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The incidence of esophageal adenocarcinoma (EA) has drastically increased in the United States since 1970s for unclear reasons. We hypothesized that the widespread usage of antibiotics has increased the procarcinogenic potential of the orodigestive microbiota along the sequence of gastroesophageal reflux (GR), Barrett's esophagus (BE) and EA phenotypes. This case control study included normal controls (NC) and three disease phenotypes GR, BE and EA. Microbiota in the mouth, esophagus, and stomach, and rectum were analyzed using 16S rRNA gene sequencing. Overall, we discovered 44 significant pairwise differences in abundance of microbial taxa between the four phenotypes, with 12 differences in the mouth, 21 in the esophagus, two in the stomach, and nine in the rectum. Along the GR→BE→EA sequence, oral and esophageal microbiota were more diversified, the dominant genus Streptococcus was progressively depleted while six other genera Atopobium, Actinomyces, Veillonella, Ralstonia, Burkholderia and Lautropia progressively enriched. In NC, Streptococcus appeared to control populations of other genera in the foregut via numerous negative and positive connections, while in disease states, the rich network was markedly simplified. Inferred gene functional content showed a progressive enrichment through the stages of EA development in genes encoding antibiotic resistance, ligands of Toll-like and NOD-like receptors, nitrate-nitrite-nitric oxide pathway and acetaldehyde metabolism. The orodigestive microbiota is in a progressive dysbiotic state along the GR-BE-EA sequence. The increasing dysbiosis and antibiotic and procarcinogenic genes in the disease states warrants further study to define their roles in EA pathogenesis.

Background There is continued uncertainty regarding the risks of hepato-pancreato-biliary cancers in patients with inflammatory bowel disease (IBD) with or without concomitant primary sclerosing cholangitis (PSC). Objective To give updated estimates on risk of hepato-pancreato-biliary cancers in patients with IBD, including pancreatic cancer, hepatocellular carcinoma, gall bladder cancer, and intra – and extrahepatic cholangiocarcinoma. Methods In a population-based cohort study, we included all patients diagnosed with IBD in Norway and Sweden from 1987 to 2016. The cohort comprised of 141,960 patients, identified through hospital databases and the National Patient Register. Participants were followed through linkage to national cancer, cause of death, and population registries. We calculated absolute risk and standardized incidence ratios (SIRs) of hepato-pancreato-biliary cancers by PSC and other clinical characteristics. Results Of the 141,960 IBD patients, 3.2% were diagnosed with PSC. During a median follow-up of 10.0 years, we identified 443 biliary tract cancers (SIR 5.2, 95% confidence interval [CI] 4.8–5.7), 161 hepatocellular carcinomas (SIR 2.4, 95% CI 2.0–2.7) and 282 pancreatic cancers (SIR 1.3, 95% CI 1.2–1.5). The relative risks were considerably higher in PSC-IBD patients, with SIR of 140 (95% CI 123–159) for biliary tract, 38.6 (95% CI 29.2–50.0) for hepatocellular, and 9.0 (95% CI 6.3–12.6) for pancreatic cancer. The SIRs were still slightly increased in non-PSC-IBD patients, compared to the general population. For biliary tract cancer, the cumulative probability at 25 years was 15.6% in PSC-IBD patients, and 0.4% in non-PSC-IBD patients. Conclusions The dramatically increased risks of hepato-pancreato-biliary cancers in PSC-IBD patients support periodic surveillance for these malignancies. While much lower, the excess relative risks in non-PSC-IBD patients were not trivial compared to non-IBD related risk factors.

Background The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. Methods The authors conducted a population-based case-control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self-reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration-response relations. Results Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26-1.68), chemical vapors (OR, 1.37; 95% CI, 1.17-1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25-1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30-1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia. Conclusions Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas. Lay summary The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC. Duration-response trends were observed with increasing duration of exposure. These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high-incidence region.

Background The vagus nerve provides essential parasympathetic innervation to the gastrointestinal system and is known to have anti-inflammatory properties. Aims To explore the relationship between vagotomy and the risk of inflammatory bowel disease (IBD) and its major categories: Crohn's disease (CD) and ulcerative colitis (UC). Methods A matched cohort comprising 15 637 patients undergoing vagotomy was identified through the Swedish Patient Register from 1964 to 2010. Each vagotomised patient was matched for birth year and gender with 40 nonvagotomised individuals on the date of vagotomy. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for IBD using flexible parametric models adjusted for matching variables, year of vagotomy, birth country, chronic obstructive pulmonary disease and comorbidity index. Results We observed 119 (0.8%) patients with vagotomy developed IBD compared to 3377 (0.5%) IBD cases in nonvagotomised individuals. The crude incidence of IBD (per 1000 person-years) was 0.38 for vagotomised patients and 0.25 for nonvagotomised individuals. We observed a time-dependent elevated risk of IBD associated with vagotomy, for instance, the HR (95% CI) was 1.80 (1.40-2.31) at year 5 and 1.49 (1.14-1.96) at year 10 post-vagotomy. The association appeared to be stronger for truncal than selective vagotomy and limited to CD (HR was 3.63 [1.94-6.80] for truncal and 2.06 [1.49-2.84] for selective vagotomy) but not UC (1.36 [0.71-2.62] for truncal and 1.25 [0.95-1.63] for selective vagotomy). Conclusions We found a positive association between vagotomy and later IBD, particularly for CD. The finding indirectly underlines the beneficial role of the vagal tone in IBD.

