Poor oral health influences head and neck cancer patient survival: an International Head and Neck Cancer Epidemiology Consortium pooled analysis.

BACKGROUND: Poor oral health has been identified as a prognostic factor potentially affecting the survival of patients with head and neck squamous cell carcinoma. However, evidence to date supporting this association has emanated from studies based on single cohorts with small-to-modest sample sizes. METHODS: Pooled analysis of 2449 head and neck squamous cell carcinoma participants from 4 studies of the International Head and Neck Cancer Epidemiology Consortium included data on periodontal disease, tooth brushing frequency, mouthwash use, numbers of natural teeth, and dental visits over the 10 years prior to diagnosis. Multivariable generalized linear regression models were used and adjusted for age, sex, race, geographic region, tumor site, tumor-node-metastasis stage, treatment modality, education, and smoking to estimate risk ratios (RR) of associations between measures of oral health and overall survival. RESULTS: Remaining natural teeth (10-19 teeth: RR = 0.81, 95% confidence interval [CI] = 0.69 to 0.95; ≥20 teeth: RR = 0.88, 95% CI = 0.78 to 0.99) and frequent dental visits (>5 visits: RR = 0.77, 95% CI = 0.66 to 0.91) were associated with better overall survival. The inverse association with natural teeth was most pronounced among patients with hypopharyngeal and/or laryngeal, and not otherwise specified head and neck squamous cell carcinoma. The association with dental visits was most pronounced among patients with oropharyngeal head and neck squamous cell carcinoma. Patient-reported gingival bleeding, tooth brushing, and report of ever use of mouthwash were not associated with overall survival. CONCLUSIONS: Good oral health as defined by maintenance of the natural dentition and frequent dental visits appears to be associated with improved overall survival among head and neck squamous cell carcinoma patients.

Machine learning for predicting survival of colorectal cancer patients.

Colorectal cancer is one of the most incident types of cancer in the world, with almost 2 million new cases annually. In Brazil, the scenery is the same, around 41 thousand new cases were estimated in the last 3 years. This increase in cases further intensifies the interest and importance of studies related to the topic, especially using new approaches. The use of machine learning algorithms for cancer studies has grown in recent years, and they can provide important information to medicine, in addition to making predictions based on the data. In this study, five different classifications were performed, considering patients' survival. Data were extracted from Hospital Based Cancer Registries of São Paulo, which is coordinated by Fundação Oncocentro de São Paulo, containing patients with colorectal cancer from São Paulo state, Brazil, treated between 2000 and 2021. The machine learning models used provided us the predictions and the most important features for each one of the algorithms of the studies. Using part of the dataset to validate our models, the results of the predictors were around 77% of accuracy, with AUC close to 0.86, and the most important column was the clinical staging in all of them.

Recent changes in trends of mortality from cervical cancer in Southeastern Brazil.

OBJECTIVE: To analyze the trends of cervical cancer mortality in Brazilian Southeastern states, and to compare them to Brazil and other regions between 1980 and 2020. METHODS: Time series study based on data from the Sistema de Informações de Mortalidade (Brazilian Mortality Information System). Death data were corrected by proportional redistribution of deaths from ill-defined causes and cervical cancer of unspecified portion. Age-standardized and age-specific rates were calculated by screening target (25-39 years; 40-64 years) and non-target (65 years or older) age groups. Annual percentage changes (APC) were estimated by linear regression model with breakpoints. The coverage of Pap Smear exam in the Unified Health System (SUS) was evaluated between 2009 and 2020 according to age group and locality. RESULTS: There were increases in corrected mortality rates both in 1980 and in 2020 in all regions, with most evident increments at the beginning of the series. There was a decrease in mortality nationwide between 1980-2020; however, the state of São Paulo showed a discrete upward trend in 2014-2020 (APC=1.237; 95%CI 0.046-2.443). Noteworthy is the trend increment in the 25-39 year-old group in all study localities, being sharper in the Southeast region in 2013-2020 (APC=5.072; 95%CI 3.971-6.185). Screening coverage rates were highest in São Paulo and lowest in Rio de Janeiro, with a consistent decline from 2012 onwards at all ages. CONCLUSIONS: São Paulo is the first Brazilian state to show a reversal trend in mortality from cervical cancer. The changes in mortality patterns identified in this study point to the need for reorganization of the current screening program, which should be improved to ensure high coverage, quality, and adequate follow-up of all women with altered test results.

