Asthma,allergy and the risk of prostate cancer: Results from the Montreal PROtEuS study

BackgroundThe few previous studies examining the association between asthma or allergy and prostate cancer (PCa) risk were inconclusive. This study aimed to evaluate these associations, and to explore in details the possible influence of current versus former allergic condition, age at onset, time since onset, and duration of each allergic condition.MethodsDetailed information on self-reported asthma and allergy was collected in the context of a large population-based case–control study conducted in Montreal, Canada. Study subjects included 1936 cases, diagnosed between 2005 and 2009, and 1995 population controls. Unconditional multivariate logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for age, ancestry and familial history of prostate cancer.ResultsThe ORs were 1.11 (95% CI: 0.89–1.40) and 0.98 (95% CI: 0.84–1.14) for ever reporting of asthma and allergy, respectively. These ORs did not substantially vary according to status (former or current), age at onset, time since onset, and duration of each allergic condition. PCa screening was not associated with allergic diseases reporting.ConclusionsOverall, our findings are in line with the absence of an association between a history of asthma or allergy, and PCa risk.     

Carotenoids and cardiovascular disease: what research gaps remain?

PURPOSE OF REVIEW: Dietary and blood carotenoids, including alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, and beta-cryptoxanthin, have been examined in a number of epidemiological studies in recent years for the risk of cardiovascular disease. This review assimilated the existing and recent literature on carotenoids and cardiovascular disease and considered what research gaps may remain. RECENT FINDINGS: Numerous large cohort studies have been published in largely American men and women that have examined dietary intake or blood levels of total or individual carotenoids with the risk of various cardiovascular endpoints. Overall, early, promising results have grown increasingly inconsistent over time. More recently, studies examining lycopene and lutein/zeaxanthin have offered more promising data on a possible, but not yet established, inverse association with the risk of cardiovascular disease. Recent epidemiological data on beta-cryptoxanthin and cardiovascular disease are lacking. Primary and secondary prevention trials have extensively examined beta-carotene, but not other carotenoids, for the risk of cardiovascular disease as either the primary or secondary endpoint with largely null results. More recent studies have focused on individual carotenoids in relation to cardiovascular disease and require a more careful evaluation of potential mechanisms of effect. SUMMARY: The promise of early epidemiological studies on carotenoids and cardiovascular disease paved the way to largely disappointing results from several large prevention trials of beta-carotene. Emerging recent evidence of potential cardioprotective effects for lycopene and other carotenoids besides beta-carotene in the diet and blood suggest that there is more to be learned in the story of carotenoids and both atherosclerotic progression and clinically manifested cardiovascular disease.     

Epidemiology of musculoskeletal disorders among computer users: lesson learned from the role of posture and keyboard use.

Reports in the scientific literature and lay press have suggested that computer users are at increased risk of upper extremity musculoskeletal disorders (MSDs). Early studies often found elevated rates of MSD outcomes among keyboard users when compared to non-users. Attention soon focused on specific aspects of keyboard work that might be responsible for the observed rate increase. In this review, the epidemiological evidence examining associations between MSD outcomes and computer user posture and keyboard use intensity (hours of computer use per day or per week) are examined. Results of epidemiological studies of posture and MSD outcomes have not been entirely consistent. Reasons for the inconsistency in results include cross-sectional study design (with possible failure to assure that measured exposure preceded health effect), imprecision of posture measures used, and difficulties involved in analyzing multiple related variables. Despite the inconsistencies, it appears from the literature that posture is an independent risk factor of modest magnitude for MSDs among computer users. It appears that lowering the height of the keyboard to or below the height of the elbow and resting the arms on the desk surface or chair armrests is associated with reduced risk of neck and shoulder MSDs. Results of epidemiological studies examining computer use (hours keying per day or per week) are more consistent than those examining posture, although some inconsistency is observed. Reasons for the inconsistency include possible selective survival bias resulting from cross-sectional study design, differences in exposure categorization, and possible interaction with other exposure variables. Overall, the literature shows that daily or weekly hours of computer use is more consistently associated with hand and arm MSDs than with neck and shoulder MSDs.     