Background: Medications that are used for treatment of metabolic disorders have been suggested to be associated with the development of amyotrophic lateral sclerosis (ALS). Methods: To examine the associations of antidiabetics and statins with the subsequent risk of ALS we conducted a population-based nested case-control study of 2475 Swedish residents diagnosed with ALS during July 2006 to December 2013 and 12375 population controls (five for each ALS case). We extracted information on filled prescriptions of antidiabetics and statins for both cases and controls from the Swedish Prescribed Drug Register during the years before ALS diagnosis. Conditional logistic regression was used to calculate odds ratios (ORs) for the associations of these medications with ALS risk. Results: Patients with ALS were less likely to have been prescribed with antidiabetics compared with controls [OR, 0.76; 95% confidence intervals (CI), 0.65–0.90]. Conversely, statins were not associated with ALS risk overall (OR, 1.08; 95% CI, 0.98–1.19), although a positive association was noted among women (OR, 1.28; 95% CI, 1.10–1.48). The latter association was mostly explained by ALS cases being more likely to have a first prescription of statins during the year before diagnosis compared with controls (OR, 2.54; 95% CI, 1.84–3.49). Conclusions: The inverse association of antidiabetics with ALS is consistent with the previously reported inverse association between type 2 diabetes and ALS risk. The increase in prescription of statins during the year before ALS diagnosis deserves attention because it might reflect an acceleration of the course of ALS due to statin use.

Previous work has shown that both long and short sleep duration is associated with increased mortality, with lowest risk around 7hr. This has had widespread impact on views on the optimal sleep duration. However, age, being employed/retired, and blue-/white-collar status, may influence the time available for sleep and thus, confound the association. We investigated the role of these factors on the association between sleep duration and mortality. We used employed and retired participants (N=25,430) from the Swedish National March Cohort and Cox proportional hazards regression to model the shape of the association. We found a significant U-shaped association in a multivariable model with a hazard ratio (HR) of 1.24 (95% confidence interval [CI] 1.10, 1.39) for 60.3years at baseline. The shape of the association did not differ between blue-/white-collar workers, nor between employed and retired groups. We conclude that the U-shaped association between sleep duration and mortality is present only in older individuals.

The relationship between risk of esophageal squamous cell carcinoma (ESCC) and adult height, changes in individual body mass index (BMI) and body shape is not established. We performed a large population‐based case‐control study, which enrolled a total of 1414 ESCC cases and 1989 controls in a high‐incidence area in China. Using face‐to‐face interview with a structured questionnaire, information on participants' heights, weights, and perceived body shapes at 20 years of age was collected. Additionally, data on weight and perceived body shape among the same participants 10 years prior to ascertainment were collected using the same method. Odd ratios (ORs) of ESCC risk in relation to BMI and body shape were estimated using unconditional logistic regression models. The adjusted results indicated that ESCC risk in adults rapidly rose as height increased, plateauing at 170 cm among men and 157 cm among women. Among participants who were underweight, normal weight, or thinner than body shape 4, body weight loss was associated with increased risk of ESCC, and body weight gain was associated with decreased incidence of ESCC (ORs ranging from 0.40 to 0.76). Notably, however, changes in body weight did not significantly affect ESCC risk among participants who were overweight, obese, or larger than body shape 3. Maintaining a fit body shape and a reasonable BMI is advisable and of vital importance to reduce the risk of ESCC, especially in high‐risk areas.

Low socioeconomic position (SEP) is a strong risk factor for incidence and premature mortality from several cancers. Our study aimed at quantifying the association between SEP and gastric cancer (GC) risk through an individual participant data meta-analysis within the “Stomach cancer Pooling (StoP) Project”. Educational level and household income were used as proxies for the SEP. We estimated pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) across levels of education and household income by pooling study-specific ORs through random-effects meta-analytic models. The relative index of inequality (RII) was also computed. A total of 9,773 GC cases and 24,373 controls from 25 studies from Europe, Asia and America were included. The pooled OR for the highest compared to the lowest level of education was 0.60 (95% CI, 0.44–0.84), while the pooled RII was 0.45 (95% CI, 0.29–0.69). A strong inverse association was observed both for noncardia (OR 0.39, 95% CI, 0.22–0.70) and cardia GC (OR 0.47, 95% CI, 0.22–0.99). The relation was stronger among H. pylori negative subjects (RII 0.14, 95% CI, 0.04–0.48) as compared to H. pylori positive ones (RII 0.29, 95% CI, 0.10–0.84), in the absence of a significant interaction (p = 0.28). The highest household income category showed a pooled OR of 0.65 (95% CI, 0.48–0.89), while the corresponding RII was 0.40 (95% CI, 0.22–0.72). Our collaborative pooled-analysis showed a strong inverse relationship between SEP indicators and GC risk. Our data call for public health interventions to reduce GC risk among the more vulnerable groups of the population. This project was supported by the “Associazione Italiana per la Ricerca sul Cancro” (AIRC), Projects no. 16715 and 21378 (Investigator Grant), by the “Fondazione Italiana per la Ricerca sul Cancro” (FIRC) and by the Italian Ministry of Health (Young Researchers, GR-2011-02347943 to SB). MR is grateful to the FIRC who supported his work from 2015 to 2017. Our study was also funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) under the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit; POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013). AF (PD/BD/105823/2014) was awarded an individual scholarship through national funding from FCT/MCTES.