Ocupação e câncer no Brasil: um desafio perene / Occupation and cancer in Brazil: a perennial challenge

Resumo Introdução: a incidência do câncer tem aumentado continuamente no mundo, especialmente em países de baixa e média renda. Objetivo: identificar e sintetizar o conhecimento sobre exposição ocupacional e câncer, com ênfase na produção científica brasileira. Métodos: ensaio elaborado com base em revisões realizadas nas bases SciELO e PubMed. Resultados: um estudo recente identificou 47 agentes ocupacionais entre os 120 agentes classificados como definitivamente cancerígenos para humanos pela Agência Internacional de Pesquisa em Câncer. Estudos realizados nas duas últimas décadas indicaram frações de câncer atribuíveis à ocupação, variando de 1,3% no Brasil a 8% na Finlândia, embora os critérios para aferir a exposição nesses estudos possam ser questionados. No Brasil, a produção científica sobre ocupação e câncer é limitada. A Revista Brasileira de Saúde Ocupacional publicou, entre janeiro de 2003 e julho de 2022, seis artigos sobre o tema. Na base PubMed, de 2012 a 2022, foram identificados 14 estudos realizados no Brasil. Conclusão: ampliar pesquisas nesta área realizadas no país é imperativo para obtenção de estimativas mais precisas de trabalhadores expostos a cancerígenos e tumores malignos relacionados, essencial para subsidiar ações de saúde pública e normas sobre limites de exposição ou banimento de agentes, reduzindo o fardo do câncer na sociedade brasileira.

Abtract Introduction: cancer incidence is increasing worldwide, especially in low- and middle-income countries. Objective: to identify and synthesize knowledge about occupational exposure and cancer, with emphasis on Brazilian scientific publications. Method: essay based on reviews carried out in the SciELO and PubMed databases. Results: a recent study identified 47 occupational agents among the 120 classified as definitively carcinogenic to humans by the International Agency for Research on Cancer. Studies carried out in the last two decades suggested fractions of cancer attributable to occupation, ranging from 1.3% in Brazil to 8% in Finland, although the criteria for measuring exposure in these studies can be questioned. In Brazil, scientific production on occupation and cancer is limited. The Revista Brasileira de Saúde Ocupacional (RBSO) published, between January 2003 to July 2022, six articles on the subject. In the PubMed database, from 2012 to 2022, 14 studies carried out in Brazil were identified. Conclusion: expanding research in this subject in Brazil is imperative to obtain more accurate estimates of workers exposed to carcinogens and related malignant tumors, essential to support public health actions and to establish norms on exposure limits or agents banning, reducing the burden of cancer in the Brazilian society.

Recent changes in trends of mortality from cervical cancer in Southeastern Brazil / Mudanças recentes nas tendências da mortalidade por câncer de colo do útero no Sudeste do Brasil

ABSTRACT OBJECTIVE To analyze the trends of cervical cancer mortality in Brazilian Southeastern states, and to compare them to Brazil and other regions between 1980 and 2020. METHODS Time series study based on data from the Sistema de Informações de Mortalidade (Brazilian Mortality Information System). Death data were corrected by proportional redistribution of deaths from ill-defined causes and cervical cancer of unspecified portion. Age-standardized and age-specific rates were calculated by screening target (25-39 years; 40-64 years) and non-target (65 years or older) age groups. Annual percentage changes (APC) were estimated by linear regression model with breakpoints. The coverage of Pap Smear exam in the Unified Health System (SUS) was evaluated between 2009 and 2020 according to age group and locality. RESULTS There were increases in corrected mortality rates both in 1980 and in 2020 in all regions, with most evident increments at the beginning of the series. There was a decrease in mortality nationwide between 1980-2020; however, the state of São Paulo showed a discrete upward trend in 2014-2020 (APC=1.237; 95%CI 0.046-2.443). Noteworthy is the trend increment in the 25-39 year-old group in all study localities, being sharper in the Southeast region in 2013-2020 (APC=5.072; 95%CI 3.971-6.185). Screening coverage rates were highest in São Paulo and lowest in Rio de Janeiro, with a consistent decline from 2012 onwards at all ages. CONCLUSIONS São Paulo is the first Brazilian state to show a reversal trend in mortality from cervical cancer. The changes in mortality patterns identified in this study point to the need for reorganization of the current screening program, which should be improved to ensure high coverage, quality, and adequate follow-up of all women with altered test results.

