Probiotic Supplement Use among Young Children in Taiwan: A Prospective Cohort Study

Objectives

The objective of this study is to provide details on probiotic supplement use among young children in Taiwan.

Participants and Methods

This study is based on the Taiwan Birth Cohort Study database. We used questionnaires to collect information on probiotic supplement use among young children from birth to 18 months of age, while also considering their demographic characteristics and other covariates. Low-birth-weight infants, preterm infants, those with birth defects, and those with caregivers who returned incomplete questionnaires were excluded. The final valid sample comprised 16,991 cases.

Results

Approximately half the children received probiotic supplements before the age of 18 months. Only 6.3% of the children received probiotic supplements during the two periods of birth to 6 months and 7 to 18 months. Firstborn children, native mothers, mothers with higher educational levels, higher family income, and parents who lead healthy lifestyles were positively related to probiotic supplement use among children. Young children who were breastfed, with eczema, or with gastrointestinal tract problems were significantly positively associated with probiotic supplement use.

Conclusion

The findings show that probiotic supplement usage among young children is associated with a more socially advantaged circumstance and certain child health factors, such as eczema, diarrhea, and constipation. Parents might use probiotic supplements for prevention or treatment of child diseases. The findings of this research could serve as a baseline for future studies, and provide insight into probiotic supplement use behavior for health professionals caring for infants and young children.     

Legume Consumption and Colorectal Adenoma Risk: A Meta-Analysis of Observational Studies

Background

The anticancer effects of legumes have been explored extensively, but evidence from epidemiologic studies on colorectal adenoma is controversial. We performed a meta-analysis to assess these issues.

Methods

A systemic search of several databases was conducted for relevant studies evaluating the relationship between legume intake and adenoma risk, with no language restriction, from January 1, 1966, to April 1, 2013.

Results

Three cohort and eleven case control studies with 8,380 cases and a total of 101,856 participants were included in the analysis; the pooled odds ratio (95% confidence interval) for the highest vs. lowest consumption categories was 0.83 (0.75–0.93), with moderate level of heterogeneity (I ² = 25.9% and P = 0.146) based on a random effects model. A decreased risk of adenoma was also observed in most of our subgroup meta-analyses.

Conclusions

Higher intake of legumes significantly reduced the risk of colorectal adenoma in our meta-analysis. Nevertheless, due to possible confounders and bias, further investigations are warranted to confirm this relationship.     

Systematic Study on Genetic and Epimutational Profile of a Cohort of Amsterdam Criteria-Defined Lynch Syndrome in Singapore

Background

Germline defects of mismatch repair (MMR) genes underlie Lynch Syndrome (LS). We aimed to gain comprehensive genetic and epigenetic profiles of LS families in Singapore, which will facilitate efficient molecular diagnosis of LS in Singapore and the region.

Methods

Fifty nine unrelated families were studied. Mutations in exons, splice-site junctions and promoters of five MMR genes were scanned by high resolution melting assay followed by DNA sequencing, large fragment deletions/duplications and promoter methylation in MLH1, MSH2, MSH6 and PMS2 were evaluated by multiplex ligation-dependent probe amplification. Tumor microsatellite instability (MSI) was assessed with five mononucleotide markers and immunohistochemical staining (IHC) was also performed.

Results

Pathogenic defects, all confined to MLH1 and MSH2, were identified in 17 out of 59 (28.8%) families. The mutational spectrum was highly heterogeneous and 28 novel variants were identified. One recurrent mutation in MLH1 (c.793C>T) was also observed. 92.9% sensitivity for indication of germline mutations conferred by IHC surpassed 64.3% sensitivity by MSI. Furthermore, 15.6% patients with MSS tumors harbored pathogenic mutations.

