The role of oral hygiene in head and neck cancer: results from International Head and Neck Cancer Epidemiology (INHANCE) consortium.

BACKGROUND: Poor oral hygiene has been proposed to contribute to head and neck cancer (HNC) risk, although causality and independency of some indicators are uncertain. This study investigates the relationship of five oral hygiene indicators with incident HNCs. METHODS: In a pooled analysis of 8925 HNC cases and 12 527 controls from 13 studies participating in the International Head and Neck Cancer Epidemiology Consortium, comparable data on good oral hygiene indicators were harmonized. These included: no denture wear, no gum disease (or bleeding), <5 missing teeth, tooth brushing at least daily, and visiting a dentist ≥once a year. Logistic regression was used to estimate the effects of each oral hygiene indicator and cumulative score on HNC risk, adjusting for tobacco smoking and alcohol consumption. RESULTS: Inverse associations with any HNC, in the hypothesized direction, were observed for <5 missing teeth [odds ratio (OR) = 0.78; 95% confidence interval (CI) 0.74, 0.82], annual dentist visit (OR = 0.82; 95% CI 0.78, 0.87), daily tooth brushing (OR = 0.83, 95% CI 0.79, 0.88), and no gum disease (OR = 0.94; 95% CI 0.89, 0.99), and no association was observed for wearing dentures. These associations were relatively consistent across specific cancer sites, especially for tooth brushing and dentist visits. The population attributable fraction for ≤ 2 out of 5 good oral hygiene indicators was 8.9% (95% CI 3.3%, 14%) for oral cavity cancer. CONCLUSION: Good oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of HNC.

A pilot study on the feasibility of European harmonized human biomonitoring: Strategies towards a common approach, challenges and opportunities.

In 2004 the European Commission and Member States initiated activities towards a harmonized approach for Human Biomonitoring surveys throughout Europe. The main objective was to sustain environmental health policy by building a coherent and sustainable framework and by increasing the comparability of data across countries. A pilot study to test common guidelines for setting up surveys was considered a key step in this process. Through a bottom-up approach that included all stakeholders, a joint study protocol was elaborated. From September 2011 till February 2012, 17 European countries collected data from 1844 mother-child pairs in the frame of DEMOnstration of a study to COordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES).(1) Mercury in hair and urinary cadmium and cotinine were selected as biomarkers of exposure covered by sufficient analytical experience. Phthalate metabolites and Bisphenol A in urine were added to take into account increasing public and political awareness for emerging types of contaminants and to test less advanced markers/markers covered by less analytical experience. Extensive efforts towards chemo-analytical comparability were included. The pilot study showed that common approaches can be found in a context of considerable differences with respect to experience and expertize, socio-cultural background, economic situation and national priorities. It also evidenced that comparable Human Biomonitoring results can be obtained in such context. A European network was built, exchanging information, expertize and experiences, and providing training on all aspects of a survey. A key challenge was finding the right balance between a rigid structure allowing maximal comparability and a flexible approach increasing feasibility and capacity building. Next steps in European harmonization in Human Biomonitoring surveys include the establishment of a joint process for prioritization of substances to cover and biomarkers to develop, linking biomonitoring surveys with health examination surveys and with research, and coping with the diverse implementations of EU regulations and international guidelines with respect to ethics and privacy.

Interpreting biomarker data from the COPHES/DEMOCOPHES twin projects: Using external exposure data to understand biomarker differences among countries.

