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1.
Sci Total Environ ; 715: 136859, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32014767

RESUMO

BACKGROUND: Little is known about whether exposure to pets influences the association between hypertension and environmental tobacco smoke (ETS). The current study aims to examine the interaction of pet ownership on ETS exposure and the development of hypertension in children. METHODS: From 2012 to 2013, a total of 9354 children, 5 to 17 years of age, were recruited from 62 schools in seven northeastern cities. BP in children was measured and hypertension was defined as an average diastolic blood pressure (DBP) or systolic blood pressure (SBP) at or above the 95th percentile for that child's age, sex, and height. Pet ownership in three different time periods (in utero, past 2 years, and currently) and ETS exposure data were collected from parents via a questionnaire. Two-level regressions were used for the data analyses. RESULTS: The data show consistent, significant interactions between exposure to pets and effects from ETS. Children who were not exposed to pets experienced stronger effects from ETS on hypertension when compared to those exposed to pets, and the protective effect of pet ownership became stronger with a greater number of pets in the home. Exposure to in utero ETS was associated with hypertension [adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI): 1.13-1.54] only for those children without pet exposure in utero but not for those with pets (aOR = 0.75; 95% CI: 0.49-1.15) (pinteraction < 0.05). Moreover, household dog ownership was related to significantly lower effects of current ETS on hypertension (aOR = 0.80, 95% CI: 0.61-1.05) compared with children without dogs (aOR = 1.26, 95% CI: 1.11-1.44) (pinteraction = 0.001). Interaction associations between ETS and pet ownership were more robust for girls than for boys and for younger than older children. CONCLUSION: This study indicates an inverse relationship between pet ownership and ETS, potentially pointing to pet ownership as protecting against the development of hypertension in children.

2.
Environ Pollut ; 256: 113422, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31672364

RESUMO

Evidence suggests that residential greenness may be protective of high blood pressure, but there is scarcity of evidence on the associations between greenness around schools and blood pressure among children. We aimed to investigate this association in China. Our study included 9354 children from 62 schools in the Seven Northeastern Cities Study. Greenness around each child's school was measured by NDVI (Normalized Difference Vegetation Index) and SAVI (Soil-Adjusted Vegetation Index). Particulate matter ≤ 1 µm (PM1) concentrations were estimated by spatiotemporal models and nitrogen dioxide (NO2) concentrations were collected from air monitoring stations. Associations between greenness and blood pressure were determined by generalized linear and logistic mixed-effect models. Mediation by air pollution was assessed using mediation analysis. Higher greenness was consistently associated with lower blood pressure. An increase of 0.1 in NDVI corresponded to a reduction in SBP of 1.39 mmHg (95% CI: 1.86, -0.93) and lower odds of hypertension (OR = 0.76, 95% CI: 0.69, 0.82). Stronger associations were observed in children with higher BMI. Ambient PM1 and NO2 mediated 33.0% and 10.9% of the association between greenness and SBP, respectively. In summary, greater greenness near schools had a beneficial effect on blood pressure, particularly in overweight or obese children in China. The associations might be partially mediated by air pollution. These results might have implications for policy makers to incorporate more green space for both aesthetic and health benefits.

3.
Hypertension ; 75(2): 347-355, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838909

RESUMO

Evidence on the associations between airborne particulates of diameter ≤1 µm (PM1) and airborne particulates of diameter ≤2.5 µm (PM2.5) and childhood blood pressure (BP) is scarce. To help to address this literature gap, we conducted a study to explore the associations in Chinese children. Between 2012 and 2013, we recruited 9354 children, aged 5 to 17 years, from 62 schools in 7 northeastern Chinese cities. We measured their BP with a mercury sphygmomanometer. We used a spatiotemporal model to estimate daily ambient PM1 and PM2.5 exposures, which we assigned to participants' home addresses. Associations between particulate matter exposure and BP were evaluated with generalized linear mixed regression models. The findings indicated that exposure to each 10 mg/m3 greater PM1 was significantly associated with 2.56 mm Hg (95% CI, 1.47-3.65) higher systolic BP and 61% greater odds for hypertension (odds ratio=1.61 [95% CI, 1.18-2.18]). PM1 appears to play an important role in associations reported between PM2.5 exposure and BP, and we found that the ambient PM1/PM2.5 ratio (range, 0.80-0.96) was associated with BP and with hypertension. Age and body weight modified associations between air pollutants and BP (P<0.01), with stronger associations among younger (aged ≤11 years) and overweight/obese children. This study provides the first evidence that long-term exposure to PM1 is associated with hypertension in children, and that PM1 might be a leading contributor to the hypertensive effect of PM2.5. Researchers and policy makers should pay closer attention to the potential health impacts of PM1.