Conclusions

Among major ethnic groups in Singapore, all pathogenic germline defects were confined to MLH1 and MSH2. Caution should be applied when the Amsterdam criteria and consensus microsatellite marker panel recommended in the revised Bethesda guidelines are applied to the local context. We recommend a screening strategy for the local LS by starting with tumor IHC and the hotspot mutation testing at MLH1 c.793C>T followed by comprehensive mutation scanning in MLH1 and MSH2 prior to proceeding to other MMR genes.     

Distinct Gene Expression Signatures in Lynch Syndrome and Familial Colorectal Cancer Type X

Introduction

Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects.

Purpose

We addressed the gene expression signatures in colorectal cancer linked to Lynch syndrome and FCCTX with the aim to identify candidate genes and to map signaling pathways relevant in hereditary colorectal carcinogenesis.

Experimental design

The 18 k whole-genome c-DNA-mediated annealing, selection, extension, and ligation (WG-DASL) assay was applied to 123 colorectal cancers, including 39 Lynch syndrome tumors and 37 FCCTX tumors. Target genes were technically validated using real-time quantitative RT-PCR (qRT-PCR) and the expression signature was validated in independent datasets.

Results

Colorectal cancers linked to Lynch syndrome and FCCTX showed distinct gene expression profiles, which by significance analysis of microarrays (SAM) differed by 2188 genes. Functional pathways involved were related to G-protein coupled receptor signaling, oxidative phosphorylation, and cell cycle function and mitosis. qRT-PCR verified altered expression of the selected genes NDUFA9, AXIN2, MYC, DNA2 and H2AFZ. Application of the 2188-gene signature to independent datasets showed strong correlation to MMR status.

Conclusion

Distinct genetic profiles and deregulation of different canonical pathways apply to Lynch syndrome and FCCTX and key targets herein may be relevant to pursue for refined diagnostic and therapeutic strategies in hereditary colorectal cancer.     

Dietary Total Antioxidant Capacity and Colorectal Cancer in the Italian EPIC Cohort

Background

Colorectal cancer is the third most common cancer worldwide. Diet has been hypothesized as involved in colorectal cancer etiology, but few studies on the influence of total dietary antioxidant intake on colorectal cancer risk have been performed.

Methods

We investigated the association between colorectal cancer risk and the total antioxidant capacity (TAC) of the diet, and also of intake of selected antioxidants, in 45,194 persons enrolled in 5 centers (Florence, Naples, Ragusa, Turin and Varese) of the European Prospective Investigation into Cancer and Nutrition (EPIC) Italy study. TAC was estimated by the Trolox equivalent antioxidant capacity (TEAC) assay. Hazard ratios (HRs) for developing colorectal cancer, and colon and rectal cancers separately, adjusted for confounders, were estimated for tertiles of TAC by Cox modeling, stratifying by center.

Results

Four hundred thirty-six colorectal cancers were diagnosed over a mean follow-up of 11.28 years. No significant association between dietary TAC and colorectal cancer incidence was found. However for the highest category of TAC compared to the lowest, risk of developing colon cancer was lower (HR: 0.63; 95% CI: 0.44–0.89, P trend: 0.008). By contrast, increasing TAC intake was associated with significantly increasing risks of rectal cancer (2nd tertile HR: 2.09; 95%CI: 1.19–3.66; 3rd tertile 2.48 95%CI: 1.32–4.66; P trend 0.007). Intakes of vitamin C, vitamin E, and ß-carotene were not significantly associated with colorectal cancer risk.

Conclusions

Further prospective studies are needed to confirm the contrasting effects of high total antioxidant intake on risk of colon and rectal cancers.     

Metabolic Syndrome and Breast Cancer Risk: A Case-Cohort Study Nested in a Multicentre Italian Cohort

Background

Metabolic syndrome (defined as at least three among abdominal obesity, high blood triglycerides, low high-density lipoprotein cholesterol, high blood glucose, and high blood pressure) is emerging as a risk factor for breast cancer; however few studies – most confined to postmenopausal women – have investigated associations between breast cancer risk and metabolic syndrome. The purpose of this study was to examine the association between metabolic syndrome and its components, and risk of breast cancer in postmenopausal and premenopausal women.

