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The DOK1 gene is a putative tumour suppressor gene located on the human chromosome 2p13 which is frequently rearranged in leukaemia and other human tumours. We previously reported that the DOK1 gene can be mutated and its expression down-regulated in human malignancies. However, the mechanism underlying DOK1 silencing remains largely unknown. We show here that unscheduled silencing of DOK1 expression through aberrant hypermethylation is a frequent event in a variety of human malignancies. DOK1 was found to be silenced in nine head and neck cancer (HNC) cell lines studied and DOK1 CpG hypermethylation correlated with loss of gene expression in these cells. DOK1 expression could be restored via demethylating treatment using 5-aza-2'deoxycytidine. In addition, transduction of cancer cell lines with DOK1 impaired their proliferation, consistent with the critical role of epigenetic silencing of DOK1 in the development and maintenance of malignant cells. We further observed that DOK1 hypermethylation occurs frequently in a variety of primary human neoplasm including solid tumours (93% in HNC, 81% in lung cancer) and haematopoietic malignancy (64% in Burkitt's lymphoma). Control blood samples and exfoliated mouth epithelial cells from healthy individuals showed a low level of DOK1 methylation, suggesting that DOK1 hypermethylation is a tumour specific event. Finally, an inverse correlation was observed between the level of DOK1 gene methylation and its expression in tumour and adjacent non tumour tissues. Thus, hypermethylation of DOK1 is a potentially critical event in human carcinogenesis, and may be a potential cancer biomarker and an attractive target for epigenetic-based therapy., (Copyright © 2011 UICC.)

The prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians. The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival. This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrence and tumor spread. In this study, we used one- and two-dimensional gel electrophoresis, mass spectrometry and immunodetection methods to analyze protein expression in oral squamous cell carcinomas. Using a refinement for classifying oral carcinomas in regard to prognosis, we analyzed small but lymph node metastasis-positive versus large, lymph node metastasis-negative tumors in order to contribute to the molecular characterization of subgroups with risk of dissemination. Specific protein patterns favoring metastasis were observed in the "more-aggressive" group defined by the present study. This group displayed upregulation of proteins involved in migration, adhesion, angiogenesis, cell cycle regulation, anti-apoptosis and epithelial to mesenchymal transition, whereas the "less-aggressive" group was engaged in keratinocyte differentiation, epidermis development, inflammation and immune response. Besides the identification of several proteins not yet described as deregulated in oral carcinomas, the present study demonstrated for the first time the role of cofilin-1 in modulating cell invasion in oral carcinomas.

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

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

Background: Epidemiological studies have identified increased risks of leukemia in children living near power lines and exposed to relatively high levels of magnetic fields. Results have been remarkably consistent, but there is still no explanation for this increase. In this study we evaluated the effect of 60 Hz magnetic fields on acute lymphocytic leukemia (ALL) in the State of São Paulo, Brazil., Methods: This case-control study included ALL cases (n=162) recruited from eight hospitals between January 2003 and February 2009. Controls (n=565) matched on gender, age, and city of birth were selected from the São Paulo Birth Registry. Exposure to extremely low frequency magnetic fields (ELF MF) was based on measurements inside home and distance to power lines., Results: For 24h measurements in children rooms, levels of ELF MF equal to or greater than 0.3microtesla (μT), compared to children exposed to levels below 0.1 μT showed no increased risk of ALL (odds ratio [OR] 1.09; 95% confidence interval [95% CI] 0.33-3.61). When only nighttime measurements were considered, a risk (OR 1.52; 95% CI 0.46-5.01) was observed. Children living within 200 m of power lines presented an increased risk of ALL (OR 1.67; 95% CI 0.49-5.75), compared to children living at 600 m or more of power lines. For those living within 50 m of power lines the OR was 3.57 (95% CI 0.41-31.44)., Conclusions: Even though our results are consistent with the small risks reported in other studies on ELF MF and leukemia in children, overall our results do not provide support for an association between magnetic fields and childhood leukemia, but small numbers and likely biases weaken the strength of this conclusion., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

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

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35)., Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case-control studies., Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08-1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95-1.09, P = 0.66; P-heterogeneity (P(het)) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12-1.34, P = 7 × 10(-6)) but not males (OR = 1.02, 95% CI = 0.97-1.08, P = 0.35; P(het) = 6 × 10(-4)). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (P(het) = 0.86)., Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers., Impact: Further research is warranted to elucidate the mechanisms underlying these observations.

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility., Competing Interests: The authors have declared that no competing interests exist.

Odds ratios for head and neck cancer increase with greater cigarette and alcohol use and lower body mass index (BMI; weight (kg)/height(2) (m(2))). Using data from the International Head and Neck Cancer Epidemiology Consortium, the authors conducted a formal analysis of BMI as a modifier of smoking- and alcohol-related effects. Analysis of never and current smokers included 6,333 cases, while analysis of never drinkers and consumers of < or =10 drinks/day included 8,452 cases. There were 8,000 or more controls, depending on the analysis. Odds ratios for all sites increased with lower BMI, greater smoking, and greater drinking. In polytomous regression, odds ratios for BMI (P = 0.65), smoking (P = 0.52), and drinking (P = 0.73) were homogeneous for oral cavity and pharyngeal cancers. Odds ratios for BMI and drinking were greater for oral cavity/pharyngeal cancer (P < 0.01), while smoking odds ratios were greater for laryngeal cancer (P < 0.01). Lower BMI enhanced smoking- and drinking-related odds ratios for oral cavity/pharyngeal cancer (P < 0.01), while BMI did not modify smoking and drinking odds ratios for laryngeal cancer. The increased odds ratios for all sites with low BMI may suggest related carcinogenic mechanisms; however, BMI modification of smoking and drinking odds ratios for cancer of the oral cavity/pharynx but not larynx cancer suggests additional factors specific to oral cavity/pharynx cancer.

Background: The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression., Methods: The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells., Results: We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR., Conclusions: A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.