Poor oral health may be involved in the pathogenesis of gastric cancer, however, some aspects have not been explored. Further, for previously studied aspects, for example, tooth-loss, the findings are inconsistent. We conducted a prospective cohort study of 19,831 participants from Uppsala, Sweden, cancer-free at baseline in 1973-1974 and followed until 2012 through linkage to national registers. We found that individuals with fewest teeth at baseline had an increased risk of gastric cancer relative to subjects with all examined teeth present (p = 1.75e-2). Presence of denture-associated lesions was also associated with an increased risk of gastric cancer (p = 1.00e-4). However, these excess risks significantly varied with attained age; estimated hazard ratio (HR) at attained age 50 for tooth loss was 4.24 [95% confidence interval (CI) 1.83-9.80] and 5.91 (95% CI 2.76-12.63) for denture-associated lesions, decreasing at an estimated 4% and 6% per year respectively, resulting in HR of 1.54 (95% CI 0.90-2.64) for tooth loss and HR 1.29 (95% CI 0.90-1.85) for denture-associated lesions at attained age 75. No increased risk of gastric cancer was found for individuals with higher levels of dental plaque, or with Candida-related or tongue lesions. In conclusion, tooth-loss and denture-associated lesions are associated with increased risks of gastric cancer. Previous conflicting findings of tooth-loss and gastric cancer risk may partly be explained by the age-varying relative risk of gastric cancer.

Viral hepatitis is a major public health concern in China, but data on national epidemiological characteristics are lacking. We collected reporting incidence data on hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in China from 2004 to 2014. Empirical mode decomposition (EMD) was performed to accurately describe the reporting incidence trends of HBV and HCV. A mathematical model was used to estimate the relative change in incidence across provinces and age groups. Nationwide, a total of 916 426 hepatitis B cases and 39 381 hepatitis C cases were recorded in 2004; the reporting incidences of HBV and HCV were 70.50/100 000 and 3.03/100 000, respectively. The overall relative changes in HBV and HCV reporting incidences in China from 2004 to 2014 were 0.98 (95% CI 0.96-1.00, P = .082) and 1.16 (95% CI 1.12-1.20, P < .001), respectively. Thirteen provinces experienced decline in HBV reporting incidence. Most provinces exhibited an increasing trend in HCV reporting incidence. People aged ≤24 displayed a significant descending trend in HBV reporting incidence; people aged ≥55 exhibited a significant increasing trend. For HCV infection, the reporting incidence increased in all age groups except the 10-14 age group. In China, the majority of provinces have experienced decline or remained stable in HBV infection but show significant increases in HCV infection. Children and adolescents are well protected from HBV infection, while relatively higher increasing rates are found among older people. HCV is much more prevalent among older people, although its emergence has shifted to younger age groups.

Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trondelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow-up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.

An association between heavy alcohol drinking and gastric cancer risk has been recently reported, but the issue is still open to discussion and quantification. We investigated the role of alcohol d ...

Objective To assess the associations of blood biomarkers of carbohydrate, lipid, and apolipoprotein metabolisms with the future risk of amyotrophic lateral sclerosis (ALS). Methods In the Apolipoprotein-related MOrtality RISk study, we enrolled 636,132 men and women during 1985–1996 in Stockholm, Sweden, with measurements of serum glucose, total cholesterol, triglycerides, apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I). Serum low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were either directly measured or calculated from total cholesterol, triglycerides, and apoA-I. The cohort was followed until the end of 2011. We used Cox models and mixed-effects models to, first, estimate the associations between these biomarkers and ALS incidence and, second, to assess the changes of these biomarkers during the 20 years before ALS diagnosis. Results One-unit increase of LDL-C (hazard ratio [HR] = 1.14; 95% confidence interval [CI] = 1.02–1.27), apoB (HR = 1.68; 95% CI = 1.17–2.42), and apoB/apoA-I ratio (HR = 1.90; 95% CI = 1.29–2.78) was associated with a higher incidence of ALS. High glucose level (≥6.11mmol/L) was associated with a lower incidence (HR = 0.62; 95% CI = 0.42–0.93), whereas high LDL-C/HDL-C (≥3.50; HR = 1.50; 95% CI = 1.15–1.96) and high apoB/apoA-I (≥0.90 for men, ≥0.8 for women; HR = 1.41; 95% CI = 1.04–1.90) ratios were associated with a higher incidence. During the 10 years before diagnosis, ALS patients had increasing levels of LDL-C, HDL-C, apoB, and apoA-I, whereas gradually decreasing levels of LDL-C/HDL-C and apoB/apoA-I ratios. Interpretation Alterations in the carbohydrate, lipid, and apolipoprotein metabolisms are associated with ALS risk and may serve as prodromal symptoms decades before ALS diagnosis. The imbalance between apoB and apoA-I as well as between LDL-C and HDL-C may be an etiological mechanism for ALS and needs to be further studied. Ann Neurol 2017;81:718–728

BACKGROUND To the authors' knowledge, no studies to date have explored familial risks of nasopharyngeal carcinoma (NPC) in detail and quantified its lifetime risk in high-incidence populations. METHODS The authors conducted a population-based case-control study of 2499 NPC cases and 2576 controls randomly selected in southern China from 2010 through 2014. Unconditional logistic regression was used to estimate multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) associated with a family history of NPC. In addition, the authors compiled a reconstructed cohort comprising 40,781 first-degree relatives of cases and controls to calculate the lifetime cumulative risk of NPC. RESULTS Individuals with a first-degree family history of NPC were found to be at a >4-fold risk of NPC (OR, 4.6; 95% CI, 3.5-6.1) compared with those without such a history, but had no excess risk of other malignancies. The excess risk was higher for a maternal than a paternal history and was slightly stronger for a sibling compared with a parental history, and for a sororal than a fraternal history. Among relatives of cases, the cumulative risk of NPC up to age 74 years was 3.7% (95% CI, 3.3%-4.2%), whereas that among relatives of controls was 0.9% (95% CI, 0.7%-1.2%). Cumulative risk was higher in siblings than in parents among relatives of cases, whereas no such difference was noted among relatives of controls. CONCLUSIONS Individuals with a family history of NPC have a substantially higher risk of NPC. These relative and cumulative risk estimates can guide the development of strategies for early detection and clinical consultation in populations with a high incidence of NPC. Cancer 2017;123:2716-25. © 2017 American Cancer Society.

