Athletes' exposure to air pollution during World Athletics Relays: A pilot study

Potential adverse consequences of exposure to air pollutants during exercise include decreased lung function, and exacerbation of asthma and exercise-induced bronchoconstriction. These effects are especially relevant for athletes and during international competitions, as they may impact athletic performance. Thus, assessing and mitigating exposure to air pollutants during exercising should be encouraged in sports venues. A comprehensive air quality assessment was carried out during the World Relays Yokohama 2019, in the stadium and the warm-up track. The pilot included on-line and off-line instrumentation for gaseous and particulate pollutants and meteo- rological parameters, and the comparison with local reference data. Air quality perception and exacerbation of symptoms of already-diagnosed diseases (mainly respiratory and cardiovascular) were assessed by athletes by means of questionnaires during training sessions. Median NO2 concentrations inside the stadium (25.6–31.9 μgm−3) were in the range of the Yokohama urban background, evidencing the impact of urban sources (e.g., traffic) on athletes' exposure during training and competition. The assessment of hourly air pollutant trends was identified as a valuable tool to provide guidance to reduce atheletes' exposure, by identifying the periods of Inhalation Track and field Respiratory diseases World Athletics 1. Introduction Evidence supports adverse effects from short-term and long-term inhalation of air pollution to the respiratory and the cardiovascular sys- tems (Brook et al., 2002; Pietropaoli et al., 2004; Gauderman et al., 2007; de Prado Bert et al., 2018). Health impacts have been assessed for gen- eral and high-risk populations, and even for general populations performing physical activities such as walking or cycling while com- muting (de Nazelle et al., 2012; Hofman et al., 2018; Luengo-Oroz and Reis, 2019; Qiu et al., 2019; Quiros et al., 2013; Rivas et al., 2014). How- ever, research is scarce on the effects of ambient air pollution on exercis- ing athletes and their athletic performance, who may have greater than average susceptibility and exposure to air pollutants because of the physiological changes that occur during prolonged exercise (Quin et al., 2019). Specifically, there are 3 reasons why athletes are at higher risk from air pollution (McCafferty, 1981): (1) increased ventilation during exer- cise; (2) a greater fraction of air is inhaled through the mouth during ex- ercise, effectively bypassing the normal nasal filtration mechanisms; and (3) the increased airflow velocity carries pollutants deeper into the respiratory tract. Furthermore, pulmonary diffusion capacity in- creases with exercise (Turcotte et al., 1997; Stokes et al., 1981; Fisher and Cerny, 1982; Flaherty et al., 2013), increasing gaseous pollutant in- take. Nasal mucociliary clearance, impaired in long-distance runners, may also contribute to the higher susceptibility of endurance athletes given that pollutants which are normally cleared from the respiratory system, are instead absorbed (Atkinson, 1987). Even though research is scarce, studies on the relationship between air quality, athletic performance, and respiratory symptoms encourage pursuing further investigations. Lichter et al. (2015) assessed the effects of particulate air pollution on soccer players in German stadiums, re- vealing that performance was reduced under poor air quality condi- tions. Bos et al. (2011) and Quin et al. (2019) observed that the health benefits of active commuting could be negatively influenced by exercis- ing in polluted environments, while Rundell and Caviston (2008) re- ported that the acute inhalation of PM1 at concentrations in the range of many urban environments could impair exercise performance. Carlisle and Sharp (2001) and Cakmak et al. (2011) concluded that O3 was particularly damaging to athletes, with subjects achieving a lower aerobic fitness score on high ozone days. Finally, long-term exposure to outdoor air pollution may trigger intermittent endogenous airway acidification episodes indicative of pollution-related lung inflammation (Ferdinands et al., 2008). These results have particularly relevant impli- cations for top-level athletes participating in international competi- tions: the performance of athletes training in highly polluted environments may be impaired compared to athletes training in cleaner environments and, similarly, athletes used to training in cleaner envi- ronments may be adversely affected when competing in highly polluted locations. Thus, assessing exposure to air pollution in athletics venues becomes a necessity when aiming at understanding environmental drivers of both athletic performance, and athletes' health. In this framework, the aim of this study was to characterize air pol- lutant concentrations in the Yokohama stadium (in the competition and the training area) during the Yokohama 2019 World Relays the day with lowest ambient concentrations. This strategy could be adopted to define training and competition schedules, and would have special added value for athletes with respiratory conditions. Personal exposure to polycyclic aromatic hydrocarbons was quantified through wearable silicone wristbands, and showed highly var- iability across volunteers. The wristbands are a simple approach to assess personal exposure to potentially toxic organic compounds. Further research would be necessary with regard to specific air pollutants that may trigger or exacerbate respiratory conditions typical of the athlete community. The availability of high time-resolved ex- posure data in the stadiums opens up the possibility to calculate doses of specific pollutants for individual ath- letes in future athletics events, to understand the impact of environmental factors on athletic performance