4.
Environ Int ; 135: 105365, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31830731

RESUMO

BACKGROUND: Experimental studies show that chlorinated polyfluorinated ether sulfonic acids (Cl-PFESA 6:2 and 8:2), one of perfluoroalkyl substances (PFAS) used as perfluorooctane sulfonate (PFOS) alternatives, are reproductive toxicants in vivo and in vitro. However, the associations between gestational exposure to Cl-PFESAs and birth outcomes are unknown. OBJECTIVES: We investigated associations between 6:2 Cl-PFESA and 8:2 Cl-PFESA in maternal serum and birth outcomes. METHODS: We measured four PFAS, including 6:2 Cl-PFESA, 8:2 Cl-PFESA, PFOS, and perfluorooctanoic acid (PFOA) in third-trimester maternal serum collected from 372 mother-child dyads participating in the Guangzhou Birth Cohort Study. Characteristics of mothers and infants were gathered from medical records and by interviewer-administered questionnaires. RESULTS: PFOS was the most abundant PFAS in maternal serum (median: 7.15 ng/mL), followed by 6:2 Cl-PFESA (median: 2.41 ng/mL). Greater maternal serum levels of all PFAS alternatives were significantly associated with lower birth weight, adjusted for confounding variables. For example, each ln-ng/mL greater concentration of 6:2 Cl-PFESA and 8:2 Cl-PFESA was associated with a 54.44 g [95% confidence interval (CI): -95.66, -13.22] and 21.15 g (95% CI: -41.44, -0.86) lower birth weight, respectively. Greater continuous maternal serum 6:2 Cl-PFESA (OR: 2.67, 95% CI: 1.73, 4.15) and PFOS (OR: 2.03, 95% CI: 1.24, 3.32) were also associated with higher risks for preterm birth, adjusted for confounders, with a possible threshold effect at the highest quartile of 6:2 Cl-PFESA. CONCLUSIONS: For the first time, we report associations between maternal serum 6:2 Cl-PFESA and 8:2 Cl-PFESA concentrations and adverse birth outcomes. Our findings suggest that PFOS alternatives may be reproductive toxicants in human populations and should be considered with caution before widespread use. Given the preliminary nature of our results, additional epidemiological and toxicological investigations are needed to more definitively assess the risks.

5.
Environ Int ; 135: 105388, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31837524

RESUMO

BACKGROUND: Residing in greener areas has several health benefits, but no study to date has examined the effects of greenness on metabolic syndrome (MetS). We aimed to assess associations between residential greenness and MetS prevalence in China, and to explore whether air pollution and physical activity mediated any observed associations. METHODS: We analyzed data from 15,477 adults who participated in the 33 Communities Chinese Health Study during 2009. We defined MetS according to standard guidelines for Chinese populations. Residential greenness was estimated using the Normalized Difference Vegetation Index (NDVI), the Soil Adjusted Vegetation Index (SAVI), and the Vegetation Continuous Field (VCF). We used generalized linear mixed models to assess the associations between greenness and MetS, and mediation analyses to explore potential mechanisms underlying the associations. RESULTS: Higher greenness levels were associated with lower odds of MetS [e.g., for every interquartile range increase of NDVI500-m, SAVI500-m, and VCF500-m, the adjusted odds ratio of MetS was 0.81 (95% confidence interval: 0.70-0.93), 0.80 (95% confidence interval: 0.69-0.93), and 0.91 (95% confidence interval: 0.83-1.00), respectively]. The direction and the magnitude of the associations persisted in several sensitivity analyses. Stratified analyses showed that age and household income modified the associations, with greater effect estimates observed in participants younger than 65 years old or those with higher household income. Particulate matter with an aerodynamic diameter ≤10 µm, nitrogen dioxide, and ozone mediated 2.1-20.3% of the associations between greenness and MetS; no evidence of mediation was observed for physical activity. CONCLUSIONS: Our findings suggest a beneficial association for residential greenness and MetS in Chinese urban dwellers, especially for participants younger than 65 years old and those with higher household income. Particulate matter with an aerodynamic diameter ≤10 µm, nitrogen dioxide and ozone, but not physical activity, may only partially mediate the association.

