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Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.

Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility of automatically retrieving information from the medical literature and leveraging this information in GWAS.We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts, and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the phenotype of interest--the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and subsequently applied it in a two-phase GWAS of oral cancer.Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (per-rare-allele log additive p-value [p(trend)] = 2.5×10(-3)). The combined OR for having one additional rare allele was 0.83 (95% CI: 0.76-0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper aerodigestive tract (UADT), but no additional association signal was found.This study highlights the potential utility of systematically incorporating prior knowledge from the medical literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url: http://services.gate.ac.uk/lld/gwas/service/config).

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Genetic susceptibility loci for oropharyngeal cancer have been reported but these studies have not always examined human papillomavirus (HPV) status. Here, the authors perform genome-wide analysis taking into account HPV16 serology status and report two independent loci in the HLA region, suggesting the protective role of HLA variants against HPV infection.

Objectives: To investigate the link between self-reported oral health and arthritis in the Scottish population using data from the Scottish Health Survey. Material and Methods: Data were available from 2008 to 2013 on self-reported arthritis, oral health conditions and oral hygiene habits from the Scottish Health Survey. Arthritis was defined in this survey by self-reported long standing illness, those who reported having arthritis, rheumatism and/or fibrositis. Oral conditions were defined by self-reported bleeding gums, toothache, biting difficulties and/or edentulousness. Oral hygiene habits were defined by self-reported brushing teeth and/or using dental floss on daily basis. Logistic regression was used for statistical analysis adjusted for age, gender, qualification, smoking and body mass index. Results: Prevalence of self-reported arthritis was 9.3% (95% confidence interval [CI] = 9.03 to 9.57). Those who reported having bleeding gums (adjusted odds ratio [OR] = 1.63; 95% CI = 1.35 to 1.96), toothache (OR = 1.32; 95% CI = 1.16 to 1.5), biting difficulties (OR = 1.95; 95% CI = 1.62 to 2.34), and being edentulous (OR = 1.22; 95% CI = 1.08 to 1.37) had an increased risk of arthritis. Brushing teeth (OR = 1.25; 95% CI = 0.74 to 2.12), and using dental floss (OR = 1.11; 95% CI = 0.89 to 1.39) were not associated with arthritis. Conclusions: Self-reported oral conditions were associated with increased risk of self-reported arthritis. Oral hygiene habits were not associated with self-reported arthritis. Further investigation is required to assess the causal association between oral hygiene, oral disease and arthritis.

Objectives: The purpose of the study was to identify the risk of orofacial cleft in the offspring of women with pre-maternal obesity/overweight when compared with pre-maternal normal weight women. Material and Methods: MEDLINE and EMBASE were searched from 1980 to July 2014 for cohort, case control and cross sectional studies. BMI were categorized according to WHO recommendation: normal weight (BMI 18.5 - 24.9), overweight (BMI 25 - 29.9) and obese (BMI ≥ 30). Results: Six studies were identified; three case control studies which were used for the meta-analysis and two cross sectional studies and one cohort study. Compared with women of recommended BMI, obese women were at increased odds of pregnancy affected by CLP (OR = 1.16; 95% CI 1, 1.34) and CP (OR = 1.14; 95% CI 0.95, 1.37). Overweight women were also at increased odds of pregnancy affected by CLP (OR = 1.06; 95% CI 0.93, 1.21) but not CP (OR = 0.89; 95% CI 0.75, 1.06). The results of the risk ratios reported in the cross sectional and cohort studies were similar to the results of the meta-analysis. Conclusions: The results of this study reveal that there is an increased risk of having offspring with orofacial cleft in obese/overweight women. The reason for this association is not known. Although, the risk is small, it is important because of the increasing incidence of obesity.

Objectives: The purpose of this study was to determine the pattern of mouthwash use and to investigate the associated factors in general population.Material and Methods: An Adult Dental Health Survey was conducted on 3,022 residents of Grampian region of Scotland (adjusted participation rate 58.2%). Participants received a questionnaire consisting of questions on oral health and behavioural factors.Results: The majority of participants (38.1%) have never used mouthwash, 17.5% used mouthwash less than once a month, 19.4% used mouthwash once every few days and 25.1% used mouthwash daily.Prevalence of use decreased with age (P < 0.001). Woman were more likely to use mouthwash than men (P = 0.004). Mouthwash use decreased with decrease in the level of deprivation (P < 0.001). Never-smokers were less likely to use mouthwash (40.3%) compared to smokers (53.1%) or those who stopped smoking (46.5%) (P < 0.001). Mouthwash was used by smaller proportion of people drinking alcohol on daily basis (36.6%), than by abstainers (42.2%) (P = 0.012).There was a positive relationship between flossing or brushing pattern and mouthwash use (P < 0.001). There was statistically significant relationship between mouthwash use and reasons for the last dental visit (P = 0.009).When compared to healthy individuals, mouthwash was used by higher proportion of people reporting that they had gum disease (P = 0.001), ulcers (P = 0.001), oral infections or swelling (P = 0.002) or other problems (P = 0.025).Conclusions: Mouthwash use in general population is associated with socio-demographic, health and behavioural factors.

