Risk Of Aerodigestive Tract Cancers Research Articles

Can gene therapy be used to prevent cancer? Gene therapy for aldehyde dehydrogenase 2 deficiency.

Approximately 8% of the world population and 35 to 45% of East Asians are carriers of the hereditary disorder, aldehyde dehydrogenase 2 (ALDH2) deficiency. ALDH2 plays a central role in the liver to metabolize ethanol. With the common E487K variant, there is a deficiency of ALDH2 function; when ethanol is consumed, there is a systemic accumulation of acetaldehyde, an intermediate product in ethanol metabolism. In ALDH2 deficient individuals, ethanol consumption acutely causes the “Alcohol Flushing Syndrome” with facial flushing, tachycardia, nausea and headaches. With chronic alcohol consumption, ALDH2 deficiency is associated with a variety of disorders, including a remarkably high risk for aerodigestive tract cancers. Acetaldehyde is a known carcinogen. The epidemiologic data relating to the association of ALDH2 deficiency and cancer risk are striking: ALDH2 homozygotes that are moderate to heavy consumers of ethanol have a 7- to 12-fold increased risk for esophageal cancer, making ALDH2 deficiency the most common hereditary disorder associated with an increased cancer risk. In this review, we summarize the genetics and biochemistry of ALDH2, the epidemiology of cancer risk associated with ALDH2 deficiency, the metabolic consequences of ethanol consumption associated with ALDH2 deficiency and gene therapy strategies to correct ALDH2 deficiency and its associated cancer risk. With the goal of reducing the risk of aerodigestive tract cancers, in the context that ALDH2 is a hereditary disorder and ALDH2 functions primarily in the liver, ALDH2 deficiency is an ideal target for the application of adeno-associated virus-mediated liver directed gene therapy to prevent cancer.

Tooth brushing, tooth loss, and risk of upper aerodigestive tract cancer: a cohort study of Japanese dentisits.

ABSTRACTPrevious studies have focused on the association between poor oral health and upper aerodigestive tract (UADT) cancer. However, whether toothbrushing and tooth loss are associated with UADT cancer risk is still unclear. Therefore, we investigated the association between toothbrushing or tooth loss and UADT cancer in the Longitudinal Evaluation of Multi-phasic, Odontological, and Nutritional Associations in Dentists (LEMONADE) cohort study. From 2001 to 2006, we recruited 20,445 dentists (mean age ± standard deviation, 51.8 ± 12.0 years; 1,607 women [7.9%]) and followed for incidence or mortality of UADT cancer through March 2014. Information on lifestyle and oral health was collected by the baseline questionnaire. The Cox proportional hazards model was used to estimate hazard ratios (HRs) for UADT cancer and corresponding 95% confidence intervals (CI) for brushing frequency and tooth loss with adjustment for covariates. During the mean follow-up of 9.5 years, we confirmed 62 incident or fatal cases of UADT cancer. Infrequent toothbrushing (< 2 times/day) was significantly associated with increased risk of UADT cancer (multivariate HR = 2.13, 95% CI: 1.04–4.37). On the contrary, tooth loss was not significantly correlated with UADT cancer risk; multivariate HR was 1.03 (95% CI: 0.41–2.61) for loss of 15–27 teeth and 1.37 (0.50–3.75) for that of 28 teeth compared to tooth loss of 0–14 teeth. In conclusion, Infrequent toothbrushing was significantly associated with the risk of UADT cancer.

Toothbrushing frequency and gastric and upper aerodigestive tract cancer risk: A meta-analysis.

Results of epidemiological studies evaluating the association between toothbrushing and gastric and upper aerodigestive tract (UADT) cancer risk showed inconsistent results. The purpose of this study was to evaluate the association between toothbrushing and gastric and UADT cancer risk and quantify the dose-response association between them. We searched the PubMed, EMBASE and Cochrane Library databases to identify relevant studies on toothbrushing and gastric and UADT cancer risk. Statistical analyses were performed using STATA 12.0 software. A total of 30 studies of involving 1194017 participants met eligibility criteria and were included in the meta-analysis. Meta-analysis using a random-effect model showed that the high frequency of toothbrushing was associated with significantly reduced risk of gastric and UADT cancers (OR: 0.55, 95% CI 0.46-0.64, P<.05). Our dose-response analysis presented that every increased toothbrushing per day might reduce oral cavity cancer risk by 6%, pharyngeal cancer risk by 11%, laryngeal cancer risk by 3%, oesophageal cancer risk by 6% and gastric cancer risk by 4%. This meta-analysis suggested the negative relationship between frequency of toothbrushing and risk of gastric and UADT cancers. Toothbrushing may be a protective factor for gastric and UADT cancers. However, this association must be further validated through large prospective studies.

