A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers

Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold-out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92-0.95 in men and AUC = 0.92, 95% CI = 0.88-0.95 in women). The 5-year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer

Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease

The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction

Juvenile idiopathic arthritis (JIA): a screening study to measure class II skeletal pattern, TMJ PDS and use of systemic corticosteroids

<b>Objective</b>: To screen patients with oligoarticular and polyarticular forms of Juvenile Idiopathic Arthritis (JIA) to determine (i) the severity of their class II skeletal pattern; (ii) temporomandibular joint signs and symptoms and (iii) use of systemic corticosteroids. <b>Design</b>: Cross-sectional screening. <b>Subjects and setting</b>: Sixty-eight children with JIA aged between 9 and 16 years old who were screened at four regional treatment centres in the UK. <b>Method</b>: Patients were screened clinically and radiographically for the presence of class II skeletal pattern and temporomandibular (TMJ) pain dysfunction syndrome. In addition, the JIA sub-type and history of disease activity and medication were recorded. <b>Main outcome measures</b>: Class II skeletal pattern, TMJ signs and symptoms, use of systemic corticosteroids. <b>Results</b>: The mean ANB values were 4·2 degrees (SD = 2·9 degrees) in the oligoarticular group and 5·1 degrees (SD = 3·8 degrees) in the polyarticular group. Just under one-third of children had a moderate or severe class II skeletal pattern and a further quarter of children had a mild class II skeletal pattern. Clinical signs and symptoms of temporomandibular joint pain dysfunction syndrome were low (<20%), except for crepitus and click which affected between 24 and 40% of JIA children. Radiographically, 57% of oligoarticular and 77% of polyarticular cases exhibited condylar erosion. Use of systemic corticosteroids varied between centres, but overall, was prescribed more in polyarticular cases (P = 0·001). <b>Conclusions</b>: Just under one-third of oligoarticular and polyarticular JIA patients exhibited a moderate or severe class II skeletal pattern. It is, therefore, likely that any future clinical trial to investigate the effect of functional appliance treatment in JIA patients, will need multicentre co-operation to fulfil potential sample size requirements. Clinical signs and symptoms of temporomandibular joint pain dysfunction syndrome were low except for crepitus and click. However, radiographic evidence of condylar erosion was high particularly in the polyarticular group. Use of systemic corticosteroids was prescribed more in polyarticular cases and this is likely to reflect the severity of the disease

Socioeconomic factors associated with risk of upper aerodigestive tract cancer in Europe

Introduction<p></p> In the European Union, there are 180,000 new cases of upper aerodigestive tract (UADT) cancer cases per year – more than half of whom will die of the disease. Socioeconomic inequalities in UADT cancer incidence are recognised across Europe. We aimed to assess the components of socioeconomic risk both independently and through their influence on the known behavioural risk factors of smoking, alcohol consumption and diet.<p></p> Patients and methods<p></p> A multicentre case–control study with 2198 cases of UADT cancer and 2141 controls from hospital and population sources was undertaken involving 14 centres from 10 countries. Personal interviews collected information on demographics, lifetime occupation history, smoking, alcohol consumption and diet. Socioeconomic status was measured by education, occupational social class and unemployment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression.<p></p> Results<p></p> When controlling for age, sex and centre significantly increased risks for UADT cancer were observed for those with low versus high educational attainment OR = 1.98 (95% CI 1.67, 2.36). Similarly, for occupational socioeconomic indicators – comparing the lowest versus highest International Socio-Economic Index (ISEI) quartile for the longest occupation gave OR = 1.60 (1.28, 2.00); and for unemployment OR = 1.64 (1.24, 2.17). Statistical significance remained for low education when adjusting for smoking, alcohol and diet behaviours OR = 1.29 (1.06, 1.57) in the multivariate analysis. Inequalities were observed only among men but not among women and were greater among those in the British Isles and Eastern European countries than in Southern and Central/Northern European countries. Associations were broadly consistent for subsite and source of controls (hospital and community).<p></p> Conclusion<p></p> Socioeconomic inequalities for UADT cancers are only observed among men and are not totally explained by smoking, alcohol drinking and diet.<p></p&gt

Life course social mobility and risk of upper aerodigestive tract cancer in men

The aim of this study was to explore associations between social mobility and tumours of the upper aero-digestive tract (UADT), focussing on life-course transitions in social prestige (SP) based on occupational history. 1,796 cases diagnosed between 1993 and 2005 in ten European countries were compared with 1585 controls. SP was classified by the Standard International Occupational Prestige Scale (SIOPS) based on job histories. SIOPS was categorised in high (H), medium (M) and low (L). Time weighted average achieved and transitions between SP with nine trajectories: H → H, H → M, H → L, M → H, M → M, M → L, L → H, L → M and L → L were analysed. Odds ratios (ORs) and 95%-confidence intervals [95%-CIs] were estimated with logistic regression models including age, consumption of fruits/vegetables, study centre, smoking and alcohol consumption. The adjusted OR for the lowest versus the highest of three categories (time weighted average of SP) was 1.28 [1.04-1.56]. The distance of SP widened between cases and controls during working life. The downward trajectory H → L gave an OR of 1.71 [0.75-3.87] as compared to H → H. Subjects with M → M and L → L trajectories ORs were also elevated relative to subjects with H → H trajectories. The association between SP and UADT is not fully explained by confounding factors. Downward social trajectory during the life course may be an independent risk factor for UADT cancers. © 2010 Springer Science+Business Media B.V