RESUMO OBJETIVO Analisar as tendências da mortalidade por câncer de colo de útero nos estados da região Sudeste e compará-las com o Brasil e demais regiões entre 1980 e 2020. MÉTODOS Estudo de série temporal com base nos dados do Sistema de Informações de Mortalidade. Os dados de óbito foram corrigidos por redistribuição proporcional das mortes por causas mal definidas e por câncer de útero de porção não especificada. Foram calculadas taxas padronizadas por idade e específicas por faixas etárias alvo de rastreamento (25-39 anos; 40-64 anos) e não alvo (65 anos ou mais). Variações percentuais anuais foram estimadas por modelo de regressão linear com pontos de quebra. A cobertura do exame Papanicolaou no Sistema Único de Saúde (SUS) foi avaliada entre 2009 e 2020 segundo faixa etária e localidade. RESULTADOS Foram verificados aumentos das taxas de mortalidade corrigidas tanto em 1980 como em 2020 em todas as regiões, com incrementos mais evidentes no início da série. Houve queda da mortalidade em todo o país entre 1980-2020, entretanto, o estado de São Paulo apresentou discreta tendência de aumento em 2014-2020 (APC=1,237; IC95% 0,046-2,443). Destaca-se o incremento da tendência no grupo de 25-39 anos em todas as localidades de estudo, mostrando-se mais acentuado na região Sudeste em 2013-2020 (APC=5,072; IC95% 3,971-6,185). As taxas de cobertura de rastreamento foram mais elevadas em São Paulo e mais baixas no Rio de Janeiro, com queda consistente a partir de 2012 em todas as idades. CONCLUSÕES São Paulo é o primeiro estado brasileiro a apresentar inversão de tendência da mortalidade por câncer de colo do útero. As mudanças nos padrões de mortalidade identificadas neste estudo apontam para a necessidade de reorganização do atual programa de rastreamento, que deve ser aperfeiçoado para garantir alta cobertura, qualidade e seguimento adequado de todas as mulheres com exames alterados.

Causes of death in former asbestos-cement workers in the state of São Paulo, Brazil.

BACKGROUND: In low- and middle-income countries, such as Brazil, studies on the causes of death in asbestos-exposed workers are scarce. METHODS: A cohort study was performed involving 988 males who had worked in the asbestos-cement industry in the state of São Paulo, with a total of 12,217 person-years of observation between 1995 and 2016. The standardized mortality ratio (SMR) stratified by age was calculated as the ratio between the observed rate and the expected rate in the state of São Paulo. RESULTS: Increased SMRs were observed for overall mortality (SMR 1.1, 95% confidence interval [CI], 0.98-1.23) and mortality due to pleural malignant neoplasms (MN) (SMR, 69.4; 95% CI, 22.55-162.1), asbestosis (SMR, 975.7; 95% CI, 396.4-2031), peritoneal MN (SMR, 5.0; 95% CI, 0.13-27.78), laryngeal MN (SMR, 1.4; 95% CI, 0.30-4.20), and pulmonary MN (SMR, 1.5; 95% CI, 0.82-2.64). CONCLUSION: The present study highlights the damage caused by asbestos exposure and reinforces the existing evidence of a causal association between exposure and increased mortality due to pleural MN, pulmonary MN, and asbestosis.

Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers.

Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes rel to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites.