Inclusion of a gene-environment interaction between alcohol consumption and the aldehyde dehydrogenase 2 genotype in a risk prediction model for upper aerodigestive tract cancer in Japanese men.

The well‐known gene‐environment interaction between alcohol consumption and aldehyde dehydrogenase 2 (ALDH2) genotype in upper aerodigestive tract cancer risk may improve our ability to identify high‐risk subjects. Here, we developed and validated risk prediction models for this cancer in Japanese men and evaluated whether adding the gene‐environment interaction to the model improved the predictive performance. We developed two case‐cohort datasets in the Japan Public Health Center‐based Prospective Study: one from subjects in the baseline survey for model development (108 cases and 4049 subcohort subjects) and the second from subjects in the 5‐year follow‐up survey for model validation (31 cases and 1527 subcohort subjects). We developed an environmental model including age, smoking status, and alcohol consumption, and a gene‐environment interaction model including age, smoking status, and the combination of alcohol consumption and the ALDH2 genotype. We found a statistically significant gene‐environment interaction for alcohol consumption and the ALDH2 genotype. The c‐index for the gene‐environment interaction model (0.71) was slightly higher than that for the environmental model (0.67). The values of integrated discrimination improvement and net reclassification improvement for the gene‐environment interaction model were also slightly higher than those for the environmental model. Goodness‐of‐fit tests suggested that the models were well calibrated. Results from external model validation by the 5‐year follow‐up survey were consistent with those from the model development by the baseline survey. The addition of a gene‐environment interaction to a lifestyle‐based model might improve the performance to estimate the probability of developing upper aerodigestive tract cancer for Japanese men.

Hypertension is associated with oral, laryngeal, and esophageal cancer: a nationwide population-based study

Several studies have reported an association between hypertension and upper aerodigestive tract cancer, but no large-scale, population-based studies have been conducted to confirm this.The aim of this study was to explore the association between hypertension and risk of upper aerodigestive tract cancer in Koreans. Participants who underwent a national health screening examination from January 1 to December 31, 2009 (n = 9,746,606) were enrolled. We assessed the development of oral, laryngeal, or esophageal cancer until 2016 using records from the Korean Health Insurance claims database during the study period. During the seven-year follow-up period, 6,062, 2,658, and 4,752 subjects were newly diagnosed with oral, laryngeal, and esophageal cancer, respectively. Participants with metabolic syndrome had the highest risk of developing oral cancer (hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.03–1.16), laryngeal cancer (HR 1.27, 95% CI 1.17–1.38), and esophageal cancer (HR 1.11, 95% CI 1.04–1.19). Hypertension was a remarkable risk factor for each cancer (HR 1.11, 95% CI 1.04–1.17 for oral cancer; HR 1.23, 95% CI 1.13–1.33 for laryngeal cancer; HR 1.25, 95% CI 1.18–1.33 for esophageal cancer) after adjusting for age and other variables including gender, smoking status, alcohol intake, exercise, body mass index, and diabetes. Patients with untreated hypertension were at highest risk of developing oral cancer (HR 1.15; 95% CI 1.05–1.26), laryngeal cancer (HR 1.25; 95% CI 1.09–1.44), and esophageal cancer (HR 1.47; 95% CI 1.33–1.63) after adjusting for confounders. Hypertension was associated with the risk of oral, laryngeal, and esophageal cancer, despite of the lack of detailed biochemical information including the cancer cell types (squamous cell carcinoma or adenocarcinoma), cancer stage, physical findings and other medical history. Further studies are warranted to determine the reasons for this association and to establish effective interventions in this vulnerable population.

Meta-analysis of the association between dietary inflammatory index (DII) and upper aerodigestive tract cancer risk.