Objective: This study aimed to assess the survival and life quality evolution of patients subjected to surgical excision of oral and oropharyngeal squamous cell carcinoma., Material and Methods: Forty-seven patients treated at a Brazilian healthcare unit specialized in head and neck surgery between 2006 and 2007 were enrolled in the study. The gathering of data comprised reviewing hospital files and applying the University of Washington Quality of Life (UW-QOL) questionnaire previously and 1 year after the surgery. Comparative analysis used Poisson regression to assess factors associated with survival and a paired t-test to compare preoperative and 1-year postoperative QOL ratings., Results: 1 year after surgery, 7 patients were not found (dropout of the cohort); 15 had died and 25 fulfilled the UW-QOL again. The risk of death was associated with having regional metastasis previously to surgery (relative risk=2.18; 95% confidence interval=1.09-5.17) and tumor size T3 or T4 (RR=2.30; 95%CI=1.05-5.04). Survivors presented significantly (p<0.05) poorer overall and domain-specific ratings of quality of life. Chewing presented the largest reduction: from 74.0 before surgery to 34.0 one year later. Anxiety was the only domain whose average rating increased (from 36.0 to 70.7)., Conclusions: The prospective assessment of survival and quality of life may contribute to anticipate interventions aimed at reducing the incidence of functional limitations in patients with oral and oropharyngeal cancer.

Background: Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers., Methods: We pooled individual-level data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models., Results: Quitting tobacco smoking for 1-4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61-0.81 compared with current smoking], with the risk reduction due to smoking cessation after > or =20 years (OR 0.23, CI 0.18-0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after > or =20 years of quitting (OR 0.60, CI 0.40-0.89 compared with current drinking), reaching the level of never drinkers., Conclusions: Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cancer.

Background: Sexual contact may be the means by which head and neck cancer patients are exposed to human papillomavirus (HPV)., Methods: We undertook a pooled analysis of four population-based and four hospital-based case-control studies from the International Head and Neck Cancer Epidemiology (INHANCE) consortium, with participants from Argentina, Australia, Brazil, Canada, Cuba, India, Italy, Spain, Poland, Puerto Rico, Russia and the USA. The study included 5642 head and neck cancer cases and 6069 controls. We calculated odds ratios (ORs) of associations between cancer and specific sexual behaviours, including practice of oral sex, number of lifetime sexual partners and oral sex partners, age at sexual debut, a history of same-sex contact and a history of oral-anal contact. Findings were stratified by sex and disease subsite., Results: Cancer of the oropharynx was associated with having a history of six or more lifetime sexual partners [OR = 1.25, 95% confidence interval (CI) 1.01, 1.54] and four or more lifetime oral sex partners (OR = 2.25, 95% CI 1.42, 3.58). Cancer of the tonsil was associated with four or more lifetime oral sex partners (OR = 3.36, 95 % CI 1.32, 8.53), and, among men, with ever having oral sex (OR = 1.59, 95% CI 1.09, 2.33) and with an earlier age at sexual debut (OR = 2.36, 95% CI 1.37, 5.05). Cancer of the base of the tongue was associated with ever having oral sex among women (OR = 4.32, 95% CI 1.06, 17.6), having two sexual partners in comparison with only one (OR = 2.02, 95% CI 1.19, 3.46) and, among men, with a history of same-sex sexual contact (OR = 8.89, 95% CI 2.14, 36.8)., Conclusions: Sexual behaviours are associated with cancer risk at the head and neck cancer subsites that have previously been associated with HPV infection.

Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day.

Background: Marijuana contains carcinogens similar to tobacco smoke and has been suggested by relatively small studies to increase the risk of head and neck cancer (HNC). Because tobacco is a major risk factor for HNC, large studies with substantial numbers of never tobacco users could help to clarify whether marijuana smoking is independently associated with HNC risk., Methods: We pooled self-reported interview data on marijuana smoking and known HNC risk factors on 4,029 HNC cases and 5,015 controls from five case-control studies within the INHANCE Consortium. Subanalyses were conducted among never tobacco users (493 cases and 1,813 controls) and among individuals who did not consume alcohol or smoke tobacco (237 cases and 887 controls)., Results: The risk of HNC was not elevated by ever marijuana smoking [odds ratio (OR), 0.88; 95% confidence intervals (95% CI), 0.67-1.16], and there was no increasing risk associated with increasing frequency, duration, or cumulative consumption of marijuana smoking. An increased risk of HNC associated with marijuana use was not detected among never tobacco users (OR, 0.93; 95% CI, 0.63-1.37; three studies) nor among individuals who did not drink alcohol and smoke tobacco (OR, 1.06; 95% CI, 0.47-2.38; two studies)., Conclusion: Our results are consistent with the notion that infrequent marijuana smoking does not confer a risk of these malignancies. Nonetheless, because the prevalence of frequent marijuana smoking was low in most of the contributing studies, we could not rule out a moderately increased risk, particularly among subgroups without exposure to tobacco and alcohol.

Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden., Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (psi) and population attributable risks (PAR)., Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (psi = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases <45 years, 73% for cases >60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America)., Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases.

Alcohol and tobacco consumption are well-recognized risk factors for head and neck cancer (HNC). Evidence suggests that genetic predisposition may also play a role. Only a few epidemiologic studies, however, have considered the relation between HNC risk and family history of HNC and other cancers. We pooled individual-level data across 12 case-control studies including 8,967 HNC cases and 13,627 controls. We obtained pooled odds ratios (OR) using fixed and random effect models and adjusting for potential confounding factors. All statistical tests were two-sided. A family history of HNC in first-degree relatives increased the risk of HNC (OR=1.7, 95% confidence interval, CI, 1.2-2.3). The risk was higher when the affected relative was a sibling (OR=2.2, 95% CI 1.6-3.1) rather than a parent (OR=1.5, 95% CI 1.1-1.8) and for more distal HNC anatomic sites (hypopharynx and larynx). The risk was also higher, or limited to, in subjects exposed to tobacco. The OR rose to 7.2 (95% CI 5.5-9.5) among subjects with family history, who were alcohol and tobacco users. A weak but significant association (OR=1.1, 95% CI 1.0-1.2) emerged for family history of other tobacco-related neoplasms, particularly with laryngeal cancer (OR=1.3, 95% CI 1.1-1.5). No association was observed for family history of nontobacco-related neoplasms and the risk of HNC (OR=1.0, 95% CI 0.9-1.1). Familial factors play a role in the etiology of HNC. In both subjects with and without family history of HNC, avoidance of tobacco and alcohol exposure may be the best way to avoid HNC., (Copyright (c) 2008 Wiley-Liss, Inc.)

