Changes in Body Mass Index Are Associated with Squamous Cell Carcinomas of Oral Cavity, Oropharynx and Larynx: A Case-Control Study in Brazil.

Head and neck cancer (HNC) significantly impacts nutritional status because the tumor limits swallowing function. In this sense, it is important to monitor the nutritional status throughout the life of any individual. A multicenter case-control study was carried out to analyze the BMI at 30 years of age, two years before diagnosis and at the time of diagnosis of individuals with oral cavity, oropharynx, and larynx cancers. It was observed that a 5% reduction in BMI during the two years before enrollment was associated with an increased risk of the oral cavity (OR = 3.73), oropharyngeal OR = 5.25), and laryngeal (OR = 5.22). Reduced BMI of more than 5% over two years before diagnosis was associated with HNC. Weight loss remained significant at diagnosis, but it is not possible to exclude reverse causality since most cases are at an advanced stage. BMI monitoring of individuals at potential risk for HNC can promote early diagnosis and nutritional interventions for HNC.

Differential Expression of Potential Biomarkers of Oral Squamous Cell Carcinoma Development.

To evaluate molecular epithelial changes, we investigated whether a profile of survivin, cyclin dependent kinase inhibitor 2A (CDKN2A), epidermal growth factor receptor (EGFR), polo like kinase 1 (PLK1), p63, p40 (Δnp63 isoform), cyclin D1 (CCND1) and BCL2 apoptosis regulator (BCL2) proteins could predict malignant transformation. Different tissue segments (tumor adjacent epithelium; dysplasia and tumor) from a total of 109 patients were analyzed by immunohistochemistry. An increased expression of survivin (p < 0.001), PLK1 (p = 0.001), and p63 (p < 0.001) in parallel to reduced immunostaining of p40 (p < 0.001) and BCL2 (p = 0.029) was observed among the tissue segments analyzed. Our study revealed that survivin, PLK1, p63, p40 and BCL2 play a role in oral tumorigenesis and represent promising biomarkers able to recognize mesenchymal phenotype induction in the transition from nonmalignant cells to tumor cells. These results reveals critical interaction between survivin, PLK1, p63, p40 promising proteins during invasive carcinoma development.

Consumption of minimally processed foods as protective factors in the genesis of squamous cell carcinoma of the head and neck in Brazil.

BACKGROUND: Head and neck cancer (HNC) is the sixth most common cancer, and two-fifths of cases could be avoided by changing lifestyle and eating habits. METHODS: This multicenter case-control study was conducted under the International Consortium on Head and Neck Cancer and Genetic Epidemiology, coordinated by the International Agency for Research on Cancer. This consortium evaluated associations between minimally processed food consumption and the risk of HNC in three Brazilian states. RESULTS: We evaluated 1740 subjects (847 cases and 893 controls). In multiple analyses including recognized risk factors for HNC, the consumption of apples and pears was associated with reduced risks of oral cavity and laryngeal cancers; the consumption of citrus fruits and fresh tomatoes was associated with a reduced risk of oral cavity cancer; the consumption of bananas was associated with a reduced risk of oropharynx cancer; the consumption of broccoli, cabbage, and collard greens was associated with reduced risks of laryngeal and hypopharyngeal cancers; and the consumption of carrots and fresh fruits was associated with a reduced risk of hypopharyngeal cancer. CONCLUSIONS: The consumption of a heathy diet rich in fruits and vegetables was associated with a reduced risk of HNC. Public policies, including government subsidies, are essential to facilitate logistical and financial access to minimally processed foods, thereby strengthening environments that promote healthy behavior.

Frequency of HPV in oral cavity squamous cell carcinoma.

BACKGROUND: The prevalence of high-risk human papillomavirus (HPV) DNA in cases of oral cavity squamous cell carcinoma (SCC) varies widely. The aim of this study is to investigate the frequency of high-risk HPV DNA in a large Brazilian cohort of patients with oral cavity SCC. METHODS: Biopsy and resected frozen and formalin-fixed paraffin-embedded specimens of oral cavity SCC were available from 101 patients who were recruited at two Brazilian centres. Stringent measures with respect to case selection and prevention of sample contamination were adopted to ensure reliability of the data. Nested PCR using MY09/MY11 and GP5+/GP6+ as well as PGMY09/11 L1 consensus primers were performed to investigate the presence of HPV DNA in the tumours. HPV-positive cases were subjected to direct sequencing. Shapiro-Wilk and Student t test were used to evaluate data normality and to compare the means, respectively. Qualitative variables were analysed by logistic regression. RESULTS: Our results demonstrate that the frequency of high-risk HPV types in oral cavity SCC is very low and is less than 4%. All HPV-positive cases were HPV16. In addition, our results do not show a significant association between the tumour clinical features and the risk factors (tobacco, alcohol and HPV) for oral cavity SCC. CONCLUSION: In the current study, we observed an overlapping pattern of risk factors that are related to tumour development. This, along with a low frequency of high-risk HPV DNA, supports the findings that HPV is not involved in the genesis of oral cavity SCC in Brazilian population.

