Association between Variants in Atopy-Related Immunologic Candidate Genes and Pancreatic Cancer Risk.

BACKGROUND: Many epidemiology studies report that atopic conditions such as allergies are associated with reduced pancreas cancer risk. The reason for this relationship is not yet understood. This is the first study to comprehensively evaluate the association between variants in atopy-related candidate genes and pancreatic cancer risk. METHODS: A population-based case-control study of pancreas cancer cases diagnosed during 2011-2012 (via Ontario Cancer Registry), and controls recruited using random digit dialing utilized DNA from 179 cases and 566 controls. Following an exhaustive literature review, SNPs in 180 candidate genes were pre-screened using dbGaP pancreas cancer GWAS data; 147 SNPs in 56 allergy-related immunologic genes were retained and genotyped. Logistic regression was used to estimate age-adjusted odd ratio (AOR) for each variant and false discovery rate was used to adjust Wald p-values for multiple testing. Subsequently, a risk allele score was derived based on statistically significant variants. RESULTS: 18 SNPs in 14 candidate genes (CSF2, DENND1B, DPP10, FLG, IL13, IL13RA2, LRP1B, NOD1, NPSR1, ORMDL3, RORA, STAT4, TLR6, TRA) were significantly associated with pancreas cancer risk. After adjustment for multiple comparisons, two LRP1B SNPs remained statistically significant; for example, LRP1B rs1449477 (AA vs. CC: AOR=0.37, 95% CI: 0.22-0.62; p (adjusted)=0.04). Furthermore, the risk allele score was associated with a significant reduction in pancreas cancer risk (p=0.0007). CONCLUSIONS: Preliminary findings suggest certain atopy-related variants may be associated with pancreas cancer risk. Further studies are needed to replicate this, and to elucidate the biology behind the growing body of epidemiologic evidence suggesting allergies may reduce pancreatic cancer risk.

Association between allergies and risk of pancreatic cancer.

BACKGROUND: Less than 10% of pancreatic cancer cases survive 5 years, yet its etiology is not well understood. Studies suggest allergies are associated with reduced pancreatic cancer risk. Our study collected additional information on allergies (including skin prick test results and differentiation of allergic/nonallergic asthma), and is the first to assess possible confounding by allergy medications. METHODS: A population-based case-control study was designed to comprehensively assess the association between allergy and pancreatic cancer risk. Pancreas cancer cases were diagnosed during 2011 to 2012, and identified through the Ontario Cancer Registry (345 cases). Population-based controls were identified using random digit dialing and age/sex frequency matched to cases (1,285 controls). Questionnaires collected lifetime allergy history (type of allergy, age at onset, skin prick testing results), allergy medications, and established pancreas cancer risk factors. Logistic regression was used to estimate odd ratios and test potential confounders, including allergy medications. RESULTS: Hay fever was associated with a significant reduction in pancreatic cancer risk [AOR = 0.68; 95% confidence intervals (CI), 0.52-0.89], and reduction was greatest for those whose skin prick test was positive for hay fever allergens. No particular patterns were observed as regards age at onset and duration of allergy. Positive dust/mold allergy skin prick test and animal allergies were associated with a statistically significant reduced pancreatic cancer risk; AOR = 0.49; 95% CI, 0.31-0.78 and AOR = 0.68; 95% CI, 0.46-0.99, respectively. Asthma was not associated with pancreatic cancer risk. CONCLUSIONS/IMPACT: These findings support the growing body of evidence that suggests certain allergies are associated with reduced pancreatic cancer risk.

High coffee intake, but not caffeine, is associated with reduced estrogen receptor negative and postmenopausal breast cancer risk with no effect modification by CYP1A2 genotype.