The authors pooled data from 15 case-control studies of head and neck cancer (9,107 cases, 14,219 controls) to investigate the independent associations with consumption of beer, wine, and liquor. In particular, they calculated associations with different measures of beverage consumption separately for subjects who drank beer only (858 cases, 986 controls), for liquor-only drinkers (499 cases, 527 controls), and for wine-only drinkers (1,021 cases, 2,460 controls), with alcohol never drinkers (1,124 cases, 3,487 controls) used as a common reference group. The authors observed similar associations with ethanol-standardized consumption frequency for beer-only drinkers (odds ratios (ORs) = 1.6, 1.9, 2.2, and 5.4 for < or =5, 6-15, 16-30, and >30 drinks per week, respectively; P(trend) < 0.0001) and liquor-only drinkers (ORs = 1.6, 1.5, 2.3, and 3.6; P < 0.0001). Among wine-only drinkers, the odds ratios for moderate levels of consumption frequency approached the null, whereas those for higher consumption levels were comparable to those of drinkers of other beverage types (ORs = 1.1, 1.2, 1.9, and 6.3; P < 0.0001). Study findings suggest that the relative risks of head and neck cancer for beer and liquor are comparable. The authors observed weaker associations with moderate wine consumption, although they cannot rule out confounding from diet and other lifestyle factors as an explanation for this finding. Given the presence of heterogeneity in study-specific results, their findings should be interpreted with caution.

Leukemia incidence in children has increased worldwide in recent decades, particularly due to the rise in acute lymphoblastic leukemia. Studies have associated exposure to non-ionizing radiation generated by low frequency magnetic fields with childhood leukemia. The current article reviews the case-control studies published on this subject. Of 152 articles tracked in different databases, ten studies from North America, Asia, and Europe met the defined selection criteria, with patients diagnosed from 1960 to 2004. Methodological limitations were observed in these articles, including difficulties with the procedures for assessing exposure. An association may exist between exposure to low frequency magnetic fields and acute lymphoblastic leukemia in children, but this association is weak, preventing the observation of consistency in the findings. Future studies from a wider range of geographic regions should focus on the analysis of acute lymphoblastic leukemia, which is the subtype with the greatest impact on the increasing overall incidence of childhood leukemia.

The objective of this paper was to assess sex and socioeconomic inequalities in lung cancer mortality in two major cities of Europe and South America. Official information on mortality and population allowed the estimation of sex- and age-specific death rates for Barcelona, Spain and São Paulo, Brazil (1995-2003). Mortality trends and levels were independently assessed for each city and subsequently compared. Rate ratios assessed by Poisson regression analysis addressed hypotheses of association between the outcome and socioeconomic covariates (human development index, unemployment and schooling) at the inner-city area level. Barcelona had a higher mortality in men (76.9/100,000 inhabitants) than São Paulo (38.2/100,000 inhabitants); although rates were decreasing for the former (-2%/year) and levelled-off for the latter. Mortality in women ranked similarly (9.1 for Barcelona, 11.5 for São Paulo); with an increasing trend for women aged 35-64 years (+7.7%/year in Barcelona and +2.4%/year in São Paulo). The socioeconomic gradient of mortality in men was negative for Barcelona and positive for São Paulo; for women, the socioeconomic gradient was positive in both cities. Negative gradients indicate that deprived areas suffer a higher burden of disease; positive gradients suggest that prosmoking lifestyles may have been more prevalent in more affluent areas during the last decades. Sex and socioeconomic inequalities of lung cancer mortality reinforce the hypothesis that the epidemiologic profile of cancer can be improved by an expanded access to existing technology of healthcare and prevention. The continuous monitoring of inequalities in health may contribute to the concurrent promotion of well-being and social justice.

Although active tobacco smoking has been identified as a major risk factor for head and neck cancer, involuntary smoking has not been adequately evaluated because of the relatively low statistical power in previous studies. We took advantage of data pooled in the International Head and Neck Cancer Epidemiology Consortium to evaluate the role of involuntary smoking in head and neck carcinogenesis. Involuntary smoking exposure data were pooled across six case-control studies in Central Europe, Latin America, and the United States. Adjusted odds ratios (OR) and 95% confidence interval (95% CI) were estimated for 542 cases and 2,197 controls who reported never using tobacco, and the heterogeneity among the study-specific ORs was assessed. In addition, stratified analyses were done by subsite. No effect of ever involuntary smoking exposure either at home or at work was observed for head and neck cancer overall. However, long duration of involuntary smoking exposure at home and at work was associated with an increased risk (OR for >15 years at home, 1.60; 95% CI, 1.12-2.28; P(trend) < 0.01; OR for >15 years at work, 1.55; 95% CI, 1.04-2.30; P(trend) = 0.13). The effect of duration of involuntary smoking exposure at home was stronger for pharyngeal and laryngeal cancers than for other subsites. An association between involuntary smoking exposure and the risk of head and neck cancer, particularly pharyngeal and laryngeal cancers, was observed for long duration of exposure. These results are consistent with those for active smoking and suggest that elimination of involuntary smoking exposure might reduce head and neck cancer risk among never smokers.