Methods

We performed a case-cohort study on 22,494 women recruited in 1993-1998 to four Italian centres (Turin, Varese, Naples, Ragusa) of the European Prospective Investigation into Cancer and Nutrition (EPIC) and followed-up for up to 15 years. A random subcohort of 565 women was obtained and 593 breast cancer cases were diagnosed. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Prentice-weighted Cox proportional hazards models.

Results

Presence of metabolic syndrome was associated with significantly increased breast cancer risk in all women (HR 1.52, 95%CI 1.14-2.02). When the analyses were repeated separately for menopausal status, the association was limited to postmenopausal women (HR 1.80, 95%CI 1.22-2.65) and absent in premenopausal women (HR 0.71, 95%CI 0.43-1.16); P for interaction between metabolic syndrome and menopausal status was 0.001. Of metabolic syndrome components, only high blood glucose was significantly associated with increased breast cancer risk in all women (HR 1.47, 95%CI 1.13-1.91) and postmenopausal women (HR 1.89, 95%CI 1.29-2.77), but not premenopausal women (HR 0.80, 95%CI 0.52-1.22; P interaction=0.004).

Conclusions

These findings support previous data indicating that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women, but not in premenopausal women, and suggest that prevention of metabolic syndrome through lifestyle changes could confer protection against breast cancer.     

Risk of Dementia in Patients with Insomnia and Long-term Use of Hypnotics: A Population-based Retrospective Cohort Study

Background

Hypnotics have been reported to be associated with dementia. However, the relationship between insomnia, hypnotics and dementia is still controversial. We sought to examine the risk of dementia in patients with long-term insomnia and the contribution of hypnotics.

Methods

Data was collected from Taiwan’s Longitudinal Health Insurance Database. The study cohort comprised all patients aged 50 years or older with a first diagnosis of insomnia from 2002 to 2007. The comparison cohort consisted of randomly selected patients matched by age and gender. Each patient was individually tracked for 3 years from their insomnia index date to identify whether the patient had a first diagnosis of dementia. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

We identified 5693 subjects with long-term insomnia and 28,465 individuals without. After adjusting for hypertension, diabetes mellitus, hyperlipidemia, and stroke, those with long-term insomnia had significantly higher risks of dementia (HR, 2.34; 95% CI, 1.92–2.85). Patients with long-term insomnia and aged 50 to 65 years had a higher increased risk of dementia (HR, 5.22; 95% CI, 2.62–10.41) than those older than 65 years (HR, 2.33; 95% CI, 1.90–2.88). The use of hypnotics with a longer half-life and at a higher prescribed dose predicted a greater increased risk of dementia.

Conclusions

Patients with long-term use of hypnotics have more than a 2-fold increased risk of dementia, especially those aged 50 to 65 years. In addition, the dosage and half-lives of the hypnotics used should be considered, because greater exposure to these medications leads to a higher risk of developing dementia.     

Trend of Cardio-Metabolic Risk Factors in Polycystic Ovary Syndrome: A Population-Based Prospective Cohort Study

Objective

To see the changes of cardio-metabolic risk factors overtime in polycystic ovary syndrome vs. control women.

Methods

This study was conducted on 637 participants (85 PCOS and 552 control reproductive aged, 18–45 years) of Tehran Lipid and Glucose Study (TLGS), an ongoing population-based cohort study with 12 years of follow-up. The cardiovascular risk factors of these groups were assessed in three-year intervals using standard questionnaires, history taking, anthropometric measures, and metabolic/endocrine evaluation. Generalized estimating equation was used to analyze the data.

