Iron has been shown to promote breast carcinogenesis in animal models through generation of oxidative stress and interaction with estrogen. Heme iron, which is found exclusively in animal-sourced ...foods, is suggested to have a more detrimental effect. Epidemiological evidence of the association between iron and breast cancer risk remains inconclusive and has not been comprehensively summarized. This systematic review and meta-analysis evaluated associations between both iron intake and body iron status and breast cancer risk.
Four electronic databases (MEDLINE, EMBASE, CINAHL, and Scopus) were searched up to December 2018 for studies assessing iron intake and/or biomarkers of iron status in relation to breast cancer risk. Using random-effects meta-analyses, pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated comparing the highest vs. lowest category of each iron measure. Dose-response meta-analyses were also performed to investigate linear and nonlinear associations.
A total of 27 studies were included in the review, of which 23 were eligible for meta-analysis of one or more iron intake/status measures. Comparing the highest vs. lowest category, heme iron intake was significantly associated with increased breast cancer risk, with a pooled RR of 1.12 (95% CI: 1.04-1.22), whereas no associations were found for dietary (1.01, 95% CI: 0.89-1.15), supplemental (1.02, 95% CI: 0.91-1.13), or total (0.97, 95% CI: 0.82-1.14) iron intake. Associations of iron status indicators with breast cancer risk were generally in the positive direction; however, a significant pooled RR was found only for serum/plasma levels (highest vs. lowest) of iron (1.22, 95% CI: 1.01-1.47), but not for ferritin (1.13, 95% CI: 0.78-1.62), transferrin saturation (1.16, 95% CI: 0.91-1.47), or total iron-binding capacity (1.10, 95% CI: 0.97-1.25). In addition, a nonlinear dose-response was observed for heme iron intake and serum iron (both P
< 0.05).
Heme iron intake and serum iron levels may be positively associated with breast cancer risk. Although associations were modest, these findings may have public health implications given the widespread consumption of (heme) iron-rich foods. In light of methodological and research gaps identified, further research is warranted to better elucidate the relationship between iron and breast cancer risk.
CDK12 (cyclin-dependent kinase 12) is a regulatory kinase with evolutionarily conserved roles in modulating transcription elongation. Recent tumor genome studies of breast and ovarian cancers ...highlighted recurrent CDK12 mutations, which have been shown to disrupt DNA repair in cell-based assays. In breast cancers, CDK12 is also frequently co-amplified with the HER2 (ERBB2) oncogene. The mechanisms underlying functions of CDK12 in general and in cancer remain poorly defined. Based on global analysis of mRNA transcripts in normal and breast cancer cell lines with and without CDK12 amplification, we demonstrate that CDK12 primarily regulates alternative last exon (ALE) splicing, a specialized subtype of alternative mRNA splicing, that is both gene- and cell type-specific. These are unusual properties for spliceosome regulatory factors, which typically regulate multiple forms of alternative splicing in a global manner. In breast cancer cells, regulation by CDK12 modulates ALE splicing of the DNA damage response activator ATM and a DNAJB6 isoform that influences cell invasion and tumorigenesis in xenografts. We found that there is a direct correlation between CDK12 levels, DNAJB6 isoform levels and the migration capacity and invasiveness of breast tumor cells. This suggests that CDK12 gene amplification can contribute to the pathogenesis of the cancer.
Purpose
There has been an alarming increase in colorectal cancer (CRC) incidence among young adults aged < 50 years, and factors driving this upward trend are unknown. This study investigated ...associations between various medical, lifestyle, and dietary factors and risk of early-onset CRC (EO-CRC).
Methods
A population-based case–control study was conducted in Ontario, Canada during 2018–2019. EO-CRC cases aged 20–49 years (
n
= 175) were identified from the Ontario Cancer Registry; sex- and age group-matched controls (
n
= 253) were recruited through random digit dialing. Data on potential a priori risk factors were collected using a web-based self-reported questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression.