Inverse Immunological Responses Induced by Allergic Rhinitis and Head and Neck Squamous Cell Carcinoma

Several epidemiological studies have investigated the relation between allergy and cancer with contradicting conclusions, and reports on immunological differences are scarce. By focusing on inflammation, the present study was designed to compare the immune response induced by allergic rhinitis (AR) and head and neck squamous cell carcinoma (HNSCC). Blood and serum was obtained from patients with symptomatic seasonal AR, and newly detected HNSCC, as well as healthy controls. Peripheral blood mononuclear cells (PBMC) and polymorphonuclear leukocytes (PMN) were isolated and cultured with or without the toll-like receptor ligands, Pam₃CSK₄, LPS, R837, and CpG. Cellular activation and cytokine release were assessed with ELISA, Luminex Multiplex Immunoassay, flow cytometry, and real-time RT-PCR. Sera from HNSCC patients showed elevated levels of innate immune cytokines, and exhibited a response profile consistent with an increased innate immune reaction. In contrast, sera and stimulated PBMC from AR patients displayed increased concentrations of T cell related cytokines, consistent with an adaptive immune response. The presented data demonstrate that AR and HNSCC induce two distinct immunological processes, indicating an inverse association between the immunological responses seen in patients with allergy and cancer of the upper airway.     

Association between family cancer history and risk of pancreatic cancer

PurposeFamily history of pancreatic adenocarcinoma is an established risk factor for the disease. However, associations of pancreatic cancer with other familial cancers are less clear. We analyzed data from the Queensland Pancreatic Cancer Study (QPCS), an Australian population-based case-control study, to investigate associations between family history of various cancer types and risk of pancreatic cancer.Materials and methodsOur study included 591 pancreatic cancer patients and 646 controls, all of whom self-reported the histories of cancer in their first-degree relatives. We used logistic regression to estimate adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Based on our results, we conducted a systematic literature review using the Medline (OVID) database to identify articles pertaining to the association between family history of melanoma and risk of pancreatic cancer. A meta-analysis including associations in five published studies, unpublished results from a study co-author and the QPCS results was then performed using the DerSimonian and Laird random-effects model.ResultsCases were more likely than controls to report a family history of pancreatic cancer (OR 2.20, 95% CI 1.16–4.19) and melanoma (OR 1.74, 95% CI 1.03–2.95), but not of breast, ovarian, respiratory, other gastrointestinal or prostate cancer. Meta-analysis of melanoma family history and pancreatic cancer risk yielded an OR of 1.22 (95% CI 1.00–1.51).ConclusionsOur results yield further evidence of increased risk of pancreatic cancer in those with family histories of the disease. We also provide suggestive evidence of an association between family history of melanoma and risk of pancreatic cancer.     

Dietary fats and cancer

The present review addresses the evidence for a possible link between dietary fat and cancer. International comparisons suggest that a high-fat diet may increase cancer risk, and this hypothesis is supported by animal experiments. However, epidemiological studies within populations show little or inconsistent associations. Taken together, the available evidence for a relation between dietary fat and cancer is weak.     

Insulin resistance and its contribution to colon carcinogenesis

The insulin resistance-colon cancer hypothesis, stating that insulin resistance may be associated with the development of colorectal cancer, represents a significant advance in colon cancer, as it emphasizes the potential for this cancer to become a modifiable disease. The fact that the incidence of insulin resistance has been increasing in the United States and much of the rest of the Western world where colon cancer remains the second leading cause of cancer death makes the exploration of the interrelationship of these conditions a subject of high priority. Here, we review the salient features of insulin resistance, defined as impaired biological response to the action of insulin. Recent epidemiological studies, evaluating potential associations between colon cancer risk and diabetes mellitus, dietary intake and metabolic factors, and IGF levels in several clinical settings, provide strong support of the insulin resistance-colon cancer hypothesis (without establishing causality). Mechanistically, insulin resistance has been associated with hyperinsulinemia, increased levels of growth factors including IGF-1, and alterations in NF-kappaB and peroxisome proliferator-activated receptor signaling, which may promote colon cancer through their effects on colonocyte kinetics. It is a reasonable expectation that in the not too distant future, critical interventions to the already mapped molecular sequence of events, which link two apparently disparate entities, combined with lifestyle changes could abrogate the development of colon cancer.     