6.
Sci Total Environ ; 702: 135040, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31726339

RESUMO

Living in greener places may protect against obesity, but epidemiological evidence is inconsistent and mainly comes from developed nations. We aimed to investigate the association between greenness and obesity in Chinese adults and to assess air pollution and physical activity as mediators of the association. We recruited 24,845 adults from the 33 Communities Chinese Health Study in 2009. Central and peripheral obesity were defined by waist circumference (WC) and body mass index (BMI), respectively, based on international obesity standards. The Normalized Difference Vegetation Index (NDVI) was used to quantify community greenness. Two-level logistic and generalized linear mixed regression models were used to evaluate the association between NDVI and obesity, and a conditional mediation analysis was used also performed. In the adjusted models, an interquartile range increase in NDVI500-m was significantly associated with lower odds of peripheral 0.80 (95% confidence interval [CI]: 0.74-0.87) and central obesity 0.88 (95% CI: 0.83-0.93). Higher NDVI values were also significantly associated with lower BMI. Age, gender, and household income significantly modified associations between greenness and obesity, with stronger associations among women, older participants, and participants with lower household incomes. Air pollution mediated 2.1-20.8% of the greenness-obesity associations, but no mediating effects were observed for physical activity. In summary, higher community greenness level was associated with lower odds of central and peripheral obesity, especially among women, older participants, and those with lower household incomes. These associations were partially mediated by air pollutants. Future well-designed longitudinal studies are needed to confirm our findings.


Assuntos
Obesidade/epidemiologia , Desenvolvimento Sustentável , Poluição do Ar , Índice de Massa Corporal , China/epidemiologia , Cidades/epidemiologia , Exercício , Humanos , Características de Residência , Fatores Socioeconômicos , População Urbana/tendências
7.
Sci Total Environ ; 699: 134397, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31677469

RESUMO

Children are vulnerable to air pollution-induced lung function deficits, and the prevalence of obesity has been increasing in children. To evaluate the joint effects of long-term PM1 (particulate matter with an aerodynamic diameter ≤ 1.0 µm) exposure and obesity on children's lung function, a cross-sectional sample of 6740 children (aged 7-14 years) was enrolled across seven northeastern Chinese cities from 2012 to 2013. Weight and lung function, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), and maximal mid-expiratory flow (MMEF), were measured according to standardized protocols. Average PM1, PM2.5, PM10 and nitrogen dioxide (NO2) exposure levels were estimated using a spatiotemporal model, and sulphur dioxide (SO2) and ozone (O3) exposure were estimated using data from municipal air monitoring stations. Two-level logistic regression and general linear models were used to analyze the joint effects of body mass index (BMI) and air pollutants. The results showed that long-term air pollution exposure was associated with lung function impairment and there were significant interactions with BMI. Associations were stronger among obese and overweight than normal weight participants (the adjusted odds ratios (95% confidence intervals) for PM1 and lung function impairments in three increasing BMI categories were 1.50 (1.07-2.11) to 2.55 (1.59-4.07) for FVC < 85% predicted, 1.44 (1.03-2.01) to 2.51 (1.53-4.11) for FEV1 < 85% predicted, 1.34 (0.97-1.84) to 2.04 (1.24-3.35) for PEF < 75% predicted, and 1.34 (1.01-1.78) to 1.93 (1.26-2.95) for MMEF < 75% predicted). Consistent results were detected in linear regression models for PM1, PM2.5 and SO2 on FVC and FEV1 impairments (PInteraction < 0.05). These modification effects were stronger among females and older participants. These results can provide policy makers with more comprehensive information for to develop strategies for preventing air pollution induced children's lung function deficits among children.


