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.     

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.     

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.     

The Differential Effects of Statins on the Risk of Developing Pancreatic Cancer: A Case–Control Study in Two Centres in the United Kingdom

Introduction

There are plausible biological mechanisms for how statins may prevent pancreatic cancer, although the evidence from epidemiological studies in the general population is conflicting. This study aims to clarify whether statins exert their effects in specific sub-groups, namely, gender, smoking status and diabetes.

Methods

A matched case–control study was conducted in patients diagnosed with pancreatic cancer, and a group of dermatology patients of similar ages and gender, diagnosed with basal cell carcinoma. Participants’ medical records were reviewed for information on statin use prior to diagnosis. Odds ratios and 95 % CIs for the development of pancreatic cancer were estimated using conditional logistic regression. Subgroup analysis was performed in men, women, smokers and those with type 2 diabetes.

Results

Two hundred fifty-two cases (median age 71 years, range 48–73 years, 51 % women) and 504 controls were identified, of which 23 % of cases were regular statin users versus 21 % of controls. In the general study population there was no association between pancreatic cancer and regular statin use (OR 0.82, 95 % CI 0.53–1.23, p = 0.33). However, in male smokers, regular statin use was associated with significantly reduced odds of pancreatic cancer compared to male smokers not prescribed a statin (OR 0.11, 95 % CI 0.01–0.96, p = 0.05). In patients with type 2 diabetes statins use was not associated with reduced odds (OR 0.92, 95 % CI 0.35–2.45, p = 0.80), with no gender effects.

Conclusions

In male smokers, statins may reduce the odds of pancreatic cancer. Statin use should be measured in aetiological studies of pancreatic cancer but analysed in specific sub-groups. Future work should investigate statins as chemopreventative agents in this high risk sub-group.     

Correlates of Suicide Among Veterans Treated in Primary Care: Case–Control Study of a Nationally Representative Sample

BACKGROUND

Veterans receiving Veterans Affairs (VA) healthcare have increased suicide risk compared to the general population. Many patients see primary care clinicians prior to suicide. Yet little is known about the correlates of suicide among patients who receive primary care treatment prior to death.

OBJECTIVE

Our aim was to describe characteristics of veterans who received VA primary care in the 6 months prior to suicide; and to compare these to characteristics of control patients who also received VA primary care.

DESIGN

This was a retrospective case–control study.

SUBJECTS

The investigators partnered with VA operations leaders to obtain death certificate data from 11 states for veterans who died by suicide in 2009. Cases were matched 1:2 to controls based on age, sex, and clinician.

MAIN MEASURES

Demographic, diagnosis, and utilization data were obtained from VA’s Corporate Data Warehouse. Additional clinical and psychosocial context data were collected using manual medical record review. Multivariate conditional logistic regression was used to examine associations between potential predictor variables and suicide.

KEY RESULTS

Two hundred and sixty-nine veteran cases were matched to 538 controls. Average subject age was 63 years; 97 % were male. Rates of mental health conditions, functional decline, sleep disturbance, suicidal ideation, and psychosocial stressors were all significantly greater in cases compared to controls. In the final model describing men in the sample, non-white race (OR?=?0.51; 95 % CI?=?0.27–0.98) and VA service-connected disability (OR?=?0.54; 95 % CI?=?0.36–0.80) were associated with decreased odds of suicide, while anxiety disorder (OR?=?3.52; 95 % CI?=?1.79–6.92), functional decline (OR?=?2.52; 95 % CI?=?1.55–4.10), depression (OR?=?1.82; 95 % CI?=?1.07–3.10), and endorsement of suicidal ideation (OR?=?2.27; 95 % CI?=?1.07–4.83) were associated with greater odds of suicide.

CONCLUSIONS

Assessment for anxiety disorders and functional decline in addition to suicidal ideation and depression may be especially important for determining suicide risk in this population. Continued development of interventions that support identifying and addressing these conditions in primary care is indicated.

     

Functional Inducible Nitric Oxide Synthase Gene Variants Associate With Hypertension: A Case–Control Study in a Finnish Population—The TAMRISK Study