Background:Epidemiological studies have reported an inconsistent relationship between dietary inflammatory index (DII) and upper aerodigestive tract (UADT) cancer risk. However, no systematic review or meta-analysis has been reported up to now. To quantify the association between DII and UADT cancer risk, we performed this meta-analysis.Methods:The PubMed, EMBASE, Web of Science and Cochrane Library database were searched for relevant studies from inception December 2018. All case-control studies investigating the association between DII and UADT cancer risk were selected.Results:A total of 9 case-control studies were identified, involving 13,714 participants. The adjusted pooled OR of UADT cancer for the highest (the most pro-inflammatory diet) vs lowest (the most anti-inflammatory diet) DII categories were 2.27 (95% CI: 1.89–2.73). Subgroup analysis showed that individuals with the highest category of DII score were independently associated with esophagus cancer (OR = 2.53, 95% CI: 1.74–3.68), oral cavity cancer (OR = 2.23, 95% CI: 1.73–2.86), pharyngeal cancer (OR = 2.02, 95% CI: 1.54–2.64), and laryngeal cancer (OR = 2.05, 95% CI: 0.85–4.93).Conclusion:This meta-analysis suggested that the most pro-inflammatory diets (the highest DII scores) are associated with increased UADT cancer risk. However, the association between DII and laryngeal cancer risk need to be further investigated.

Association between dietary inflammatory index and upper aerodigestive tract cancer risk: A systematic review and dose-response meta-analysis.

The relationship between dietary inflammatory index (DII) and upper aerodigestive tract (UADT) cancer risk have been investigated in a growing number of epidemiological studies. However, their findings were inconsistent, and no systematic review or meta-analysis has been conducted up to now. This meta-analysis was carried out to examine potential dose-response relationship between DII score and UADT cancer risk. A systematic search was conducted for relevant studies in PubMed and Web of Science up to March 28, 2019. Categorical meta-analysis as well as linear and non-linear dose-response meta-analysis were performed to evaluate association between DII and UADT cancer risk. Nine case-control studies with a total of 4138 cases and 15,326 healthy controls were eligible in the present meta-analysis. The pooled odds ratios (ORs) of UADT cancer risk were 2.07 [95% confidence interval (CI): 1.82, 2.35] for the highest DII score compared with the lowest and 1.53 (95% CI: 1.39, 1.69) for higher DII score compared with lower score, respectively. Furthermore, a one-unit increment in DII score was associated with an increased risk of 18% for UADT cancers (OR: 1.18; 95% CI: 1.15, 1.21). An upward trend towards a positive association between elevated DII score and UADT cancer risk was also observed in non-linear dose-response meta-analysis. The present meta-analysis provides evidence of highly pro-inflammatory diets that might increase risk of UADT cancers. Therefore, reducing pro-inflammatory components in diets should be considered to prevent and control UADT cancers.

Periodontitis, oral hygiene habits, and risk of upper aerodigestive tract cancers: a case-control study in Maharashtra, India.

Chronic destructive periodontitis, a cause of systemic inflammation, affects some 10% to 15% of adults across the globe, with severity of disease increasing with age. The aim of this study was to explore the relationship between periodontitis and oral hygiene habits and upper aerodigestive tract(UADT) cancers. We conducted a case-control study, which included 240 UADT cancer cases and 240 controls matched by gender and age (±5years) from 2 different hospitals in Pune, India.In-person interviews and intraoral examinations were conducted for all patients. Severe periodontitis and greater than 5 missing teeth were associated with a significant risk of UADT cancers (adjusted odds ratio [OR] 2.25, 95% confidence interval [CI] 1.12-4.91; adjusted OR 3.28, 95% CI 1.95-5.49). Among the self-reported oral hygiene habits, dental checkups only at the time of pain was associated with an elevated risk for UADT cancers (adjusted OR 4.12; 95% CI 2.63-6.47). Topical application of mishri (black powder obtained by roasting and grinding tobacco) on gums (adjusted OR 3.06; 95% CI 1.75-5.35) and toothbrushing frequency less than once daily; (adjusted OR 2.09; 95% CI 1.27-3.45) were also associated with an elevated risk. Furthermore, the habit of ever chewing tobacco was associated with an elevated risk of severe periodontitis. Severe periodontitis is associated with an elevated risk for UADT cancers, and tobacco chewing strengthens this association in this population.