Assuntos
Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Obesidade/epidemiologia , Adolescente , Poluentes Atmosféricos/análise , Criança , China/epidemiologia , Cidades , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/efeitos dos fármacos , Masculino , Dióxido de Nitrogênio/análise , Sobrepeso , Ozônio/análise , Material Particulado/análise , Testes de Função Respiratória , Dióxido de Enxofre , Capacidade Vital
8.
JAMA Netw Open ; 2(12): e1917862, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31851349

RESUMO

Importance: Few studies have investigated the association between greenness and childhood attention-deficit/hyperactivity disorder (ADHD). Objective: To evaluate the association between greenness surrounding schools or kindergartens and symptoms of ADHD in children. Design, Setting, and Participants: This population-based cross-sectional study was performed between April 2012 and January 2013 in 7 cities in northeastern China. This analysis included 59 754 children (aged 2-17 years) from 94 schools and kindergartens, who had resided in the study area for 2 years or longer. Data were analyzed from April 15, 2019, to October 10, 2019. Exposures: Greenness surrounding each child's school or kindergarten was estimated using 2 satellite image-derived vegetation indexes: the normalized difference vegetation index and the soil-adjusted vegetation index. Main Outcomes and Measures: Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) scales were used to measure ADHD symptoms (9 inattention symptoms and 9 hyperactivity-impulsivity symptoms). Parents or guardians rated the frequency of each of 18 ADHD symptoms during the preceding 6 months. Children with 6 or more symptoms of either inattention or hyperactivity-impulsivity were defined as having ADHD symptoms. Generalized linear mixed models were applied to estimate the association between greenness and ADHD symptoms. Results: The mean (SD) age of the 59 754 study participants was 10.3 (3.6) years, and 29 494 (49.4%) were girls. A total of 2566 participants (4.3%) had ADHD symptoms. Greenness levels differed substantially across schools and kindergartens. The normalized difference vegetation index within 500 m of a school or kindergarten ranged from -0.09 to 0.77. Greater greenness levels were associated with lower odds of ADHD symptoms. In covariate-adjusted models, a 0.1-unit increase in normalized difference vegetation index or soil-adjusted vegetation index within 500 m of a school or kindergarten was significantly associated with lower odds of ADHD symptoms (odds ratios, 0.87 [95% CI, 0.83-0.91] and 0.80 [95% CI, 0.74-0.86], respectively; P < .001 for both). The associations were robust in a series of sensitivity analyses. Conclusions and Relevance: These findings suggest that there may be a beneficial association between school-based greenness and ADHD symptoms in Chinese children. Future longitudinal and mechanistic studies are needed to confirm the findings of this cross-sectional analysis and further explore potential mechanisms of this association.

9.
Mutagenesis ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31424514

RESUMO

We review here data on familial risk in colorectal cancer (CRC) generated from the Swedish Family-Cancer Database, the largest resource of its kind in the world. Although the concordant familial risk for CRC (i.e. CRC risk in families of CRC patients) has been reasonably well established, the studies on discordant familial risks (i.e. CRC risk in families with any other cancers) are rare. Because different cancers could be caused by shared genetic susceptibility or shared environment, data of associations of discordant cancers may provide useful information for identifying common risk factors. In analyses between any of 33 discordant cancers relative risks (RRs) for discordant cancers were estimated in families with increasing numbers of probands with CRC; in the reverse analyses, RRs for CRC were estimated in families with increasing numbers of probands with discordant cancers. In separate analyses, hereditary non-polyposis colorectal cancer (HNPCC) families were excluded from the study, based on HNPCC related double primary cancers, to assess the residual familial RRs. We further reviewed familial risks of colon and rectal cancers separately in search for distinct discordant associations. The reviewed data suggested that colon cancer was associated with a higher familial risk for CRC compared to rectal cancer. The previous data had reported associations of CRC with melanoma, thyroid and eye cancers. Nervous system cancer was only associated with colon cancer, and lung cancer only associated with rectal cancer. The reviewed data on discordant association may provide guidance to gene identification and may help genetic counseling.