Increased inducible nitric oxide synthase (iNOS) activity and expression has been associated with hypertension, but less is known whether the 2 known functional polymorphic sites in the iNOS gene (g.–1026 C/A (rs2779249), g.2087 G/A (rs2297518)) affect susceptibility to hypertension. The objective of this study was to investigate the association between the genetic variants of iNOS and diagnosed hypertension in a Finnish cohort.This study included 320 hypertensive cases and 439 healthy controls. All participants were 50-year-old men and women and the data were collected from the Tampere adult population cardiovascular risk study (TAMRISK). DNA was extracted from buccal swabs and iNOS single nucleotide polymorphisms (SNPs) were analyzed using KASP genotyping PCR. Data analysis was done by logistic regression.At the age of 50 years, the SNP rs2779249 (C/A) associated significantly with hypertension (P = 0.009); specifically, subjects carrying the A-allele had higher risk of hypertension compared to those carrying the CC genotype (OR = 1.47; CI = 1.08–2.01; P = 0.015). In addition, a 15-year follow-up period (35, 40, and 45 years) of the same individuals showed that carriers of the A-allele had more often hypertension in all of the studied age-groups. The highest risk for developing hypertension was obtained among 35-year-old subjects (odds ratio [OR] 3.83; confidence interval [CI] = 1.20–12.27; P = 0.024). Those carrying variant A had also significantly higher readings of both systolic (P = 0.047) and diastolic (P = 0.048) blood pressure during the follow-up. No significant associations between rs2297518 (G/A) variants alone and hypertension were found. However, haplotype analysis of rs2779249 and rs2297518 revealed that individuals having haplotype H3 which combines both A alleles (CA–GA, 19.7% of individuals) was more commonly found in the hypertensive group than in the normotensive group (OR = 2.01; CI = 1.29–3.12; P = 0.002).In conclusion, there was a significant association between iNOS genetic variant (rs2779249) and hypertension in the genetically homogenous Finnish population. Those who carried the rare A-allele of the gene had higher risk for hypertension already at the age of 35 years.     

The Efficacy of Percutaneous Transhepatic Gallbladder Drainage on Acute Cholecystitis in High-Risk Elderly Patients Based on the Tokyo Guidelines: A Retrospective Case–Control Study

To evaluate the efficacy of percutaneous transhepatic gallbladder drainage (PTGD) for high-risk elderly patients with acute cholecystitis.Retrospective analysis of 159 acute cholecystitis patients who were admitted to General Surgery Division III of the First Affiliated Hospital of Dalian Medical University between January 2005 and November 2012. A total of 123 patients underwent laparoscopic cholecystectomy (LC), and 36 received only PTGD treatment. The LC patients were divided into 3 groups based on their preoperative treatment: group A, emergency patients (33 patients); group B (26 patients), patients who were treated with PTGD prior to LC; and group C (64 patients), patients who received nonsurgical treatment prior to LC. General conditions, LC surgery duration, intraoperative blood loss, rate of conversion to open surgery, incidence of postoperative complications, total fasting time, and total hospitalization time were analyzed and compared among the 3 groups.The remission rates of patients in the PTGD treatment groups (including group B and PTGD treatment only group) were significantly higher within 24 and 48 hours than those of patients who received nonsurgical treatment prior to LC (P < 0.05). Among the patients in the 3 surgery groups, the operation conversion rate (19.2%) of group B was significantly higher than that of group A (3.0%) and group C (1.6%) (P < 0.05). The total hospitalization time of the patients in group B (18.5 ± 4.5 days) was longer than that of the patients in group A (8.2 ± 3.9 days) and group C (10.5 ± 6.4 days). The total fasting time of the patients in group A (2.4 ± 1.2 days) was significantly shorter than that of those in group B (4.1 ± 1.7 days) and group C (3.4 ± 2.7 days) (P < 0.05).For high-risk elderly patients, if there is any emergency surgery contraindication, PTGD therapy may be safe and effective and can relieve the symptoms within a short time. For acute cholecystitis patients without surgery contraindications, emergency surgery should be performed as soon as possible after diagnosis.     

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.     

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.     

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.     

A Phase II Study of the Docetaxel–Carboplatin Chemotherapy Regimen in Advanced Non-Small-Cell Lung Cancer

The efficacy of the docetaxel–carboplatin combination chemotherapy was studied in various phase II studies. Based on these data we aimed to test the regimen in previously untreated patients with advanced advanced non-smoking lung cancer (NSCLC) with docetaxel 80 mg/m² a standard dose of carboplatin at AUC = 5, in an attempt to define the efficacy and tolerability of the combination in an open-label phase II study. Patients with histologically confirmed advanced NSCLC stage IIIB and IV were candidates for the present study. Docetaxel was administered at 80 mg/m² over 1 h by intravenous (IV) infusion followed by carboplatin AUC = 5 in 30 min IV infusion, both on day 1, and recycled every 21 days. Sixty patients received 263 courses of therapy in total; 231/263 (88%) were administered according to the planned doses, and 48/60 (80%) patients received chemotherapy without decrement of the dose; 32/263 (12%) of the courses were administered with a 10%–30% dose reduction. Complete responses (CR) were seen in 5 patients (8.3%) and partial responses (PR) in 16 patients (26.7%) for an overall response rate of 35%. Median duration of response was 7.5 months [95% confidence interval (CI)-7.1–7.9], time to progression (TIP) 11.5 months (95% CI-8.2–14.8), median overall survival (OS) 15.0 months (95% CI-10.8–19.2). One-year survival was 61.7%. Toxicity was acceptable; it was calculated according to the administered cycles and was mainly neutropenia: grade 3, 9% and grade 4, 2%; anemia: grade 3, 8%; nausea and vomiting: grade 3, 8%. The outpatient regimen of docetaxel–carboplatin is effective with acceptable toxicity in patients with advanced NSCLC.     

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.     

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.     

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.     

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 (