Objectives: The aim of the current study was to investigate whether there was a relationship between a history of third molar removal and the prevalence of orofacial pain in a sample of the general population.Material and methods: A survey was conducted in South East Cheshire, United Kingdom (81% participation rate). Information was collected using postal questionnaires (n = 1510) and dental records (n = 809).Results: Participants who reported third molar extractions were more likely to report orofacial pain (RR = 1.29; 95% confidence interval [CI] 1.01 - 1.65). Participants with a more recent history of extractions (< 8 years ago) as recorded in dental records were more likely to report orofacial pain compared to those who had all third molar present (RR = 1.91; 95% CI 1.10 - 3.32).Conclusions: This research suggests that self-reported third molar removal is linked to self-reported orofacial pain, however evidence from one study is not sufficient to give an unequivocal answer.

Objectives: The purpose of this project was to determine the level of mouth cancer awareness and to investigate the associated factors in a United Kingdom (UK) general population sample. Material and Methods: Adult Dental Health Survey (2010) was conducted in a sample of 3,353 adult residents in the Grampian region of the UK (adjusted participation rate 58%). Participants completed a questionnaire consisting of questions on oral health, health behaviour, quality of life and cancer awareness. Results: Overall, 81% of participants were aware of mouth cancer. This was associated with younger age, higher levels of education and better general health. Current smokers and alcohol drinkers were more aware of mouth cancer. When asked about risk factors for mouth cancer, the following were identified by the respondents: smoking (84%), poor oral hygiene (60%), drinking alcohol heavily (59%), poor diet (37%), stress (15%), being overweight (6%), drinking hot liquids (5%), eating spicy food (3%), using mouthwash (2%) and kissing someone (1%). Smokers were more likely to identify smoking as a risk factor for mouth cancer. Similarly, those who consumed alcohol almost daily were more likely to identify heavy alcohol drinking as a risk factor. Conclusions: Awareness of mouth cancer is high in respondents from the general population, and participants were able to identify the most important risk factors. Knowledge of tobacco and alcohol as risk factors was highest amongst those exposed to them. The study proposed that the prevention strategies should focus not only on increasing knowledge, but also on changing health behaviour.

Objectives: Dentures are worn by around 20% of the population, yet if they become displaced they may enter the gastrointestinal or respiratory system, sometimes with grave consequences. The aim of this study was to review recent published literature in order to identify the epidemiology of patients and characteristics of swallowed and aspirated dental prostheses, and propose strategies to minimise these risks. Material and Methods: A fifteen year retrospective of published case series and case reports was carried out. Photographs, radiographs and descriptions of the dental prostheses were gathered, as well as the patient’s presenting complaint, the anatomical site where the denture was caught and the procedure required to remove the denture. Results: Ninety one separate events of swallowed or aspirated dentures were identified from 83 case reports and series from 28 countries. Average age was 55 years, and these were 74% male. Photographs were retrieved for 49 of these dentures. Clasps were present in 25 of the dentures. There was no significant difference between clasped and unclasped dentures for perforation rates, need for open surgery and spontaneously passed dentures. Conclusions: We discuss the implications of this study regarding denture designs, specifically the importance of using a radiopaque acrylic, using clasps when required even if there is a risk of aspiration, advising patients to return if a denture is loose or damaged, and finally that all patients who wear a denture are at risk of aspiration and swallowing events, and associated morbidity and mortality.

Objectives: To conduct a systematic review of epidemiological literature to determine the incidence of bisphosphonate related osteonecrosis of the jaw occurring either spontaneously or after dental surgery, in children and adolescents diagnosed with osteogenesis imperfecta. Material and Methods: MEDLINE, HMIC and EMBASE were used to search for English-language articles published from 1946 - 2013. Inclusion criteria consisted of population based studies of children and adolescents (24 years and younger) diagnosed with osteogenesis imperfecta, only studies which included a dental examination, and patients treated with intravenous bisphosphonates were included. Articles were excluded if patients had any other co-morbidity which could affect osteonecrosis of the jaw, and those which treated patients with oral bisphosphonates only. Results: Five studies consisting of four retrospective cohort studies and one case series were identified. Study populations ranged from 15 to 278 patients and number of subjects with osteogenesis imperfecta ranged from 15 to 221. Mean duration of intravenous bisphosphonate use ranged from 4.5 to 6.8 years. All patients were clinically examined and no patients were found to have osteonecrosis of the jaw. Conclusions: There is no evidence to support hypothesis of causal relationship between bisphosphonates and osteonecrosis of the jaw in children and adolescents with osteogenesis imperfecta. More prospective studies on bisphosphonate use in osteogenesis imperfecta needs to be carried out.