Occupational socioeconomic risk associations for head and neck cancer in Europe and South America: individual participant data analysis of pooled case-control studies within the INHANCE Consortium.

BACKGROUND: The association between socioeconomic disadvantage (low education and/or income) and head and neck cancer is well established, with smoking and alcohol consumption explaining up to three-quarters of the risk. We aimed to investigate the nature of and explanations for head and neck cancer risk associated with occupational socioeconomic prestige (a perceptual measure of psychosocial status), occupational socioeconomic position and manual-work experience, and to assess the potential explanatory role of occupational exposures. METHODS: Pooled analysis included 5818 patients with head and neck cancer (and 7326 control participants) from five studies in Europe and South America. Lifetime job histories were coded to: (1) occupational social prestige-Treiman's Standard International Occupational Prestige Scale (SIOPS); (2) occupational socioeconomic position-International Socio-Economic Index (ISEI); and (3) manual/non-manual jobs. RESULTS: For the longest held job, adjusting for smoking, alcohol and nature of occupation, increased head and neck cancer risk estimates were observed for low SIOPS OR=1.88 (95% CI: 1.64 to 2.17), low ISEI OR=1.74 (95% CI: 1.51 to 1.99) and manual occupations OR=1.49 (95% CI: 1.35 to 1.64). Following mutual adjustment by socioeconomic exposures, risk associated with low SIOPS remained OR=1.59 (95% CI: 1.30 to 1.94). CONCLUSIONS: These findings indicate that low occupational socioeconomic prestige, position and manual work are associated with head and neck cancer, and such risks are only partly explained by smoking, alcohol and occupational exposures. Perceptual occupational psychosocial status (SIOPS) appears to be the strongest socioeconomic factor, relative to socioeconomic position and manual/non-manual work.

Caesarean sections, prenatal and postnatal conditions and childhood acute lymphoblastic leukaemia: A case-control study in the State of São Paulo, Brazil.

INTRODUCTION: Brazil has high rates of caesarean sections, which has been suggested as a risk factor for acute lymphoblastic leukaemia (ALL). In addition, some pre- and postnatal conditions have been identified as relevant in the etiology of ALL. OBJECTIVES: Investigate the association of caesarean sections, pre- and postnatal conditions with childhood ALL in the State of São Paulo. METHODS: Population-based case-control study including children that are below10 years old. Information on study variables was obtained through face to face interviews, through a questionnaire, and the State of São Paulo Declarations of Live Births database. The conditional and unconditional logistic regression approaches were used to calculate the odds ratio (OR) of the associations between caesarean sections, pre- and postnatal conditions with ALL, and 95 % confidence intervals (95 % CI). RESULTS: We observed a weak and non-statistically significant risk for ALL among children exposed to caesarean sections (unconditional logistic regression OR 1.08; 95 % CI 0.70-1.66; conditional logistic regression OR 1.21; 95 % CI 0.72-2.02), but among children under 3 years old and born through a caesarean sections, the risk of ALL was greater (unconditional logistic regression OR 1.70; 95 % CI 0.69-4.21). A negative association for ALL was observed among children with mothers who reported 12 years of schooling or more (unconditional logistic regression OR 0.34; 95 % CI 0.16-0.69). CONCLUSIONS: We found a tenuous suggestive association between caesarean sections and childhood ALL. The mother's high level of education showed an inverse association with ALL.

Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration.

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. RESULTS: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). CONCLUSIONS: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

Occupational exposure to organophosphate pesticides and hematologic neoplasms: a systematic review. / Exposição ocupacional a agrotóxicos organofosforados e neoplasias hematológicas: uma revisão sistemática.