Results

Overall mean of insulin (3.55, CI: 0.66–6.45), HOMA-IR (0.63, CI: 0.08–1.18), and HOMA-β (45.90, CI: 0.86–90.93) were significantly higher in PCOS than in healthy women after adjustment for age, BMI, and baseline levels. However, the negative interaction (follow-up years × PCOS status) of PCOS and normal women converged overtime. Comparing third follow-up with first, insulin and HOMA-IR decreased 10.6% and 5%, respectively in PCOS women; and increased 6.7% and 14.6%, respectively in controls (P<0.05). The results did not show any significant result for other cardio-metabolic variables including WC, lipid profile, FPG, 2-h PG, SBP, and DBP.

Conclusion

While the insulin level and insulin resistance rate were higher in reproductive aged PCOS than in healthy women, the difference of these risk factors decreased overtime. Thus, the metabolic consequences of PCOS women in later life may be lower than those initially anticipated.     

Risk of Psychiatric Disorders following Polycystic Ovary Syndrome: A Nationwide Population-Based Cohort Study

Background

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. A higher prevalence of psychiatric comorbidities, including depressive disorder, anxiety disorder, and bipolar disorder has been proved in patients with PCOS. However, a clear temporal causal relationship between PCOS and psychiatric disorders has not been well established.

Objective

We explored the relationship between PCOS and the subsequent development of psychiatric disorders including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder.

Methods

We identified patients who were diagnosed with PCOS by an obstetrician-gynecologist in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without PCOS who were matched according to age and sex. The occurrence of subsequent new-onset psychiatric disorders was evaluated in both cohorts based on diagnoses made by psychiatrists.

Results

The PCOS cohort consisted of 5431 patients, and the comparison cohort consisted of 21,724 matched control patients without PCOS. The incidence of depressive disorder (hazard ratio [HR] 1.296, 95% confidence interval [CI] 1.084–.550), anxiety disorder (HR 1.392, 95% CI 1.121–1.729), and sleep disorder (HR 1.495, 95% CI 1.176–1.899) were higher among the PCOS patients than among the patients in the comparison cohort. In addition, a higher incidence of newly diagnosed depressive disorder, anxiety disorder, and sleep disorder remained significantly increased in all of the stratified follow-up durations (0–1, 1–5, ≥5 y).

Conclusions

PCOS might increase the risk of subsequent newly diagnosed depressive disorder, anxiety disorder, and sleep disorder. The risk of newly diagnosed bipolar disorder, which has often been reported in the literature to be comorbid with PCOS, was not significantly elevated.     

Genetic Variation in the Base Excision Repair Pathway,Environmental Risk Factors,and Colorectal Adenoma Risk

Cigarette smoking, high alcohol intake, and low dietary folate levels are risk factors for colorectal adenomas. Oxidative damage caused by these three factors can be repaired through the base excision repair pathway (BER). We hypothesized that genetic variation in BER might modify colorectal adenoma risk. In a sigmoidoscopy-based study, we examined associations between 182 haplotype tagging SNPs in 14 BER genes, and colorectal adenoma risk, and examined their potential role as modifiers of the effect cigarette smoking, alcohol intake, and dietary folate levels. Among all individuals, no statistically significant associations between BER SNPs and adenoma risk persisted after correction for multiple comparisons. However, among Asian-Pacific Islanders we observed two SNPs in FEN1 and one in NTHL1, and among African-Americans one SNP in APEX1 that were associated with colorectal adenoma risk. Significant associations were also observed between SNPs in the NEIL2 gene and rectal adenoma risk. Three SNPS modified the effect of smoking (MUTYH interaction p = 0.002; OGG1 interaction p = 0.013); FEN1 interaction p = 0.013)), one SNP in LIG3 modified the effect of alcohol consumption (interaction p = 0.024) and two SNPs in LIG3 modified the effect of dietary folate (interaction p = 0.001 and p = 0.08) on colorectal adenoma risk. These findings support a role for genetic variants in the BER pathway as potential modifiers of colorectal adenoma risk. Our findings strengthen the role of oxidative damage induced by key lifestyle and dietary risk factors in colorectal adenoma formation.     

