Effects of an App-Based Intervention Program to Reduce Substance Use, Gambling, and Digital Media Use in Adolescents and Young Adults: A Multicenter, Cluster-Randomized Controlled Trial in Vocational Schools in Germany.

Vocational students are a risk group for problematic substance use and addictive behaviors. The study aim was to evaluate the effects of an app-based intervention on tobacco, e-cigarettes, alcohol, and cannabis use as well as gambling and digital media-related behaviors in the vocational school setting. A total of 277 classes with 4591 students (mean age 19.2 years) were consecutively recruited and randomized into an intervention (IG) or waitlist control group (CG). Students from IG classes received access to an app, which encouraged a voluntary commitment to reduce or completely abstain from the use of a specific substance, gambling, or media-related habit for 2 weeks. Substance use, gambling, and digital media use were assessed before and after the intervention in both groups with a mean of 7.7 weeks between assessments. Multi-level logistic regression models were used to test group differences. Intention-to-treat-results indicated that students from IG classes had a significantly larger improvement on a general adverse health behavior measure compared to CG (OR = 1.24, p = 0.010). This difference was mainly due to a significantly higher reduction of students' social media use in the IG (OR = 1.31, p < 0.001). Results indicate that the app "Meine Zeit ohne" is feasible for the target group and seems to have a small but measurable impact on students' health behavior.

Do smoking, nutrition, alcohol use, and physical activity vary between regions in Germany? - results of a cross-sectional study.

BACKGROUND: Previous studies on lifestyle risk factors mainly focused on age- or gender-specific differences. However, lifestyle risk factors also vary across regions. Aim of the present study was to examine the extent to which prevalence rates of SNAP (smoking, nutrition, alcohol consumption, physical activity) vary between East and West Germany or North and South Germany. METHODS: Data came from the population-representative 2015 Epidemiological Survey of Substance Abuse (ESA) comprising 9204 subjects aged 18 to 64 years. To assess an east-west or south-north gradient, two binary logistic regression models were carried out for each SNAP factor. RESULTS: The logistic regression models revealed statistically significant differences with higher rates of at-risk alcohol consumption and lower rates of unhealthy nutrition in East Germany compared to West Germany. Significant differences between North and South Germany were found for at-risk alcohol consumption with higher rates of at-risk alcohol consumption in South Germany. Daily smoking and low physical activity were equally distributed across regions. CONCLUSIONS: The implementation of measures reducing at-risk alcohol consumption in Germany should take the identified east-west and south-north gradient into account. Since the prevalence of unhealthy nutrition was generally high, prevention and intervention measures should focus on Germany as a whole instead of specific regions.

[The use of E-Cigarettes in the German Population: Results of the Epidemiological Survey of Substance Abuse 2015]. / Die Nutzung von E-Zigaretten in der deutschen Bevölkerung ­ Ergebnisse des Epidemiologischen Suchtsurvey 2015.

AIM: Estimates of e-cigarette consumption in Germany vary considerably. The use of e-cigarettes for tobacco cessation is critically discussed. Based on current data, the distribution of the consumption of e-cigarettes and their use in the adult general population of Germany will be presented. METHODS: The 2015 Epidemiological Survey of Substance Abuse, a nationwide survey of 18 to 64 year-old people in Germany (n=9,204, response rate: 52,2%), was used as data basis. RESULTS: E-cigarettes were known to most of the respondents (85,3%, 43,5 Mio.), whereas only 2,9% (1,5 Mio.) used e-cigarettes in the last 30 days. Higher risk of consuming e-cigarettes was seen in younger people (OR=0,95, 95%-KI=(0,93; 0,97)), men (OR=1,45, 95%-KI=(1,02; 2,07)) and smokers (OR=12,53, 95%-KI=(8,71; 18,03)). About a third of smokers and ex-smokers of conventional cigarettes (36,6%) who consumed e-cigarettes used these for tobacco cessation of which one fifth (21,3%) was able to quit smoking. CONCLUSION: E-cigarette users seem to be more likely to be male, younger and smokers of conventional cigarettes. In addition to curiosity, the change in smoking behavior is an important motive for consumption. The results indicate that the use of e-cigarettes can contribute to tobacco cessation, the majority of users, however, continue to consume conventional and/or e-cigarettes.