In 2011 and 2012, the COPHES/DEMOCOPHES twin projects performed the first ever harmonized human biomonitoring survey in 17 European countries. In more than 1800 mother-child pairs, individual lifestyle data were collected and cadmium, cotinine and certain phthalate metabolites were measured in urine. Total mercury was determined in hair samples. While the main goal of the COPHES/DEMOCOPHES twin projects was to develop and test harmonized protocols and procedures, the goal of the current paper is to investigate whether the observed differences in biomarker values among the countries implementing DEMOCOPHES can be interpreted using information from external databases on environmental quality and lifestyle. In general, 13 countries having implemented DEMOCOPHES provided high-quality data from external sources that were relevant for interpretation purposes. However, some data were not available for reporting or were not in line with predefined specifications. Therefore, only part of the external information could be included in the statistical analyses. Nonetheless, there was a highly significant correlation between national levels of fish consumption and mercury in hair, the strength of antismoking legislation was significantly related to urinary cotinine levels, and we were able to show indications that also urinary cadmium levels were associated with environmental quality and food quality. These results again show the potential of biomonitoring data to provide added value for (the evaluation of) evidence-informed policy making.

Gender differences in cadmium and cotinine levels in prepubertal children.

Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age-sex groups: boys (6-8 years, 9-10 years and 11 years old), and girls (6-7 years, 8-9 years, 10-11 years). The number of subjects per group was between 23 and 53. The cut off values were set at 0.1 µg/L for Cd, and 0.8 µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level. In the total subsample group, the median level of Cd was 0.180 µg/L (range 0.10-0.69 µg/L), and for cotinine the median wet weight value was 1.50 µg/L (range 0.80-39.91 µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation between levels of cadmium and creatinine in all children of both genders. This shows that even at such low levels the possible effect of cadmium on kidney function was present and measurable. An increase in Cd levels was evident with age. Cadmium levels were significantly different between 6-7 year old girls, 11 year old boys and 10-11 year old girls. As there was a balanced distribution in the number of subjects from countries included in the study, bias due to data clustering was not probable. The impact of low Cd levels on kidney function and gender differences in Cd levels needs further investigation.

Indoor air pollution from solid fuels and risk of upper aerodigestive tract cancers in central and eastern Europe.

BACKGROUND: Indoor air pollution from solid fuels is a potentially important risk factor for cancer, yet data on cancers from organs other than the lung are scarce. We investigated if indoor air pollution from coal and wood are risk factors for additional cancers, particularly that of the upper aerodigestive tract (oral cavity, larynx, pharynx and esophagus) in the high-risk areas of central and eastern Europe. METHODS: We used data from multi-center hospital-based case-control study of 1065 histologically confirmed upper aerodigestive tract cancer cases and 1346 controls. Standardized questionnaires were used to collect information on residential fuel use for cooking and heating. Using unconditional logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for upper aerodigestive tract cancer risk after adjusting for potential confounders. RESULTS: Lifelong wood use was associated with pharyngeal and esophageal (OR 4.05, 95% CI: 1.30-12.68 and OR 2.71, 95% CI: 1.21-6.10, respectively). We observed an exposure-response relationship between duration of wood use and risk of pharyngeal cancer among those who had never used coal (P(trend)=0.04), ruling out the possibility of residual confounding by coal. Similarly, we observed an increased risk of laryngeal cancers and head & neck cancers among those who always used coal, with a noted exposure-response relationship (P(trend)<0.01). CONCLUSIONS: Our results suggest a possible role of indoor air pollution from solid fuel use in head and neck carcinogenesis in the high risk area of central and eastern Europe.

Gas cooking is associated with small reductions in lung function in children.

Inconsistent effects of gas cooking on lung function have been reported. In a previous study from Austria, we demonstrated a significant, though small, reduction of lung function parameters in children living in homes with gas stoves. We used a larger international database to check if this finding can be generalised. To study the relative impact of cooking with gas on lung function parameters of primary school children in a wide range of geographical settings, we analysed flow and volume data of approximately 24,000 children (aged 6-12 yrs) from nine countries in Europe and North America. Exposure information was obtained by comparable questionnaires and spirometry according to an American Thoracic Society/European Respiratory Society protocol. Linear regressions were used, controlling for individual risk factors and study area. Heterogeneity between study-specific results and mean effects were estimated using meta-analytical tools. On average, gas cooking reduced lung function parameters. Overall effects were small (-0.1-0.7%) and only significant for forced vital capacity and forced expiratory volume in 1 s. There was some indication that allergic children were more affected by gas cooking. Under current housing conditions, gas cooking is associated with only small reductions in lung function.