Environmental Contaminants in the Botanical Dietary Supplement Ginseng and Potential Human Risk

Botanical dietary supplements have a long history of use in Europe and Asia, but the use of these products is becoming increasing popular in the United States. Because these products are classified as dietary supplements, the U.S. Food and Drug Administration does not routinely monitor them for environmental contaminants. Ginseng served as a model botanical dietary supplement and was purchased from suppliers in the United States, Europe, and Asia. Samples were analyzed for metals (e.g., cadmium, nickel) and chlorinated pesticides (e.g., PCNB, DDT, and metabolites). Flame and furnace atomic absorption spectrophotometry were utilized for analysis of metals, while gas chromatography (GC) and GC-mass spectrophotometry were utilized for analysis of chlorinated pesticides. Because no formalized guidelines exist to determine risk of botanical dietary supplements, U.S. Environmental Protection Agency guidelines for protection of human health were used. Metals and chlorinated organics were found in Ginseng samples, but the concentrations posed no noncarcinogenic hazard; however, a 1000?mg/d dose for 350?d/yr resulted in 1 × 10^?6 carcinogenic risk in 19% of the Ginseng samples analyzed. At a lower usage rate (42?d/yr), no samples exceeded 1 × 10^?6 risk. Chlorinated organics, such as aldrin and heptachlor epoxide, accounted for the carcinogenic risk (1 X 10-6) in the Ginseng samples.     

Obesity,Metabolic Syndrome and Risk of Atrial Fibrillation: A Swedish,Prospective Cohort Study

AimWe aimed to investigate whether different measures of obesity could similarly predict atrial fibrillation, and whether the atrial fibrillation risk associated with obesity is dependent on presence of metabolic syndrome.ResultsDuring a mean follow-up of 13.6 years, 285 incident atrial fibrillation cases were recorded. One standard deviation increment of each obesity measure was associated with increased atrial fibrillation risk as: body mass index 1.25 (1.12 – 1.40), waist circumference 1.35 (1.19 – 1.54) and sagittal abdominal diameter 1.28 (1.14 – 1.44). Compared to normal weight subjects without metabolic syndrome, increased atrial fibrillation risk was noted for overweight subjects with metabolic syndrome, 1.67 (1.16 – 2.41), obese subjects without metabolic syndrome, 1.75 (1.11 – 2.74) and obese subjects with metabolic syndrome, 1.92 (1.34 – 2.74). Compared to subjects with normal waist circumference without metabolic syndrome, subjects with elevated waist circumference and metabolic syndrome suffered increased atrial fibrillation risk, 2.03 (1.44 – 2.87).ConclusionsBody mass index, waist circumference and sagittal abdominal diameter could similarly predict atrial fibrillation. Obesity was associated with an increased atrial fibrillation risk regardless of metabolic syndrome, whereas overweight and elevated waist circumference was associated with increased atrial fibrillation risk only if metabolic syndrome was present.     

The Risk of Asthma in Patients with Ankylosing Spondylitis: A Population-Based Cohort Study

BackgroundThe relationship between asthma and ankylosing spondylitis (AS) is controversial. We examined the risk of asthma among AS patients in a nationwide population.MethodsWe conducted a retrospective cohort study using data from the National Health Insurance (NHI) system of Taiwan. The cohort included 5,974 patients newly diagnosed with AS from 2000 to 2010. The date of diagnosis was defined as the index date. A 4-fold of general population without AS was randomly selected frequency matched by age, gender and the index year. The occurrence and hazard ratio (HR) of asthma were estimated by the end of 2011.ResultsThe overall incidence of asthma was 1.74 folds greater in the AS cohort than in the non-AS cohort (8.26 versus 4.74 per 1000 person-years) with a multivariable Cox method measured adjusted HR of 1.54 (95% confidence interval (CI), 1.34–1.76). The adjusted HR of asthma associated with AS was higher in women (1.59; 95% CI, 1.33–1.90), those aged 50–64 years (1.66; 95% CI, 1.31–2.09), or those without comorbidities (1.82; 95% CI, 1.54–2.13).ConclusionPatients with AS are at a higher risk of developing asthma than the general population, regardless of gender and age. The pathophysiology needs further investigation.     