Purpose: Oral and oropharyngeal tumor resection may be associated with disfigurement and dysfunctions that affect essential domains of life. This study aimed at assessing the immediate impact of primary surgery on the health-related quality of life for these patients., Patients and Methods: Forty-seven patients with squamous cell carcinoma of the lips, oral cavity, or oropharynx, and undergoing treatment in the head and neck surgery center of a large general hospital in the city of São Paulo, Brazil, from October 2005 to September 2006, completed the University of Washington Quality of Life questionnaire pre- and postoperatively (before hospital discharge). A paired t test evaluated differences between assessments; Poisson regression estimated ratios of ratings attributed to each domain (pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder pain, taste, saliva, mood, and anxiety) per patient stratified by sociodemographic, clinical, and behavioral characteristics., Results: The immediate impact of surgery on health-related quality of life corresponded to a 31.1% reduction in the overall rating. The most affected domains were chewing (-73.5%), taste (-61.4%), swallowing (-57.3%), speech (-46.0%), and pain (-42.3%). Anxiety (+65.5%) was the sole domain that improved immediately after surgery. Comparisons involving subgroups of patients indicated that different clinical conditions (regional metastasis, tumor size, and location) were not associated with discrepant health-related quality of life immediately after surgery., Conclusions: The routine pre- and postoperative assessment of health-related quality of life may contribute to evaluate treatment effectiveness, which would otherwise rely exclusively on assessing end-point results such as survival and tumor relapse. This information is relevant to attenuate the prejudicial impact of surgery on the physical and psychosocial functioning of patients.

Background: Large inequalities of mortality by most cancers in general, by mouth and pharynx cancer in particular, have been associated to behaviour and geopolitical factors. The assessment of socioeconomic covariates of cancer mortality may be relevant to a full comprehension of distal determinants of the disease, and to appraise opportune interventions. The objective of this study was to compare socioeconomic inequalities in male mortality by oral and pharyngeal cancer in two major cities of Europe and South America., Methods: The official system of information on mortality provided data on deaths in each city; general censuses informed population data. Age-adjusted death rates by oral and pharyngeal cancer for men were independently assessed for neighbourhoods of Barcelona, Spain, and São Paulo, Brazil, from 1995 to 2003. Uniform methodological criteria instructed the comparative assessment of magnitude, trends and spatial distribution of mortality. General linear models assessed ecologic correlations between death rates and socioeconomic indices (unemployment, schooling levels and the human development index) at the inner-city area level. Results obtained for each city were subsequently compared., Results: Mortality of men by oral and pharyngeal cancer ranked higher in Barcelona (9.45 yearly deaths per 100,000 male inhabitants) than in Spain and Europe as a whole; rates were on decrease. São Paulo presented a poorer profile, with higher magnitude (11.86) and stationary trend. The appraisal of ecologic correlations indicated an unequal and inequitably distributed burden of disease in both cities, with poorer areas tending to present higher mortality. Barcelona had a larger gradient of mortality than São Paulo, indicating a higher inequality of cancer deaths across its neighbourhoods., Conclusion: The quantitative monitoring of inequalities in health may contribute to the formulation of redistributive policies aimed at the concurrent promotion of wellbeing and social justice. The assessment of groups experiencing a higher burden of disease can instruct health services to provide additional resources for expanding preventive actions and facilities aimed at early diagnosis, standardized treatments and rehabilitation.

Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P = 10(-10) and 10(-9), respectively). These effects became more apparent with increasing alcohol consumption (P for trend = 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology.

Objective: To assess the association between oral health and hygiene practices and oral cancer., Methods: Hospital-based case-control study in the metropolitan area of São Paulo, southeastern Brazil, from 1998 to 2002. A total 309 patients with squamous cell carcinoma of the mouth and the pharynx and 468 controls matched by sex and age were included in the study. Cases were recruited in seven reference hospitals and controls were selected in five out of the seven participating hospitals. Detailed information on smoking, alcohol consumption, schooling, oral health status and hygiene practices were obtained through interviews. Odds ratios (OR) and 95% confidence intervals (95% CI), adjusted by sex, age, schooling, smoking, alcohol consumption as well as the variables oral health status and hygiene practices were estimated using unconditional logistic regression analyses., Results: The use of complete dental prosthesis was not associated with oral cancer but regular gum bleeding showed a strong association (OR 3.1; 95% CI 1.2-7.9). Those who never attended a dental visit were more likely to have oral cancer (OR 2.5; 95% CI 1.3-4.8). Daily mouthwash use showed a stronger association to pharynx (OR 4.7; 95% CI 1.8-12.5) than mouth cancer (OR 3.2; 95% CI 1.6-6.3)., Conclusions: Gum bleeding, no dental care, and daily mouthwash use were factors associated with oral cancer regardless of tobacco and alcohol consumption.

Poor oral health has been reported as a risk factor in the etiology of head and neck cancer. Data on oral health were ascertained as part of two multicenter case-control studies comprising 924 cases and 928 controls in central Europe and 2,286 cases and 1,824 controls in Latin America. Incident cases of squamous cell carcinoma of the head and neck (oral cavity, pharynx, larynx) and esophagus, as well as age (in quinquennia)- and sex frequency-matched controls, were enrolled from 1998 to 2003. Poor condition of the mouth (central Europe: odds ratio (OR) = 2.89, 95% confidence interval (CI): 1.74, 4.81; Latin America: OR = 1.89, 95% CI: 1.47, 2.42), lack of toothbrush use (Latin America: OR = 2.36, 95% CI: 1.28, 4.36), and daily mouthwash use (Latin America: OR = 3.40, 95% CI: 1.96, 5.89) emerged as risk factors for head and neck cancer, independent of tobacco use and alcohol consumption. Missing between six and 15 teeth was an independent risk factor for esophageal cancer (central Europe: OR = 2.84, 95% CI: 1.26, 6.41; Latin America: OR = 2.18, 95% CI: 1.04, 4.59). These results indicate that periodontal disease (as indicated by poor condition of the mouth and missing teeth) and daily mouthwash use may be independent causes of cancers of the head, neck, and esophagus.

The most solidly established risk factors for laryngeal cancer are tobacco and alcohol. As for occupational factors, the only established carcinogen is exposure to strong inorganic acid mists. However, asbestos, pesticides, paints, gasoline, diesel engine emissions, dusts, and other factors have been reported in the literature as occupational agents that increase the risk of laryngeal cancer. A hospital-based case-control study was conducted to investigate occupational risk factors for laryngeal cancer. Detailed data on smoking, alcohol consumption, and occupational history were collected for 122 laryngeal cancers and 187 controls matched by frequency (according to sex and age). Laryngeal cancer was associated with exposure to respirable free crystalline silica (OR = 1.83; 95%CI: 1.00-3.36), soot (from coal, coke, fuel oil, or wood) (odds ratio - OR = 1.78; 95% confidence interval - 95%CI: 1.03-3.03), fumes (OR = 2.55; 95%CI: 1.14-5.67), and live animals (OR = 1.80; 95%CI: 1.02-3.19).