Patterns of multiple lifestyle risk factors and their link to mental health in the German adult population: a cross-sectional study.

OBJECTIVES: Lifestyle risk factors, such as drinking or unhealthy diet, can expotentiate detrimental health effects. Therefore, it is important to investigate multiple lifestyle risk factors instead of single ones. The study aims at: (1) identifying patterns of lifestyle risk factors within the adult general population in Germany and (2) examining associations between the extracted patterns and external factors. DESIGN: Cross-sectional study. SETTING: General German adult population (aged 18-64 years). PARTICIPANTS: Participants of the 2015 Epidemiological Survey of Substance Abuse (n=9204). PRIMARY OUTCOME MEASURES: Lifestyle risk factors (daily smoking, at-risk alcohol consumption, unhealthy diet, low physical activity, weekly use of pharmaceuticals, as well as consumption of cannabis and other illicit drugs). RESULTS: A latent class analysis was applied to identify patterns of lifestyle risk factors, and a multinomial logistic regression was carried out to examine associations between the extracted classes and external factors. A total of four classes were extracted which can be described as healthy lifestyle (58.5%), drinking lifestyle (24.4%), smoking lifestyle (15.4%) and a cumulate risk factors lifestyle (1.7%). Individuals who were male, at younger age and single as well as individuals with various mental health problems were more likely to show multiple lifestyle risk factors. CONCLUSIONS: Healthcare professionals should be aware of correlations between different lifestyle risk factors as well as between lifestyle risk groups and mental health. Health promotion strategies should further focus especially on younger and single men.

[E-cigarettes: Perceived harmfulness and use for smoking cessation]. / E-Zigaretten: Einschätzung von Gesundheitsgefahren und Nutzung zur Tabakentwöhnung.

BACKGROUND: The perception that e­cigarettes are less harmful than traditional tobacco products can influence the consumption of e­cigarettes. OBJECTIVES: Three questions were examined: (1) How do different population groups perceive health risks of e­cigarettes? (2) Do sociodemographic variables explain differences in the risk assessment of e­cigarettes? (3) Does the perception of health risks predict the use of e­cigarettes for smoking cessation? METHODS: Data came from the 2015 Epidemiological Survey of Substance Abuse (ESA) with a sample size of n = 9204 participants, aged 18 to 64 years (response rate 52.2%). Data were collected by telephone, online, or by written questionnaires. Assessments of risk perception of e­cigarettes and conventional cigarettes (more harmful, just as harmful, less harmful, do not know) were compared. Descriptive statistics and logistic regressions were performed. RESULTS: Individuals with lower education rated e­cigarettes as more harmful. Older people and women perceived e­cigarettes as just as harmful. Smokers considered e­cigarettes to be more harmful than or just as harmful as conventional tobacco products. The likelihood of using e­cigarettes for smoking cessation was higher if people thought they were less harmful than conventional cigarettes. CONCLUSIONS: Only one-third of the population knows that e­cigarettes are less harmful to health than conventional cigarettes. The perception of health risks is related to the usage of e­cigarettes for smoking cessation.

Awareness of alcohol as a risk factor for cancer is associated with public support for alcohol policies.

BACKGROUND: Globally, alcohol is causally related to 2.5 million deaths per year and 12.5% of these are due to cancer. Previous research has indicated that public awareness of alcohol as a risk factor for cancer is low and this may contribute to a lack of public support for alcohol policies. The aim of this study was to investigate the relationship between awareness of the alcohol-cancer link and support for a range of alcohol policies in an English sample and policy context. METHODS: A cross-sectional survey of 2100 adult residents in England was conducted in which respondents answered questions regarding awareness of the link between alcohol and cancer and support for 21 policy proposals. Principal component analysis (PCA) was used to reduce the 21 policy proposals down to a set of underlying factors. Multiple regression analyses were conducted to estimate the relationship between awareness of the alcohol-cancer link and each of these policy factors. RESULTS: Thirteen per cent of the sample were aware of the alcohol-cancer link unprompted, a further 34% were aware when prompted and 53% were not aware of the link. PCA reduced the policy items to four policy factors, which were named price and availability, marketing and information, harm reduction and drink driving. Awareness of the alcohol-cancer link unprompted was associated with increased support for each of four underlying policy factors: price and availability (Beta: 0.06, 95% CI: 0.01, 0.10), marketing and information (Beta: 0.05, 95% CI: 0.00, 0.09), harm reduction (Beta: 0.09, 95% CI: 0.05, 0.14), and drink driving (Beta: 0.16, 95% CI: 0.11, 0.20). CONCLUSIONS: Support for alcohol policies is greater among individuals who are aware of the link between alcohol and cancer. At the same time, a large proportion of people are unaware of the alcohol-cancer link and so increasing awareness may be an effective approach to increasing support for alcohol policies.