DNA adducts as markers of exposure and risk

Many carcinogens exert their biological effects through the formation of DNA adducts by metabolically activated intermediates. Detecting the presence of DNA adducts in human tissues is, therefore, a tool for molecular epidemiological studies of cancer. A large body of evidence demonstrates that DNA adducts are useful markers of carcinogen exposure, providing an integrated measurement of carcinogen intake, metabolic activation, and delivery to the target macromolecule in target tissues. Monitoring accessible surrogate tissues, such as white blood cells, also provides a means of investigating occupational or environmental exposure in healthy individuals. Such exposure to carcinogens, e.g. to polycyclic aromatic hydrocarbons, has been demonstrated in several industries and in defined populations, respectively, by the detection of higher levels of adducts. Adducts detected in many tissues of smokers are at levels significantly higher than in non-smokers, although the magnitude of the elevation does not predict the magnitude of the risk. While such associations do not demonstrate causality, they do, importantly, lend plausibility to observed associations between smoking and cancer. However, there is still resistance to the notion that such monitoring can inform, rather than merely confirm, epidemiological investigations of cancer causation. Interestingly, smoking was recently causally linked to cervical cancer after years of being considered a confounding factor; yet smoking-related adducts have been known to be present in cervical epithelium for some time. In the few prospective studies thus far, elevated adduct levels have been found in individuals who subsequently developed cancer compared with individuals who did not. The potential for biomarker measurements, such as DNA adducts, to provide answers to the origin of many cases of human cancer for which an environmental cause is suspected, needs to be exploited more fully in future epidemiological studies.     

Androgens and breast cancer

The role of androgens on breast cancer development and progression has not been fully elucidated. Several in vivo and in vitro studies demonstrate that androgens have an inhibitory effect on the mammary epithelium, whereas the majority of epidemiological studies report a positive association between high androgen levels and risk of breast cancer. Expression of the androgen receptor is a positive prognostic factor. Understanding the role of androgens in breast carcinogenesis is important because many women use testosterone replacement for the alleviation of symptoms brought on by menopause, in particular high-risk women who undergo surgical menopause at an early age. We overview the literature examining a role of androgens in the etiology of breast cancer.     

Mobile phones, radiofrequency fields, and health effects in children--epidemiological studies

In 2004, when WHO organized a workshop on children's sensitivity to electromagnetic fields, very few studies on radiofrequency fields were available. With the recent increase in mobile phone use among children and adolescents, WHO has identified studies on health effects in this age-group as a high priority research area. There are no empirical data supporting the notion that children and adolescents are more susceptible to RF exposure, but the number of studies is still relatively small. There are a few cross-sectional studies on well-being, cognitive effects and behavioral problems, and some cohort studies, mainly of maternal use of mobile phones during pregnancy. Cancer outcomes have been studied in relation to environmental RF exposure, e.g. from transmitters, and only one study on mobile phone use in children and adolescents and brain tumor risk has been published. Several methodological limitations need to be taken into consideration when interpreting the findings of the epidemiological studies. The cross-sectional design does not allow determination of the temporal sequence of exposure and outcome, and for several outcomes there is a large potential for reversed causality, i.e. that the outcome causes an increased RF exposure rather than the opposite. Biases such as recall errors in self-reported mobile phone use, lack of confounding control, e.g. of other aspects of mobile phone use than RF fields, trained behaviors, and pubertal development, makes causal interpretations impossible. Future studies need to include prospectively collected exposure information, incident outcomes, and proper confounding control. Monitoring of brain tumor incidence trends is strongly recommended.     