Exposure to indoor mould and children's respiratory health in the PATY study.

BACKGROUND: Living in a damp or mouldy home reportedly damages children's respiratory health, yet mould appears not to be a prominent risk factor in the public's perception. Analyses of data on over 58,000 children from the Pollution and the Young (PATY) study are presented. In this collaboration, researchers from 12 cross-sectional studies pooled their data to assess the effects of air quality on a spectrum of children's respiratory disorders. METHOD: Original studies were conducted in Russia, North America and 10 countries in Eastern and Western Europe. Pooled analyses were restricted to children aged 6-12 years. Associations between visible mould reported in the household and a spectrum of eight respiratory and allergic symptoms were estimated within each study. Logistic regressions were used, controlling for individual risk factors and for study area. Heterogeneity between study-specific results and mean effects (allowing for heterogeneity) were estimated using meta-analysis. RESULTS: Visible mould was reported by 13.9% of respondents in Russia, increasing to 39.1% in North America. Positive associations between exposure to mould and children's respiratory health were seen with considerable consistency across studies and across outcomes. Confounder-adjusted combined ORs ranged from 1.30 (95% CI 1.22 to 1.39) for "nocturnal cough" to 1.50 (1.31 to 1.73) for "morning cough". Evidence of stronger effects in more crowded households was statistically significant for only asthma and sensitivity to inhaled allergens. No consistent interactions between mould and age, sex or parental smoking were found. CONCLUSION: Indoor mould exposure was consistently associated with adverse respiratory health outcomes in children living in these diverse countries.

Dietary risk factors for squamous cell carcinoma of the upper aerodigestive tract in central and eastern Europe.

OBJECTIVE: The incidence of squamous cell carcinoma of upper aerodigestive tract (UADT: oral cavity, pharynx, larynx, and esophagus) has been increasing in central and eastern European countries. We investigated the relationship between diet and UADT cancers in these high risk areas. METHODS: We used data from hospital-based case-control study of 948 UADT cancer cases and 1,228 controls conducted in Romania, Hungary, Poland, Russia, Slovakia, and Czech Republic. Standardized questionnaire were used to collect information on 23 different food items, along with alcohol and tobacco consumptions. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the UADT cancers after adjusting for center, age, sex, tobacco & alcohol intake, and other food groups. RESULTS: Consumption of dairy product was negatively associated with selected UADT cancers: larynx (OR: 0.38, CI: 0.23-0.62) and esophagus (OR: 0.55, CI: 0.33-0.93). While consumption of yellow/orange vegetables were inversely associated with oral/pharyngeal and laryngeal cancer (OR: 0.53, CI: 0.35-0.81 and OR: 0.62, CI: 0.38-1.00, respectively), preserved vegetable was positively associated with oral/pharyngeal and laryngeal cancer risk (p (trend) < 0.01 for both). CONCLUSION: Specific dietary components may play a role in the development of UADT cancers in the high-risk region of central and eastern Europe.

No association between MDM2 SNP309 promoter polymorphism and basal cell carcinoma of the skin.

BACKGROUND: The MDM2 oncoprotein promotes cell survival and cell cycle progression by inhibiting the p53 tumour suppressor protein. Further, overexpression of the MDM2 gene can inhibit DNA double-strand break repair in a p53-independent manner. Recent studies have shown that a single nucleotide polymorphism (SNP) in the intronic promoter region of MDM2 (called SNP309) can significantly change the expression of MDM2 and thereby suppress the p53 pathway. This SNP was also found to be associated with the onset and risk of different cancer types. Basal cell carcinoma of the skin (BCC) is one of the most common neoplasms in the world. BCC development is associated with environmental factors (especially sun exposure) as well as heritable factors. OBJECTIVES: The present case-control study investigated the association of the MDM2 SNP309 with the risk and the age at onset of BCC. Methods Data from 509 individuals affected by BCC and 513 healthy controls were genotyped with TaqMan polymerase chain reaction. RESULTS: Cases and controls showed a similar genotype distribution and the SNP did not modify the age at onset of BCC. CONCLUSIONS: These results suggest that the MDM2 SNP309 alone affects neither the risk nor the age at onset of BCC.