Associations between caffeine and coffee consumption and breast cancer risk are uncertain, with studies suggesting inverse and null associations. Variation in cytochrome P450 1A2 (CYP1A2), a gene responsible for caffeine metabolism, may modify these associations. Cases (n = 3,062) were recruited through the Ontario Cancer Registry and controls (n = 3,427) through random digit dialing. Logistic regression was used to evaluate associations between breast cancer risk and intakes of 7 caffeine-containing items and total caffeine, and examine whether a genetic variant in CYP1A2 (rs762551) modified these associations. Analyses were stratified by estrogen receptor (ER), menopausal, and smoking status. Generally, coffee and caffeine were not associated with breast cancer risk; however, a significant reduction in risk was observed with the highest category of coffee consumption [≥5 cups per day vs. never, multivariate-adjusted odds ratio (MVOR) = 0.71, 95% confidence interval (CI): 0.51, 0.98]. Variant rs762551 did not modify associations. In stratified analyses, high coffee intake was associated with reduced risk of ER- (MVOR = 0.41, 95% CI: 0.19, 0.92) and postmenopausal breast cancer (MVOR = 0.63, 95% CI: 0.43, 0.94). High coffee consumption, but not total caffeine, may be associated with reduced risk of ER- and postmenopausal breast cancers, independent of CYP1A2 genotype. Further studies are needed to replicate these findings.

Association between allergies, asthma, and breast cancer risk among women in Ontario, Canada.

PURPOSE: To investigate the association between allergies, asthma, and breast cancer risk in a large, population-based case-control study. METHODS: Breast cancer cases (n = 3,101) were identified using the Ontario Cancer Registry and population controls (n = 3,471) through random digit dialing. Self-reported histories of allergies, hay fever, and asthma were collected by questionnaire. Logistic regression was used to assess associations between breast cancer risk and history of allergy/hay fever and asthma, with 16 possible confounders examined. Analyses were stratified by menopausal status. RESULTS: A history of allergies or hay fever was associated with a small reduction in breast cancer risk [age-adjusted odds ratio (AOR) = 0.86, 95 % confidence interval (CI) 0.77-0.96] and did not differ by menopausal status. Asthma was not associated with breast cancer risk overall; however, among premenopausal women, asthma was associated with a reduced risk of breast cancer (AOR = 0.72, 95 % CI 0.54-0.97). CONCLUSIONS: A history of allergies may be associated with a modest reduction in breast cancer risk. Asthma does not appear to be associated with breast cancer risk overall; however, asthma may be associated with reduced breast cancer risk among premenopausal women.

Consumption of flaxseed, a rich source of lignans, is associated with reduced breast cancer risk.

PURPOSE: To investigate the association between intake of flaxseed-the richest source of dietary lignans (a class of phytoestrogens)-and breast cancer risk. METHODS: A food frequency questionnaire was used to measure the consumption of flaxseed and flax bread by 2,999 women with breast cancer and 3,370 healthy control women who participated in the Ontario Women's Diet and Health Study (2002-2003). Logistic regression was used to investigate associations between consumption of flaxseed and flax bread and breast cancer risk. Confounding by established and suspected breast cancer risk factors, as well as dietary factors, was assessed. RESULTS: Flaxseed or flax bread was consumed at least weekly by 21 % of control women. None of the 19 variables assessed were identified as confounders of the associations between flaxseed or flax bread and breast cancer risk. Consumption of flaxseed was associated with a significant reduction in breast cancer risk (odds ratio (OR) = 0.82, 95 % confidence interval (CI) 0.69-0.97), as was consumption of flax bread (OR = 0.77, 95 % CI 0.67-0.89). CONCLUSIONS: This Canadian study is, to our knowledge, the first to report on the association between flaxseed alone and breast cancer risk and has found that flaxseed intake is associated with a reduction in breast cancer risk. As dietary intake of flaxseed is modifiable, this finding may be of public health importance with respect to breast cancer prevention.

Effectiveness and cost-effectiveness of pediatric rotavirus vaccination in British Columbia: a model-based evaluation.

