Neural Autoantibody Evaluation in Functional Gastrointestinal Disorders: A Population-Based Case–Control Study

Background  

Our goal is to investigate the serum profile of neural autoantibodies in community-based patients with irritable bowel syndrome (IBS) or functional dyspepsia. The pathogenesis of functional gastrointestinal (GI) disorders, including IBS and dyspepsia, are unknown. Theories range from purely psychological to autoimmune alterations in GI tract neuromuscular function.     

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.     

Inducible Nitric Oxide Synthase (iNOS): Why a Different Production in COVID-19 Patients of the Two Waves?

Profound clinical differences between the first and second waves of COVID-19 were observed in Europe. Nitric oxide (NO) may positively impact patients with Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) infection. It is mainly generated by inducible nitric oxide synthase (iNOS). We studied serum iNOS levels together with serum interleukin (IL)-6 and IL-10 in patients with SARS-CoV-2 infection in the first wave (n = 35) and second wave (n = 153). In the first wave, serum iNOS, IL-6, IL-10 levels increased significantly, in line with the World Health Organization (WHO) score severity, while in the second wave, iNOS did not change with the severity. The patients of the second wave showed lower levels of iNOS, IL-6, and IL-10, as compared to the corresponding subgroup of the first wave, suggesting a less severe outcome of COVID-19 in these patients. However, in the severe patients of the second wave, iNOS levels were significantly lower in patients treated with steroids or azithromycin before the hospitalization, as compared to the untreated patients. This suggests an impairment of the defense mechanism against the virus and NO-based therapies as a potential therapy in patients with low iNOS levels.     

Genetic Susceptibility to Lung Cancer Based on Candidate Genes in a Sample from the Mexican Mestizo Population: A Case–Control Study

Background

Lung cancer (LC) is the leading cause of mortality caused by neoplasias worldwide. Although cigarette smoking is the primary cause, not all smokers develop LC. Polymorphic variations in genes associated with carcinogen metabolism, DNA repair, and cell-cycle dysregulation may alter an individual risk of developing LC. A polygenic cancer model was proposed, which considers genetic susceptibility to cancer is a global mechanism and suggests that it might be defined by the contributions of low-risk alleles in several candidate genes. This study focused on the analysis of 15 polymorphisms in 12 low-penetrance genes in a case–control study of a sample of Mexican Mestizo population.

Methods

A case–control study was performed with a total of 572 unrelated individuals, including 190 cases with a primary LC diagnosis and 382 healthy controls. The polymorphic status of the individuals was determined by TaqMan probe and RFLP techniques. The association between LC and genotype score (GS) was assessed by logistic regression.

Results

The results suggests a protective effect of the genotypes Arg/Lys of AhR rs2066853 (odds ratio [OR] 0.55, p = 0.03), Ile/Val of CYP1A1 rs1048943 (OR 0.49, p = 0.009), Tyr/His of EPHX1 rs1051740 (OR 0.53, p = 0.03), and A/A of CCND1 rs603965 (OR 0.44, p = 0.02). Analyses using the GS suggest that average cases have a larger number of risk alleles than controls (Student’s t test ?4.85, p = 0.001; OR 1.25, p < 0.001).

Conclusions

Our results suggest significant differences between the GS for the cases and controls, which support the hypothesis underlying the additive and polygenic models for lung cancer risk depending on the polymorphisms in low-penetrance genes.     

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.     

Risk Factors Involved in Patients with Bleeding Peptic Ulcers: A Case–Control Study

Our objectives were to (1) identify the risk factors involved in patients with peptic ulcer disease and determine if they predict bleeding in these patients, (2) determine the association between these risk factors, and (3) analyze the cost effectiveness of various tests for Helicobacter pylori (H. pylori). Two-hundred and thirty patients were included in our study between January 2004 and June 2005 (128 bleeding peptic ulcer disease patients constituted the cases, 102 nonbleeding ulcer patients constituted the controls). H. pylori infection was assessed by urease test and biopsy from gastric antrum. There was no statistically significant difference between these groups regarding sex, age, or location of ulcer. Nonsteroidal anti-inflammatory drug (NSAID) use was higher in the case group (P < 0.001), and the rate of H. pylori infection was lower in these patients (P < 0.05). There was no interaction between NSAID use and H. pylori infection in predicting bleeding ulcer risk (P = 0.08). Sensitivity and specificity for urease test in detecting H. pylori was 75% and 99.7%, respectively. So a positive urease test does not need confirmation with biopsy, which is cost effective.     