Case-control study in basal cell carcinoma of the skin: single nucleotide polymorphisms in three interleukin promoters pre-analysed in pooled DNA.

BACKGROUND: Basal cell carcinoma (BCC) is one of the most common neoplasms in the world. Development of BCC is associated with environmental factors (especially sun exposure) as well as heritable factors. OBJECTIVES: To analyse three single nucleotide polymorphisms (SNPs) in the promoter regions of interleukin (IL) genes in genomic DNA from 527 cases of BCC and 530 matched controls and to examine if DNA pooling is a useful method on which to base decisions regarding further SNP analysis. METHODS: The SNPs analysed were IL6-597, IL10-1082 and IL1B-511. The SNPs were first analysed from pooled DNA and afterwards from individual samples. The DNA pools resulted from a division of the samples into cases and controls, female and male, and three age groups. In these pools the allele frequencies were estimated by two methods, real-time polymerase chain reaction with allele-specific primers, and quantitative sequencing. RESULTS: No significant association was found when the allele frequencies in cases and controls were compared. However, by analysis of the individual genotypes we found SNP IL6-597 G/A to be significantly associated with BCC risk (P =0.007). Hereby the heterozygous genotype 'GA' had a protective effect (odds ratio 0.64, 95% confidence interval 0.49-0.84). No significant association was found for IL10-1082 and IL1B-511. CONCLUSIONS: The association of SNP IL6-597 with BCC could be found only by individual genotyping, but would have been missed if only data from the pooling analysis had been known.

Parental education and children's respiratory and allergic symptoms in the Pollution and the Young (PATY) study.

Inequalities in health between socio-economic groups are a major public health concern. The current authors studied associations between parental socio-economic status (SES) and children's respiratory and allergic symptoms in 13 diverse countries, including the Russian Federation, North America (Canada and the USA), and countries across Eastern and Western Europe. Data of 57,000 children aged 6-12 yrs, originating from eight cross-sectional studies, were analysed. SES was defined by parental education. Respiratory and allergic symptoms were defined by parental questionnaire reports. Multiple logistic regressions showed that low parental education was associated with a decreased risk of inhalant allergy and itchy rash in school children. Furthermore, low parental education was associated with an increased prevalence of wheeze and nocturnal dry cough. No clear association was found between parental education and prevalence of doctor-diagnosed asthma and bronchitis. Part of the difference between socio-economic groups with regard to their children's symptoms was explained by established risk factors, such as parental allergy, smoking during pregnancy, pet ownership, crowding, mould/moisture in the home, use of gas for cooking, and air pollution (particulate matter with a diameter of <10 microm). However, differences remained after adjusting for these variables. Children's health was associated with parental education. The association could not fully be explained by established risk factors.

Nutrition and respiratory health in children in six Central and Eastern European countries.