Increased Risk of Acute Coronary Syndrome among Patients with Urinary Stone Disease: A Nationwide Population-Based Cohort Study

Background/Objectives

Urinary stones (US) are associated with systemic metabolic and endocrine disorders that share risk factors typically associated with acute coronary syndrome (ACS).

Methods

For this investigation, 30 142 patients with US were set as the research group, and 121 768 randomly selected patients were set as the comparison group through frequency matching by age, sex, and index year. Each patient was individually tracked to identify those who developed ACS during the follow-up period. Cox proportional hazards regression and the Kaplan-Meier method were adopted to calculate the hazard ratios of ACS risk and plot the survival curve.

Results

Overall, 275 (13.4 per 10 000 person-y) and 736 events (9.1 per 10 000 person-y) were observed among patients in the research and comparison cohorts, respectively. The patients with US had a substantially lower ACS-free survival rate compared with that of the patients in the comparison cohort (P<.001). After adjusting for potential risk factors, the patients with US were observed to have a 1.22-fold higher risk of ACS compared with patients in the comparison cohort (95% confidence interval = 1.05–1.40, P<.001), particularly among younger patients.

Conclusions

The results indicate that US is associated with increased risk of developing ACS, particularly among young (≤49 years) and male adults. Future studies should examine the possible mechanisms of US-related ACS morbidity by conducting multicenter recruitment and measurements of laboratory data.     

A Snack Dietary Pattern Increases the Risk of Hypercholesterolemia in Northern Chinese Adults: A Prospective Cohort Study

The evidence about the effect of dietary patterns on blood cholesterol from cohort studies was very scarce. The study was to identify the association of dietary patterns with lipid profile, especially cholesterol, in a cohort in north China. Using a 1-year food frequency questionnaire, we assessed the dietary intake of 4515 adults from the Harbin People’s Health Study in 2008, aged 20-74 years. Principle component analysis was used to identify dietary patterns. The follow-up was completed in 2012. Fasting blood samples were collected for the determination of blood lipid concentrations. Logistic regression models were used to evaluate the association of dietary patterns with the incidence of hypercholesterolemia, hypertriglyceridemia, and low-HDL cholesterolemia. Five dietary patterns were identified (“staple food”, “vegetable, fruit and milk”, “potato, soybean and egg”, “snack”, and “meat”). The relative risk (RR) between the extreme tertiles of the snack dietary pattern scores was 1.72 (95% CI = 1.14, 2.59, P = 0.004) for hypercholesterolemia, 1.39 (1.13, 1.75, P = 0.036) for hypertriglyceridemia, after adjustment for age, sex, education, body mass index, smoking, alcohol consumption, energy intake, exercise and baseline lipid concentrations. There was a significant positive association between the snack dietary pattern scores and fasting serum total cholesterol (SRC (standardized regression coefficient) = 0.262, P = 0.025), LDL-c (SRC = 0.324, P = 0.002) and triglycerides (SRC = 0.253, P = 0.035), after adjustment for the multiple variables above. Moreover, the adjusted RR of hypertriglyceridemia between the extreme tertiles was 0.73 (0.56, 0.94, P = 0.025) for the vegetable, fruit and milk dietary pattern, and 1.86 (1.33, 2.41, P = 0.005) for the meat dietary pattern. The snack dietary pattern was a newly emerged dietary pattern in northern Chinese adults. It appears conceivable that the risk of hypercholesterolemia can be reduced by changing the snack dietary pattern.