Egg Consumption and Risk of Upper Aero-Digestive Tract Cancers: A Systematic Review and Meta-Analysis of Observational Studies

Limited data are available that summarize the relation between egg intake and the risk of upper aero-digestive tract (UADT) cancers. This systematic review and meta-analysis was conducted to investigate the association between egg intake and the risk of UADT cancers. Medline/PubMed, ISI web of knowledge, EMBASE, Scopus, and Google Scholar were searched using relevant keywords. Observational studies conducted on humans investigating the association between egg consumption and the risk of UADT cancers were included. Overall, 38 studies with a total of 164,241 subjects (27, 025 cases) were included. Based on 40 effect sizes from 32 case-control studies, we found a 42% increased risk of UADT cancers among those with the highest egg consumption (ranging from ≥1 meal/d to ≥1 time/mo among studies) compared to those with the lowest intake (ranging from 0-20g/d to never consumed among studies) (overall OR: 1.42; 95% CI: 1.19, 1.68; P<0.001). However, this association was only evident in hospital-based case-control (HCC) studies (OR=1.50; 95% CI: 1.34, 1.68; P<0.001 for 'oropharyngeal and laryngeal cancer' and OR: 1.27; 95% CI: 1.08, 1.50; P=0.004 for esophageal cancer) and not in population-based case-control (PCC) studies (OR=1.25; 95% CI: 0.59, 2.67; P=0.56 for 'oropharyngeal and laryngeal cancer' and OR: 1.29; 95% CI: 0.92, 1.81; P=0.13 for esophageal cancer). In addition, the association was not significant in prospective cohort studies (overall OR: 0.86; 95% CI: 0.71, 1.04; P=0.11). Considering individual cancers, a positive association was observed between the highest egg consumption, compared with the lowest, and risk of oropharyngeal (OR: 1.88; 95% CI: 1.61, 2.20; P<0.001), laryngeal (OR: 1.83; 95% CI: 1.45, 2.32; P<0.001), oral & pharyngeal & laryngeal (OR: 1.37; 95% CI: 1.12, 1.67; P<0.001), and esophageal cancers (OR: 1.28; 95% CI: 1.10,1.48; P=0.001). We also found an inverse association between egg intake and the risk of oral cancer (OR: 0.78; 95% CI: 0.62, 0.99; P=0.04). In conclusion, high egg consumption (ranging from ≥1 meal/d to ≥1 time/mo among studies) was associated with increased risk of UADT cancers only in HCC studies but not in PCC or prospective cohort studies. PROSPERO registration number: CRD42018102619.

Identification of acrolein metabolites in human buccal cells, blood, and urine after consumption of commercial fried food.

ScopeAcrolein is a highly electrophilic α,β‐unsaturated aldehyde and is associated with human diseases. It is formed by Maillard reaction during food processing and could be detected in the emissions of overheated cooking oils. Consequently, humans are at risk of acrolein exposure through consumption of such prepared food.Methods and resultsWe conducted three human studies that healthy subjects (21–30 years) were served fried foods including fried chicken and French fries from three commercial fast food restaurants. Acrolein‐related metabolites including urinary 3‐hydroxypropyl mercapturic acid (3‐HPMA), serum acrolein‐protein conjugates (Acr‐FDP), and buccal acrolein‐induced DNA damages (Acr‐dG adducts) along with GSH levels in serum or buccal cells were investigated for different times after consumption.ConclusionUrinary 3‐HPMA levels were increased after 2‐hr consumption of fried food with an elimination half‐life of 10 hr. In addition, increased Acr‐dG adducts in oral cavity were inversely correlated to buccal glutathione (GSH) levels after consumption. However, there was no significant change in systemic GSH levels or Acr‐FDP adducts in serum. These results indicate that exposure of acrolein from consuming fried food affects local oral cavity homeostasis. This may provide a possible link between intake of fried food and increased risk of upper aerodigestive tract cancers.