BACKGROUND: The results of studies on the effect of nutrition on respiratory diseases are inconsistent. The role of nutrition in children's respiratory health was therefore analysed within the cross sectional Central European Study on Air Pollution and Respiratory Health (CESAR). METHOD: A total of 20 271 children aged 7-11 were surveyed in six European countries. Respiratory health and food intake were assessed using questionnaires. Associations between four symptoms and nutritional factors were evaluated using logistic regression, controlling for area plus other potential confounders. RESULTS: All symptoms showed initial associations with nutritional factors. Low consumption of fish and of summer and winter fruit were the most consistent predictors. In a fully adjusted model low fish intake remained a significant independent predictor of persistent cough (OR=1.18; 95% CI 1.04 to 1.34), wheeze ever (OR=1.14; 95% CI 1.03 to 1.25) and current wheeze (OR=1.21; 95% CI 1.06 to 1.39) and a weaker predictor of winter cough (OR=1.10; 95% CI 0.99 to 1.23). Low summer fruit intake was a predictor of winter cough (OR=1.40; 95% CI 1.10 to 1.79) and persistent cough (OR=1.35; 95% CI 1.01 to 1.82). Low winter fruit intake was associated with winter cough (OR=1.28; 95% CI 1.09 to 1.51). Associations between symptoms and vegetable intake were inconsistent. Low summer intake was significantly associated with winter cough (OR=1.23; 95% CI 1.03 to 1.47) but, overall, winter intake had inverse associations with both coughs. Associations between winter vegetable intake and wheeze varied considerably between countries. CONCLUSION: A number of associations were found between respiratory symptoms and low intake of fish, fruit and vegetables in children. Low fish intake was the most consistent predictor of poor respiratory health. Fruit and vegetable intake showed stronger associations with cough than with wheeze.

Respiratory symptoms, bronchitis and asthma in children of Central and Eastern Europe.

The multicentre Central European Study of Air Pollution and Respiratory Health (CESAR) aimed to measure the respiratory health of schoolchildren using a standardised questionnaire in six countries of Central and Eastern Europe (CEE), allowing comparisons within this region and with other European countries. A cross-sectional study was conducted in 25 urban areas of Bulgaria, Czech Republic, Hungary, Poland, Romania, and Slovakia in 1996. Parents of 21,743 schoolchildren of age 7-11 yrs completed a questionnaire based on items from the World Health Organization and International Study of Asthma and Allergies in Childhood questions on cough and wheeze symptoms, as well as on diagnoses by doctors. Life-time prevalence of bronchitis was 55.9%, asthma 3.9%, and asthmatic, spastic or obstructive bronchitis 12.3%. In CEE countries the prevalence of bronchitis is higher and prevalence of asthma appears lower than in Western Europe. However, if asthma is defined as a diagnosis of either asthma or asthmatic, spastic or obstructive bronchitis, then its prevalence is comparable to Western Europe, or higher. In this region, within-country variation for most respiratory parameters is less than between-country variation. Between-country comparisons in doctors' diagnoses appear dependent on the choice of definition of asthma. Europe-wide comparisons in prevalence of respiratory symptoms and diagnosis are reported in this study. Some of the East-West difference in asthma prevalence may be attributable to differences in diagnostic practice.

Immune biomarkers in relation to exposure to particulate matter: a cross-sectional survey in 17 cities of Central Europe.

Human population data on air pollution and its effects on the immune system are scarce. A survey was conducted within the framework of the Central European Study of Air Quality and Respiratory Health (CESAR) to measure a panel of immune biomarkers in children of Bulgaria, Czech Republic, Hungary, Poland, Romania, and Slovakia. Seventeen cities were chosen to represent a wide range of exposure to outdoor air pollution. In each, ambient particulate matter of less than 10 microns diameter and less than 2.5 microns diameter (PM10 and PM2.5) were measured with a Harvard impactor. Blood was collected from 366 school children aged 9 to 11 yr between 11 April and 10 May 1996. The percentage of B, total T, CD4+, CD8+, and natural killer (NK) lymphocytes was determined by flow cytometry (Becton Dickinson); total immunoglobulins of class G, M, A and E (IgG, IgM, IgA, and IgE) were measured in serum using nephelometry (Behring). Associations between PM and each log-transformed biomarker concentration were studied by linear regression, in a two-stage model. The yearly average concentrations varied from 41 to 96 micrograms/m3 for PM10 across the 17 study areas, from 29 to 67 micrograms/m3 for PM2.5, and from 12 to 38 micrograms/m3 for PM10-2.5 (coarse). Number of B, CD4+, CD8+, and NK lymphocytes increased with increasing concentration of PM, having adjusted for age, gender, parental smoking, laboratory of analysis, and recent respiratory illness. Differences in lymphocyte number were larger and statistically significant for exposure to PM2.5. Similar results were found when we examined the association between PM and lymphocyte number separately for each laboratory. Total IgG was increased with increasing concentration of PM, significantly in the case of PM2.5. When we repeated the analyses with two other statistical approaches the results did not differ from those reported here. The effect of coarse PM on lymphocyte numbers appears small in comparison to PM2.5. One possible interpretation of our findings is that long-term exposure to airborne particulates leads to inflammation of the airways and activation of the cellular and humoral immune system.