10.
J Biol Chem ; 294(25): 9959-9972, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31092598

RESUMO

Mesoderm development is a finely tuned process initiated by the differentiation of pluripotent epiblast cells. Serine/threonine kinase 40 (STK40) controls the development of several mesoderm-derived cell types, its overexpression induces differentiation of mouse embryonic stem cells (mESCs) toward the extraembryonic endoderm, and Stk40 knockout (KO) results in multiple organ failure and is lethal at the perinatal stage in mice. However, molecular mechanisms underlying the physiological functions of STK40 in mesoderm differentiation remain elusive. Here, we report that Stk40 ablation impairs mesoderm differentiation both in vitro and in vivo Mechanistically, STK40 interacts with both the E3 ubiquitin ligase mammalian constitutive photomorphogenesis protein 1 (COP1) and the transcriptional regulator proto-oncogene c-Jun (c-JUN), promoting c-JUN protein degradation. Consequently, Stk40 knockout leads to c-JUN protein accumulation, which, in turn, apparently suppresses WNT signaling activity and impairs the mesoderm differentiation process. Overall, this study reveals that STK40, together with COP1, represents a previously unknown regulatory axis that modulates the c-JUN protein level within an appropriate range during mesoderm differentiation from mESCs. Our findings provide critical insights into the molecular mechanisms regulating the c-JUN protein level and may have potential implications for managing cellular disorders arising from c-JUN dysfunction.

11.
PLoS One ; 14(3): e0214410, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30921367

RESUMO

While treatment for testicular cancer (TC) has become standardized after the 1980s with an associated significant improvement in patient survival, this has been accompanied by an increased risk of second primary cancers (SPCs). Patients were identified from the Swedish Cancer Registry spanning the years from 1980 to 2015, including 8788 individuals with primary TC and their SPCs. Relative risks (RRs) for SPC were calculated using the generalized Poisson regression model. SPCs were diagnosed in 9.4% of patients with TC and half of them were late onset cancers not common in the population in their 40s. Overall RR of SPCs (excluding second TC) was 1.30 (95%CI: 1.20-1.40), including high risks for seven solid cancers, non-Hodgkin lymphoma and leukemia. Second TC was the most common SPC and the RR of 17.19 (95%CI: 14.89-19.85) was the highest recorded. Cancers known to be fatal as first primary cancers were also fatal as SPC in TC patients. Survival at 30 years of follow-up was approximately 80% for TC patients without SPC but it decreased to 40% for patients with SPC. The unexpected finding that half of the identified SPCs were typical late onset cancers in the middle-aged population raises concerns that therapy may facilitate premature aging. The risks of SPC are clinically important for the long-term management of TC patients and the high-mortality calls for a future management strategy.


Assuntos
Segunda Neoplasia Primária/diagnóstico , Neoplasias Testiculares/patologia , Idoso , Causas de Morte , Bases de Dados Factuais , Humanos , Linfoma não Hodgkin/diagnóstico , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/epidemiologia , Sistema de Registros , Risco , Seminoma/mortalidade , Seminoma/patologia , Análise de Sobrevida , Suécia/epidemiologia , Neoplasias Testiculares/mortalidade
12.
Science ; 364(6436): 184-188, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30846611

RESUMO

Tissue regenerative potential displays striking divergence across phylogeny and ontogeny, but the underlying mechanisms remain enigmatic. Loss of mammalian cardiac regenerative potential correlates with cardiomyocyte cell-cycle arrest and polyploidization as well as the development of postnatal endothermy. We reveal that diploid cardiomyocyte abundance across 41 species conforms to Kleiber's law-the ¾-power law scaling of metabolism with bodyweight-and inversely correlates with standard metabolic rate, body temperature, and serum thyroxine level. Inactivation of thyroid hormone signaling reduces mouse cardiomyocyte polyploidization, delays cell-cycle exit, and retains cardiac regenerative potential in adults. Conversely, exogenous thyroid hormones inhibit zebrafish heart regeneration. Thus, our findings suggest that loss of heart regenerative capacity in adult mammals is triggered by increasing thyroid hormones and may be a trade-off for the acquisition of endothermy.