The Consumption of New Psychoactive Substances and Methamphetamine.

BACKGROUND: The abuse of new psychoactive substances (NPS) and methamphetamine has severe adverse effects. Here we provide the first report of regional patterns in NPS and methamphetamine consumption in Germany, on the basis of epidemiologic data from six federal states (Bavaria, Hamburg, Hesse, North Rhine-Westphalia, Saxony, and Thuringia). METHODS: Data were derived from the 2015 Epidemiological Survey of Substance Abuse (Epidemiologischer Suchtsurvey) and supplemented with additional cases from the federal states that were studied. The numbers of persons included in the representative samples of persons aged 18 to 64 in each state were 1916 (Bavaria), 1125 (Hamburg), 1151 (Hesse), 2008 (North Rhine-Westphalia), 1897 (Saxony), and 1543 (Thuringia). Potential risk factors for the lifetime prevalence of consumption were studied by logistic regression. RESULTS: The lifetime prevalence of methamphetamine consumption in the individual states ranged from 0.3% (North Rhine-Westphalia) to 2.0% (Saxony). Thuringia and Saxony displayed values that were significantly higher than average. For NPS, the figures ranged from 2.2% (Bavaria) to 3.9% (Hamburg), but multivariate analysis revealed no statistically significant differences between the states. Higher age and higher educational level were associated with lower consumption of NPS and methamphetamine, while smoking and cannabis use were each associated with higher consumption. CONCLUSION: NPS consumption is equally widespread in all of the federal states studied. Methamphetamine is rarely consumed; its consumption appears to be higher in Saxony and Thuringia. The risk factor analysis reported here should be interpreted cautiously in view of the low case numbers with respect to consumption.

Self-Reported Knowledge, Correct Knowledge and use of UK Drinking Guidelines Among a Representative Sample of the English Population.

AIMS: Promotion of lower risk drinking guidelines is a commonly used public health intervention with various purposes, including communicating alcohol consumption risks, informing drinkers' decision-making and, potentially, changing behaviour. UK drinking guidelines were revised in 2016. To inform potential promotion of the new guidelines, we aimed to examine public knowledge and use of the previous drinking guidelines, including by population subgroup. METHODS: A demographically representative, cross-sectional online survey of 2100 adults living in England in July 2015 (i.e. two decades after adoption of previous guidelines and prior to introduction of new guidelines). Univariate and multivariate logistic regressions examined associations between demographic variables, alcohol consumption (AUDIT-C), smoking, and knowledge of health conditions and self-reported knowledge and use of drinking guidelines. Multinomial logistic regression examined the same set of variables in relation to accurate knowledge of drinking guidelines (underestimation, accurate-estimation, overestimation). RESULTS: In total, 37.8% of drinkers self-reported knowing their own-gender drinking guideline, of whom 66.2% gave an accurate estimate. Compared to accurate estimation, underestimation was associated with male gender, lower education and AUDIT-C score, while overestimation was associated with smoking. Few (20.8%) reported using guidelines to monitor drinking at least sometimes. Drinking guideline use was associated with higher education, overestimating guidelines and lower AUDIT-C. Correctly endorsing a greater number of health conditions as alcohol-related was associated with self-reported knowledge of guidelines, but was not consistently associated with accurate estimation or use to monitor drinking. CONCLUSIONS: Two decades after their introduction, previous UK drinking guidelines were not well known or used by current drinkers. Those who reported using them tended to overestimate recommended daily limits. SHORT SUMMARY: We examined public knowledge and use of UK drinking guidelines just before new guidelines were released (2016). Despite previous guidelines being in place for two decades, only one in four drinkers accurately estimated these, with even fewer using guidelines to monitor drinking. Approximately 8% of drinkers overestimated maximum daily limits.