OBJECTIVE: To update findings of observational analytical studies on the association between occupational exposure to organophosphates and hematologic malignancies. METHODOLOGY: Systematic literature review, including cohort and case-control studies, without limitation of publication time, in Portuguese and English. The articles were traced from June 2017 to July 2019 in PubMed, MEDLINE, LILACS, Web of Science, and Scopus databases. The qualitative bias risk assessment was performed using the Newcastle-Ottawa Scale and the Downs and Black Checklist. Results were presented according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). RESULTS: Seventeen studies evaluated as good/high methodological quality were eligible. Exposure to diazinon (1 cohort), phonophos (1 cohort), dichlorvos, crotoxiphos and famphur (1 case control) was associated with leukemia, while exposure to organophosphate was associated to lymphomas (6 case control); the risk of non-Hodgkin's lymphoma was higher in those exposed to diazinon (1 control case) and malathion (3 control case) than non-exposed ones. Multiple myeloma occurred more commonly in organophosphate exposed than in non-exposed individuals (1 case-control). CONCLUSION: Occupational exposure to organophosphates increases the risk of hematologic malignancies, especially among individuals with longer exposure periods. Worker monitoring and exposure control measures are recommended.

Laryngeal Cancer Risks in Workers Exposed to Lung Carcinogens: Exposure-Effect Analyses Using a Quantitative Job Exposure Matrix.

INTRODUCTION: Various established occupational lung carcinogens are also suspected risk factors for laryngeal cancer. However, individual studies are often inadequate in size to investigate this relatively rare outcome. Other limitations include imprecise exposure assessment and inadequate adjustment for confounders. METHODS: This study applied a quantitative job exposure matrix (SYN-JEM) for four established occupational lung carcinogens to five case-control studies within the International Head and Neck Cancer Epidemiology Consortium. We used occupational histories for 2256 laryngeal cancer cases and 7857 controls recruited from 1989 to 2007. We assigned quantitative exposure levels for asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined (to address highly correlated exposures) via SYN-JEM. We assessed effects of occupational exposure on cancer risk for males (asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined) and females (asbestos and respirable crystalline silica), adjusting for age, study, tobacco smoking, alcohol consumption, and asbestos exposure where relevant. RESULTS: Among females, odds ratios (ORs) were increased for ever versus never exposed. Among males, P values for linear trend were <0.05 for estimated cumulative exposure (all agents) and <0.05 for exposure duration (respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined); strongest associations were for asbestos at >90th percentile cumulative exposure (OR = 1.3, 95% confidence interval [CI] = 1.0, 1.6), respirable crystalline silica at 30+ years duration (OR = 1.4, 95% CI = 1.2, 1.7) and 75th-90th percentile cumulative exposure (OR = 1.4, 95% CI = 1.1, 1.8), chromium-VI at >75th percentile cumulative exposure (OR = 1.9, 95% CI = 1.2, 3.0), and chromium-VI and nickel combined at 20-29 years duration (OR = 1.5, 95% CI = 1.1, 2.2). CONCLUSIONS: These findings support hypotheses of causal links between four lung carcinogens (asbestos, respirable crystalline silica, chromium-VI, and nickel) and laryngeal cancer.

Exposição ocupacional a agrotóxicos organofosforados e neoplasias hematológicas: uma revisão sistemática / Occupational exposure to organophosphate pesticides and hematologic neoplasms: a systematic review

RESUMO: Objetivo: Atualizar achados de estudos observacionais analíticos sobre a associação entre exposição ocupacional a organofosforados e neoplasias hematológicas. Métodos: Revisão sistemática de literatura, incluindo estudos de coorte e caso controle, sem limitação de tempo de publicação, nos idiomas português e inglês. O rastreamento de artigos foi feito no período de junho de 2017 a julho de 2019 nas bases de dados PubMed, MEDLINE, LILACS, Web of Science e Scopus. A avaliação qualitativa de risco de viés foi feita com a Escala Newcastle-Otawa e com o Checklist Downs e Black. Os resultados foram apresentados segundo as recomendações da Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Resultados: Foram elegíveis 17 estudos avaliados como de boa/alta qualidade metodológica. A exposição a diazinon (um coorte), fonofós (um coorte), diclorvós, crotoxifós e fanfur (um caso controle) associou-se à leucemia, enquanto a exposição a organofosforados associou-se aos linfomas (seis caso controle). O risco de linfoma não-Hodgkin foi maior para os indivíduos expostos a diazinon (um caso controle) e malation (três caso controle), em relação aos não expostos. O mieloma múltiplo ocorreu mais comumente em expostos a organofosforados do que entre os não expostos (um caso controle). Conclusão: A exposição ocupacional a organofosforados aumenta o risco de neoplasias hematológicas, sobretudo entre os indivíduos com maior período de exposição. Medidas de monitoramento de trabalhadores e de controle da exposição são recomendadas.