Radiation Hormesis and Cancer

Despite the long history of radiation hormesis and the public health concerns with low-level exposures to ionizing radiation, there has been surprisingly little formal evaluation of whether hormetic effects are displayed with respect to radiation exposure and cancer incidence (i.e., reduced cancer risk at low radiation doses compared to controls, enhanced cancer risk at higher doses) until relatively recently. This paper reviews data relevant to the question of radiation hormesis and cancer with particular emphasis on experimental studies in animal models exposed to low levels of ionizing radiation. Data exist that provide evidence both consistent with and/or supportive of radiation hormesis. Other biomedical research provides potentially important mechanistic insight: low dose exposures have the capacity to activate immune function to prevent the occurrence of tumor development and metastasis; low doses of radiation have been shown to reduce mutagenic responses and induce endogenous antioxidant responses. These findings are consistent with epidemiological data suggesting an inverse relationship between background radiation and cancer incidence and with occupational epidemiological investigations in which low-dose exposure groups display markedly lower standardized mortality rates than the referent or control group.     

Antihistamine use and immunoglobulin E levels in glioma risk and prognosis

Objective: An inverse association between personal history of allergies/asthma and glioma risk has been fairly consistently reported in the epidemiologic literature. However, the role of regular antihistamine use remains controversial due to a small number of studies reporting contradictory findings. We evaluated the association between regular use of oral antihistamines and glioma risk, adjusting for a number of relevant factors (e.g., immunoglobulin E levels and history of chickenpox). Methods: We used a subset of the Harris County Case-Control Study, which included 362 pathologically confirmed glioma cases and 462 cancer-free controls, to evaluate this association using unconditional multivariable logistic regression. These models were run among the overall study population and stratified by allergy status. Cox regression was utilized to examine whether antihistamine use was associated with mortality among all cases and separately among high-grade cases. Results: Antihistamine use was strongly associated with glioma risk among those with a positive allergy/asthma history (OR: 4.19, 95% CI: 2.06–8.51), but not among those with a negative history (OR: 1.59, 95% CI: 0.95–2.67). There were no significant associations between antihistamine use and survival among cases. Conclusion: The current study implies that regular antihistamine use may increase glioma risk. However, several larger studies are necessary before definitive conclusions can be drawn.     

The role of infection in sudden infant death syndrome

Studies on the potential role of infectious agents in sudden infant death syndrome (SIDS) have been published over the years in a variety of journals. The aim of this special issue of FEMS Immunology and Medical Microbiology is to bring together a group of the most recent studies from Europe, Australia and Canada which cover epidemiology and laboratory studies examining hypotheses relating to infection and inflammation in SIDS. The articles in this issue examine evidence for the involvement of specific micro-organisms in SIDS and the problems relating to experimental studies on infection in relation to the underlying pathology of these deaths. There is an update on the evidence for the common bacterial hypothesis proposed in 1987 examining risk factors identified in epidemiological studies, particularly how the prone sleeping position could affect bacterial colonisation or induction of toxins. Evidence for induction of inflammatory responses in SIDS infants is reviewed and the relation of these responses to mechanisms proposed as causes of death assessed. Factors found to be associated with reduction of the risk of SIDS (breast feeding and immunisation) are examined in relation to some of the toxigenic bacteria implicated in these deaths. Finally, the high incidence of SIDS in some ethnic groups is examined as a potential model to investigate the contributions of genetic, environmental and cultural differences to susceptibility of infants not only to SIDS but to serious respiratory tract infections.     

Insufficient Milk Supply and Breast Cancer Risk: A Systematic Review

Background

An association between insufficient milk supply, the inability of a mother''s breast milk to provide sufficiently for her infant, and breast cancer has been suggested by observations in animal models. To determine if an association has been reported in epidemiological studies of human breast cancer, a systematic review of the literature has been conducted. We also sought to identify the methodological limitations of existing studies to guide the design of any future prospective studies in this field.

Methodology/Principal Findings

PubMed, EMBASE, Web of Science, BIOSIS, and CAB abstracts were searched. We selected any study that (1) assessed breast cancer in association with breastfeeding history and (2) examined the relationship between insufficient milk supply with breast cancer. Seven relevant studies were identified that met both criteria. There was statistically significant heterogeneity among the results which likely reflects clinically significant differences in definitions of insufficient milk supply and reference groups that were used. Among premenopausal women who had experienced insufficient milk supply, odds ratios (ORs) for breast cancer risk ranged from 0.9 to 16.3. Among postmenopausal women, ORs ranged from 0.6 to 6.7. Based on the range of odds ratios obtained in the studies reported in this review, it remains unclear if there is a true association between insufficient milk supply and breast cancer.