Risk of second primary cancer following myeloid neoplasia and risk of myeloid neoplasia as second primary cancer: a nationwide, observational follow up study in Sweden

Although advances in the treatment of myeloid neoplasms have led to improved patient survival, this improvement has been accompanied by an increased risk of second primary cancer (ie, the risk of another cancer after myeloid neoplasia). We aimed to assess bi-directional associations between myeloid cancers and other cancers-ie, development of second primary cancer in patients who have previously had myeloid cancer, and risks of myeloid neoplasia in patients who have previously had another cancer-to provide insight into possible mechanisms beyond side-effects of treatment and shared risk factors. Using the Swedish Family-Cancer Database, we identified 35 928 individuals with primary myeloid cancer, including myeloproliferative neoplasms, acute myeloid leukaemia, chronic myeloid leukaemia, and myelodysplastic syndrome diagnosed between 1958 and 2015. The Swedish Family-Cancer Database includes every individual registered as a resident in Sweden starting in 1932, with full parental history. The primary endpoint was the assessment of relative risks (RRs) for second primary cancer, which we performed using means of incidence rate ratios, regressed over a generalised Poisson model. Between 1958 and 2015, overall relative risk of second primary cancers was significantly increased after acute myeloid leukaemia (RR 1·29, 95% CI 1·17-1·41), chronic myeloid leukaemia (1·52, 1·35-1·69), myelodysplastic syndrome (1·42, 1·26-1·59), and all myeloproliferative neoplasms (1·37, 1·30-1·43) relative to the incidence of these cancers as first primary cancer. With myeloid neoplasia as a second primary cancer, risks were significantly increased for acute myeloid leukaemia (1·57, 1·48-1·65), chronic myeloid leukaemia (1·26, 1·13-1·40), and myelodysplastic syndrome (1·54, 1·42-1·67) relative to the incidence of these myeloid neoplasms as first primary cancers. Relative risk of upper aerodigestive tract cancer, squamous cell skin cancer, and non-Hodgkin lymphoma as second primary cancers were increased after all four types of myeloid neoplasia relative to their incidence as first primary cancers. High risks of myelodysplastic syndrome and acute myeloid leukaemia as second primary cancers were found after haematological cancers (RRs between 5·08 and 10·04). The relative risks of second primary cancer are important for the long-term management of patients with myeloid cancers. The bi-directional associations of myeloid cancers with many other cancers suggest a number of candidate mechanisms that might contribute to the development and aetiology of a second primary cancer. These mechanisms might include immune dysfunction or the effects of treatment, and these should be assessed in future investigations. Deutsche Krebshilfe, Jane and Aatos Erkko Foundation, Sigrid Juselius Foundation, Finnish Cancer Organizations, Swedish Research Council, ALF from Region Skåne, and Bloodwise.

Dietary inflammatory index and risk of upper aerodigestive tract cancer in Japanese adults.

BackgroundThe inflammatory potential of diet that has been shown to be associated with cancer risk. We examined the association between dietary inflammatory potential as measured by the dietary inflammatory index (DII®) and risk of upper aerodigestive tract cancers in a Japanese case-control study.ResultsA positive association was observed between increasing DII scores and overall upper aerodigestive tract cancers, and across anatomic subsites. For upper aerodigestive tract cancers, the ORQ4vsQ1 = 1.73 (95% CI: 1.37–2.20); head and neck cancer, the ORQ4vsQ1 was 1.92 (95% CI: 1.42–2.59); and for esophageal cancer, the ORQ4vsQ1 was1.71 (95% CI: 1.54–1.90). Risks for hypopharyngeal and nasopharyngeal cancers were greatly elevated: (ORQ4vsQ1 = 4.05 (95% CI: 1.24–13.25) for hypopharyngeal cancer and ORQ4vsQ1 = 4.99 (95% CI: 1.14–21.79) for nasopharyngeal cancer.ConclusionA more pro-inflammatory diet was associated with an elevated risk of upper aerodigestive tract cancers after accounting for important confounders. All anatomic subsites, except larynx, showed the consistently elevated risk with increasing DII score. Those subsites with known etiological associations with persistent infection showed the largest elevation in risk. These results warrant further evaluation in future studies.Materials and MethodsThis is a case-control study of 1,028 cases and 3,081 age- and sex-matched non-cancer controls recruited at Aichi Cancer Center. DII scores were computed based on estimates of macro- and micro-nutrients from a self-administered food frequency questionnaire. Scores were further categorized into quartiles (based on the distribution in controls). Conditional logistic regression models were fit to estimate odds ratio (OR) and 95% confidence intervals (CIs) adjusted for smoking, ethanol consumption, alcohol flushing, number of teeth, and occupation group.