Assuntos
Coração/fisiologia , Miócitos Cardíacos/fisiologia , Poliploidia , Regeneração/fisiologia , Hormônios Tireóideos/fisiologia , Animais , Regulação da Temperatura Corporal , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Diploide , Camundongos , Miócitos Cardíacos/classificação , Filogenia , Receptores dos Hormônios Tireóideos/genética , Receptores dos Hormônios Tireóideos/fisiologia , Regeneração/efeitos dos fármacos , Regeneração/genética , Transdução de Sinais , Hormônios Tireóideos/farmacologia , Peixe-Zebra
13.
Dis Colon Rectum ; 62(2): 189-195, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30640834

RESUMO

BACKGROUND: Many studies have indicated that colon and rectal cancers differ in etiology and histology. OBJECTIVE: The aim of this study was to investigate whether the associations of colon and rectal cancers with any other (discordant) cancer were site specific. DESIGN: A novel approach was implemented in which cancer risks were analyzed in families with increasing numbers of family members diagnosed with defined cancers. The novel assumption was that, for a true familial association, the risk should increase by the number of affected family members. In separate analyses, familial risks were calculated after the exclusion of putative families with hereditary nonpolyposis colorectal cancer. SETTINGS: The study was conducted using the Swedish Family-Cancer Database. MAIN OUTCOME MEASURES: The outcome measure was relative risk. RESULTS: Relative risks of colorectal cancer and colon cancer were higher when family members were diagnosed with colon cancer than when family members were diagnosed with rectal cancer (incidence rate ratio for colorectal: 1.82 (95% CI, 1.74-1.90) vs 1.61 (95% CI, 1.51-1.71); incidence rate ratio for colon: 1.92 (95% CI, 1.83-2.02) vs 1.56 (95% CI, 1.45-1.69)). Relative risks for 10 discordant cancers were increased in colon or rectal cancer families, whereas none of the relative risks differed significantly between colon and rectal cancers. After deleting hereditary nonpolyposis colorectal cancer families, the relative risks of endometrial and ovarian cancers were no longer significant. LIMITATIONS: Genetic data are unavailable in the database. CONCLUSIONS: Our results suggested that familial risks for colon cancer were higher than risks for rectal cancer in families of patients with colorectal cancer and colon cancer. The relationships of lung cancer and nervous system cancer with colorectal cancer were site specific. The associations of colon and rectal cancers with lung cancer, myeloma, and cancer of unknown primary appeared not to point out known syndromes and may suggest involvement of a novel predisposition. See Video Abstract at http://links.lww.com/DCR/A791.


Assuntos
Adenocarcinoma/epidemiologia , Neoplasias do Colo/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias do Endométrio/epidemiologia , Família , Neoplasias Ovarianas/epidemiologia , Neoplasias Retais/epidemiologia , Risco , Adenocarcinoma/genética , Neoplasias do Colo/genética , Neoplasias Colorretais/genética , Bases de Dados Factuais , Neoplasias do Endométrio/genética , Feminino , Humanos , Masculino , Neoplasias Ovarianas/genética , Neoplasias Retais/genética , Suécia/epidemiologia
14.
Environ Pollut ; 259: 113857, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31918137

RESUMO

Previous epidemiological and experimental studies have shown that legacy perfluoroalkyl acids (PFAAs) are immunotoxic. However, whether the immunosuppressive effects in PFAA alternatives which recently have been widely detected in the environment are unknown. To address this knowledge gap, we investigated the relationship of serum legacy PFAAs and PFAA alternatives with the antibody of hepatitis B virus in adults. We recruited 605 participants from a cross-sectional study, the Isomer of C8 Health Project in China. We measured two representative legacy PFAAs (perfluorooctane sulfonate, PFOS and perfluorooctanoic acid, PFOA), and three PFAA alternatives (two chlorinated polyfluorinated ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) in serum using ultra-performance liquid chromatograph-tandem mass spectrometry (UPLC-MS/MS). We applied linear and logistic regression models to analyze associations between serum PFAAs and hepatitis B surface antibody (HBsAb) with multivariable adjustments. We found negative associations between serum PFAAs concentrations and HBsAb. Lower serum HBsAb levels (log mIU/mL) were observed for each log-unit increase in linear PFOS (ß = -0.31, 95% confidential interval: 0.84, -0.18), 6:2 PFESA (ß = -0.81, 95% CI: 1.20, -0.42), 8:2 PFESA (ß = -0.29, 95% CI: 0.43, -0.14) and PFBA (ß = -0.18, 95% CI: 0.28, -0.08). The association between PFAAs and HBsAb seronegative seemed to be higher for 6:2 PFESA (odds ratio = 3.32, 95% CI: 2.16, 5.10) than its predecessors, linear PFOS (OR = 1.96, 95% CI: 1.37, 2.81) and branched PFOS isomers (OR = 1.64, 95% CI: 1.05, 2.56). We report new evidence that exposure to PFAA alternatives are associated with lower HBsAb in adults. This association seems to be stronger in 6:2 PFESA than PFOS. Our results suggest that more studies are needed to clarify the potential toxicity of PFAA alternatives in human which will facilitate better chemical regulations for PFAAs.