ABSTRACT: Objective: To update findings of observational analytical studies on the association between occupational exposure to organophosphates and hematologic malignancies. Methodology: Systematic literature review, including cohort and case-control studies, without limitation of publication time, in Portuguese and English. The articles were traced from June 2017 to July 2019 in PubMed, MEDLINE, LILACS, Web of Science, and Scopus databases. The qualitative bias risk assessment was performed using the Newcastle-Ottawa Scale and the Downs and Black Checklist. Results were presented according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Results: Seventeen studies evaluated as good/high methodological quality were eligible. Exposure to diazinon (1 cohort), phonophos (1 cohort), dichlorvos, crotoxiphos and famphur (1 case control) was associated with leukemia, while exposure to organophosphate was associated to lymphomas (6 case control); the risk of non-Hodgkin's lymphoma was higher in those exposed to diazinon (1 control case) and malathion (3 control case) than non-exposed ones. Multiple myeloma occurred more commonly in organophosphate exposed than in non-exposed individuals (1 case-control). Conclusion: Occupational exposure to organophosphates increases the risk of hematologic malignancies, especially among individuals with longer exposure periods. Worker monitoring and exposure control measures are recommended.

Age at start of using tobacco on the risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium (INHANCE).

BACKGROUND: Tobacco use is a well-established risk factor for head and neck cancer (HNC). However, less is known about the potential impact of exposure to tobacco at an early age on HNC risk. METHODS: We analyzed individual-level data on ever tobacco smokers from 27 case-control studies (17,146 HNC cases and 17,449 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects logistic regression models. RESULTS: Without adjusting for tobacco packyears, we observed that younger age at starting tobacco use was associated with an increased HNC risk for ever smokers (OR<10 years vs. ≥30 years: 1.64, 95% CI: 1.35, 1.97). However, the observed association between age at starting tobacco use and HNC risk became null after adjusting for tobacco packyears (OR<10 years vs. ≥30 years: 0.97, 95% CI: 0.80, 1.19). In the stratified analyses on HNC subsites by tobacco packyears or years since quitting, no difference in the association between age at start and HNC risk was observed. CONCLUSIONS: Results from this pooled analysis suggest that increased HNC risks observed with earlier age at starting tobacco smoking are largely due to longer duration and higher cumulative tobacco exposures.

Lung Cancer Mortality Trends in a Brazilian City with a Long History of Asbestos Consumption.

There are scarce epidemiological studies on lung cancer mortality in areas exposed to asbestos in developing countries. We compared the rates and trends in mortality from lung cancer between 1980 and 2016 in a municipality that made extensive use of asbestos, Osasco, with rates from a referent municipality with lower asbestos exposure and with the rates for the State of São Paulo. We retrieved death records for cases of lung cancer (ICD-9 C162) (ICD-10 C33 C34) from 1980 to 2016 in adults aged 60 years and older. The join point regression and age-period-cohort models were fitted to the data. Among men, there was an increasing trend in lung cancer mortality in Osasco of 0.7% (CI: 0.1; 1.3) in contrast to a mean annual decrease for Sorocaba of -1.5% (CI: -2.4; -0.6) and a stable average trend for São Paulo of -0.1 (IC: -0.3; 0.1). Similar increasing trends were seen in women. The age-period-cohort model showed an increase in the risk of death from 1996 in Osasco and a reduction for Sorocaba and São Paulo State during the same period. Our results point to a need for a special monitoring regarding lung cancer incidence and mortality in areas with higher asbestos exposure.