Alcohol-Derived Acetaldehyde Exposure in the Oral Cavity.

Alcohol is classified by the International Agency for Research on Cancer (IARC) as a human carcinogen and its consumption has been associated to an increased risk of liver, breast, colorectum, and upper aerodigestive tract (UADT) cancers. Its mechanisms of carcinogenicity remain unclear and various hypotheses have been formulated depending on the target organ considered. In the case of UADT cancers, alcohol’s major metabolite acetaldehyde seems to play a crucial role. Acetaldehyde reacts with DNA inducing modifications, which, if not repaired, can result in mutations and lead to cancer development. Despite alcohol being mainly metabolized in the liver, several studies performed in humans found higher levels of acetaldehyde in saliva compared to those found in blood immediately after alcohol consumption. These results suggest that alcohol-derived acetaldehyde exposure may occur in the oral cavity independently from liver metabolism. This hypothesis is supported by our recent results showing the presence of acetaldehyde-related DNA modifications in oral cells of monkeys and humans exposed to alcohol, overall suggesting that the alcohol metabolism in the oral cavity is an independent cancer risk factor. This review article will focus on illustrating the factors modulating alcohol-derived acetaldehyde exposure and effects in the oral cavity.

Possible role of diet in cancer: systematic review and multiple meta-analyses of dietary patterns, lifestyle factors, and cancer risk

Evidence of an association between dietary patterns derived a posteriori and risk of cancer has not been reviewed comprehensively. The aim of this review was to investigate the relation between a posteriori-derived dietary patterns, grouped as healthy or unhealthy, and cancer risk. The relation between cancer risk and background characteristics associated with adherence to dietary patterns was also examined. PubMed and Embase electronic databases were searched. A total of 93 studies including over 85 000 cases, 100 000 controls, and 2 000 000 exposed individuals were selected. Data were extracted from each identified study using a standardized form by two independent authors. The most convincing evidence (significant results from prospective cohort studies) supported an association between healthy dietary patterns and decreased risk of colon and breast cancer, especially in postmenopausal, hormone receptor-negative women, and an association between unhealthy dietary patterns and increased risk of colon cancer. Limited evidence of a relation between an unhealthy dietary pattern and risk of upper aerodigestive tract, pancreatic, ovarian, endometrial, and prostatic cancers relied only on case-control studies. Unhealthy dietary patterns were associated with higher body mass index and energy intake, while healthy patterns were associated with higher education, physical activity, and less smoking. Potential differences across geographical regions require further evaluation. The results suggest a potential role of diet in certain cancers, but the evidence is not conclusive and may be driven or mediated by lifestyle factors.

Development of a prediction model and estimation of cumulative risk for upper aerodigestive tract cancer on the basis of the aldehyde dehydrogenase 2 genotype and alcohol consumption in a Japanese population.

Alcohol consumption and the aldehyde dehydrogenase 2 (ALDH2) polymorphism are associated with the risk of upper aerodigestive tract cancer, and a significant gene-environment interaction between the two has been confirmed in a Japanese population. To aid the development of a personalized prevention strategy, we developed a risk-prediction model and estimated absolute risks stratified by a combination of the ALDH2 genotype and alcohol consumption. We carried out two age-matched and sex-matched case-control studies: one (630 cases and 1260 controls) for model derivation and the second (654 cases and 654 controls) for external validation. On the basis of data from the derivation study, a prediction model was developed by fitting a conditional logistic regression model using the following predictors: age, sex, smoking, drinking, and the ALDH2 genotype. The risk model, including a combination of the ALDH2 genotype and alcohol consumption, provided high discriminatory accuracy and good calibration in both the derivation and the validation studies: C statistics were 0.82 (95% confidence interval 0.80-0.84) and 0.83 (95% confidence interval 0.81-0.85), respectively, and the calibration plots of both studies remained close to the ideal calibration line. Cumulative risks were obtained by combining odds ratios estimated from the risk model with the age-specific incidence rate and population size. For heavy drinkers with a heterozygous genotype, the cumulative risk at age 80 was above 20%. In contrast, risk in the other groups was less than 5%. In conclusion, modification of alcohol consumption according to the ALDH2 genotype will have a major impact on upper aerodigestive tract cancer prevention. These findings represent a simple and practical model for personalized cancer prevention.