To further examine the association between oral hygiene and esophageal squamous cell carcinoma (ESCC) risk and the effect modification of other exposures, we conducted a population-based case-control study between 2010 and 2012 in Taixing, China, a high-risk area for ESCC. Cases were primarily recruited from endoscopy units at local hospitals, supplemented by linkage to the local Cancer Registry. Control subjects were frequency matched to cases by sex and age (5-year groups) and were randomly selected from the Taixing Population Registry. For the current analysis, data from 616 histopathologically confirmed cases and 770 controls with complete information on oral hygiene were analyzed. Unconditional logistic regression models, including oral hygiene indicators and potential behavioral confounders, were used to derive odds ratios (ORs) and 95% confidence intervals (CIs). Tooth loss was only marginally significantly associated with ESCC risk (yes vs no, OR=1.29, 95% CI 0.94-1.74). However, the excess risk increased with increasing numbers of lost teeth (more than 6 teeth lost vs none, OR=1.48, 95% CI 1.04-2.11). Tooth brushing once or less per day, compared with tooth brushing twice or more per day, was associated with a 1.81-fold increased risk of ESCC. In the stratification analyses, the increased risks associated with these indicators of oral health were more pronounced in older subjects (age ≥ 70 years), women, non-smokers, and non-drinkers. Further studies are warranted to verify these findings and to explore the underlying mechanisms, e.g., changed oral microbiota, associated with poor oral hygiene. This article is protected by copyright. All rights reserved.

Smoking is associated with prostate cancer mortality. The Scandinavian smokeless tobacco product snus is a source of nicotine but not the combustion products of smoke and has not been studied with ...

A small proportion of individuals infected with Epstein-Barr virus (EBV) develop nasopharyngeal carcinoma (NPC). Timing of initial exposure could alter immunological responses to primary EBV infection and explain variation in cancer risk later in life. We measured early life family structure as a proxy for the timing of primary EBV infection to examine whether earlier age at infection alters NPC risk. We utilized data from 480 NPC cases and 1291 unaffected siblings from Taiwanese NPC multiplex families (≥ 2 family members with NPC, N=2921). Information on birth order within the family was derived from questionnaires. We utilized logistic regression models to examine the association between birth order and NPC, accounting for correlations between relatives. Within these high-risk families, older siblings had an elevated risk of NPC. Compared with being a first-born child, the risk (95% CIs) of NPC associated with a birth order of two, three, four, and five or more was 1.00 (0.71, 1.40), 0.88 (0.62, 1.24), 0.74 (0.53, 1.05), and 0.60 (0.43, 0.82), respectively (P for trend = 0.002). We observed no associations between NPC risk and the number of younger siblings or cumulative infant-years exposure. These associations were not modified by underlying genetic predisposition or family size. We observed that early life family structure was important for NPC risk in NPC multiplex families, with older siblings having a greater risk of disease. Future studies focusing on more direct measures of the immune response to EBV in early childhood could elucidate the underlying mechanisms. This article is protected by copyright. All rights reserved.

The strong male predominance in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the androgen pathway influence risk of developing BE and EAC. This genetic-epidemiological analysis included 14 studies from Australia, Europe and North America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed using a gene-based approach: versatile gene-based test association study. This method evaluates associations between a trait and all SNPs within a specific gene rather than each SNP marker individually as in a conventional GWAS. The data were stratified for sex, body-mass index, waist-to-hip ratio, tobacco smoking and gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383 BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were associated with risk of BE in the sexes combined (p = 0.002) and in males (p = 0.003), but not in females separately (p = 0.3). This association was found in tobacco smokers (p = 0.003) and in BE patients without reflux (p = 0.004), but not in nonsmokers (p = 0.2) or those with reflux (p = 0.036). SNPs within JMJD1C were associated with risk of EAC in females (p = 0.001). However, none of these associations replicated in a subsequent sample. Fourteen other genes studied did not reach statistically significant levels of association with BE, EAC or the combination of BE and EAC, after correcting for the number of genes included in the analysis. In conclusion, genetic variants in the androgen-related genes CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but replication data with larger sample sizes are needed.

Poor oral hygiene has been proposed to increase the risk for pancreatic cancer. We aim to assess this hypothesis, using number of teeth, dental plaque and oral mucosal lesions examined at baseline as a proxy for oral hygiene. During 1973-74 a population-based prevalence study of oral mucosal lesions was carried out in Uppsala County in central Sweden. We followed the study population through linkages with the Swedish Cancer and Total Population registers. A total of 19,924 participants were included, and 126 pancreatic cancer cases were identified during an average of 28.7 years of follow-up. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) for pancreatic cancer were estimated using Cox proportional hazards regression models. Overall, subjects with fewer teeth at baseline tended to have an increased risk for pancreatic cancer, although the estimates were not statistically significant. Among subjects with more than 10 teeth, those with unacceptable dental plaque had an HR of 2.1 (95% CI: 1.0, 4.7), compared with those without dental plaque after adjustment for potential confounding factors. Individuals with Candida-related or denture-related oral mucosal lesions, or tongue lesions, compared with those without any of the three studied lesions, had a 70, 30 and 80% excess risk of developing pancreatic cancer, respectively. Presence of more than one type of studied lesions further increased the risk for pancreatic cancer. In conclusion, our findings provide evidence to support the hypothesis that poor oral hygiene plays an important role in the development of pancreatic cancer.