BACKGROUND: Rotavirus gastroenteritis (RVGE) is associated with widespread morbidity and mortality in children worldwide. In high-income countries, including Canada, the burden of RVGE relates largely to morbidity and healthcare utilization. Two live rotavirus vaccines (RotaTeq(®) (Merck Frosst Canada Ltd.) and Rotarix™ (GlaxoSmithKline Inc.)), are now approved for use in Canada, but their economic attractiveness has not been evaluated in the Canadian context. METHODS: We performed a model-based economic analysis using a Markov chain Monte Carlo simulation of RVGE in populations of British Columbia children. Models were parameterized based on best available data on disease natural history and epidemiology, vaccine effectiveness and cost, and healthcare costs, and calibrated such that projections of healthcare utilization and vaccine coverage closely matched empirical estimates. Robustness of projections was evaluated in deterministic and probabilistic sensitivity analyses. RESULTS: Based on the best available data, childhood immunization against RVGE was projected to prevent 63-81 infections per 100 children vaccinated, and to prevent substantial numbers of outpatient medical visits. It was projected that either vaccine would prevent 1-2 hospitalizations per 100 children immunized. Vaccination was projected to increase healthcare costs: immunization with Rotarix™ would prevent incident infections at a cost of approximately $10 per infection prevented or $2400 per quality-adjusted life-year gained. Vaccination with RotaTeq™ would be more costly and less effective and would not be preferred. Projections were robust in the face of wide-ranging sensitivity analyses. INTERPRETATION: The use of currently available vaccines against RVGE in British Columbia children is projected to result in a substantial reduction in the burden of illness and healthcare utilization associated with RVGE, with a modest increase in healthcare costs. RVGE vaccination should be considered "highly cost-effective" relative to other commonly available health interventions.

The social determinants of health and pandemic H1N1 2009 influenza severity.

OBJECTIVES: We explored the effects of social determinants of health on pandemic H1N1 2009 influenza severity and the role of clinical risk factors in mediating such associations. METHODS: We used multivariate logistic regression with generalized estimating equations to examine the associations between individual- and ecological-level social determinants of health and hospitalization for pandemic H1N1 2009 illness in a case-control study in Ontario, Canada. RESULTS: During the first pandemic phase (April 23-July 20, 2009), hospitalization was associated with having a high school education or less and living in a neighborhood with high material or total deprivation. We also observed the association with education in the second phase (August 1-November 6, 2009). Clinical risk factors for severe pandemic H1N1 2009 illness mediated approximately 39% of the observed association. CONCLUSIONS: The main clinical risk factors for severe pandemic H1N1 2009 illness explain only a portion of the associations observed between social determinants of health and hospitalization, suggesting that the means by which the social determinants of health affect pandemic H1N1 2009 outcomes extend beyond clinically recognized risk factors.

The consequences of waiting for cataract surgery: a systematic review.

BACKGROUND: Cataract surgery is the most common operative procedure performed in Canada, and how patients are affected by wait times for this surgery has important clinical, public health and health policy considerations. We conducted a systematic review to understand the relation between wait time for cataract surgery and patient outcomes and the variables that modify this relation. METHODS: We performed an electronic search of 11 databases and the proceedings of 4 conferences. The search was restricted to studies published after the transition to phacoemulsification (1990). We assessed the quality of the included studies using the Jadad Scale for randomized controlled trials and the Newcastle-Ottawa Scale for cohort and case-control studies. The data were found to be inappropriate for meta-analysis, thus we performed a qualitative synthesis. RESULTS: We found a total of 27 studies that met our inclusion criteria. When these studies were reviewed, a dichotomy was observed for the wait time-outcome relation: outcomes associated with wait times of or= 6 months. Patients who waited more than 6 months to receive cataract surgery experienced more vision loss, a reduced quality of life and had an increased rate of falls compared with patients who had wait times of less than 6 weeks. The outcomes associated with wait times between 6 weeks and 6 months remain unclear. INTERPRETATION: Patients who wait more than 6 months for cataract surgery may experience negative outcomes during the wait period, including vision loss, a reduced quality of life and an increased rate of falls.

