) may be risk factors for CP, whereas HDL-c may be a CP protective factor (OR, 0.833; P < 0.01).The HDL-c levels decreased and GLU levels increased in the CP group compared with those in the NC group; AMY was positively correlated with LDL-c and UAMY was positively correlated with TC and LDL-c; GLU and TC may be risk factors for CP; and HDL-c may be a CP protective factor. This may be the first time that such results have been reported. These findings will contribute to primary prevention and control of CP progression.     

Celiac Disease and Lymphoma Risk: A Multicentric Case–Control Study in Spain

Celiac disease is a highly prevalent condition frequently misdiagnosed because of heterogeneity of the clinical symptoms. It is well recognized that enteropathy-associated T-cell lymphoma is an uncommon lymphoma type linked to celiac disease; it has also been suggested that other types of lymphomas may be associated with celiac disease. Our aim was to estimate the risk of all lymphoma associated with celiac disease. Serological markers and personal interviews were obtained from 298 consecutive lymphoma cases and 251 matched controls recruited in four Spanish hospitals. Celiac disease was detected in two cases (0.67%; n = 298) and in three controls (1.2%; n = 251). Treated celiac disease was observed in one patient with lymphoma and in two control subjects. In our series, there was no evidence that celiac disease was a risk factor for lymphoma (OR = 0.62, 95% CI = 0.10-3.79). Serological screening for CD is not recommended in people with lymphoma.     

Association of 24 bp Duplication of Human CHIT1 Gene with Asthma in a Heterozygous Population of North India: A Case–Control Study

Purpose

CHIT1 is expressed by pulmonary macrophages, which is typically the site of entry for many environmental fungi that may increase the risk of pulmonary fungal infection and lead to hypersensitivity. The conserved expression of this gene in humans suggests its physiological importance in the mammalian lung.

Methods

The present study was conducted with a total of 964 subjects, including 483 healthy controls and 481 asthma patients. DNA samples were extracted from blood, and the genotyping was done using polymerase chain reaction method.

Results

Statistical analysis revealed that the 24 bp duplication in CHIT1 gene polymorphism shows highly significant association in heterozygous (wild/dup) genotype with OR 1.74, 95 % CI (1.29–2.36), and p = 0.000. However, the homozygous mutant genotype (dup/dup) was found to be non-significant with OR 1.06, 95 % CI (0.69–1.63), and p = 0.786. The combination of both wild/dup and dup/dup was also found to be highly significant with OR 1.57, 95 % CI (1.18–2.11), and p = 0.002.

Conclusions

This is the first study conducted in India which reports a significant association between 24 bp duplication in CHIT1 gene polymorphism and asthma in the studied North Indian population.     

The Expression of Hypoxia-Inducible Factor-1α in Hepatitis B Virus-Related Hepatocellular Carcinoma: Correlation with Patients’ Prognosis and Hepatitis B Virus X Protein

Hypoxia inducible factor-1α (HIF-1α) was well correlated with carcinogenesis and tumor progression in many kinds of cancer. In this study, high expression of HIF-1α was found in 37 of the 72 (51.39%) tumor specimens, and significantly correlated with venous invasion and lymphonode invasion. Patients with high expression of HIF-1α had a significantly shorter overall survival rate and disease-free survival rate than those with low expression. Multivariate analysis showed high HIF-1α expression was a borderline independent factor of overall survival. HIF-1α expression was also found to be significantly correlated with the expression of hepatitis B virus X protein (HBx), and over-expressed HBx upregulated HIF-1α protein expression in vitro. These results suggested that HIF-1α, which was partially regulated by HBx, might be a prognostic marker of HBV-related HCC patients. Dr. Huahong Xie, Dr. Jiugang Song, and Dr. Kaige Liu contributed equally to this study.     

CLPTM1L Genetic Polymorphisms and Interaction With Smoking and Alcohol Drinking in Lung Cancer Risk: A Case–Control Study in the Han Population From Northwest China

Genetic variants of cleft lip and palate trans-membrane 1-like (CLPTM1L) genes in the p15.33 region of chromosome 5 were previously identified to influence susceptibility to lung cancer. We examined the association of single nucleotide polymorphisms (SNPs) in CLPTM1L genes with lung cancer and explored their potential effects on the relationship between environmental risk factors (smoking, drinking) and lung cancer in a Chinese Han population.We genotyped 9 single nucleotide polymorphisms (SNPs) of CLPTM1L in a case–control study with 228 lung cancer cases and 301 controls from northwest China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression.We identified that the minor alleles of rs451360, rs402710, and rs31484 in CLPTM1L were associated with a 0.52-fold, 0.76-fold, and 0.70-fold decreased risk of lung cancer in allelic model analysis, respectively. In the genetic model analysis, we found rs402710 and rs401681 were associated with decreased lung cancer risk. Further stratification analysis showed that rs380286 displayed a significantly decreased lung cancer risk (OR = 0.65, P = 0.041) in the non-drinkers. In addition, Haplotype “GTTATCTGT” was found to be associated with decreased lung cancer risk (OR = 0.50, P = 0.033).Our results verified that genetic variants of CLPTM1L contribute to lung cancer susceptibility in the northwest Chinese Han population. Additionally, we found that consumption of alcohol may interact with CLPTM1L polymorphisms to contribute to overall lung cancer susceptibility.     