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.     

Minidose Aspirin and Gastrointestinal Bleeding—A Retrospective,Case–Control Study in Hospitalized Patients

Low or minimal doses of aspirin are widely used for prevention of cardiovascular diseases. Aspirin is known to produce severe adverse gastrointestinal effects, such as bleeding and perforation. Less is known about the risk associated with minidose aspirin. Our aim was to assess the possible association of upper gastrointestinal tract bleeding with minidose aspirin therapy. A retrospective controlled design was used. Patients hospitalized for melena or hematemesis between January 1, 2000, and December 31, 2001, were identified by ICD-9 codes, and their clinical findings were compared to these of patients without upper gastrointestinal bleeding hospitalized during the same period and matched for age and sex. Bleeding was attributed to therapy if patients used a nonsteroidal anti-inflammatory drug or aspirin therapy within 30 days before hospitalization. The study group included 318 patients (59% male), and the control group 141 (65% male). Mean ages were 67 ± 19 and 64 ± 19 years, respectively. Study patients had more accompanying diseases, used more medications, and required more blood transfusions than controls (37%, vs. 2% of controls; P < 0.001). Minidose aspirin was used by 28% of the study group and 18% of the controls (P = 0.03). The average dose was 40 ± 86 and 21 ± 55 mg/day, respectively (P = 0.012). Only 26% of the study patients received a gastric protective agent. On multivariate analysis, aspirin consumption was the only independent risk factor for upper gastrointestinal tract bleeding. There appears to be an association between minidose aspirin treatment and hospitalization for upper gastrointestinal tract bleeding. Despite the advanced age of the patients, only one-quarter were treated with gastric protective agent.     

Ischemic Stroke in Young Adults and Preexisting Psychiatric Disorders: A Nationwide Case–Control Study

Previous studies showed that psychiatric disorders such as major depression, bipolar disorders, and alcohol misuse are associated with an increased risk of ischemic stroke. However, the link between psychiatric disorders and stroke in the young population is rarely investigated.Using the Taiwan National Health Insurance Research Database, 2063 young adults aged between 18 and 45 years with ischemic stroke and 8252 age- and sex-matched controls were enrolled in our study between 1998 and 2011. Participants who had preexisting psychiatric disorders were identified.After adjusting for preexisting physical disorders and demographic data, patients with ischemic stroke had an increased risk of having preexisting psychiatric disorders, including bipolar disorder (odds ratio [OR]: 2.23, 95% confidence interval [CI]: 1.06∼4.67), unipolar depression (OR: 2.15, 95% CI: 1.62∼2.86), anxiety disorders (OR: 2.63, 95% CI: 1.87∼3.69), and alcohol use disorders (OR: 2.86, 95% CI: 1.79∼4.57). Young ischemic stroke (age ≥30 years) was related to the risk of preexisting unipolar depression (OR: 1.49, 95% CI: 1.05∼2.11), anxiety disorders (OR: 1.99, 95% CI: 1.33∼2.97), and alcohol use disorders (OR: 2.54, 95% CI: 1.55∼4.14); very young stroke (age <30 years) was only associated with the risk of preexisting unipolar depression (OR: 4.15, 95% CI: 1.47∼11.72).Patients who had experienced ischemic stroke at age younger than 45 years had a higher risk of having pre-existing bipolar disorder, unipolar depression, anxiety disorders, and alcohol use disorders than those who did not after adjusting for demographic data and stroke-related medical comorbidities.Ischemic strokes in adults younger than 45 years of age were regarded as a relatively uncommon event in the proportion of <5% of all ischemic strokes.¹ However, other epidemiological studies have shown a higher proportion of approximately 10% of all ischemic strokes occurring in young adults.^2,3 Compared with stroke in the elderly, stroke in the young adult resulted in a disproportionately great personal, familial, and socioeconomic impacts and consequences by leaving patients disabled before their most productive years.^4,5 The most significantly established risk factors for young ischemic stroke included hypertension, dyslipidemia, diabetes mellitus, and smoking.^5–7The association between psychiatric disorders and stroke has gained the clinical and scientific attention in the past decade.^8–10 For example, Tsai et al¹¹ followed 80,569 patients with schizophrenia for 5 years, and revealed that those with schizophrenia were 1.13 times more likely to have a stroke (95% confidence interval [CI]: 1.05∼1.22). Li et al¹² followed 1003 patients with major depression and 4012 controls for 9 years and found that patients with major depression had a higher risk of stroke (odds ratio [OR]: 1.55, 95% CI: 1.08∼2.211) than the control group during the follow-up. Dong et al⁸ reported a significant positive association between depression and subsequent risk of stroke (relative risk [RR]: 1.34, 95% CI: 1.17∼1.54). Prieto et al''s¹⁰ meta-analysis study composed of 27,092 bipolar patients showed that the risk of stroke in bipolar disorder was significantly increased (RR: 1.74, 95% CI 1.29∼2.35). The First National Health and Nutrition Examination Survey in United States demonstrated that more anxiety symptoms at baseline were associated with increased risk of incident stroke (hazard ratio [HR]: 1.14, 95% CI: 1.03∼1.25).⁹ Following 19,544 men aged 40 to 59 years for 11 years, Iso et al¹³ determined that alcohol consumption was positively associated with the risk of stroke with a 68% excess risk among drinkers of ≥450 g ethanol per week compared with occasional drinkers. However, stroke in the above studies occurred in the late mid-life or in old age but not in the younger age groups. The association between young stroke and psychiatric disorders was less investigated and still unclear.In our study, using the Taiwan National Health Insurance Research Database (NHIRD) with a large sample size and a retrospective study design, we investigated the association between the young ischemic stroke and the risk of preexisting psychiatric disorders, including schizophrenia, bipolar disorder, major depression, anxiety disorders, and alcohol use disorder.     