Lifetime exposure to brominated trihalomethanes in drinking water and swimming pool attendance are associated with chronic lymphocytic leukemia: a Multicase-Control Study in Spain (MCC-Spain)

Background: Chronic lymphocytic leukemia (CLL) etiology is poorly understood, and carcinogenic chemicals in drinking and recreational water are candidates. Objective: To evaluate the association between drinking-water exposure to trihalomethanes (THMs) and nitrate as well as lifetime swimming pool attendance and CLL. Methods: During 2010-2013, hospital-based CLL cases and population-based controls were recruited in Spain, providing information on residential histories, type of water consumed and swimming pool attendance. Average THMs and nitrate levels in drinking water were linked to lifetime water consumption. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using mixed models. Results: Final samples for residential tap water analyses and swimming pool attendance analyses were 144 cases/1230 controls and 157 cases/1240 controls, respectively. Mean (SD) values for average lifetime residential brominated THMs and chloroform in tap water (μg/L), and ingested nitrate (mg/day) were 48.1 (35.6), 18.5 (6.7) and 13.7 (9.6) respectively in controls; and 72.9 (40.7), 17.9 (5.4), and 14.1 (8.8) in CLL cases. For each 10 μg/L increase of brominated THMs and chloroform lifetime-average levels, the ORs (95% CI) were 1.22 (1.14, 1.31) and 0.54 (0.34, 0.87), respectively. For each 5 mg/day increase of ingested nitrate, the OR of CLL was 0.91 (0.80, 1.04). The OR of lifetime pool users (vs. non-users) was 2.38 (1.61, 3.52). Upon performing annual frequency of attending pools analysis through categorization, the second and third categories showed an ORs of 2.36 (1.49, 3.72) and 2.40 (1.51, 3.83), respectively, and P-trend of 0.001. Impact statement: This study identifies an association of long-term exposure to THMs in drinking water, at concentrations below the regulatory thresholds and WHO guidelines, and swimming pool attendance, with chronic lymphocytic leukemia (CLL). These unprecedented findings are highly relevant since CLL is an incurable cancer with still unknown etiology and because the widespread exposure to chlorination by-products that remain in drinking and recreational water worldwide. Despite the demonstrated carcinogenicity in animals of several chlorination by-products, little is known about their potential risks on human health. This study makes a significant contribution to the search for environmental factors involved in the etiology of CLL and to the evidence of the health impact of these high prevalent water contaminants.The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01889, PI11/00226, PI12/01270, PI12/00715, PI14/0613, PI15/00914, PI17CIII/00034), by the Fundación Marqués de Valdecilla (API 10/09), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723, 2021SGR01354 and 2014SGR850, by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.S

Long-Term Exposure to Nitrate and Trihalomethanes in Drinking Water and Prostate Cancer: A Multicase–Control Study in Spain (MCC-Spain)