Background: At least 75% of head and neck cancers are attributable to a combination of cigarette smoking and alcohol drinking. A precise understanding of the independent association of each of these factors in the absence of the other with the risk of head and neck cancer is needed to elucidate mechanisms of head and neck carcinogenesis and to assess the efficacy of interventions aimed at controlling either risk factor., Methods: We examined the extent to which head and neck cancer is associated with cigarette smoking among never drinkers and with alcohol drinking among never users of tobacco. We pooled individual-level data from 15 case-control studies that included 10,244 head and neck cancer case subjects and 15,227 control subjects, of whom 1072 case subjects and 5775 control subjects were never users of tobacco and 1598 case subjects and 4051 control subjects were never drinkers of alcohol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. All statistical tests were two-sided., Results: Among never drinkers, cigarette smoking was associated with an increased risk of head and neck cancer (OR for ever versus never smoking = 2.13, 95% CI = 1.52 to 2.98), and there were clear dose-response relationships for the frequency, duration, and number of pack-years of cigarette smoking. Approximately 24% (95% CI = 16% to 31%) of head and neck cancer cases among nondrinkers in this study would have been prevented if these individuals had not smoked cigarettes. Among never users of tobacco, alcohol consumption was associated with an increased risk of head and neck cancer only when alcohol was consumed at high frequency (OR for three or more drinks per day versus never drinking = 2.04, 95% CI = 1.29 to 3.21). The association with high-frequency alcohol intake was limited to cancers of the oropharynx/hypopharynx and larynx., Conclusions: Our results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiology.

Dietary factors associated with oral cancer were investigated in a case-control hospital-based study in the city of São Paulo, Brazil, from 1998 to 2002. A total of 835 subjects, 366 with histologically confirmed incident cases of oral-cavity or pharyngeal cancer and 469 controls participated in the study. Dietary data were collected with a food frequency questionnaire (FFQ). Odds ratios (OR) and 95% confidence intervals (95%CI) were obtained from unconditional logistic regression, adjusted for potential confounders. Inverse associations with risk of oral cancer were found for the highest intake of beans, OR = 0.37 (95%CI: 0.22-0.64), raw vegetables, OR = 0.51 (95%CI: 0.29-0.93) and the intermediate tertile of rice and pasta intake, OR = 0.56 (95%CI: 0.38-0.83). Positive associations were observed for the highest intake of eggs, OR = 1.84 (95%CI: 1.23-2.75), potatoes, OR = 2.22 (95%CI: 1.53-3.25), and milk, OR= 1.80 (95%CI: 1.09-2.98). Some traditional Brazilian foods like rice and beans emerged as protective factors against oral cancer, independently of other risk factors.

Objective: To analyze the association between dietary patterns and oral cancer., Methods: The study, part of a Latin American multicenter hospital-based case-control study, was conducted in São Paulo, Southeastern Brazil, between November 1998 and March 2002 and included 366 incident cases of oral cancer and 469 controls, frequency-matched with cases by sex and age. Dietary data were collected using a food frequency questionnaire. The risk associated with the intake of food groups defined a posteriori, through factor analysis (called factors), was assessed. The first factor, labeled "prudent," was characterized by the intake of vegetables, fruit, cheese, and poultry. The second factor, "traditional," consisted of the intake of rice, pasta, pulses, and meat. The third factor, "snacks," was characterized as the intake of bread, butter, salami, cheese, cakes, and desserts. The fourth, "monotonous," was inversely associated with the intake of fruit, vegetables and most other food items. Factor scores for each component retained were calculated for cases and controls. After categorization of factor scores into tertiles according to the distribution of controls, odds ratios and 95% confidence intervals were calculated using unconditional multiple logistic regression., Results: "Traditional" factor showed an inverse association with cancer (OR=0.51; 95% CI: 0.32; 0.81, p-value for trend 0.14), whereas "monotonous" was positively associated with the outcome (OR=1.78; 95% CI: 1.78; 2.85, p-value for trend <0.001)., Conclusions: The study data suggest that the traditional Brazilian diet, consisting of rice and beans plus moderate amounts of meat, may confer protection against oral cancer, independently of any other risk factors such as alcohol intake and smoking.

Objective: To evaluate the results of the 2004 oral cancer prevention and early diagnosis program carried out in conjunction with the annual flu vaccination campaign for the elderly in the state of São Paulo, Brazil., Methods: Data concerning the follow-up of patients referred for diagnostic investigation of soft tissue lesions identified on visual inspection were collected from the reports issued by the State Health Department/Oral Health Technical Center. The following two characteristics were evaluated as indicators of the program's effectiveness: (1) the number of people whose problem was resolved at the primary care level or in referral services and (2) the number of persons with a confirmed diagnosis of oral cancer. The following indicators were used to assess program ineffectiveness: (1) patients not appearing at the referral unit, (2) inability of the primary care services to resolve the problem, and (3) the absence of follow-up information on patients., Results: In 2004, 238 087 people >/= 60 years old were examined, corresponding to 6.8% of the state population in this age group (3 494 555 people). The program was carried out in 23 of the state's 24 health regions. However, only 8 of the regions recorded follow-up information. Of the 5 280 people in the 8 regions who were referred for diagnostic investigation of soft tissue lesions, 60.5% had their problem resolved, 0.5% (26 cases) had a confirmed diagnosis of oral cancer, and 22.5% did not have the diagnostic investigation completed. For 16.5% of the cases referred for further study, there was no information available concerning follow-up and outcomes., Conclusions: The oral cancer prevention and early diagnosis program was ineffective, given the lack of monitoring of results in most parts of the state of São Paulo, and the high proportion of patients whose soft tissue lesion was not resolved. The usefulness of continuing the program in future years needs to be evaluated.