A highly enantioselective oxidative cyclopropanation of 1,6-enynes catalyzed by cationic Au(I)/chiral phophoramidite complexes is presented. The new method provides convenient access to densely functionalized bicyclo[3.1.0]hexanes bearing three contiguous quaternary and tertiary stereogenic centers with high enantioselectivity (up to e.r. 98:2). Control experiments suggest that the quinoline moiety of the β-gold vinyloxyquinolinium intermediate in the reaction plays an important role in promoting good enantioselectivity through a transitional auxiliary effect in the transition state.

The etiology of esophageal squamous cell carcinoma (ESCC) in the high risk area of northern Iran is only partially known. We aimed to investigate prolonged animal contact as a risk factor for ESCC in this population. From 2003 to 2007, we administered a validated questionnaire to 300 ESCC cases and 571 randomly selected controls matched for neighborhood of residence, age (±2 years) and sex. Questions on lifelong exposure to equines, ruminants, canines, and poultry, including duration and level of contact, were asked in a face-to-face interviews. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for potential confounders. A total of 94.7% of cases and 68.7% of controls reported lifelong history of contact with ruminants. After controlling for potential confounders, contact with ruminants was associated with an eightfold increase (95% CI: 3.92-14.86) in risk of ESCC, and increments in duration of contact raised the risk estimates in a dose-dependent manner. Contact with equines and poultry did not significantly change associated OR for ESCC risk and contact with ruminants. OR (95% CI) for contact with canines was 1.99 (1.35-2.93) which after exclusion of contact with ruminants was not significant (OR for contact only with canine: 3.18, 95% CI: 0.73-13.17). These results add to the evidence that contact with ruminants may increase the risk of ESCC.

ABO blood serotype A is known to be associated with risk of gastric cancer (GC), but little is known how ABO alleles and the fucosyltransferase (FUT) enzymes and genes which are involved in Lewis antigen formation [and in Helicobacter pylori (H. pylori) binding and pathogenicity] may be related to GC risk in a European population. The authors conducted an investigation of 32 variants at ABO and FUT1-7 loci and GC risk in a case-control study of 365 cases and 1,284 controls nested within the EPIC cohort (the EPIC-Eurgast study). Four variants (including rs505922) in ABO, and allelic blood group A (AO+AA, odds ratio=1.84, 95%CI=1.20-2.80) were associated with diffuse-type GC; however, conditional models with other ABO variants indicated that the associations were largely due to allelic blood group A. One variant in FUT5 was also associated with diffuse-type GC, and four variants (and haplotypes) in FUT2 (Se), FUT3 (Le) and FUT6 with intestinal-type GC. Further, one variant in ABO, two in FUT3 and two in FUT6 were associated with H. pylori infection status in controls, and two of these (in FUT3 and FUT6) were weakly associated with intestinal-type GC risk. None of the individual variants surpassed a Bonferroni corrected p-value cutoff of 0.0016; however, after a gene-based permutation test, two loci [FUT3(Le)/FUT5/FUT6 and FUT2(Se)] were significantly associated with diffuse- and intestinal-type GC, respectively. Replication and functional studies are therefore recommended to clarify the role of ABO and FUT alleles in H. pylori infection and subtype-specific gastric carcinogenesis.

BACKGROUND The utility of circulating Epstein-Barr Virus (EBV) DNA as a tumor marker for nasopharyngeal carcinoma (NPC) detection suggests that it might improve the diagnostic performance of anti-EBV antibody markers in NPC screening. In this study, the authors evaluated whether circulating EBV DNA load is capable of distinguishing NPC patients from high-risk individuals who have positive anti-EBV antibodies. METHODS In a population-based NPC screening trial in Sihui City and Zhongshan City, Guangdong Province, China, the authors previously identified 862 high-risk participants with 2 screening markers, immunoglobulin A (IgA) antibodies to EBV capsid antigen (VCA/IgA) and nuclear antigen-1 (EBNA1/IgA). In the current study, real-time polymerase chain reaction was used to measure the baseline plasma EBV DNA load among 825 participants (97%). Follow-up was extended to the end of 2011 to evaluate the diagnostic and predictive values of plasma EBV DNA load. RESULTS By using 0 copies/mL as the cutoff value, plasma EBV DNA had a sensitivity of 86.8% (33 of 38 patients) for NPC detected within the first year of follow-up, yielding a positive predictive value of 30% (33 of 110 participants) and a negative predictive value of 99.3% (696 of 701 participants). The patients who had early stage NPC had lower sensitivity (81.5%; 22 of 27 patients) than those who had advanced NPC (100%; 11 of 11 patients). For the 14 patients who had NPC detected after 1 year of follow-up, only 50% (7 of 14 patients) tested positive for EBV DNA at baseline. CONCLUSIONS The plasma EBV DNA load may improve the accuracy of diagnosing NPC in high-risk individuals, but it appears to have limited value in screening patients who have early stage NPC and predicting NPC development. Cancer 2014;120:1353–1360. © 2014 American Cancer Society.

Because of the differences in bacterial epitopes and host characteristics, infections with Helicobacter pylori (H. pylori) induce different immune responses. We explored the possibility that certain antibody response patterns are more closely linked to gastric adenocarcinoma (GAC) than others. In a Swedish population-based case-control study, serum samples were obtained from 268 cases and 222 controls, aged 40–79 years and frequency-matched according to age and sex. We measured antibodies against 17 H. pylori proteins using multiplex serology. Associations were estimated with multivariably adjusted logistic regression models, using odds ratio (OR) with 95% confidence interval (CI) as measures of relative risk. Associations were essentially confined to non-cardia GAC but did not differ significantly between intestinal and diffuse subtypes. Point estimates for all antibodies were above unity, 15 significant with top three being CagA (OR = 9.2), GroEL (6.6), HyuA (3.6). ORs were substantially attenuated in individuals with chronic atrophic gastritis. Principal component analysis identified two significant factors: a CagA-dominant factor (antibodies against CagA, VacA and Omp as prominent markers), and a non-CagA factor (antibodies against NapA and Catalase as prominent markers). Both factors showed dose-dependent associations with non-cardia GAC risk (CagA-dominant factor, highest vs. lowest quartiles, OR = 16.2 [95% CI 4.8–54.9]; non-CagA factor OR = 5.3 [95% CI 2.1–13.3]). Overall, our results confirm that serum antibodies against different H. pylori proteins are associated with the presence of non-cardia GAC. Although strongest association is detected by antibodies against CagA and covarying proteins, a pattern of antibodies unrelated to CagA is also significantly linked to the risk of non-cardia GAC.