15.
PLoS One ; 13(10): e0205000, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30281663

RESUMO

Ovarian cancer is a heterogeneous disease. Data regarding familial risks for specific proband, age at diagnosis and histology are limited. Such data can assist genetic counseling and help elucidate etiologic differences among various histologic types of ovarian malignancies. By using the Swedish Family-Cancer Database, we calculated relative risks (RRs) for detailed family histories using a two-way comparison, which implied e.g. estimation of RRs for overall ovarian cancer when family history was histology-specific ovarian cancer, and conversely, RRs for histology-specific ovarian cancer when family history was overall ovarian cancer. In families of only mother, only sisters or both mother and sisters diagnosed with ovarian cancer, cancer risks for ovary were 2.40, 2.59 and 10.40, respectively; and were higher for cases diagnosed before the age of 50 years. All histological types showed a familial risk in two-way analyses, except mucinous and sex cord-stromal tumors. RRs for concordant histology were found for serous (2.47), endometrioid (3.59) and mucinous ovarian cancers (6.91). Concordant familial risks were highest for mucinous cancer; for others, some discordant associations, such as endometrioid-undifferentiated (9.27) and serous-undifferentiated (4.80), showed the highest RRs. Familial risks are high for early-onset patients and for those with multiple affected relatives. Sharing of different histological types of ovarian cancer is likely an indication of the complexity of the underlying mechanisms.


Assuntos
Neoplasias Ovarianas/epidemiologia , Linhagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mães , Risco , Irmãos , Adulto Jovem
16.
PLoS One ; 13(10): e0206721, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30365548

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0205000.].

17.
Int J Cancer ; 143(10): 2449-2457, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30238973

RESUMO

Second primary cancers (SPCs) account for an increasing proportion of all cancer diagnoses. It is unlikely that prior therapy is solely responsible for SPC risk. To investigate risk of SPC after diagnosis of non-Hodgkin lymphoma (NHL) and 10 of its subtypes we conducted a novel bidirectional analysis, SPCs after NHL and NHL as SPC. Using the Swedish Family-Cancer Database, we identified 19,833 individuals with primary NHL diagnosed between 1993 and 2015. We calculated relative risks (RRs) of SPCs in NHL survivors and, for bi-directional analysis, risk of NHL as SPC. The overall RRs were significantly bidirectionally increased for NHL and 7 cancers. After diagnosis of NHL risks were increased for upper aerodigestive tract (RR = 1.96), colorectal (1.35), kidney (3.10), bladder (1.54) and squamous cell skin cancer (SCC) (4.12), melanoma (1.98) and Hodgkin lymphoma (9.38). The concordance between RRs for each bidirectional association between NHL and 31 different cancers was highly significant (r = 0.86, p < 0.0001). Melanoma was bidirectionally associated with all 10 subtypes of NHL. The observed bidirectional associations between NHL and cancer suggest that therapy-related carcinogenic mechanisms cannot solely explain the findings. Considering that skin SCC and melanoma are usually treated by surgery and that these cancers and NHL are most responsive of any cancer to immune suppression, the consistent bidirectional results provide population-level evidence that immune suppressed state is a key underlying mechanism in the context of SPCs. Furthermore, the quantified risks for NHL subtypes have direct clinical application in the management of NHL patients.