Objectives: Pain is a common complication in head and neck cancer. The aim of this paper is to evaluate the evidence from randomised control trials investigating pharmacological and non-pharmacological methods of pain management in head and neck cancer. Material and Methods: Medline, Embase and the Cochrane library databases were searched. Squamous cell carcinomas of the head and neck excluding nasopharyngeal and salivary gland cancers were included. The limits were “human” and “randomised clinical trials”. A quality assessment was carried out. Results: 13 studies were included with a total of 644 participants. The primary outcome for most of these papers was pain control post-treatment. Levels of bias varied between the studies. Majority (12 out of the 13 studies) reported intervention to be superior to the control or standard therapy in pain management. Only 46% of the studies were carried out on an intention to treat basis. Two studies reported high dropout rates, with one at 66%. Conclusions: There is insufficient evidence from randomised clinical trials to suggest an optimal pharmacological intervention for head and neck cancer pain post-treatment. Further high quality randomised clinical trials should be conducted to develop an optimal management strategy for head and neck cancer pain.

Objectives: The purpose of this study was to develop and validate the mouthwash use questionnaire to determine the lifetime exposure to alcohol from mouthwash and verify that it was suitable for use in general population.Material and Methods: Data were available from three consecutive studies, all collecting information on mouthwash use. In addition, supermarkets and online stores were screened for the brands of mouthwash they sold. Alcohol content of mouthwash was identified from various sources, including laboratory measurements. Alcohol-containing mouthwash use was converted to glasses of wine equivalent.Results: Mouthwash was used by 62% of the participants, and the main benefits reported were refreshment of bad breath (75%), elimination of bacteria (68%) and reduction of plaque formation (47%). Majority mouthwashes used by the participants contained alcohol (61%). Life-time exposure from alcohol in mouthwash was relatively small for most of the study participants: 79% had rinsed for less than one year with alcohol equivalent of one glass of wine per day. There was substantial agreement in mouthwash reporting between different occasions (Kappa > 0.62).Conclusions: The questionnaire can be used to investigate mouthwash use in the general population and to measure alcohol intake from mouthwash.

Objectives: Pain is a major symptom in patients with cancer; however information on head and neck cancer related pain is limited. The aim of this review was to investigate the prevalence of pain and associated factors among patients with HNC. Material and Methods: The systematic review used search of MEDLINE, EMBASE and CINAHL databases to December 2011. Cancers of the oral mucosa, oropharynx, hypopharynx and larynx were included in this review with pain as main outcome. The review was restricted to full research reports of observational studies published in English. A checklist was used to assess the quality of selected studies. Results: There were 82 studies included in the review and most of them (84%) were conducted in the past ten years. Studies were relatively small, with a median of 80 patients (IQR 44, 154). The quality of reporting was variable. Most studies (77%) used self-administered quality of life questionnaires, where pain was a component of the overall scale. Only 33 studies reported pain prevalence in HNC patients (combined estimate from meta-analysis before (57%, 95% CI 43% - 70%) and after (42%, 95% CI 33% - 50%) treatment. Only 49 studies (60%) considered associated factors, mostly tumour- or treatment-related. Conclusions: The study has shown high levels of pain prevalence and some factors associated with higher levels of pain. There is a need for higher quality studies in a priority area for the care of patients with head and neck cancer.

Previous molecular epidemiological studies on head and neck cancer have examined various single nucleotide polymorphisms, but there are very few documented associations. In the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we evaluated associations between SNPs in the metabolism, cell cycle, and DNA repair pathways and the risk of head and neck cancer. We analyzed individual-level pooled data from 14 European, North American, Central American and Asia case-control studies (5,915 head and neck cancer cases and 10,644 controls) participating in the INHANCE consortium. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for SNP effects, adjusting for age, sex, race, and country. We observed an association between head and neck cancer risk and MGMT Leu84Phe heterozygotes (OR=0.79, 95% CI=0.68-0.93), XRCC1 Arg194Trp rare homozygotes (OR=2.3, 95% CI=1.1-4.7), ADH1B Arg48His homozygotes Arg/Arg (OR=2.7, 95% CI=1.9-4.0), ADH1C Ile350Val homozygotes Ile/Ile (OR=1.2, 95% CI=1.1-1.4), and the GSTM1 null genotype (OR=1.1, 95% CI=1.0-1.2). Among these results, MGMT Leu84Phe, ADH1B Arg48His, ADH1C Ile350Arg, and the GSTM1 null genotype had fairly low false positive report probabilities (