Occupations and the Risk of Head and Neck Cancer: A Pooled Analysis of the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

OBJECTIVE: To investigate the associations between head and neck cancer (HNC) risk and occupations. METHODS: We harmonized data on occupations in a pooled analysis of 8839 HNC cases and 13,730 controls in International Head and Neck Cancer Epidemiology (INHANCE) consortium. Logistic regression was used to estimate odds ratios (ORs) for associations of occupations and HNC risk. Population attributable fraction (PAF) for occupations was calculated using the formula PEC × (OR - 1)/OR. RESULTS: Trend of increasing HNC risk was found with increasing duration of employment for many occupations, including cooks (OR = 1.36; 95% confidence interval [CI] 1.09 to 1.68), cleaners (OR = 1.38; 95% CI 1.13 to 1.69), painters (OR = 1.82; 95% CI 1.42 to 2.35). The PAF for a priori occupations was 14.5% (95% CI 7.1% to 21.9%) for HNC. CONCLUSIONS: We found associations between certain occupations and HNC risks, including for subsites, with a duration-response relationship.

Joint effects of intensity and duration of cigarette smoking on the risk of head and neck cancer: A bivariate spline model approach.

OBJECTIVES: This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures. MATERIALS AND METHODS: We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework. RESULTS: For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers. CONCLUSION: Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.

Mendelian Randomization and mediation analysis of leukocyte telomere length and risk of lung and head and neck cancers.

BACKGROUND: Evidence from observational studies of telomere length (TL) has been conflicting regarding its direction of association with cancer risk. We investigated the causal relevance of TL for lung and head and neck cancers using Mendelian Randomization (MR) and mediation analyses. METHODS: We developed a novel genetic instrument for TL in chromosome 5p15.33, using variants identified through deep-sequencing, that were genotyped in 2051 cancer-free subjects. Next, we conducted an MR analysis of lung (16 396 cases, 13 013 controls) and head and neck cancer (4415 cases, 5013 controls) using eight genetic instruments for TL. Lastly, the 5p15.33 instrument and distinct 5p15.33 lung cancer risk loci were evaluated using two-sample mediation analysis, to quantify their direct and indirect, telomere-mediated, effects. RESULTS: The multi-allelic 5p15.33 instrument explained 1.49-2.00% of TL variation in our data (p = 2.6 × 10-9). The MR analysis estimated that a 1000 base-pair increase in TL increases risk of lung cancer [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.20-1.65] and lung adenocarcinoma (OR = 1.92, 95% CI: 1.51-2.22), but not squamous lung carcinoma (OR = 1.04, 95% CI: 0.83-1.29) or head and neck cancers (OR = 0.90, 95% CI: 0.70-1.05). Mediation analysis of the 5p15.33 instrument indicated an absence of direct effects on lung cancer risk (OR = 1.00, 95% CI: 0.95-1.04). Analysis of distinct 5p15.33 susceptibility variants estimated that TL mediates up to 40% of the observed associations with lung cancer risk. CONCLUSIONS: Our findings support a causal role for long telomeres in lung cancer aetiology, particularly for adenocarcinoma, and demonstrate that telomere maintenance partially mediates the lung cancer susceptibility conferred by 5p15.33 loci.

Epidemiological science and cancer control.

Epidemiological methods are essential for the discovery of cancer risks and prognostic factors as well as for the evaluation of cancer prevention measures. In this review, we discuss epidemiological surveillance procedures for data collection and processing to guide and evaluate the consequences of anticancer efforts for populations, assess the identification of cancer risk factors, examine barriers to cancer screening and recommended rules for early diagnosis programs. Epidemiological studies have shown that hindrances to cancer information assessment are currently encountered in developing countries. Known cancer risk factors include social determinants, lifestyle factors, occupational exposures, infectious agents, and genetic and epigenetic alterations. Challenges remain in studying the effectiveness of cancer screening; screening can have detrimental effects, and few cancers clearly benefit from screening. Currently, epidemiology faces the challenge of dealing with distinct levels of data, including factors related to social status, lifestyle and genetics, to reconstruct the causal traits of cancer. Additionally, translating epidemiological knowledge into cancer control demands more implementation studies in the population.