BACKGROUND: Nitrate and trihalomethanes (THMs) in drinking water are widespread and are potential human carcinogens.OBJECTIVE: We evaluated the association between drinking-water exposure to nitrate and THMs and prostate cancer.METHODS: During the period 2008-2013, 697 hospital-based incident prostate cancer cases (97 aggressive tumors) and 927 population-based controls were recruited in Spain, providing information on residential histories and type of water consumed. Average nitrate and THMs levels in drinking water were linked with lifetime water consumption to calculate waterborne ingestion. Odds ratios (OR) and 95% confidence intervals (CI) were esti-mated using mixed models with recruitment area as random effect. Effect modification by tumor grade (Gleason score), age, education, lifestyle, and dietary factors was explored.RESULTS: Mean ( +/- standard deviation) adult lifetime waterborne ingested nitrate (milligrams per day), brominated (Br)-THMs (micrograms per day), and chloroform (micrograms per day) were 11.5 ( +/- 9.0), 20.7 ( +/- 32.4), and 15.1 ( +/- 14.7) in controls. Waterborne ingested nitrate >13.8 vs. = 8. Associations were higher in the youngest and those with lower intakes of fiber, fruit/vegetables, and vitamin C. Waterborne ingested THMs were not associated with prostate cancer. Residential tap water levels of Br-THMs and chloroform showed, respectively, inverse and positive associations with prostate cancer.CONCLUSIONS: Findings suggest long-term waterborne ingested nitrate could be a risk factor of prostate cancer, particularly for aggressive tumors. High intakes of fiber, fruit/vegetables and vitamin C may lower this risk. Association with residential levels but not ingested chloroform/Br-THM may suggest inhalation and dermal routes could be relevant for prostate cancer. https://doi.org/10.1289/EHP1139

Exposure to widespread drinking water chemicals, blood inflammation markers, and colorectal cancer

Background: Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water associated with colorectal cancer risk but mechanisms are not well understood. Objectives: We explored the association between exposure to THMs and nitrate in drinking water and inflammation markers, and the link with colorectal cancer risk. Methods: A subset of 198 colorectal cancer cases and 205 controls from the multicase-control study MCC-Spain were included. Average concentration of THMs (chloroform, bromodichloromethane, dibromochloromethane, bromoform) and nitrate in tap water at the residence was estimated from age 18 until 2 years before the interview ("long term") and for a recent period (3 years before diagnosis). Serum levels of EGF, eotaxin, G-CSF, IL-17E, IL-1rA, IL-8, IP-10, MDC, MPO, periostin, VEGF, and C-reactive protein (CRP) were measured. We estimated the linear association between inflammation markers and exposure among controls, and the odds ratio of colorectal cancer associated with THM and nitrate exposure, and inflammation markers. A mediation analysis was conducted to identify inflammation markers in the pathway between THM/nitrate exposure and colorectal cancer. Results: Serum concentrations of EGF, IL-8, IL-17E and eotaxin increased with recent residential levels of brominated THMs, chloroforom and/or total THM. No associations were observed for nitrate and for long-term residential THM levels. All residential exposures except chloroform were positively associated with colorectal cancer. Serum concentrations of VEGF and periostin were positively associated with colorectal cancer, while EGF was inversely associated. One protein-exposure combination (periostin-recent ingested brominated THMs) slightly mediated the association with colorectal cancer risk. Discussion: Results suggest that estimated THM exposure is involved in inflammation processes. However, the study design was limited to stablish etiologically relevant associations between the protein levels and colorectal cancer risk. The lack of association between nitrate exposure and inflammation markers suggests other biological mechanisms are involved in the link with colorectal cancer.Acknowledgements: We acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. This work was funded by the 7th Framework Programme EXPOSOMICS Project (grant agreement 308610), the Acci´on Transversal del C´ancer del Consejo de Ministros del 11/10/2007, and the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI11/00226) FIS grants

The Association of Nighttime Fasting Duration and Prostate Cancer Risk: Results from the Multicase-Control (MCC) Study in Spain