Role of medical history and medication use in the aetiology of upper aerodigestive tract cancers in Europe: the ARCAGE study

<b>Background:</b> The study aimed to investigate the role of medical history (skin warts, Candida albicans, herpetic lesions, heartburn, regurgitation) and medication use (for heartburn; for regurgitation; aspirin) in the aetiology of upper aerodigestive tract (UADT) cancer. Methods: A multicentre (10 European countries) case–control study [Alcohol-Related CAncers and GEnetic susceptibility (ARCAGE) project].<p></p> <b>Results:</b> There were 1779 cases of UADT cancer and 1993 controls. History of warts or C. albicans infection was associated with a reduced risk [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.68–0.94 and OR 0.73, 95% CI 0.60–0.89, respectively] but there was no association with herpetic lesions, heartburn, regurgitation or medication for related symptoms. Regurgitation was associated with an increased risk for cancer of the oesophagus (OR 1.47, 95% CI 0.98–2.21). Regular aspirin use was not associated with risk of UADT cancer overall but was associated with a reduced risk for cancer of oesophagus (OR 0.51, 95% CI 0.28–0.96), hypopharynx (OR 0.53, 95% CI 0.28–1.02) and larynx (OR 0.74, 95% CI 0.54–1.01).<p></p> <b>Conclusions:</b> A history of some infections appears to be a marker for decreased risk of UADT cancer. The role of medical history and medication use varied by UADT subsites with aspirin use associated with a decreased risk of oesophageal cancer and suggestive of a decreased risk of hypopharyngeal and laryngeal cancers.<p></p&gt

Alcohol-related cancers and genetic susceptibility in Europe: The ARCAGE project: Study samples and data collection

Cancers of the upper aerodigestive tract (UADT) include those of the oral cavity, pharynx (other than nasopharynx), larynx, and esophagus. Tobacco smoking and consumption of alcoholic beverages are established causes of UADT cancers, whereas reduced intake of vegetables and fruits are likely causes. The role of genetic predisposition and possible interactions of genetic with exogenous factors, however, have not been adequately studied. Moreover, the role of pattern of smoking and drinking, as well as the exact nature of the implicated dietary variables, has not been clarified. To address these issues, the International Agency for Research on Cancer initiated in 2002 the alcohol-related cancers and genetic susceptibility (ARCAGE) in Europe project, with the participation of 15 centers in 11 European countries. Information and biological data from a total of 2304 cases and 2227 controls have been collected and will be used in a series of analyses. A total of 166 single nucleotide polymorphisms of 76 genes are being studied for genetic associations with UADT cancers. We report here the methodology of the ARCAGE project, main demographic and lifestyle characteristics of the cases and controls, as well as the distribution of cases by histology and subsite. About 80% of cases were males and fewer than 20% of all cases occurred before the age of 50 years. Overall, the most common subsite was larynx, followed by oral cavity, oropharynx, esophagus and hypopharynx. Close to 90% of UADT cancers were squamous cell carcinomas. A clear preponderance of smokers and alcohol drinkers among UADT cases compared with controls was observed. European Journal of Cancer Prevention 18:76-84 © 2009 Wolters Kluwer Health

Occupation and risk of upper aerodigestive tract cancer: The ARCAGE study

We investigated the association between occupational history and upper aerodigestive tract (UADT) cancer risk in the ARCAGE European case-control study. The study included 1,851 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1,949 controls. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ever employment in 283 occupations and 172 industries, adjusting for smoking and alcohol. Men (1,457 cases) and women (394 cases) were analyzed separately and we incorporated a semi-Bayes adjustment approach for multiple comparisons. Among men, we found increased risks for occupational categories previously reported to be associated with at least one type of UADT cancer, including painters (OR = 1.74, 95% CI: 1.01-3.00), bricklayers (1.58, 1.05-2.37), workers employed in the erection of roofs and frames (2.62, 1.08-6.36), reinforced concreters (3.46, 1.11-10.8), dockers (2.91, 1.05-8.05) and workers employed in the construction of roads (3.03, 1.23-7.46), general construction of buildings (1.44, 1.12-1.85) and cargo handling (2.60, 1.17-5.75). With the exception of the first three categories, risks both increased when restricting to long duration of employment and remained elevated after semi-Bayes adjustment. Increased risks were also found for loggers (3.56, 1.20-10.5) and cattle and dairy farming (3.60, 1.15-11.2). Among women, there was no clear evidence of increased risks of UADT cancer in association with occupations or industrial activities. This study provides evidence of an association between some occupational categories and UADT cancer risk among men. The most consistent findings, also supported by previous studies, were obtained for specific workers employed in the construction industry. © 2011 UICC