Parasite Infection and Tuberculosis Disease among Children: A Case–Control Study

We conducted a case–control study to examine associations between parasite infection, including protozoa infection, and tuberculosis (TB) in children in Lima, Peru. We enrolled 189 matched-pairs. In multivariable conditional logistic regression analyses, Blastocystis hominis infection (rate ratio = 0.30, 95% confidence interval = 0.14–0.64, P = 0.002) was strongly associated with a lower risk of TB. We observed a statistically significant inverse linear dose-response relationship between Blastocystis hominis infection and TB. These findings should be confirmed in future prospective studies.Globally, infectious diseases account for more than half of deaths among children less than five years of age.¹ Studies examining the ways in which some infectious diseases interact identify worrisome synergistic relationships in which infection with one disease increases susceptibility to or worsens the prognosis of another.^2–4 The relationship between parasite infection and tuberculosis (TB) has gained increasing attention over the past decade: both animal studies and epidemiologic studies in humans have found evidence indicating that chronic helminth infection may increase the risk of TB and reduce the effectiveness of the Bacillus Calmette–Guérin vaccine.^5,6Protozoa infection, another type of parasitic infection, is common in urban areas lacking clean water access and may result in severe malnutrition as a consequence of chronic diarrhea or anorexia. Protozoa infection can be asymptomatic and may result in elevated levels of cytokines such as interferon-γ (IFN-γ),^7,8 a critical mediator in the host immune response to Mycobacterium tuberculosis. We report on the relationship between various parasite infections, including protozoa infection, and TB among children in Lima, Peru.We conducted this case–control study in two of five health regions in the Lima metropolitan area as described.⁹ Parasite infestation, with protozoa pathogens in particular, is common in Lima, with more than 40% of adults and children infected.^10,11 Eligible cases were children < 15 years of age who received an initial TB diagnosis at the Instituto Nacional de Salud del Niño, the main pediatric tuberculosis referral center in Peru, or a participating health clinic during the study period of February 2010–September 2011. Healthy controls (i.e., no chronic cough or fever) without a history of TB were identified by using a random walk or friend referral and matched to cases by neighborhood, age, and enrollment date. Ethical approval for this study protocol was granted by the Office of Human Research Administration at the Harvard School of Public Health in Boston, Massachusetts and the Instituto Nacional de Salud del Niño in Lima, Peru. Guardians provided informed consent, and children ≥ 8 years of age provided informed assent.To assess parasite infection, we requested that children provide two scotch-tape specimens applied to the anal area for identification of Enterobius vermicularis¹² and three stool samples: the first two samples were preserved with 10% formalin and the third was a fresh sample. An accredited laboratory (Blufstein Laboratorio Clínico, S.A.) in Lima examined stool samples by using direct smear microscopy and spontaneous sedimentation methods and scotch tape specimens by using the Graham method.¹² Laboratory personnel were blinded to the case status of participants. We excluded pairs in which either the case or control did not contribute ≥ 1 stool and scotch tape specimen. Children and their guardians were asked to respond to an interview related to sociodemographic, clinical, and lifestyle factors.We conducted conditional logistic regression analyses, stratified by each matched pair. To create the final multivariable model, we included binary variables for the presence of infection with any parasite species that was found in at least 5% of controls; we also included variables that were identified a priori as potential confounders (