Nighttime fasting has been inconclusively associated with a reduced risk of cancer. The purpose of this study was to investigate this association in relation to prostate cancer risk. We examined data from 607 prostate cancer cases and 848 population controls who had never worked in night shift work from the Spanish multicase-control (MCC) study, 2008-2013. Through an interview, we collected circadian information on meal timing at mid-age. We estimated odds ratios (OR) and 95% confidence intervals (CI) with unconditional logistic regression. After controlling for time of breakfast, fasting for more than 11 h overnight (the median duration among controls) was associated with a reduced risk of prostate cancer compared to those fasting for 11 h or less (OR = 0.77, 95% 0.54-1.07). Combining a long nighttime fasting and an early breakfast was associated with a lower risk of prostate cancer compared to a short nighttime fasting and a late breakfast (OR = 0.54, 95% CI 0.27-1.04). This study suggests that a prolonged nighttime fasting duration and an early breakfast may be associated with a lower risk of prostate cancer. Findings should be interpreted cautiously and add to growing evidence on the importance of chrononutrition in relation to cancer risk.Funding: Instituto de Salud Carlos III FIS PI11/01889. Anna Palomar-Cros is supported by a MINECO (Ministry of Economy in Spain) fellowship. We acknowledge support from the Spanish State Research Agency and Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program

Risk model for prostate cancer using environmental and genetic factors in the spanish multi-case-control (MCC) study

Prostate cancer (PCa) is the second most common cancer among men worldwide. Its etiology remains largely unknown compared to other common cancers. We have developed a risk stratification model combining environmental factors with family history and genetic susceptibility. 818 PCa cases and 1,006 healthy controls were compared. Subjects were interviewed on major lifestyle factors and family history. Fifty-six PCa susceptibility SNPs were genotyped. Risk models based on logistic regression were developed to combine environmental factors, family history and a genetic risk score. In the whole model, compared with subjects with low risk (reference category, decile 1), those carrying an intermediate risk (decile 5) had a 265% increase in PCa risk (OR = 3.65, 95% CI 2.26 to 5.91). The genetic risk score had an area under the ROC curve (AUROC) of 0.66 (95% CI 0.63 to 0.68). When adding the environmental score and family history to the genetic risk score, the AUROC increased by 0.05, reaching 0.71 (95% CI 0.69 to 0.74). Genetic susceptibility has a stronger risk value of the prediction that modifiable risk factors. While the added value of each SNP is small, the combination of 56 SNPs adds to the predictive ability of the risk model

Association of occupational heat exposure and colorectal cancer in the MCC-Spain study

Objective Heat exposure and heat stress/strain is a concern for many workers. There is increasing interest in potential chronic health effects of occupational heat exposure, including cancer risk. We examined potential associations of occupational heat exposure and colorectal cancer (CRC) risk in a large Spanish multi-case- control study.Methods We analyzed data on 1198 histologically confirmed CRC cases and 2690 frequency-matched controls. The Spanish job-exposure matrix, MatEmEsp, was used to assign heat exposure estimates to the lifetime occupa-tions of participants. Three exposure indices were assessed: ever versus never exposed, cumulative exposure and duration (years). We estimated odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression adjusting for potential confounders.Results Overall, there was no association of ever, compared with never, occupational heat exposure and CRC (OR 1.09, 95% CI 0.92-1.29). There were also no associations observed according to categories of cumulative exposure or duration, and there was no evidence for a trend. There was no clear association of ever occupational heat exposure and CRC in analysis conducted among either men or women when analyzed separately. Positive associations were observed among women in the highest categories of cumulative exposure (OR 1.81, 95% CI 1.09-3.03) and duration (OR 2.89, 95% CI 1.50-5.59) as well as some evidence for a trend (P<0.05).Conclusion Overall, this study provides no clear evidence for an association between occupational heat exposure and CRC

Aberrant Epstein-Barr virus antibody patterns and chronic lymphocytic leukemia in a Spanish multicentric case-control study