Conclusions/Significance

Although some studies have shown a strong positive association, there is no consistent evidence for an effect of insufficient milk supply on breast cancer risk. Exposure definitions are in need of improvement in order to focus on primary insufficient milk supply. Reference groups consisting of women who have successfully breastfed may also introduce positive bias (inflation of the odds ratio) into study results because of the protective effect of prolonged breastfeeding in the control group.     

Statistical Aspects of the Use of Biomarkers in Nutritional Epidemiology Research

Few strong and consistent associations have arisen from observational studies of dietary consumption in relation to chronic disease risk. Measurement error in self-reported dietary assessment may be obscuring many such associations. Attempts to correct for measurement error have mostly used a second self-reported assessment in a subset of a study cohort to calibrate the self-reported assessment used throughout the cohort, under the dubious assumption of uncorrelated measurement errors between the two assessments. The use, instead, of objective biomarkers of nutrient consumption to produce calibrated consumption estimates provides a promising approach to enhance study reliability. As summarized here, we have recently applied this nutrient biomarker approach to examine energy, protein, and percent of energy from protein, in relation to disease incidence in Women’s Health Initiative cohorts, and find strong associations that are not evident without biomarker calibration. A major bottleneck for the broader use of a biomarker-calibration approach is the rather few nutrients for which a suitable biomarker has been developed. Some methodologic approaches to the development of additional pertinent biomarkers, including the possible use of a respiratory quotient from indirect calorimetry for macronutrient biomarker development, and the potential of human feeding studies for the evaluation of a range of urine- and blood-based potential biomarkers, will briefly be described.     

Causality,menopause, and depression: a critical review of the literature.

OBJECTIVE: To assess whether causal criteria can be used to find out whether there is support in published research for maintaining that menopause causes depression. DESIGN: Ninety four articles from 30 years of research examining the relation of natural menopause to depression were traced by using Medline and systematic follow up of reference lists. Specified exclusion and inclusion criteria were applied, and the resulting 43 epidemiological primary research articles were classified and tabulated according to sample and measures used and the researchers'' own conclusion as to whether or not an association had been established. This material was qualitatively evaluated with Hill''s nine criteria for causality. RESULT: There is insufficient evidence at present to maintain that menopause causes depression. In addition to methodological and statistical problems, a temporal problem in the menopause concept hinders research in this area. CONCLUSION: Causal criteria can usefully be used to structure a literature review. Further theoretical work is required to integrate standard clinical epidemiological concepts.     

Fish and Fish Oil Intake in Relation to Risk of Asthma: A Systematic Review and Meta-Analysis

Although laboratory studies suggest that long-chain n-3 polyunsaturated fatty acids (LCn3PUFAs) may reduce risk of asthma, epidemiological data remain controversial and inconclusive. We quantitatively reviewed the epidemiological studies published through December 2012 in PubMed and EMBASE by using a fixed-effects or random-effects model. Eleven studies, comprised of 99,093 individuals (3,226 cases), were included in the final dataset. Of them, 7 studies examined associations between intake of fish or LCn3PUFA and risk of asthma: 4 studies in children (996 cases from 12,481 children) and 3 in adults (1,311 cases from 82,553 individuals). Two studies (69 cases from 276 infants) investigated LCn3PUFA levels in mothers’ milk, and two studies assessed maternal fish consumption (786 cases from 2,832 individuals) during lactation and/or plasma LCn3PUFA levels during pregnancy (64 cases from 951 infants) in relation to offspring’s asthma. The pooled relative risk of child asthma were 0.76 (95% CI, 0.61–0.94) for fish consumption and 0.71 (95% CI, 0.52–0.96) for LCn3PUFA intake. No statistically significant association was found in studies among adults. Epidemiological data to date indicate that fish or LCn3PUFA intake may be beneficial to prevent asthma in children. Further studies are needed to establish causal inference and to elucidate the potential mechanisms.     