Polymorphisms in methylenetetrahydrofolate reductase and cystathionine beta-synthase in oral cancer - a case-control study in southeastern Brazilians.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) is a serious public health problem, due to its high mortality rate and worldwide rising incidence. OSCC susceptibility is mediated by interactions between genetic and environmental factors. Studies suggest that genetic variants encoding enzymes involved in folate metabolism may modulate OSCC risk by altering DNA synthesis/repair and methylation process. OBJECTIVE: The goals of this study were to evaluate the association of three genotypic polymorphism (MTHFR C677T, MTHFR A1298C and CBS 844ins68) and oral cancer risk in southeastern Brazilians and evaluate the interactions between polymorphisms and clinical histopathological parameters. METHODS: This case-control study included 101 cases and 102 controls in the state of Espírito Santo, Brazil. MTHFR genotyping was done by PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism) and CBS genotyping by PCR (polymerase chain reaction) analysis. RESULTS: MTHFR C677T polymorphism was associated with lymph node involvement. Genotype CT+TT acted as a protective factor. MTHFR A1298C AC+CC genotype was associated with tumor differentiation, and possibly with a better prognosis. In risk analysis, no correlation was observed between genotypes and OSCC. CONCLUSION: We concluded that MTHFR C677T, MTHFR A1298C and CBS 844ins68 polymorphisms were not associated with OSCC risk in southeastern Brazilians; however, we suggest a prognosis effect associated with MTHFR C677T and A1298C polymorphisms in OSCC.

Promoter hypermethylation in primary squamous cell carcinoma of the oral cavity and oropharynx: a study of a Brazilian cohort.

Epigenetic silencing of cancer-related genes plays an important role in oral/oropharyngeal squamous cell carcinoma (OSCC). We evaluated promoter hypermethylation of 4 cancer-related genes in OSCCs of a Brazilian cohort and determined its relationship with exposure to alcohol, tobacco, HPV infection and clinicopathological parameters. CDKN2A (cyclin-dependent kinase inhibitor 2A or p16), SFN (stratifin or 14-3-3 σ), EDNRB (endothelin receptor B) and RUNX3 (runt-related transcript factor-3) had their methylation patterns evaluated by MSP analysis in OSCC tumors (n = 45). HPV detection was carried out by PCR/RFLP. Aberrant methylation was detected in 44/45 (97.8 %) OSCC; 24.4 % at CDKN2A, 77.8 % at EDNRB, 17.8 % at RUNX3 and 97.8 % at SFN gene. There was no significant association between methylation patterns and clinical parameters. HPV (subtype 16) was detected in 3 out of 45 patients (6 %). Our findings indicate that HPV infection is uncommon and methylation is frequent in Brazilian OSCCs, however, EDNRB and SFN gene methylation are not suitable OSCC biomarkers due to indistinct methylation in tumoral and normal samples. In contrast, CDKN2A and RUNX3 genes could be considered differentially methylated genes and potential tumor markers in OSCCs.

Methylation analysis of cancer-related genes in non-neoplastic cells from patients with oral squamous cell carcinoma.

Early detection of Oral Squamous Cell Carcinoma (OSCC) is important to reduce mortality rates and to help provide successful cancer treatment. Hypermethylation of CpG islands is a common epigenetic mechanism that leads to gene silencing in tumors and could be a useful biomarker in OSCC. Abnormal DNA hypermethylation can occur very early in cancer development and may be induced by exposure to environmental carcinogens. We set out to investigate the methylation status of cancer-related genes in normal oral exfoliated cells from OSCC patients and healthy volunteers, as well as possible associations with alcohol/tobacco exposure or specific tumor characteristics. The methylation status of CDKN2A (cyclin-dependent kinase inhibitor 2A or p16), SFN (stratifin or 14-3-3 σ), EDNRB (endothelin receptor B) and RUNX3 (runt-related transcript factor-3) was evaluated by MSP (Methylation-Specific Polymerase Chain Reaction) analysis in non-neoplastic oral epithelial cells from OSCC patients (n = 70) and cancer-free subjects (n = 41). Hypermethylation was observed in CDKN2A, EDNRB and SFN genes, whereas no methylation was found in the RUNX3 gene. CDKN2A hypermethylation occurred only in the OSCC group (5.7%) while SFN and EDNRB hypermethylation occurred in both groups. There was no association between hypermethylation and smoking, drinking habits or specific tumor characteristics.