Air pollution and incidence of gastric and upper aerodigestive tract cancer in 15 European cohorts

Introduction: Associations with smoking and occupational exposures indicate that air pollution could be associated with increased risk of gastric and upper aerodigestive tract (UADT) cancers. However, data from large cohort studies is lacking. We evaluate the association between long-term exposure to ambient air pollution and gastric and UADT cancer incidence in European adult populations. Methods: Baseline addresses of individuals were geocoded and air pollution was assessed by land-use regression models for particulate matter (PM) below 10 µm (PM10), below 2.5 µm (PM2.5), between 2.5-10 µm (PMcoarse), PM2.5absorbance in 12 cohorts and for nitrogen oxides in 15 cohorts, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses. Combined estimates were determined with meta-analyses random effects models. Results: We included data on 305,319 individuals contributing 4,303,965 person-years at risk (average follow-up 14.1 years). 743 incident cases of gastric cancer and 927 of UADT cancer occurred. The hazard ratio for an increase of 5µg/m3 of PM2.5 was (1.39 (95%-CI 1.00;1.93) for gastric cancer and 1.06 (95%-CI 0.63;1.79) for UADT cancer. The corresponding HRs for PM10 were 1.07 (0.80-1.45) and 0.94 (0.65-1.36), respectively and for NO2 1.03 (0.92-1.15) and 0.95 (0.86-1.06), respectively. No statistically significant associations were found for any of the other exposure measures. Adjustment for the other pollutants and additional, mainly dietary, factors did not influence markedly the effect estimate for PM2.5 and gastric cancer. Restriction to study participants with stable addresses over follow-up resulted in a small increase of the effect estimate with a decrease in precision. Conclusion: This large multicentre study shows an association between exposure to PM2.5 and gastric cancer but not UADT cancer, suggesting that long- term air pollution could contribute to the risk of gastric cancer

675 - Development of a prediction model and estimation of cumulative risk for upper aerodigestive tract cancer based on aldehyde dehydrogenase 2 (ALDH2) genotype and alcohol consumption in a Japanese population

675 - Development of a prediction model and estimation of cumulative risk for upper aerodigestive tract cancer based on aldehyde dehydrogenase 2 (ALDH2) genotype and alcohol consumption in a Japanese population

Effects of ADH1B and ALDH2 Genetic Polymorphisms on Alcohol Elimination Rates and Salivary Acetaldehyde Levels in Intoxicated Japanese Alcoholic Men.

The genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) are associated with the risk of alcoholism and upper aerodigestive tract cancer in alcoholics. Salivary ethanol (sEtOH) levels are well correlated with blood EtOH levels. To study the effects of ADH1B and ALDH2 genotypes on the alcohol elimination rate (AER) and salivary acetaldehyde (sAcH) levels, we measured the sEtOH and sAcH levels twice at a 1-hour intervals in 99 intoxicated Japanese alcoholic men who had stopped drinking for 4 or more hours. The initial sEtOH levels did not differ between the ADH1B*2 group (n=50) and the ADH1B*1/*1 group (n=49) (median: 0.617 vs. 0.762mg/ml). The salivary AER (sAER) increased as the sEtOH levels increased (p<0.0001). After stratification according to the sEtOH levels (<0.4, 0.4 to 0.99, and ≥1.00mg/ml), the median sAER of the ADH1B*2 group was 0.075, 0.188, and 0.228mg/ml/h, respectively, and that of the ADH1B*1/*1 group was 0.037, 0.115, and 0.233mg/ml/h, respectively. The sAER of the ADH1B*2 group was faster than that of the ADH1B*1/*1 group overall (p=0.001) and when the sEtOH category was 0.4 to 0.99mg/ml (p<0.0001). The ADH1B genotype and the sEtOH levels had an interaction effect on the sAER (p=0.036). A multiple linear regression analysis with a stepwise procedure selected the ADH1B*2 allele (p=0.004) and the sEtOH levels (p<0.0001) as positive predictors of sAER. The sAER did not differ according to the ALDH2 genotype. The sAcH levels were higher than the blood AcH levels reported in alcoholics, probably because of AcH production by oral microorganisms. The sAcH of the ALDH2*1/*2 group (n=18) was higher than that of the ALDH2*1/*1 group (n=81) overall (p=0.0008) and when the corresponding sEtOH category was ≥1.00mg/ml (median: 3.195 vs. 1.776μg/ml, p=0.009). A multiple linear regression analysis selected the ALDH2*1/*2 and the sEtOH levels as positive predictors of the sAcH levels (p<0.0001). The enhanced AER in ADH1B*2 carriers and the increased sAcH levels in ALDH2*1/*2 carriers among intoxicated alcoholics provide possible mechanisms explaining how each genetic polymorphism affects the risk of alcoholism and upper aerodigestive tract cancer.