Association Between Catalase Gene Polymorphisms and Risk of Chronic Hepatitis B,Hepatitis B Virus-Related Liver Cirrhosis and Hepatocellular Carcinoma in Guangxi Population: A Case–Control Study

Reactive oxygen species (ROS) play critical roles in hepatocarcinogenesis. The catalase (CAT) enzyme is involved in the repair of ROS. Therefore, we investigate the association between CAT gene polymorphisms and the risk of hepatocellular carcinoma (HCC).A total of 715 subjects were divided into 4 groups: 111 chronic hepatitis B (CHB) patients, 90 hepatitis B virus (HBV)-related liver cirrhosis (LC) patients, 266 HBV-HCC patients, and 248 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect CAT gene rs1001179, rs769217, and rs7943316 polymorphisms.Binary logistic regression analyses adjusting for sex, age, ethnicity, smoking and alcohol consumption, and body mass index suggested that subjects carrying the rs769217 T allele were at marginally increased risk of CHB, LC, and HCC, with adjusted odds ratios (ORs) of 1.51 (95% confidence interval [CI] = 1.04–2.20, P = 0.029), 1.48 (95% CI = 1.03–2.14, P = 0.035), and 1.51 (95% CI = 1.14–1.98, P = 0.004), respectively. Similarly, those individuals carrying the rs769217 TT genotype had a moderately increased risk of CHB, LC, and HCC, with adjusted ORs of 2.11 (95% CI = 1.05–4.22, P = 0.035), 2.00 (95% CI, 1.01–3.95, P = 0.047), and 1.93 (95% CI = 1.14–3.28, P = 0.015), respectively. Moreover, subjects carrying the rs769217 CT genotype and at least 1 copy of the T allele (dominant model) were 1.78 times and 1.83 times more likely to develop HCC, respectively (OR = 1.78, 95% CI = 1.16–2.73, P = 0.009 and OR = 1.83, 95% CI = 1.23–2.71, P = 0.003). This association between CAT rs769217 T alleles and HCC risk is significantly strengthened among men, nonsmokers, nondrinkers, and among individuals <50 years of age. Furthermore, we found 1 high-risk haplotype GTA for CHB (OR = 1.45, 95% CI = 1.05–2.01) and 1 protective haplotype GCA for HCC risk (OR = 0.67, 95% CI = 0.52–0.87). We did not found any significant difference in CAT rs1001179 and rs7943316 polymorphisms between controls and cases.Our findings suggest that the CAT rs769217 T allele is associated with increased risk of CHB, HBV-LC, and HBV-HCC in Guangxi population.     

TLR4 rs1927911, but Not TLR2 rs5743708, Is Associated With Atherosclerotic Cerebral Infarction in the Southern Han Population: A Case–Control Study

The objective of this study was to explore the association of toll-like receptor (TLR) 4 rs1927911 and TLR2 rs5743708 with atherosclerotic cerebral infarction (ACI) and their effects on blood pressure, fasting blood glucose, and blood lipids in the Han population of Hunan Province.TLR4 rs1927911 and TLR2 rs5743708 were detected by polymerase chain reaction and restriction fragment length polymorphism in 170 patients with ACI and 149 healthy controls.Our results indicated that the genotype and allele frequencies of TLR4 rs1927911 were significantly different between ACI patients and controls, whereas those of TLR2 rs5743708 were not significantly different between the 2 groups. For TLR4 rs1927911, blood pressure, fasting blood sugar, and serum lipid levels were not significantly different among different genotypes in the ACI and control groups.The rs1927911 polymorphism of the TLR4 gene may be a risk factor for ACI in the Southern Han population of Hunan Province; however, it may not be associated with blood pressure, fasting blood sugar, or blood lipids.     