Purpose Validated measures of asthma and eczema at the population level remain a challenge. Our aim was to ascertain if register-based information on asthma/eczema medication can function as a prox ...

The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case-control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR = 0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR = 1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR = 0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non-significantly associated with an increased pancreatic cancer risk (OR = 1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR = 5.66; 95% CI: 1.59, 20.19, p value for interaction

Background: The epidemiological evidence on head injury and the risk of Parkinson's disease (PD) has been inconsistent. Methods: We examined the relation between previous hospitalization for head injury and PD using a population-based nested case-control design based on the Swedish National Patient Register from 2001 until 2007, including 18,648 PD cases and 93,240 controls, randomly selected from the general population. Exposure was defined as hospitalization for head injury between 1987 and index date. Results: Overall, previous hospitalization resulting from head injury was associated with an increased risk of PD; this association appeared to be largely explained by head injuries experienced recently, especially within 1 year before PD ascertainment. Conclusions: Our results do not provide convincing evidence for a causal relationship between head injury later in life and PD. © 2012 Movement Disorder Society

On theoretical grounds, nicotine has been implicated as a modifier of cancer progression. We investigated possible associations of smoking or use of Scandinavian moist snuff (snus) with survival after cancer among Swedish male construction workers. Snus use is associated with substantial exposure to nicotine but not to the combustion products in smoke. Among 336,381 workers with detailed information on tobacco use in 1971-1992, we observed 40,230 incident cancers. Complete follow-up through 2007 was accomplished through linkage to population and health registers. Hazard ratios (HRs) and 95% confidence intervals (CIs) for death from any cause, cancer-specific death and death from other causes were derived from Cox proportional hazards regression models adjusted for age at diagnosis, body mass index at study entry and period of diagnosis. Never users of any tobacco served as reference. Increased risks of cancer-specific death were observed both among exclusive smokers (HR(all cancer) 1.15, 95% CI: 1.10-1.21) and never-smoking snus users (1.15, 95% CI: 1.05-1.26). As regards deaths due to other causes, exclusive smokers had higher relative risks than exclusive snus users (p = 0.03). A history of tobacco use, even exclusive use of the seemingly benign snus, is associated with moderately increased cancer-specific mortality. Although nicotine might play a role, the mechanisms warrant further investigation.

Item does not contain fulltext Smoking is an established risk factor for pancreatic cancer, previously investigated by the means of questionnaires. Using cotinine as a biomarker for tobacco exposure allows more accurate quantitative analyses to be performed. This study on pancreatic cancer, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC cohort), included 146 cases and 146 matched controls. Using liquid chromatography-mass spectrometry, plasma cotinine levels were analyzed on average 8.0 years before cancer onset (5-95% range: 2.8-12.0 years). The relation between plasma cotinine levels and pancreatic cancer was analyzed with conditional logistic regression for different levels of cotinine in a population of never and current smokers. This was also done for the self-reported number of smoked cigarettes per day at baseline. Every increase of 350 nmol/L of plasma cotinine was found to significantly elevate risk of pancreatic cancer [odds ratio (OR): 1.33, 95% confidence interval (CI): 1.11-1.60]. People with a cotinine level over 1187.8 nmol/L, a level comparable to smoking 17 cigarettes per day, have an elevated risk of pancreatic cancer, compared to people with cotinine levels below 55 nmol/L (OR: 3.66, 95% CI: 1.44-9.26). The results for self-reported smoking at baseline also show an increased risk of pancreatic cancer from cigarette smoking based on questionnaire information. People who smoke more than 30 cigarettes per day showed the highest risk compared to never smokers (OR: 4.15, 95% CI: 1.02-16.42). This study is the first to show that plasma cotinine levels are strongly related to pancreatic cancer.

Background An association between asthma and antibiotic usage has been demonstrated, and the issue of reverse causation and confounding by indication is much debated. Objective Our aim was to study the association between different classes of antibiotics and prescription of asthma medication in a register-based cohort of all Swedish children, born between July 2005 and June 2009, ever treated with antibiotics. Methods Data on dispensed prescriptions of antibiotics (ATC-codes J01) and asthma medication (ATC-codes R03A-D) were requested from the Prescribed Drug Register. The association between dispensed prescriptions of different classes of antibiotics and asthma medication was analysed with Cox regression and a descriptive sequence symmetry analysis. Results In total, 211 192 children had received prescriptions of antibiotics. There was a strong association between prescription of antibiotics and prescription of asthma medication. The hazard ratios (HRs) for asthma medication associated with prescription of amoxicillin, penicillin, cephalosporin and macrolides (Gram-positive infections) were stronger than HRs associated with prescription of sulphonamides, trimethoprim and quinolones (urinary tract infections) and flucloxacillin (skin and soft tissue infections), e.g. first year HR = 2.27 (95% confidence intervals 2.17-2.37) as compared with HR = 1.04 (0.78-1.40). The HR associated with broad spectrum antibiotics was significantly higher than the narrow spectrum. Conclusions and clinical relevance Our data suggest that the association between antibiotics and asthma is subject to either reverse causation or confounding by indication due to respiratory tract infections. This implies that careful consideration is required as to whether or not symptoms from the respiratory tract in early childhood should be treated with antibiotics or asthma medication.