Public awareness of the link between alcohol and cancer in England in 2015: a population-based survey.

BACKGROUND: Public knowledge of the association between alcohol and cancer is reported to be low. We aimed to provide up-to-date evidence for England regarding awareness of the link between alcohol and different cancers and to determine whether awareness differs by demographic characteristics, alcohol use, and geographic region. METHODS: A representative sample of 2100 adults completed an online survey in July 2015. Respondents were asked to identify which health outcomes, including specific cancers, may be caused by alcohol consumption. Logistic regressions explored whether demographic, alcohol use, and geographic characteristics predicted correctly identifying alcohol-related cancer risk. RESULTS: Unprompted, 12.9% of respondents identified cancer as a potential health outcome of alcohol consumption. This rose to 47% when prompted (compared to 95% for liver disease and 73% for heart disease). Knowledge of the link between alcohol and specific cancers varied between 18% (breast) and 80% (liver). Respondents identified the following cancers as alcohol-related where no such evidence exists: bladder (54%), brain (32%), ovarian (17%). Significant predictors of awareness of the link between alcohol and cancer were being female, more highly educated, and living in North-East England. CONCLUSION: There is generally low awareness of the relationship between alcohol consumption and cancer, particularly breast cancer. Greater awareness of the relationship between alcohol and breast cancer in North-East England, where a mass media campaign highlighted this relationship, suggests that population awareness can be influenced by social marketing.

Hepatitis C virus seroprevalence in the general female population from 8 countries.

BACKGROUND: Hepatitis C virus (HCV) infection is a significant global health issue because it is widespread and persistent and can cause serious liver diseases. OBJECTIVES: The aim of this study is to estimate HCV prevalence in women from the general population in different geographical areas worldwide and to assess the potential role of sexual behaviour in the virus transmission. STUDY DESIGN: Each participating centre recruited a random sample of women from the general population aged from less than 20 to more than 75 years. The study included 8130 women from 8 countries with information on sociodemographic factors, reproductive and sexual behaviour, smoking habit and HPV DNA through individual interviews. A blood sample was also collected to perform serological tests. We estimated the prevalence ratios associated to HCV to evaluate the effect of sexual behaviour in viral transmission. RESULTS: Women were reactive to a minimum of two HCV antigens, including at least one non structural protein were considered as positive (33% of the samples were classified as positive, 40% as negative, and 27% as indeterminate (N=402), that were considered as not positive). The age-adjusted HCV seroprevalence varied significantly by regions (0.3% in Argentina to 21.1% in Nigeria). We found no association between HCV prevalence and age, educational level, smoking habit and any of the available variables for sexual behaviour and reproductive history. CONCLUSIONS: This large study showed heterogeneous distribution of HCV seroprevalence in female and provides evidence of the null impact of sexual behaviour in HCV transmission.

Estimating and explaining the effect of education and income on head and neck cancer risk: INHANCE consortium pooled analysis of 31 case-control studies from 27 countries.

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels.

Adult height and head and neck cancer: a pooled analysis within the INHANCE Consortium.

Several epidemiological studies have shown a positive association between adult height and cancer incidence. The only study conducted among women on mouth and pharynx cancer risk, however, reported an inverse association. This study aims to investigate the association between height and the risk of head and neck cancer (HNC) within a large international consortium of HNC. We analyzed pooled individual-level data from 24 case-control studies participating in the International Head and Neck Cancer Epidemiology Consortium. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated separately for men and women for associations between height and HNC risk. Educational level, tobacco smoking, and alcohol consumption were included in all regression models. Stratified analyses by HNC subsites were performed. This project included 17,666 cases and 28,198 controls. We found an inverse association between height and HNC (adjusted OR per 10 cm height = 0.91, 95% CI 0.86-0.95 for men; adjusted OR = 0.86, 95% CI 0.79-0.93 for women). In men, the estimated OR did vary by educational level, smoking status, geographic area, and control source. No differences by subsites were detected. Adult height is inversely associated with HNC risk. As height can be considered a marker of childhood illness and low energy intake, the inverse association is consistent with prior studies showing that HNC occur more frequently among deprived individuals. Further studies designed to elucidate the mechanism of such association would be warranted.