Air pollution and childrens' respiratory morbidity in the Tata area, Hungary.

Air pollution represents one of the most important environmental health hazards in Hungary. Irritant gases, like SO2 and NO2 levels exceed national and international standards in many settlements. Tata, a small town, situated in a basin, is one of the most polluted areas in Hungary. Longitudinal and cross-sectional studies have been conducted in children in the winter period of 1993/1994, with respect to SO2 and NO2 concentration. Average SO2 levels exceeded the national standard levels and daily peaks as high as 450 micrograms/m were recorded. Excessive NO2 levels were also found but they were not as high as those of SO2. Acute respiratory morbidity, based on a uniform protocol was recorded daily and evaluated on a daily and weekly basis. A statistically significant correlation with SO2 levels was observed in relation to the frequency of acute daily respiratory morbidity. Other health parameters, like pulmonary function, haematology and sensory performance were also tested. Although no statistically significant correlations were observed, the tendency in all parameters demonstrated impairment, in relation with ambient air pollution. Smoking history of the family did not alter significantly the pulmonary functions of other parameters.

Respiratory disease surveillance in Hungary.

In October 1989, the Hungarian National Institute of Hygiene initiated the Children's Acute Respiratory Morbidity (CHARM) Surveillance System to assess the association between nine reportable respiratory diseases and air pollution. The weekly number of physician-diagnosed, reportable respiratory diseases among four age groups of children (less than 1, 1-2, 3-5, and 6-14 years) was tabulated for Sopron, a city with 60,000 residents. We calculated the proportion of diseases occurring during weeks with low, moderate, and high sulfur dioxide (SO2) and nitrogen dioxide (NO2) concentrations. The weekly averages of the 24-hour median SO2 concentrations were divided into thirds at less than or equal to 17.6, greater than 17.6 to less than or equal to 26.3, and greater than 26.3 micrograms/m3 (range: 0.9-79.6 micrograms/m3), and the NO2 concentrations at less than or equal to 29.8, greater than 29.8 to less than or equal to 44.1, and greater than 44.1 micrograms/m3 (range: 4.2-90.1 micrograms/m3). During 1990, 11,474 respiratory disease cases occurred among the 4,020 children less than 15 years of age living in Sopron and monitored by the CHARM system. The two most frequently reported disease categories were rhinitis/tonsillitis/pharyngitis (71.5%) and acute bronchitis (8.5%). Sixty-seven percent of pneumonia cases occurred when SO2 concentrations were highest. We found no association between levels of NO2 and respiratory diseases. The CHARM Surveillance System may characterize more fully which groups of children develop particular respiratory diseases following exposure to air pollution.

[Correlation between air pollution and respiratory morbidity in children at Dorog]. / A levegöszennyezettség mértéke és a gyermekek légúti megbetegedése közötti összefüggés vizsgálata Dorogon.

The authors studied the dynamical association between the level of air pollution and the respiratory morbidity among children. By examination of the records of 1127 children, the frequency of acute respiratory diseases, and especially bronchitis, was found to be very high in the first 3 years of age, and extremely high among infants. The prevalence of the children with chronic nonspecific pulmonary diseases was found to be approximately 3 times higher than the national average. Correlation analysis showed high correlation between the acute respiratory morbidity of the total children population of age 0-14 living in Dorog and the level of SO2 pollution. This was especially true for the bronchitis morbidity among infants (with a correlation coefficient of 0.92). The authors stress the importance of the primary prevention, claiming that the development of chronic nonspecific pulmonary diseases could be prevented by controlling the harmful environmental factors.