Results
Family history of CRC in a first- or second-degree relative (OR 2.37; 95% CI 1.47–3.84), longer sedentary time (≥ 10 vs. < 5 h/day, OR 1.93; 95% CI 1.02–3.65), greater consumption of sugary drinks (≥ 7 vs. < 1 drinks/week, OR 2.99; 95% CI 1.57–5.68), and a more Westernized dietary pattern (quartile 4 vs. 1, OR 1.92; 95% CI 1.01–3.66) were each associated with an increased risk of EO-CRC. Conversely, calcium supplement use (OR 0.53; 95% CI 0.31–0.92), history of allergy or asthma (OR 0.62; 95% CI 0.39–0.98), and greater parity in females (≥ 3 vs. nulliparity, OR 0.29; 95% CI 0.11–0.76) were each associated with a reduced risk.
Conclusion
Modifiable factors, particularly sedentary behavior and unhealthy diet including sugary drink consumption, may be associated with EO-CRC risk. Our findings, if replicated, may help inform prevention strategies targeted at younger persons.
Despite extensive literature on falls among seniors, little is known about gender-specific risk factors. To determine the prevalence of falls by gender and sociodemographic, lifestyle/behavioral, and ...medical factors, we conducted a cross-sectional study in a nationally representative sample of Canadian adults who were 65 years of age or older (n = 14,881) from the Canadian Community Health Survey-Healthy Aging (2008-2009). Logistic regression models were applied to investigate gender-specific associations between potential risk factors and falls. In men, stroke (odds ratio (OR) = 1.91), nutritional risk (OR = 1.86), post-secondary school degree (OR = 1.68), eye disorder (OR = 1.35), widowed/separated/divorced marital status (OR = 1.28), and arthritis (OR = 1.27) were independently associated with significantly higher odds of falls. In women, significant independent correlates of falls included stroke (OR = 1.53), age of 85 years or older (OR = 1.51), nutritional risk (OR = 1.39), consumption of at least 1 alcoholic drink per week (OR = 1.39), use of 5 or more medications (OR = 1.36), arthritis (OR = 1.36), diabetes (OR = 1.31), and osteoporosis (OR = 1.22). Higher physical activity levels were protective in both genders, and higher household income was protective in women. Gender should be considered when planning fall prevention strategies.
Iron deficiency and overload may negatively impact women's health. There has been limited assessment of iron status and its associated factors among Canadian women.
This study investigated ...associations of various sociodemographic, lifestyle, medication, and dietary factors with body iron stores among pre- and postmenopausal women in Canada.
Analyses were conducted using cross-sectional, nationally representative survey and biomarker data from women aged 20-79 y (n = 6362) in the Canadian Health Measures Survey (2009-2017). Body iron stores were assessed by measuring serum concentrations of ferritin (SF). Information on potential correlates was collected during an in-home interview. Multivariable linear regression analyses were performed to evaluate associations with SF concentration, and logistic regression was used to estimate associations with iron deficiency (SF <15 μg/L) or elevated iron stores (SF >150 μg/L).
Geometric mean SF concentrations were significantly higher in postmenopausal than in premenopausal women (73.2 versus 33.8 μg/L; P < 0.001). The prevalence of iron deficiency among pre- and postmenopausal women was 16.0% and 4.0%, respectively, whereas that of elevated iron stores was 2.7% and 21.0%, respectively. After simultaneous adjustment for multiple factors, including high-sensitivity CRP (inflammation marker), we found that age, East/Southeast Asian (versus White) race/ethnicity, alcohol, and red meat consumption were positively associated with SF concentration among pre- and postmenopausal women. In addition, aspirin use and dairy consumption were inversely associated with SF concentration among postmenopausal women only. Similar patterns were observed for associations with elevated iron stores among postmenopausal women, whereas higher grain consumption was associated with an increased prevalence of iron deficiency among premenopausal women.
Sociodemographic, lifestyle, medication, and dietary factors are correlated with iron status determined by SF concentration among Canadian women. The findings may have implications for intervention strategies aimed at optimizing body iron stores in pre- and postmenopausal women.