The aim of this study was to investigate the effects of GCKR polymorphism on the prevalence of overweight and obesity in Chinese female subjects using a gene-wide tagging- single nucleotide polymorphism (tSNP) strategy. We conducted a genetic association study in the Taizhou Retiree Women Cohort, a sub-cohort of the Taizhou longitudinal study. We genotyped four tSNPs (rs4425043, rs780094, rs814295, and rs8179206) of the GCKR gene using the Taqman assay in 2,851 female subjects and investigated their associations with overweight and obesity. Odds ratios and their 95% confidence intervals (CIs) were derived from ordered logistic regression model. We observed significant association between rs4425043 and body-mass-index-defined overweight and obesity. The frequencies of A allele of the rs4425043 exhibited a significant increasing trend from normal weight (13.20%), overweight (15.08%), to obese subjects (17.10%) (P = 0.006). Individuals with the GA or AA genotypes showed a 31% excessive risk to develop overweight or obesity (95% CI: 1.12-1.52, P = 0.001). In addition, we observed significantly increased levels of fasting plasma glucose associated with variations of both rs780094 and rs814295 (5.03, 5.09, and 5.15 mmol/L for rs780094 AA, GA and GG genotypes, respectively, and 5.03, 5.11, and 5.20 mmol/L for rs814295 AA, GA and GG genotypes, respectively). In conclusion, a novel polymorphism (rs4425043) in the GCKR gene increases the risk of overweight and obesity in Chinese women. Previous report that other polymorphisms in the GCKR gene are associated with glucose levels have also been confirmed.

Aliment Pharmacol Ther 2011; 33: 578-584 SUMMARY: Background Time-trend analyses of incidence and mortality in bleeding peptic ulcer show divergent results. Aim To conduct a detailed national analysis of hospitalisation of and mortality from bleeding peptic ulcer in Sweden. Method Data from all hospitalisations at departments with primary responsibility for patients with bleeding ulcer in Sweden, with main diagnosis or co-diagnosis of bleeding ulcer from 1987 to 2005 were retrieved from the Hospital Discharge Register. A validation study was performed due to an uncertainty in diagnostic setting after the introduction of ICD-10 in 1997. Annual hospitalisation rates per 100 000 inhabitants in relation to gender, age and ulcer location were calculated as well as age-standardised 30-day mortality rates. Results Hospitalisations for bleeding ulcer decreased from 63.9 to 35.3 per 100 000 inhabitants per year during the study period. The decrease was greater among men (men: from 80.4 to 40.9; women: from 47.7 to 29.7) and in younger age groups. Bleeding gastric ulcer decreased in both genders, and bleeding duodenal ulcer decreased most among men, but was stable in a subgroup of elderly women. Median age increased from 70 to 76 years. Standardised 30-day mortality increased from 5.3% to 6.2%. The increased mortality was found in those aged more than 65 years and with duodenal ulcer disease, whereas mortality remained unchanged in those with bleeding gastric ulcer. Conclusion Hospitalisation rates for bleeding peptic ulcer have markedly decreased in Sweden in all age groups. The 30-day mortality is low compared with other nationwide studies in the western world, but has increased among patients with duodenal ulcer disease. (Less)

Although some authorities consider smoking to be an established risk factor for colorectal cancer, the international literature is not entirely consistent. Further, only 1 study has addressed the association with smokeless tobacco and none with Scandinavian moist snuff (snus). This retrospective cohort study included 336,381 male Swedish construction workers with detailed information on tobacco use at cohort entry in 1971-1992. Complete follow-up through 2007 was accomplished by means of linkage to population and health registers. Hazard ratios (HRs) and 95% confidence intervals (CIs) derived from Cox proportional hazards regression models estimated relative risks, adjusted for age and body mass index. Subjects who were never-users of any tobacco served as reference. After up to 37 years of follow-up, pure smoking was associated with a marginally increased risk of colon cancer (HR 1.08, 95% CI 0.99-1.19), a modestly elevated risk of rectal cancer (HR 1.16, 95% CI 1.04-1.30) and a substantial excess risk of anal cancer (HR 2.41, 95% CI 1.06-5.48). Snus use was not significantly associated with an increased risk of colorectal or anal cancer, although the point estimate for colon cancer was similar to that observed among smokers. Swedish data provide meager support for the association between tobacco use and colorectal cancer. A general tendency among Swedish men to quit smoking in recent decades might have attenuated true associations. A link between smoking and anal cancer was confirmed.

Data from prospective studies on blood pressure and prostate cancer risk are limited, and results are inconclusive. Baseline measurements of height, weight and blood pressure were available in 336,159 men in the Swedish Construction Workers cohort. During an average of 22.2 years of follow-up, 10,002 incident cases and 2,601 fatal cases of prostate cancer were identified in National registers. For 5,219 cases, tumor characteristics were available; 2,817 tumors were classified as nonaggressive and 2,402 as aggressive. Relative risks of disease were estimated from Cox regression models, using attained age as time-scale, and adjusting for birth year, smoking status and body mass index (BMI). Top compared to bottom quintile level of systolic or diastolic blood pressure was associated with a significant 15-20% decreased risk of incident prostate cancer (p for trend: systolic < 0.0001, diastolic = 0.3), but blood pressure was not significantly associated with risk of fatal prostate cancer. BMI was not associated with prostate cancer incidence, but was positively associated with fatal prostate cancer; men in the top quintile had a 30% increased risk (p for trend = 0.0004). The associations between blood pressure and BMI and nonaggressive tumors were similar to those of incident prostate cancer, and associations with aggressive tumors were similar to those of fatal prostate cancer. Data from our study suggest that hypertension is associated with a decreased risk of incident prostate cancer, but the explanation for this finding is unclear. Our study support a positive association between overweight and risk of fatal prostate cancer.