Association of marijuana smoking with oropharyngeal and oral tongue cancers: pooled analysis from the INHANCE consortium.

BACKGROUND: The incidence of oropharyngeal and oral tongue cancers has increased over the last 20 years which parallels increased use of marijuana among individuals born after 1950. METHODS: A pooled analysis was conducted comprising individual-level data from nine case-control studies from the United States and Latin America in the INHANCE consortium. Self-reported information on marijuana smoking, demographic, and behavioral factors was obtained from 1,921 oropharyngeal cases, 356 oral tongue cases, and 7,639 controls. RESULTS: Compared with never marijuana smokers, ever marijuana smokers had an elevated risk of oropharyngeal [adjusted OR (aOR), 1.24; 95% confidence interval (CI): 1.06-1.47] and a reduced risk of oral tongue cancer (aOR, 0.47; 95% CI, 0.29, 0.75). The risk of oropharyngeal cancer remained elevated among never tobacco and alcohol users. The risk of oral tongue cancer was reduced among never users of tobacco and alcohol. Sensitivity analysis adjusting for potential confounding by HPV exposure attenuated the association of marijuana use with oropharyngeal cancer (aOR, 0.99; 95% CI, 0.71-1.25), but had no effect on the oral tongue cancer association. CONCLUSIONS: These results suggest that the association of marijuana use with head and neck carcinoma may differ by tumor site. IMPACT: The associations of marijuana use with oropharyngeal and oral tongue cancer are consistent with both possible pro- and anticarcinogenic effects of cannabinoids. Additional work is needed to rule out various sources of bias, including residual confounding by HPV infection and misclassification of marijuana exposure.

Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ≤ 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.

DNA methylation changes associated with risk factors in tumors of the upper aerodigestive tract.

Cancers of the upper aerodigestive tract (UADT) are common forms of malignancy associated with tobacco and alcohol exposures, although human papillomavirus and nutritional deficiency are also important risk factors. While somatically acquired DNA methylation changes have been associated with UADT cancers, what triggers these events and precise epigenetic targets are poorly understood. In this study, we applied quantitative profiling of DNA methylation states in a panel of cancer-associated genes to a case-control study of UADT cancers. Our analyses revealed a high frequency of aberrant hypermethylation of several genes, including MYOD1, CHRNA3 and MTHFR in UADT tumors, whereas CDKN2A was moderately hypermethylated. Among differentially methylated genes, we identified a new gene (the nicotinic acetycholine receptor gene) as target of aberrant hypermethylation in UADT cancers, suggesting that epigenetic deregulation of nicotinic acetycholine receptors in non-neuronal tissues may promote the development of UADT cancers. Importantly, we found that sex and age is strongly associated with the methylation states, whereas tobacco smoking and alcohol intake may also influence the methylation levels in specific genes. This study identifies aberrant DNA methylation patterns in UADT cancers and suggests a potential mechanism by which environmental factors may deregulate key cellular genes involved in tumor suppression and contribute to UADT cancers.

Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium.

To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 case-control studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR = 0.76, 95% CI = 0.59-0.96) and with ever use of calcium supplement (OR = 0.64, 95% CI = 0.42-0.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR = 0.72, 95% CI = 0.54-0.97) and more than 365 tablets of cumulative calcium intake (OR = 0.36, 95% CI = 0.16-0.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of HNC.

Inactivation of the putative suppressor gene DOK1 by promoter hypermethylation in primary human cancers.