Change in Self-Reported Health Status among Immigrants in the United States: Associations with Measures of Acculturation

Although acculturation may have positive effects for immigrants, including better socioeconomic profiles and increased occupational opportunities, their health profiles deteriorate with longer duration in the U.S. Prior research indicates that increasing acculturation is associated with some poorer health outcomes among immigrants in the U.S. However, most of these studies have used length of stay or English language proficiency as proxies for acculturation, and have mainly examined self-reported “current” health outcomes. This study advances knowledge on associations between acculturation and health among immigrants by explicitly examining self-reported “change” in health since immigration, in relation to acculturation-related variables. We use data from the New Immigrant Survey (NIS; 2003-2004), a cross-sectional study of legal immigrants to the U.S. In addition to testing more conventionally examined proxies of acculturation (length of stay and English proficiency), we also examine English language use and self-reported change in diet. Multivariable logistic regression analyses on 5,982 participants generally supported previous literature indicating a deleterious impact of acculturation, with increasing duration of stay and greater self-reported change in diet being associated with a poorer change in health since moving to the U.S. Although English language proficiency and use were associated with greater odds of reporting a worse change in health when examined individually, they were non-significant in multivariable models including all acculturation measures. Findings from this study suggest that when taking into account multiple measures of acculturation, language may not necessarily indicate unhealthy assimilation and dietary change may be a pathway leading to declines in immigrant health. Increasing duration in the U.S. may also reflect the adoption of unhealthy behaviors, as well as greater exposure to harmful sources of psychosocial stress including racial and anti-immigrant discrimination. Our study suggests that multiple indicators of acculturation may be useful in examining the effect of acculturation on changes in health among immigrants.     

Pesticides and cancer: insights into toxicoproteomic-based findings

Humans are often exposed to a variety of pollutants that contribute to an individual's risk for diseases including cancer. Animal, cell cultures and epidemiological lines of evidence demonstrate that exposure to various environmental pollutants including pesticides are associated with increasing frequency of cancers. Organophosphates, organochlorines, carbamates, pyrethroids, the major groups of pesticides, have been reported to be carcinogenic in various models. However, the results of these studies are still controversial, nevertheless, their mechanism of action is clear. Therefore, new strategies in toxicological research are needed for efficient screening for adverse effects of pesticides on complex living systems. Biomarkers can be employed to identify causal associations and to make better quantitative and qualitative estimates of those associations at relevant levels of exposure. This will enable us to deepen our understanding of mechanism behind their carcinogenic potential. Deciphering the associations between pesticide exposure and cancer, following toxicoproteomics application, will be useful in the development of potential predictive biomarkers of pesticide induced carcinogenicity. Therefore, the thrust of this article was to review the risk of cancer due to pesticide exposure and significant toxicoproteomic-based studies conducted so far, to identify the novel molecules as possible biomarkers for cancer following pesticide exposure.     

Carcinogen-DNA adducts as a biomarker for cancer risk

Carcinogen-DNA adducts are thought to be a useful biomarker in epidemiologic studies seeking to show that environmental exposures to xenobiotics cause cancer. This paper reviews the literature in this field from an epidemiologic perspective and identifies several common problems in the epidemiologic design and analysis of these studies. Carcinogen-DNA adducts have been used in studies attempting to link xenobiotic exposures to hepatocellular carcinoma, smoking related cancers and breast cancer. Adduct measurements have been useful in further implicating aflatoxin exposure in the etiology of hepatocellular carcinoma. For smoking related cancers, associations with carcinogen-DNA adducts are commonly seen in current smokers but less so in ex- or non-smokers. In breast cancer the associations have been inconsistent and weak and there is little evidence that carcinogen-DNA adducts implicate xenobiotic exposures in the etiology of breast cancer. Methodological issues common to these studies are the use of target versus surrogate tissues and how this choice impacts control selection, disease effects on adduct levels, the time period reflected by adduct levels, the use of inappropriate statistical analyses and small sample sizes. It is unclear whether the lack of association between carcinogen-DNA adducts and cancer reflects a lack of association between the xenobiotic exposure of interest and cancer or the effects of these methodological issues. A greater focus needs to be placed on designs that allow measurements of adduct levels in tissues collected years prior to cancer diagnosis, there is little need for further hospital based case-control studies in which adducts are measured at the time of or after diagnosis. New designs that address these issues are suggested in the paper.