Background: Alcohol intake and tobacco smoke, in addition to other environmental and genetic factors, have been associated with head and neck cancer. We evaluated the role of metabolic enzyme polymorphisms on the risk of head and neck cancer in a hospital-based case-control study., Methods: CYP1A1MspI, CYP2E1PstI, GSTM1, and GSTT1polymorphisms were evaluated in 103 histologically confirmed head and neck cancer cases and 102 controls by means of polymerase chain reaction-restriction fragment length polymorphism methods., Results: GSTM1null increased the risk of head and neck cancer (odds ratio [OR], 2.2; 95% confidence interval [95% CI], 1.24-3.79), oral cancer (OR, 2.8; 95% CI, 1.28-5.98), and pharyngeal cancer (OR, 2.2; 95% CI, 1.08-4.63). CYP2E1PstI polymorphism indicated a risk for oral cancer (OR, 3.6; 95% CI, 1.29-11.56). The joint effect of GSTM1 null and CYP1A1 polymorphism increased the risk of head and neck cancer (OR, 2.4; 95% CI, 1.13-5.10)., Conclusions: GSTM1 null alone or associated with CYP1A1 increased the risk of head and neck cancer; the CYP2E1PstI mutated allele increased the risk for only oral cancer., ((c) 2006 Wiley Periodicals, Inc.)

Objective: To investigate cancer deaths among rubber industry workers according to company size., Methods: This historical cohort study included 9,188 male workers, engaged as members of a workers' union in São Paulo, Southeastern Brazil, between 1975 and 1985, alive in January 1990 and followed until the end of 2000. Overall and specific cancer deaths were compared within the cohort, with subjects stratified according to company size and economic activity, sector of work, and worker qualification. Risk set assessment and conditional logistic regression were used to estimate relative risks, adjusted for age, time since first job, and duration of employment in the rubber industry., Results: When compared to employees of larger companies, workers employed in small companies showed greater risk of death due to any type of cancer (RR=2.33, 95% CI: 0.90-6.03), stomach tumors (RR=3.47; 95% CI: 2.57-4.67), and upper aero-digestive tract tumors (RR=2.49; 95% CI: 1.78-3.48). Risk of death was greater among workers employed in maintenance (RR=2.23; 95% CI: 0.73-6.76); expedition, storage and transportation (RR=2.97; 95% CI: 0.77-11.38); and production (RR=3.51; 95% CI: 1.07-11.57), when compared to workers engaged in clerical work and support activities., Conclusions: Our results provide further evidence for an increased risk of stomach and upper aero-digestive tract tumors--and possibly of all types of cancer--among rubber industry workers employed in small companies when compared to employees of larger companies.

To estimate the risk of occupation in oral and oropharyngeal cancer, a hospital-based case-control study was conducted in Greater Metropolitan São Paulo, Brazil. The study included 325 cases and 468 controls, frequency-matched with cases by sex and age, and interviewed from January 1999 to March 2002. Occupational risks were examined by industry and job titles and restricted to males (266 cases, 362 controls). Odds ratios (OR) were calculated by unconditional logistic regression, controlling for age, smoking, and alcohol. Males working in vehicle maintenance shops (26 cases, 12 controls) showed adjusted OR = 2.45 (95%CI: 1.14-5.27), increasing among those employed 10 or more years (OR = 7.90; 95%CI: 2.03-30.72). Occupation as vehicle repair worker (14 cases, 7 controls) showed OR = 2.10 (95%CI: 0.78-5.68), increasing among workers exposed 10 or more years (OR = 26.21; 95%CI: 2.34-294.06). Other industries and occupations revealed OR higher than 1.5, but not statistically significant. In conclusion, employment in vehicle maintenance shops and occupation as vehicle repair worker showed risk for oral cancer, independently of smoking and alcohol. More prolonged exposure increased the risk.

Individual cancer susceptibility seems to be related to factors such as changes in oncogenes and tumor suppressor genes expression, and differences in the action of metabolic enzymes and DNA repair regulated by specific genes. Epidemiological studies on genetic polymorphisms of human xenobiotics metabolizing enzymes and cancer have revealed low relative risks. Research considering genetic polymorphisms prevalence jointly with environmental exposures could be relevant for a better understanding of cancer etiology and the mechanisms of carcinogenesis and also for new insights on cancer prognosis. This study reviews the approaches of molecular epidemiology in cancer research, stressing case-control and cohort designs involving genetic polymorphisms, and factors that could introduce bias and confounding in these studies. Similarly to classical epidemiological research, genetic polymorphisms requires considering aspects of precision and accuracy in the study design.

Context and Objective: Diet and nutrition are environmental factors in health/disease relationships. From the epidemiological viewpoint, diet represents a complex set of highly correlated exposures. Our objective was to identify patterns of food intake in a group of individuals living in São Paulo, and to develop objective dietary measurements for epidemiological purposes. DESIGN AND LOCAL: Exploratory factor analysis of data in a case-control study in seven teaching hospitals in São Paulo., Methods: The participants were 517 patients (260 oral cancer cases and 257 controls) admitted to the study hospitals between November 1998 and March 2001. The weekly intake frequencies for dairy products, cereals, meat, processed meat, vegetables, pulses, fruits and sweets were assessed by means of a semi-quantitative food frequency questionnaire. Dietary patterns were identified by factor analysis, based on the intake of the eight food groups, using principal component analysis as an extraction method followed by varimax rotation., Results: Factor analysis identified three patterns that accounted for 55% of the total variability within the sample. The first pattern ("prudent") was characterized by vegetable, fruit and meat intake; the second ("traditional") by cereals (mainly rice) and pulses (mainly beans); and the third ("snacks") by dairy products and processed meat., Conclusion: This study identified food intake patterns through an a posteriori approach. Such analysis may be useful for nutritional intervention programs and, after computing scores for each individual according to the patterns identified, for establishing a relationship between diet and other epidemiological measurements of interest.