Association between OGG1 Ser326Cys polymorphism and risk of upper aero-digestive tract and gastrointestinal cancers: a meta-analysis

Cancers of the upper aero-digestive and gastrointestinal tract are one of the major causes of mortality around the world. DNA repair genes play a vital role in preventing carcinogenesis by maintaining genomic integrity. Polymorphisms in the nucleotide sequence of DNA repair genes are often reported to be associated with an increased risk for different cancers. The OGG1 gene encodes the enzyme 8-oxoguanine DNA glycosylase which removes oxidatively damaged bases of DNA. Several studies report that the OGG1 Ser326Cys polymorphism increases the risk for cancers of the upper aero-digestive and gastrointestinal tract. However, other studies provide evidence that such an association does not exist. A meta-analysis to assess the role of OGG1 Ser326Cys polymorphism in the cancers of the upper aero-digestive and gastrointestinal tract was therefore undertaken in order to resolve this ambiguity. Seventeen studies were recruited for this meta-analysis after screening 58 articles with a total of 5533 cases and 6834 controls for which the odds ratio with 95 % confidence interval was calculated. Begg’s funnel test and Egger’s test were performed for calculating publication bias. Our study reveals an association between OGG1 Ser326Cys polymorphism and cancer susceptibility of the upper aero-digestive and gastrointestinal tract (CG + GG vs CC; odds ratio, OR 1.22; 95 % CI 1.05–1.41; GG vs CG + CC; OR 1.36; 95 % CI 1.09–1.70; GG vs CC; OR 1.46; 95 % CI 1.12–1.92). Subgroup analysis based on cancer types and ethnicity also revealed the association of OGG1 Ser326Cys polymorphism to the risk for upper aero-digestive and gastrointestinal tract cancers among both the Asian and the Caucasian populations. No risk was however observed for smoking habits and OGG1 Ser326Cys polymorphism. In conclusion, OGG1 Ser326Cys polymorphism may be associated with the increased risk for aero-digestive tract and gastro-intestinal cancers in both Asian and Caucasian populations.

Long-Term Alcohol Consumption and Breast, Upper Aero-Digestive Tract and Colorectal Cancer Risk: A Systematic Review and Meta-Analysis.

Cancers of female breast, upper aero-digestive tract (UADT) (oral cavity, pharynx, larynx, oesophagus) and colorectum are causally related to alcohol consumption. Although alcohol consumption is likely to vary during life, the few studies that have explicitly measured lifetime consumption or intake over time have not been summarised. We therefore conducted a systematic review and meta-analysis. Studies were identified by searching the Medline, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and Scopus databases through January 2015 using broad search criteria. Studies reporting relative risks (RR) for quantitatively defined categories of alcohol consumption over time for breast, UADT or colorectal cancer were eligible. A two-stage random-effects meta-analysis was used to estimate a dose-response relationship between alcohol intake and each cancer site. RRs were also calculated for the highest relative to the lowest intake category. Sixteen articles for breast, 16 for UADT and 7 for colorectal cancer met the eligibility criteria. We observed a weak non-linear dose-response relationship for breast cancer and positive linear dose-response relationships for UADT and colorectal cancer. The pooled RRs were 1.28 (95% confidence interval, CI: 1.07, 1.52) for breast, 2.83 (95% CI: 1.73, 4.62) for UADT, 4.84 (95% CI: 2.51, 9.32) for oral cavity and pharynx, 2.25 (95% CI: 1.49, 3.42) for larynx, 6.71 (95% CI: 4.21, 10.70) for oesophageal and 1.49 (95% CI: 1.27, 1.74) for colorectal cancer. Our findings confirm dose-dependent associations between long-term alcohol intake and breast, UADT and colorectal cancer.