Introduction
Le sommeil est essentiel à la fois au bien-être physique et au bien-être
mental. Cette étude a examiné les facteurs sociodémographiques, comportementaux,
environnementaux, psychosociaux ...et les facteurs de santé associés à la durée du sommeil
chez les Canadiens à différentes étapes de la vie.
Méthodologie
Nous avons analysé des données de l’Enquête canadienne sur les mesures
de la santé (2009-2013), représentatives à l’échelle nationale et portant sur 12 174 Canadiens
de 3 à 79 ans. En fonction de leur âge, les répondants ont été distribués en cinq
groupes correspondant à cinq étapes de vie : les enfants préscolaires (3 et 4 ans), les
enfants (5 à 13 ans), les adolescents (14 à 17 ans), les adultes (18 à 64 ans) et les aînés
(65 à 79 ans). La durée du sommeil a été classée en trois catégories (recommandée, courte
et longue) suivant les directives établies. Des modèles de régression logistique ont été
utilisés pour dégager des corrélats d’une durée de sommeil courte ou longue propres à
chaque étape de vie.
Résultats
La proportion de Canadiens jouissant de la quantité recommandée de sommeil
diminue avec l’âge, de 81 % chez les enfants préscolaires à 53 % chez les aînés.
Les facteurs statistiquement significatifs associés à un sommeil court sont une ethnicité
non blanche et un revenu familial faible chez les enfants préscolaires, une ethnicité non
blanche et la résidence avec un seul parent chez les enfants et l’exposition à la fumée
secondaire chez les adolescents. Les garçons ayant un trouble d’apprentissage ou un
trouble du déficit de l’attention avec hyperactivité et les garçons adolescents sédentaires
avaient des chances significativement plus élevées de connaître un sommeil court. Chez
les adultes et les aînés, le stress chronique et l’arthrite ont été associés tous deux à un
sommeil court. Le sommeil long a été quant à lui associé à un trouble de l’humeur et
une autoperception d'une mauvaise santé générale ou passable chez les adultes et à un
faible sens d’appartenance communautaire chez les adultes ainsi que chez les aînés de
sexe masculin.
Conclusion
Notre étude de population a dégagé une grande variété de facteurs associés à
un sommeil court ou long à différentes étapes de la vie, ce qui pourrait jouer un rôle dans
l'élaboration des interventions visant à promouvoir une durée de sommeil saine.
Iron has been suggested to contribute to breast cancer development through oxidative stress generation. Our study investigated associations between iron intake and breast cancer risk, overall and by ...menopausal and estrogen receptor/progesterone receptor (ER/PR) status, and modification by oxidative stress‐related genetic polymorphisms (MnSOD, GSTM1 and GSTT1). A population‐based case–control study (3,030 cases and 3,402 controls) was conducted in Ontario, Canada. Iron intake (total, dietary, supplemental, heme, nonheme) was assessed using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models. Interactions between iron intake and genotypes were assessed among 1,696 cases and 1,761 controls providing DNA. Overall, no associations were observed between iron intake and breast cancer risk. Among premenopausal women, total, dietary and dietary nonheme iron were positively associated with ER–/PR– breast cancer risk (all ptrend < 0.05). Among postmenopausal women, supplemental iron was associated with reduced breast cancer risk (OR>18 vs. 0 mg/day = 0.68, 95% CI: 0.51–0.91), and dietary heme iron was associated with an increased risk, particularly the ER–/PR– subtype (ORhighest vs. lowest quintile = 1.69, 95% CI: 1.16–2.47; ptrend = 0.02). Furthermore, GSTT1 and combined GSTM1/GSTT1 polymorphisms modified some of the associations. For example, higher dietary iron was most strongly associated with increased breast cancer risk among women with GSTT1 deletion or GSTM1/GSTT1 double deletions (pinteraction < 0.05). Findings suggest that iron intake may have different effects on breast cancer risk according to menopausal and hormone receptor status, as well as genotypes affecting antioxidant capacity.
What's new?