Single Nucleotide Polymorphisms of the Sirtuin 1 (SIRT1) Gene are Associated With age-Related Macular Degeneration in Chinese Han Individuals: A Case–Control Pilot Study

To investigate whether 3 variants in sirtuin 1 (SIRT1) gene contributed differently in patients with age-related macular degeneration (AMD) in a Chinese Han population.We conducted a case–control study in a group of Chinese patients with AMD (n = 253) and contrasted the results against a control group (n = 292). Three single nucleotide polymorphisms (SNPs) of SIRT1 gene including rs12778366, rs3740051, and rs4746720 were genotyped using improved multiplex ligase detection reaction. The association between targeted SNPs and AMD was then analyzed by codominant, dominant, recessive, and allelic models.The genotyping data of rs12778366, rs3740051, and rs4746720 revealed significant deviations from Hardy–Weinberg equilibrium tests in the AMD group but not in the control group.We detected significantly differences of rs12778366 allele distribution between 2 groups in recessive and codominant model (P < 0.05). Homozygous carriers of the risk allele C displayed a higher chance of developing AMD (P = 0.036, odds ratio = 3.227; 95% confidence interval: 1.015–10.265).Our study, for the first time, raises the possibility that genetic variations of SIRT1 could be implicated in the pathophysiology of AMD in the Chinese Han population.     

Comparison of UHPLC and HPLC in Benzodiazepines Analysis of Postmortem Samples: A Case–Control Study

The aim of this study was to compare system efficiency and analysis duration regarding the solvent consumption and system maintenance in high-pressure liquid chromatography (HPLC) and ultra high-pressure liquid chromatography (UHPLC).In a case–control study, standard solutions of 7 benzodiazepines (BZs) and 73 biological samples such as urine, tissue, stomach content, and bile that screened positive for BZs were analyzed by HPLC and UHPLC in laboratory of forensic toxicology during 2012 to 2013. HPLC analysis was performed using a Knauer by 100-5 C-18 column (250 mm × 4.6 mm) and Knauer photodiode array detector (PAD). UHPLC analysis was performed using Knauer PAD detector with cooling autosampler and Eurospher II 100-3 C-18 column (100 mm × 3 mm) and also 2 pumps. The mean retention time, standard deviation, flow rate, and repeatability of analytical results were compared by using 2 methods.Routine runtimes in HPLC and UHPLC took 40 and 15 minutes, respectively. Changes in mobile phase composition of the 2 methods were not required. Flow rate and solvent consumption in UHPLC decreased. Diazepam and flurazepam were detected more frequently in biological samples.In UHPLC, small particle size and short length of column cause effective separation of BZs in a very short time. Reduced flow rate, solvent consumption, and injection volume cause more efficiency and less analysis costs. Thus, in the detection of BZs, UHPLC is an accurate, sensitive, and fast method with less cost of analysis.     

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.     

Aspirin May Prevent Cholangiocarcinoma: A Case–Control Study from the United Kingdom

Background

The proliferation of cholangiocarcinoma cells is suppressed in cell culture by nonsteroidal antiinflammatory drugs (NSAIDs) through the inhibition of cyclo-oxygenase-2 enzyme and also by statins which decrease the production of mediators of the cell cycle.

Aims

To investigate whether there is an inverse association between NSAIDs, including aspirin, and the development of cholangiocarcinoma and, for the first time in a Western population, between statin use and the development of cholangiocarcinoma.

Methods

This epidemiological study had a case–control design in which cases of cholangiocarcinoma diagnosed in Norwich between 2004 and 2010 and in Leicester in 2007 were identified from clinical databases. Controls were patients with basal cell carcinomas treated in the respective dermatology departments. The case notes of all subjects were reviewed to confirm diagnoses and obtain information on medication use. The data were analyzed using unconditional logistic regression to calculate odds ratios (OR) with 95 % confidence intervals (CI).

Results

In total, 81 cases of cholangiocarcinoma and 275 controls were identified. For all cases there was radiological evidence of cancer and 86 % of the cases involved the extrahepatic biliary system. Aspirin use was inversely associated with the development of cholangiocarcinoma (OR 0.45, 95 % CI 0.22–0.92), but there were no significant associations between the development of cholangiocarcinoma and NSAIDs (OR 0.39; 95 % CI 0.11–1.42) or statins (OR 0.58; 95 % CI 0.28–1.19).

Conclusions

The epidemiological data from this study support the biological evidence for aspirin having a protective effect against the development of cholangiocarcinoma. Aspirin use should be measured in future etiological studies and assessed as a chemoprevention agent in those at high risk of developing this type of cancer.