Marcos Brasilino de Carvalho

Cigarette, Cigar, and Pipe Smoking and the Risk of Head and Neck Cancers: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ≤ 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.

Immediate Impact of Primary Surgery on Health-Related Quality of Life of Hospitalized Patients With Oral and Oropharyngeal Cancer

PURPOSEnOral 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.nnnPATIENTS AND METHODSnForty-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.nnnRESULTSnThe 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.nnnCONCLUSIONSnThe 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.

Oral health, hygiene practices and oral cancer

OBJECTIVEnTo assess the association between oral health and hygiene practices and oral cancer.nnnMETHODSnHospital-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.nnnRESULTSnThe 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).nnnCONCLUSIONSnGum bleeding, no dental care, and daily mouthwash use were factors associated with oral cancer regardless of tobacco and alcohol consumption.

Dietary patterns and risk of oral cancer: a case-control study in São Paulo, Brazil.

OBJECTIVEnTo analyze the association between dietary patterns and oral cancer.nnnMETHODSnThe 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.nnnRESULTSnTraditional 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).nnnCONCLUSIONSnThe 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.

Survival and quality of life of patients with oral and oropharyngeal cancer at 1-year follow-up of tumor resection.

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.

Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10−8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2–TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci—9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301–HLA-DQA1*0103–HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10−9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10−6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

Genomics and proteomics approaches to the study of cancer-stroma interactions

BackgroundThe 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.MethodsThe 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.ResultsWe 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.ConclusionsA 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.

Fatores dietéticos e câncer oral: estudo caso-controle na Região Metropolitana de São Paulo, Brasil

Dietary factors associated with oral cancer were investigated in a case-control hospital-based study in the city of Sao 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.

Validade discriminante do questionário de qualidade de vida da Universidade de Washington no contexto brasileiro

OBJETIVO: Avaliar a validade discriminante do questionario de qualidade de vida da Universidade de Washington para pacientes com câncer de cabeca e pescoco e identificar possiveis fatores sociodemograficos que modifiquem seus resultados. METODOS: Foram entrevistados 47 pacientes com câncer de boca e orofaringe em estagio pre-cirurgico em um hospital no sul do municipio de Sao Paulo em 2007, e 141 pacientes sem câncer, pareados por sexo e idade em uma proporcao de tres para um, que foram atendidos em ambulatorios do mesmo hospital em 2008. Os resultados obtidos para os dois grupos foram comparados pelo teste t de Student. Para os pacientes sem câncer utilizou-se analise de regressao de Poisson para avaliar possiveis fatores de modificacao da qualidade de vida. RESULTADOS: O escore geral de qualidade de vida foi significantemente mais elevado (p < 0,001) para os pacientes sem câncer (91,1) do que para os pacientes com câncer (80,6). Observacoes analogas foram efetuadas para oito dos doze dominios de qualidade de vida compreendidos no questionario (dor, aparencia, degluticao, mastigacao, fala, ombros, paladar e ansiedade). Como possiveis fatores de modificacao dos escores de qualidade de vida foram identificados renda familiar (com impacto nos dominios de recreacao, p = 0,017, e funcao dos ombros, p = 0,049), escolaridade (em ansiedade, p = 0,003), sexo (em funcao dos ombros, p = 0,038) e dor de dente (em mastigacao, p = 0,015). CONCLUSOES: O questionario tem validade discriminante, pois seus escores sao especificamente mais afetados para pacientes com câncer. Reforca-se a indicacao do questionario para monitorar o tratamento e recomenda-se avaliar os fatores que podem causar impacto nesses indicadores.

Cumulative Coffee Consumption and Reduced Risk of Oral and Oropharyngeal Cancer

We examined the association between coffee consumption and oral cancer in a hospital-based case-control study comprising 143 patients with oral and oropharyngeal squamous cell carcinoma attended at 3 major hospitals in São Paulo, Brazil, and 240 controls without cancer, recruited from outpatient units of the same hospitals and matched with cases by sex and age. Associations were assessed by multivariate logistic regression conditioned on sociodemographic and behavioral characteristics. Tobacco smoking, alcohol drinking, and higher intake of bacon and deep-fried foods were directly related to disease; the inverse was observed to family income and salad intake. Coffee consumption and tobacco smoking were partially correlated (Spearman correlation coefficient 0.14 among cases, 0.31 among controls). When adjusted for all covariates, a cumulative coffee consumption higher than 18.0 daily liters × year during lifetime was indicated to be protective against disease (adjusted odds ratio 0.39, 95% confidence interval 0.16–0.94, P = 0.037). This observation may have pharmacological implications for clinical medication of these cancers and is relevant to programs aimed at reducing the burden of disease.