Iron may increase breast cancer risk through oxidative stress. Epidemiological evidence remains inconclusive, however, with few studies considering differences by type of iron, menopausal/hormone receptor status, and genetic variability. Results from this large population‐based case–control study do not support associations of iron intake with overall breast cancer risk; however, statistically significant associations were observed by menopausal and hormone receptor status. Higher intakes of total and nonheme iron in premenopausal women, and heme iron in postmenopausal women, increased risk of estrogen/progesterone receptor‐negative breast cancer. Furthermore, women with genotypes resulting in reduced antioxidant capacity may be more susceptible to high iron intake effects.
Introduction
La crise actuelle des opioïdes est un problème de santé publique majeur au
Canada. Il est nécessaire de connaître les facteurs de risque en amont associés à la consommation
d’opioïdes ...pour éclairer les efforts de prévention des blessures, de promotion
de la santé et de réduction des méfaits.
Méthodologie
Nous avons analysé les données sur les blessures subies par des personnes
traitées dans les services d’urgence (SU) de onze hôpitaux pédiatriques et de six
hôpitaux généraux au Canada et recueillies par le Système canadien hospitalier
d’information et de recherche en prévention des traumatismes en ligne (SCHIRPTe) entre
mars 2011 et juin 2017. Nous avons identifié les blessures apparemment liées aux opioïdes
au moyen de chaînes de recherche et nous les avons vérifiées manuellement. Nous avons
calculé des rapports proportionnels de blessures (RPB) en fonction de l’âge et du sexe
ainsi que des intervalles de confiance à 95 % pour comparer les blessures liées à la consommation
d’opioïdes à l'ensemble des blessures figurant dans le SCHIRPTe. Une régression
binomiale négative a été utilisée pour déterminer les tendances au fil du temps. Nous
avons effectué des analyses qualitatives des informations descriptives afin d'en dégager
les thèmes communs spécifiques à chaque étape de vie.
Résultats
Nous avons identifié 583 cas d'intoxications ou de blessures apparemment
liées aux opioïdes dans le SCHIRPTe pour la période allant de mars 2011 à juin 2017. La
majorité concernaient des femmes (55 %) et sont survenues au domicile des patients
(51 %). Quarante-cinq pour cent des blessures étaient des automutilations intentionnelles.
Chez les enfants (1 à 9 ans), la plupart des blessures ont été causées par une consommation
accidentelle d’opioïdes laissés sans surveillance. Chez les jeunes (10 à 19 ans)
et les adultes (20 à 49 ans), la consommation d’opioïdes était associée à une maladie
mentale sous-jacente. Dans l’ensemble, on observe une augmentation de la variation
annuelle moyenne en pourcentage (VAMP) du taux de blessures (pour 100 000 cas dans le
SCHIRPTe) depuis 2012 (VAMP = 11,9 %, p $lt; 0,05), particulièrement marquée chez les
hommes (VAMP = 16,3 %, p $lt; 0,05). Les personnes victimes de blessures apparemment
liées à la consommation d’opioïdes étaient plus susceptibles d’être admises à l’hôpital
que les personnes victimes d'autres types de blessure (RPB = 5,3, IC à 95 % : 4,6 à 6,2).
Conclusion
Les déterminants en amont des blessures liées à l’utilisation d’opioïdes sont
complexes et varient probablement selon les sous-populations. La surveillance continue
des facteurs de risque est donc importante afin d'obtenir les données probantes nécessaires
à la prévention d’autres surdoses et décès.
Nous avons utilisé les médias sociaux comme source de données potentielle pour obtenir
de l’information en temps réel sur l’usage des opioïdes et sur les perceptions entourant
ces substances au ...Canada. Nous avons recueilli des messages sur Twitter au moyen d’une
plateforme d’analyse des médias sociaux entre le 15 juin et le 13 juillet 2017, puis nous
les avons analysés afin d'y déceler les thèmes récurrents. Nous avons souvent relevé des
messages concernant l’usage d’opioïdes à des fins médicales ainsi que des commentaires
sur les efforts d’intervention déployés par le gouvernement du Canada dans le cadre de la
crise des opioïdes. Les résultats de l’étude pourraient aider à orienter les pratiques en
santé publique ainsi qu'à soutenir les intervenants communautaires dans leurs efforts
pour contrer la crise.
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