Objective: To develop a population-based matrix of job-exposure to crystalline silica in Brazil and to estimate its validity., Methods: An epidemiologist and an industrial hygienist developed a matrix of job-exposure in four stages: coding of occupation variable; coding of industry variable; consensual exposure classification between researchers; and estimate of registered workforce in 1995 for each level of exposure. The cross-tabulation of the variables industry (25 columns) and occupation (347 lines) resulted in 8,675 cells, classified according to silica exposure in four levels: non-exposed, possibly exposed, probably exposed, and definitively exposed. For validating the job-exposure matrix, five industries (mining and quarrying, construction, foundry, management of technical personal and textiles), were re-coded according to exposure by external experts. Reliability of the study and external experts was evaluated by agreement measured using kappa analysis., Results: The job-exposure matrix showed high coding agreement, ranging from 64.0% for foundry to 94.0% for mining. Kappa analysis showed good agreement in mining (0.9), and low or average for other sectors (ranging from 0.1 to 0.5). High specificity was found in foundry (86.5%) and mining (100.0%). Construction had 56% specificity., Conclusions: The study job-exposure matrix showed good accuracy and seems to be appropriate for estimating silica exposure among Brazilian workers.

The city of São Paulo exhibits one of the highest incidences of laryngeal cancer in world and Brazil presents remarkable occurrence, compared with other Latin American countries. Around 8,000 new cases and 3,000 deaths by laryngeal cancer occur annually in the Brazilian population. In the city of São Paulo, incidence rates for laryngeal cancer among males have been decreasing since the late 1980s while, among females, the rates have shown a stable trend. This phenomenon is probably the expression of changes in gender behavior related to tobacco smoking. Several risk factors are involved in the genesis of laryngeal cancer. The most important are tobacco smoking and alcohol intake, but occupational hazards have also been associated with the disease, such as asbestos, strong inorganic acids, cement dust and free crystalline silica. Additionally, salted meat and total fat intake have been linked to elevated risk of laryngeal cancer. Conversely, several studies have confirmed that fruits, raw leaf vegetables and legumes protect against this cancer. Some researchers have postulated a possible association between laryngeal squamous cell carcinoma and human papilloma virus (HPV), but this is not universally accepted. Gastroesophageal reflux disease is weakly, but consistently correlated with laryngeal cancer. Familial cancer clusters, particularly of head and neck tumors, seem to increase the risk of laryngeal cancer. Some genetic polymorphisms, such as of genes that code for xenobiotic-metabolizing enzymes, have shown elevated risk for laryngeal cancer according to recent studies. Public health policies regarding the control of tobacco smoking and alcohol consumption, and also surveillance of carcinogen exposure in occupational settings, could have an impact on laryngeal cancer. No proposals for screening have been recommended for laryngeal cancer, but one diagnostic goal should be to avoid treatment delay when suspected symptoms have been observed.

The proportion of cancer attributed to occupation varies, and estimates are partially dependent on the characteristics of exposed populations, type of tumor, and methodology. The main difficulty for estimating these proportions is the reconstruction of past individual occupational exposure. Appropriate methods for retrospective occupational exposure assessment are essential in epidemiological studies in order to avoid misclassification. In this review, qualitative and quantitative methods are discussed, considering that such evaluations require progressive approaches without a previously established hierarchy. Methods to evaluate exposure through environmental and biological measurements, questionnaires, interviews, expert panels, and job-exposure matrices are compared as to their advantages, limitations, accuracy, and validity. In health surveillance, all the above-mentioned methods can be applied, but the use of job-exposure matrices is emphasized, especially using secondary databases.

A study was carried out on the occurrence of oral and pharynx cancer among populations living in five Brazilian geographic regions, by using incidence and mortality rates and trends. Information on survival was also analyzed. Complementary information regarding prevalence of the disease risk factors has been supplied in the attempt to establish some etiological connections with the incidence and mortality observed. Two clear patterns for the occurrence of oral and pharyngeal cancer have been detected: a pattern for the north (including the northern, northeastern and midwestern regions, which are the poorest ones) and a pattern for the south (including the southern and southeastern regions). The southern pattern revealed incidence rates higher than 15 per 100,000 among males, and the northern pattern displayed lower rate levels. Similarly, mortality rates in the south were higher than three per 100,000 and the northern pattern was characterized by lower rates. Other cancers linked to tobacco smoking, such as esophagus, larynx, lung and bladder cancer kept the same pattern of incidence and mortality rates related to oral and pharyngeal cancer in males per region. Information on survival of patients with oral and pharyngeal cancer was very restricted in Brazil, thus hindering the survival analysis per region, but the studies conducted allowed to conclude that the majority of diagnoses were conducted in advanced stages of the disease and implied the low 5-year survival rate observed in Brazil. Tongue tumors displayed the worst survival rates. The southern region shares specific risk factors involved in the oral and pharyngeal cancer present in the Argentinean and Uruguayan populations, namely heavy tobacco smoking and alcohol consumption, as well as high intake of charcoal-grilled red meat and mate. In addition to these risks, part of the oral and pharyngeal cancer registered in Brazil might be linked to a few factors present among people with low life standards, including poor oral hygiene and nutrition.

Context: Around 90% of lung cancer worldwide is attributable to cigarette smoking, although less than 20% of cigarette smokers develop lung cancer. Other factors such as diet, chronic lung diseases, occupation and possibly environmental agents also contribute to this cancer. Genetic factors seem to play a role in lung cancer, but the precise characteristics influencing lung cancer susceptibility are not known, since genetic factors are easily obscured by the strong environmental determinants of lung cancer, particularly smoking., Objective: To estimate the effect that cancer occurrence among first-degree relatives has on the risk of lung cancer., Design: Hospital-based case-control study., Setting: The metropolitan region of São Paulo, Brazil., Participants: 334 incident lung cancer cases and 578 controls matched by hospitals., Main Measurements: By means of a structured questionnaire, cases and controls were interviewed about cancer occurrence in first-degree relatives, tobacco smoking, exposure to passive smoking, occupation, migration and socioeconomic status. Non-conditional logistic regression was used to calculate the risk of familial cancer aggregation, the effect of cancer in first-degree relatives and smoking in conjunction, and for controlling confounders., Results: The adjusted odds ratio (OR) revealed a slight, but not statistically significant, excess risk of lung cancer for subjects with a history of lung cancer in relatives (OR 1.21; 95% confidence interval [CI] 0.50 - 2.92). The same was found among those with a history of other tobacco-related cancers in relatives (OR 1.36; 95% CI 0.87 - 2.14). A step gradient effect was observed regarding lung cancer risk, in accordance with increases in the number of pack-years of cigarette consumption. An interaction between familial cancer aggregation and tobacco smoking was detected., Conclusions: A mildly elevated risk of lung cancer among persons with a positive history of lung and other tobacco-related cancers was observed. The finding of an interaction between the variables of familial cancer aggregation and smoking suggests that familial cancer aggregation could be considered as a marker of susceptibility, increasing the risk of lung cancer among smokers. These results improve our knowledge of lung carcinogenesis and can guide future cancer genetic studies.