The DOK1 gene is a putative tumour suppressor gene located on the human chromosome 2p13 which is frequently rearranged in leukaemia and other human tumours. We previously reported that the DOK1 gene can be mutated and its expression down-regulated in human malignancies. However, the mechanism underlying DOK1 silencing remains largely unknown. We show here that unscheduled silencing of DOK1 expression through aberrant hypermethylation is a frequent event in a variety of human malignancies. DOK1 was found to be silenced in nine head and neck cancer (HNC) cell lines studied and DOK1 CpG hypermethylation correlated with loss of gene expression in these cells. DOK1 expression could be restored via demethylating treatment using 5-aza-2'deoxycytidine. In addition, transduction of cancer cell lines with DOK1 impaired their proliferation, consistent with the critical role of epigenetic silencing of DOK1 in the development and maintenance of malignant cells. We further observed that DOK1 hypermethylation occurs frequently in a variety of primary human neoplasm including solid tumours (93% in HNC, 81% in lung cancer) and haematopoietic malignancy (64% in Burkitt's lymphoma). Control blood samples and exfoliated mouth epithelial cells from healthy individuals showed a low level of DOK1 methylation, suggesting that DOK1 hypermethylation is a tumour specific event. Finally, an inverse correlation was observed between the level of DOK1 gene methylation and its expression in tumour and adjacent non tumour tissues. Thus, hypermethylation of DOK1 is a potentially critical event in human carcinogenesis, and may be a potential cancer biomarker and an attractive target for epigenetic-based therapy.

Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium.

We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p (trend) < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p (trend) = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p (trend) = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p (trend) < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97).

Genome-wide association study of HPV seropositivity.

High-risk α mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers, whereas ß cutaneous HPV types (e.g. HPV8) have been implicated in non-melanoma skin cancer. Although antibodies against the capsid protein L1 of HPV are considered as markers of cumulative exposure, not all infected persons seroconvert. To identify common genetic variants that influence HPV seroconversion, we performed a two-stage genome-wide association study. Genome-wide genotyping of 316 015 single nucleotide polymorphisms was carried out using the Illumina HumanHap300 BeadChip in 4811 subjects from a central European case-control study of lung, head and neck and kidney cancer that had serology data available on 13 HPV types. Only one association met genome-wide significance criteria, namely that between HPV8 seropositivity and rs9357152 [odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.24-1.50 for the minor allele G; P=1.2 × 10(-10)], a common genetic variant (minor allele frequency=0.33) located within the major histocompatibility complex (MHC) II region at 6p21.32. This association was subsequently replicated in an independent set of 2344 subjects from a Latin American case-control study of head and neck cancer (OR=1.35, 95% CI=1.18-1.56, P=2.2 × 10(-5)), yielding P=1.3 × 10(-14) in the combined analysis (P-heterogeneity=0.87). No heterogeneity was noted by cancer status (controls/lung cancer cases/head and neck cancer cases/kidney cancer cases). This study provides a proof of principle that genetic variation plays a role in antibody reactivity to HPV infection.

An examination of male and female odds ratios by BMI, cigarette smoking, and alcohol consumption for cancers of the oral cavity, pharynx, and larynx in pooled data from 15 case-control studies.

BACKGROUND: Greater tobacco smoking and alcohol consumption and lower body mass index (BMI) increase odds ratios (OR) for oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers; however, there are no comprehensive sex-specific comparisons of ORs for these factors. METHODS: We analyzed 2,441 oral cavity (925 women and 1,516 men), 2,297 oropharynx (564 women and 1,733 men), 508 hypopharynx (96 women and 412 men), and 1,740 larynx (237 women and 1,503 men) cases from the INHANCE consortium of 15 head and neck cancer case-control studies. Controls numbered from 7,604 to 13,829 subjects, depending on analysis. Analyses fitted linear-exponential excess ORs models. RESULTS: ORs were increased in underweight (< 18.5 BMI) relative to normal weight (18.5-24.9) and reduced in overweight and obese categories (≥ 25 BMI) for all sites and were homogeneous by sex. ORs by smoking and drinking in women compared with men were significantly greater for oropharyngeal cancer (p < 0.01 for both factors), suggestive for hypopharyngeal cancer (p = 0.05 and p = 0.06, respectively), but homogeneous for oral cavity (p = 0.56 and p = 0.64) and laryngeal (p = 0.18 and p = 0.72) cancers. CONCLUSIONS: The extent that OR modifications of smoking and drinking by sex for oropharyngeal and, possibly, hypopharyngeal cancers represent true associations, or derive from unmeasured confounders or unobserved sex-related disease subtypes (e.g., human papillomavirus-positive oropharyngeal cancer) remains to be clarified.