Prevalence and Risk Factors of Cognitive Impairment in Parkinson Disease: A Population-Based Case–Control Study in Taiwan

The aim of this study was to evaluate the Parkinson disease (PD) prevalence of cognitive impairment in Taiwan.The case–control study consisted of 6177 cognitive impairment patients and 24,708 noncognitive impairment as controls for the period of 2006 to 2010 and both of the groups aged ≥50 years. The multivariable logistic regression analyses were used to estimate the odds ratio (OR) for cognitive impairment, and the 95% confidence intervals (CIs) among patients with PD were compared with those of non-PD patients.PD (adjusted odds ratio [aOR] is 3.07, 95% CI 2.76–3.41) is the one of the most contributed risk factors for cognitive impairment. Besides, we found a remarkable result of the diagnosed cognitive impairment of PD that was found highest in the first 6 months (aOR 11.98, 95% CI 8.51–16.86) and then decrease the incident year by year. The PD prevalence in a patient with cognitive impairment in our data present is 12.1% lower than those with truly dementia published previously and documented by western studies.We found a remarkable result of the diagnosed cognitive impairment of PD that was found highest in the first 6 months and then decrease the incident year by year.     

Lack of Association Between the TGF-β<Subscript>1</Subscript> Gene and Development of COPD in Asians: A Case–Control Study and Meta-analysis

Abnormalities in the transforming growth factor-β₁ (TGF-β₁) gene are thought to be linked to chronic obstructive pulmonary disease (COPD). We investigated the association between the single nuclear polymorphisms (SNPs) of TGF-β₁ and the risk of COPD in a case–control study and meta-analysis. We genotyped 160 cases and 177 control subjects in a local hospital using the Mass-Array^TM Technology Platform and then tested the association of four SNPs in TGF-β₁ (rs6957, rs1800469, rs2241712, and rs2241718) with COPD. Plasma TGF-β₁ level measurement was performed later. A database covering all papers published up to October 30, 2010, was then reviewed. Statistical analysis was performed using Revman 5.0 and STATA 11.0 software. No association was found between TGF-β₁ gene SNPs and an increased risk of COPD in Asians. By meta-analysis, the link of two polymorphisms, rs1800469 and rs1982073, was investigated in seven and eight studies, respectively, involving 1508 COPD patients and 2608 control subjects. The results showed that there was no significant association between an increased risk of COPD in carriers of the T allele (TT+TC) versus the CC genotype in rs1800469 and rs1982073. In ethnic subgroup analysis, the risk of COPD associated with the rs1800469 T allele was not significantly elevated among Asians. TGF-β₁ gene polymorphisms are not associated with an increased risk of COPD in the Asian population.     

Occupational Exposure and the Risk of Barrett’s Esophagus: A Case–Control Study

Background

Case–control studies in the United States and Europe have linked occupational exposure to volatile sulfur compounds, solvents, and pesticide to increased risk of esophageal adenocarcinoma. However, the association between occupational exposures and the risk of Barrett’s esophagus (BE) is unclear given the absence of studies in this area.

Methods

This is a case–control study in patients undergoing endoscopy who were either referred directly or were eligible for screening colonoscopy and recruited from primary care clinics. All participants completed a survey on (1) self-reported occupational exposures to asbestos, metal dust, organic solvents, and pesticides, and (2) self reported longest held job and job-related activities. The latter were assigned by an industrial hygienist who was blinded to the case and control status into one of 99 standard occupational categories used by the US Department of Labor. Each occupational category was then assigned an expected level of exposure to the same four classes of agents in addition to radiation. We compared the self-reported exposure and the expected occupational exposure based on the self-reported occupation between cases with definitive BE and controls without BE. We examined the associations adjusting for age, sex, race, and patient recruitment source in a multivariable logistic regression analysis.

Results

We examined 226 cases of definitive BE and 1,424 controls without BE. There was a greater proportion of patients with self-reported asbestos exposure in cases than controls (16.2 % vs. 12.0 %; p = 0.08) but no significant differences in metal dust, organic solvents, or pesticides. The multivariate model did not show an independent association between self-reported asbestos exposure and BE. For the calculated occupational exposure, there were no significant differences between cases and controls for asbestos (29.6 % vs. 27.5 %; p = 0.5), metal dust, organic solvents, pesticides, or radiation exposure. Among commonly reported occupation, there were significantly greater proportion of retail sales workers in BE cases than controls (10.8 % vs. 4.9 %; p = 0.01).

Conclusions

Exposure to asbestos and sedentary jobs may be risk factors for Barrett’s esophagus. Further studies are needed to confirm this finding.     

Sporadic Duodenal Adenoma and Association with Colorectal Neoplasia: A Case–Control Study

Background

Sporadic duodenal adenomas are uncommon. Prior studies show that patients with sporadic duodenal adenoma have increased risk of colorectal neoplasia and should undergo colorectal screening. However, the nature of the risk, location, and type of colorectal neoplasia are not well studied.

Aim

We aimed to identify the risk of colorectal neoplasia in patients who have duodenal adenomas.

Methods

A retrospective case–control study was conducted to identify sporadic duodenal adenoma patients using the databases at one academic center. Colonoscopic findings including histology and location of colorectal cancer neoplasia in sporadic duodenal adenoma patients were compared with a control group of patients without duodenal adenomas who underwent both gastroduodenoscopy and colonoscopy.

Results

Hundred and two patients with sporadic duodenal adenomas or adenocarcinomas were identified. Colonoscopy was performed in 47 patients (46 %), and colorectal neoplasia was present in 22 (46 %). There was a significantly higher rate of colorectal neoplasia in patients with sporadic duodenal adenoma (43 %) compared to the control group (24 %) odds ratio 4.8, 95 % confidence interval (1.7–7.4), but not for advanced colorectal adenoma (9 vs. 26 %, p = 0.17). Case patients had significantly more right-sided lesions than matched controls (p = 0.02).

Limitations

Single-center, retrospective study.

Conclusions

Individuals with sporadic duodenal adenomas have a significantly higher risk of colorectal neoplasia and proximal location of neoplasia. Therefore, these patients should undergo colonoscopy with particular attention to the right colon.