Identification of molecular biomarkers is a common result of current cancer epidemiological research. Both genetic and molecular epidemiology have enjoyed impressive developments in recent decades, with important repercussions on traditional epidemiological approaches. In this paper we evaluate the new frontiers of cancer epidemiology, incorporating both genetic and molecular biology approaches. We examine the current knowledge of molecular biomarkers for exposure and susceptibility to cancer, the role of gene mutations in carcinogenesis, and their application to epidemiological studies. By exploring the status of relevant biomarkers, these approaches become effective in evaluating exposure and susceptibility and show enormous potential for elucidating mechanisms of carcinogenesis and the effect of risk factors in cancer. However, these approaches are necessarily more invasive and raise several ethical issues for consideration by both researchers in public health and society as a whole.

The incidence rates of mouth cancer vary from low to high among the countries of Latin America and the Caribbean. This review will examine incidence and mortality rates according to risk factors for the disease. Studies of local populations are reviewed and common patterns established. Although the incidence rate of mouth cancer is decreasing in some countries, a large increase is observed in southern South America. This trend will probably be maintained over the next few decades. Specific risk factors have been identified: high tobacco smoking and alcohol drinking prevalence, high intake of charcoal-grilled red meat, and mate drinking. The increase in tobacco smoking among females will have a strong impact on the incidence of mouth cancer in the future. In some Latin American and Caribbean countries, lay educational information on cancer is scant. The importance of improving information systems on cancer and the development of tobacco smoking and alcohol control programs are stressed. The training of health practitioners in the early detection and treatment of mouth lesions is a public health goal that could improve survival, but the difficulties encountered by people from the lowest socioeconomic strata in obtaining access to primary health care could hinder this objective. Semin Oncol 28:158-168., (Copyright 2001 by W.B. Saunders Company.)

During the last two decades, incidence rates of occupational accidents have been decreasing in Brazil. Mortality has also decreased, but not as sharply as incidence. Changes in reporting of occupational accidents have been the main argument used to explain such trends. This time-series study covering occupational accidents from 1970 to 1995 clearly shows the link between occupational accidents and social and economical determinants. Comparing 14 Brazilian States, a positive linear regression (r=0.80) was detected between proportion of workers in industrial production and accidents. In the 1980s, Brazil's economic recession led to an increase in unemployment. The decline in industrial jobs - those with a higher risk of accidents ( was accented by the restructuring of production and increased use of computer and robotics technologies in various manufacturing sectors. The result was a heavy shift of the work force from industry to commerce and services - jobs entailing lower risk of accidents. These factors influenced trends in occupational accidents in Brazil during this 25-year period.

In a hospital-based case-control study, 316 lung cancer cases and 536 controls were interviewed for their occupational, smoking, passive smoking, cancer in the family and residential histories as well as social economic status, by trained interviewers, using a standardized questionnaire. Cases and controls were matched by hospital, sex and age. The study was carried out between 1st July 1990 and 31st January 1991 in 14 hospitals in the Metropolitan Region of S. Paulo, the most highly industrialized and urbanized region in Brazil. Score criteria were developed for the ordering of the individuals of the study by occupational exposure to know carcinogens to the lung, in order to evaluate this exposure during the occupational life of each person. The criteria accumulated information on exposure to carcinogens as regards type, sector of work and time in each employment. The unconditional logistic regression analysis showed an odds ratio of 1.97 (95% IC: 1.52 to 2.55) for the highest exposure group. This result showed that workers linked to the production sectors of several industries have about twice the risk of developing lung cancer as workers involved in non-industrial activities.

Over the course of recent decades, Brazil has become an industrialized society. From an epidemiological perspective and considering changes that have been occurring in the Brazilian population, particularly concerning demographic and epidemiological transitions, this paper discusses the need to adapt the epidemiological surveillance system in order to incorporate the surveillance of non-transmissible diseases. The authors analyze the information system for work-related accidents in the Workers' Health Program, under SUDS (the Unified Decentralized Health System) for the Mandaqui Region (in the Northern part of the city of São Paulo), based on data from a local metalworking industry identified by the information system as a high-risk site for work-related accidents. The article also focuses on the importance of organized workers participating in actions to control work-related accidents. Although such participation is not always possible, the health sector must incorporate the workers' own concrete experience in order to develop more effective actions to prevent accidents at the workplace.

The epidemiological approach to occupational accidents and diseases adopted in Brazil is inadequate for many reasons, among them being: 1) the fact that only employers may notify work accidents, thus permitting notorious undernotification of these occupational hazards; 2) the available information does not permit a better understanding of the causal relationship between work accidents and diseases; 3) the official policy exists only for purposes of insurance compensation. The official documents for occupational disease and accident registration are the CTA (Work accident report) and FTA (Casualty treatment card). The Worker's Health Program of SUDS-R-6 proposed, in October, 1988 a method for the codification, registration in a micro-computer data bank and analysis of this information, based on the records presently in use (CAT) for public health service planning and accident prevention purposes. The major interest was in identifying the most common types of accidents in the region and the work environments in which they most frequently occur. The target population were the workers who attended the health units lisenced to deal with work accidents and diseases, in the Northern region of S. Paulo City. The data presented below refer to the months of October, November and December, 1988, the first three months of the project. During that period a total of 2,339 accidents were registered. They were classified as: typical work accidents - 87%: commuting accidents which occurred between the home and the work-place--18% and work diseases (only 2 cases). The majority of workers (50%) were between 25 and 45 years of age, approximately 7% were under 18. Male workers represented 83.2% of accident cases.(ABSTRACT TRUNCATED AT 250 WORDS)