Background: Epstein-Barr virus (EBV)-related malignancies harbour distinct serological responses to EBV antigens. We hypothesized that EBV serological patterns can be useful to identify different stages of chronic lymphocytic leukemia. Methods: Information on 150 cases with chronic lymphocytic leukemia and 157 frequency-matched (by age, sex and region) population-based controls from a Spanish multicentre case-control study was obtained. EBV immunoglobulin G serostatus was evaluated through a peptide-based ELISA and further by immunoblot analysis to EBV early antigens (EA), nuclear antigen (EBNA1), VCA-p18, VCA-p40 and Zebra. Two independent individuals categorized the serological patterns of the western blot analysis. Patients with very high response and diversity in EBV-specific polypeptides, in particular with clear responses to EA-associated proteins, were categorized as having an abnormal reactive pattern (ab_EBV). Adjusted odds ratios (OR) and 95% confidence interval (CI) were estimated using logistic regression models. Results: Almost all subjects were EBV-IgG positive (>95% of cases and controls) whereas ab_EBV patterns were detected in 23% of cases (N = 34) and 11% of controls (N = 17; OR: 2.44, 95% CI, 1.29 to 4.62; P = 0.006), particularly in intermediate/high risk patients. Although based on small numbers, the association was modified by smoking with a gradual reduction of ab_EBV-related OR for all Rai stages from never smokers to current smokers. Conclusions: Highly distinct EBV antibody diversity patterns revealed by immunoblot analysis were detected in cases compared to controls, detectable at very early stages of the disease and particularly among non smokers. This study provides further evidence of an abnormal immunological response against EBV in patients with chronic lymphocytic leukemia

Polymorphisms in GSTT1, GSTZ1, and CYP2E1, Disinfection By-products, and Risk of Bladder Cancer in Spain

Background: Bladder cancer has been linked with long-term exposure to disinfection by-products (DBPs) in drinking water.Objectives: In this study we investigated the combined influence of DBP exposure and polymorphisms in glutathione S-transferase (GSTT1, GSTZ1) and cytochrome P450 (CYP2E1) genes in the metabolic pathways of selected by-products on bladder cancer in a hospital-based case–control study in Spain. Methods: Average exposures to trihalomethanes (THMs; a surrogate for DBPs) from 15 years of age were estimated for each subject based on residential history and information on municipal water sources among 680 cases and 714 controls. We estimated effects of THMs and GSTT1, GSTZ1, and CYP2E1 polymorphisms on bladder cancer using adjusted logistic regression models with and without interaction terms. Results: THM exposure was positively associated with bladder cancer: adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.2 (0.8–1.8), 1.8 (1.1–2.9), and 1.8 (0.9–3.5) for THM quartiles 2, 3, and 4, respectively, relative to quartile 1. Associations between THMs and bladder cancer were stronger among subjects who were GSTT1 +/+ or +/– versus GSTT1 null (pinteraction = 0.021), GSTZ1 rs1046428 CT/TT versus CC (pinteraction = 0.018), or CYP2E1 rs2031920 CC versus CT/TT (pinteraction = 0.035). Among the 195 cases and 192 controls with high-risk forms of GSTT1 and GSTZ1, the ORs for quartiles 2, 3, and 4 of THMs were 1.5 (0.7–3.5), 3.4 (1.4–8.2), and 5.9 (1.8–19.0), respectively. Conclusions: Polymorphisms in key metabolizing enzymes modified DBP-associated bladder cancer risk. The consistency of these findings with experimental observations of GSTT1, GSTZ1, and CYP2E1 activity strengthens the hypothesis that DBPs cause bladder cancer and suggests possible mechanisms as well as the classes of compounds likely to be implicated.This work was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute (N02-CP-11015), the Fondo de Investigación Sanitaria (00/0745, G03/174, G03/160, C03/09, and C03/90), and the Instituto de Salud Carlos III, Spanish Health Ministry (CP06/00341