Assuntos
Doenças do Sistema Imunitário/epidemiologia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/imunologia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/imunologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/patologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/patologia , Risco , Suécia/epidemiologia
18.
Sci Rep ; 8(1): 11561, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30069056

RESUMO

Familial risk of ovarian cancer is well-established but whether ovarian cancer clusters with other cancers and the clusters differ by histology remains uncertain. Using data from the Swedish Family-Cancer Database, we explored familial associations of ovarian cancer with other cancers with a novel approach; relative risk for (histology-specific) ovarian cancer was estimated in families with patients affected by other cancers, and conversely, risks for other cancers in families with (histology-specific) ovarian cancer patients. Eight discordant cancers were associated with ovarian cancer risk, of which family history of breast cancer showed a dose-response (P-trend <0.0001). Conversely, risks of eight types of cancer increased in families with ovarian cancer patients, and dose-responses were shown for risks of liver (P-trend = 0.0083) and breast cancers (P-trend <0.0001) and cancer of unknown primary (P-trend = 0.0157). Some cancers were only associated with histology-specific ovarian cancers, e.g. endometrial cancer was only associated with endometrioid type but with highest significance. Novel associations with virus-linked cancers of the nose and male and female genitals were found. The results suggest that ovarian cancer shares susceptibility with a number of other cancers. This might alert genetic counselors and challenge approaches for gene and gene-environment identification.


Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Predisposição Genética para Doença , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/epidemiologia , Análise por Conglomerados , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Medição de Risco , Suécia/epidemiologia
19.
Lancet Haematol ; 5(8): e368-e377, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30075833

RESUMO

BACKGROUND: Although advances in the treatment of myeloid neoplasms have led to improved patient survival, this improvement has been accompanied by an increased risk of second primary cancer (ie, the risk of another cancer after myeloid neoplasia). We aimed to assess bi-directional associations between myeloid cancers and other cancers-ie, development of second primary cancer in patients who have previously had myeloid cancer, and risks of myeloid neoplasia in patients who have previously had another cancer-to provide insight into possible mechanisms beyond side-effects of treatment and shared risk factors. METHODS: Using the Swedish Family-Cancer Database, we identified 35 928 individuals with primary myeloid cancer, including myeloproliferative neoplasms, acute myeloid leukaemia, chronic myeloid leukaemia, and myelodysplastic syndrome diagnosed between 1958 and 2015. The Swedish Family-Cancer Database includes every individual registered as a resident in Sweden starting in 1932, with full parental history. The primary endpoint was the assessment of relative risks (RRs) for second primary cancer, which we performed using means of incidence rate ratios, regressed over a generalised Poisson model. FINDINGS: Between 1958 and 2015, overall relative risk of second primary cancers was significantly increased after acute myeloid leukaemia (RR 1·29, 95% CI 1·17-1·41), chronic myeloid leukaemia (1·52, 1·35-1·69), myelodysplastic syndrome (1·42, 1·26-1·59), and all myeloproliferative neoplasms (1·37, 1·30-1·43) relative to the incidence of these cancers as first primary cancer. With myeloid neoplasia as a second primary cancer, risks were significantly increased for acute myeloid leukaemia (1·57, 1·48-1·65), chronic myeloid leukaemia (1·26, 1·13-1·40), and myelodysplastic syndrome (1·54, 1·42-1·67) relative to the incidence of these myeloid neoplasms as first primary cancers. Relative risk of upper aerodigestive tract cancer, squamous cell skin cancer, and non-Hodgkin lymphoma as second primary cancers were increased after all four types of myeloid neoplasia relative to their incidence as first primary cancers. High risks of myelodysplastic syndrome and acute myeloid leukaemia as second primary cancers were found after haematological cancers (RRs between 5·08 and 10·04). INTERPRETATION: The relative risks of second primary cancer are important for the long-term management of patients with myeloid cancers. The bi-directional associations of myeloid cancers with many other cancers suggest a number of candidate mechanisms that might contribute to the development and aetiology of a second primary cancer. These mechanisms might include immune dysfunction or the effects of treatment, and these should be assessed in future investigations. FUNDING: Deutsche Krebshilfe, Jane and Aatos Erkko Foundation, Sigrid Juselius Foundation, Finnish Cancer Organizations, Swedish Research Council, ALF from Region Skåne, and Bloodwise.


Assuntos
Neoplasias da Medula Óssea/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Suécia/epidemiologia , Adulto Jovem
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