Evidence for the effect of omega-3 fatty acids on progression of age-related macular degeneration: a systematic review.

BACKGROUND: As part of a larger systematic review on the effect of omega-3 fatty acids on eye health, the aim of this report was to appraise and synthesize the evidence for the effects of omega-3 fatty acids in slowing down the progression of age-related macular degeneration (AMD) and/or decreasing the rate of progression to advanced forms of AMD. METHODS: A comprehensive search was undertaken in six databases (MEDLINE, PreMEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CAB Health, and Dissertation Abstracts). RESULTS: Two unique studies, one randomized clinical trial (RCT) and one prospective cohort study, satisfied the eligibility criteria and were included in the review. The RCT reported evidence on the effect of omega-3 fatty acids in slowing down the progression of AMD. The prospective cohort study addressed the question: what is the evidence that omega-3 fatty acids decrease the rate of progression to advanced forms of AMD? CONCLUSIONS: Clinical research on this topic is scarce. Only two studies were eligible to be included in this review. Although one study result indicated efficacy of preventing AMD progression to its advanced form, this result needs to be duplicated and supported by future research.

The evidence for efficacy of omega-3 fatty acids in preventing or slowing the progression of retinitis pigmentosa: a systematic review.

BACKGROUND: Studies in preterm and term human infants have suggested that a dietary supply of omega-3 fatty acids is essential for optimal visual development. Several basic science studies support the hypothesis that omega-3 fatty acids may be useful therapeutic agents for pathologies of the retina and lens. As part of a systematic review of the effect of omega-3 fatty acids on eye health, the purpose of this study was to conduct a systematic review of the scientific-medical literature to appraise and synthesize the evidence for the effects of omega-3 fatty acids in preventing the development or progression of retinitis pigmentosa. METHODS: A comprehensive search was undertaken in MEDLINE, PREMEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Global Health, and Dissertation Abstracts. Unpublished literature was sought through manual searches of reference lists of included studies and key review articles and from the files of content experts. Searches were not restricted by language of publication, publication type, or study design. Eligibility criteria were applied to screen eligible studies on two levels. Data extraction and quality assessment were performed. RESULTS: Six studies published between 1995 and 2004 met eligibility criteria in investigating the question of the possible value of omega-3 fatty acids in slowing the progression of retinitis pigmentosa. Meta-analysis was not performed because there was not enough available information for formal quantitative analysis. INTERPRETATION: There are trends in improvement of some retinitis pigmentosa outcomes with omega-3 fatty acids in the higher quality studies. Clinical research is preliminary in this field, however. Accordingly, definitive answers will require significantly more observational and interventional clinical research.

Efficacy of omega-3 fatty acids in preventing age-related macular degeneration: a systematic review.

TOPIC: What is the evidence for efficacy of dietary and/or supplemental omega-3 fatty acids in preventing age-related macular degeneration (AMD)? CLINICAL RELEVANCE: Age-related macular degeneraion is the leading cause of blindness and vision impairment in persons older than 50 years living in North America. There is no cure for AMD, and treatment does not usually restore vision but only prevents disease progression to a modest degree. omega-3 fatty acids are considered potentially important antioxidants and are being considered as an arm of the Age-Related Eye Disease Study II clinical trial. METHODS/LITERATURE REVIEWED: Keywords were searched in Medline, Pre-Medline, Embase, and the Cochrane Library on Ovid. There was no restriction on the year or language of publication. RESULTS: There were 6 observational studies found, but the specific outcomes, exposures, and covariates studied all varied greatly. CONCLUSION: There is some clinical evidence for protection of AMD from omega-3 fatty acids. However, the results are not consistent. Hence, our conclusion is that this issue is neither clearly supported nor refuted by the present world literature. This is an intriguing and extremely important question but needs further study first with prospective cohort designs and, if positive, randomized clinical trials.