Background: Helicobacter pylori, a known risk factor of gastric cancer, rarely colonize the deeper portion of normal gastric glands, where the mucus is rich in α-1,4-linked N-acetylglucosamine capped O-glycans, that strongly inhibit H. pylori growth in vitro. Materials and methods: We investigated the association between genetic variation in the O-glycan transferase encoding gene (a4GnT) and H. pylori infection and gastric cancer risk using a Polish population-based case–control study (273 gastric cancer patients and 377 controls). Results: A haplotype at the rs2622694–rs397266 locus was associated with H. pylori infection, with the A-A haplotype associated with a higher risk compared with the most frequent G-G haplotype (odds ratio 2.30; 95% confidence interval 1.35–3.92). The association remained significant after correction for multiple tests (global p value: nominal 0.002, empirical 0.045). Neither this haplotype nor the tagSNPs were associated with overall gastric cancer risk. Conclusion: a4GnT genetic variation may be relevant to H. pylori infection, but not to gastric cancer risk.

Udgivelsesdato: 2008-Nov-7 Many case-control studies have suggested that higher consumption of fruit and vegetables is associated with a lower risk of pancreatic cancer, whereas cohort studies do not support such an association. We examined the associations of the consumption of fruits and vegetables and their main subgroups with pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is comprised of over 520,000 subjects recruited from 10 European countries. The present study included 555 exocrine pancreatic cancer cases after an average follow-up of 8.9 years. Estimates of risk were obtained by Cox proportional hazard models, stratified by age at recruitment, gender, and study center, and adjusted for total energy intake, weight, height, history of diabetes mellitus, and smoking status. Total consumption of fruit and vegetables, combined or separately, as well as subgroups of vegetables and fruits were unrelated to risk of pancreatic cancer. Hazard ratios (95% CI) for the highest versus the lowest quartile were 0.92 (0.68-1.25) for total fruit and vegetables combined, 0.99 (0.73-1.33) for total vegetables, and 1.02 (0.77-1.36) for total fruits. Stratification by gender or smoking status, restriction to microscopically verified cases, and exclusion of the first 2 years of follow-up did not materially change the results. These results from a large European prospective cohort suggest that higher consumption of fruit and vegetables is not associated with decreased risk of pancreatic cancer. (c) 2008 Wiley-Liss, Inc.

No increased risks of specific types of cancer following breast implantation have been consistently reported, but data on risk beyond 15 years are limited. We have pooled the results of 2 nationwide cohort studies of 3,486 Swedish and 2,736 Danish women who underwent cosmetic breast implantation between 1965 and 1993. Cancer incidence through 2002 was ascertained through nationwide cancer registries. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated to compare cancer incidence among women with implants with women in the general population. Mean duration of follow up was 16.6 years (range 0.1–37.8 years). Over 50% of women were followed for 15 years or more after breast implantation and 13.3% for at least 25 years. There was a reduced incidence of breast cancer (SIR 5 0.73; 95% CI 0.58–0.90), whereas lung cancer was above expectation (SIR 5 1.64; 95% CI 1.10–2.36). The increased risk of lung cancer is expected due to the high prevalence of smoking among the women with implants in our study. With respect to other site-specific cancers, no significantly increased or decreased SIR was observed. This study, which includes women followed for almost 4 decades, represents the longest follow up of women with cosmetic breast implants to date. The results provide no evidence of an association between breast implants and any type of cancer. ' 2008 Wiley-Liss, Inc.

Although Scandinavian moist snuff ("snus"), no doubt, is a safer alternative to smoking, there is limited evidence against an association with gastroesophageal cancers. In a retrospective cohort study, we investigated esophageal and stomach cancer incidence among 336,381 male Swedish construction workers who provided information on tobacco smoking and snus habits within a health surveillance program between 1971 and 1993. Essentially complete follow-up through 2004 was accomplished through linkage to several nationwide registers. Multivariable Cox proportional hazards regression models estimated relative risks (RR) and 95% confidence intervals (CIs). Compared to never-users of any tobacco, smokers had increased risks for adenocarcinoma (RR = 2.3, 95% CI 1.4-3.7) and squamous cell carcinoma (RR = 5.2, 95% CI 3.1-8.6) of the esophagus, as well as cardia (RR = 2.1, 95% CI 1.5-3.0) and noncardia stomach (RR = 1.3, 95% CI 1.2-1.6) cancers. We also observed excess risks for esophageal squamous cell carcinoma (RR = 3.5, 95% CI 1.6-7.6) and noncardia stomach cancer (RR = 1.4, 95% CI 1.1-1.9) among snus users who had never smoked. Although confounding by unmeasured exposures, and some differential misclassification of smoking, might have inflated the associations, our study provides suggestive evidence for an independent carcinogenic effect of snus. © 2007 Wiley-Liss, Inc.

From 1970 to 2002 in the Stockholm area, we revealed a parallel three-fold increase in the incidence of tonsillar cancer and the proportion of human papillomavirus (HPV) positive tonsillar cancer cases, indicating a possible role of HPV infection in this disease. We have now examined whether HPV and viral load in pre-treatment tonsillar cancer biopsies correlates to disease prognosis, and whether the presence of HPV-16 E6 and E7 mRNA could be ascertained. The presence of HPV-16, but not viral load, in tonsillar cancer was shown to be a favourable prognostic factor for clinical outcome. Moreover, E6 and/or E7 were expressed in almost all assessable HPV-16 positive cases, supporting an oncogenic role of HPV-16 in tonsillar cancer.