HUMAN DNA QUANTIFICATION IN THE STOOLS OF PATIENTS WITH COLORECTAL CANCER

Background - Colorectal cancer is one of the main cause of cancer in the world. Colonoscopy is the best screen method, however the compliance is less than 50%. Quantification of human DNA (hDNA) in the feces may be a possible screen non-invasive method that is a consequence of the high proliferation and exfoliation of cancer cells. Objective - To quantify the human DNA in the stools of patients with colorectal cancer or polyps. Methods - Fifty patients with CRC, 26 polyps and 53 with normal colonoscopy were included. Total and human DNA were analyzed from the frozen stools. Results - An increased concentration of hDNA in the stools was observed in colorectal cancer patients compared to controls and polyps. Tumors localized in the left side of the colon had higher concentrations of hDNA. There were no difference between polyps and controls. A cut off of 0.87 ng/mL of human DNA was determined for colorectal cancer patients by the ROC curve, with a sensitivity of 66% and a specificity of 86.8%. For polyps the cut off was 0.41, the sensitivity was 41% and the specificity 77.4%. Conclusion - A higher concentration of hDNA had been found in colorectal cancer patients The quantification of hDNA from the stools can be a trial method for the diagnosis of colorectal cancer.

Contexto - O câncer colorretal é, mundialmente, uma das principais causas de câncer. A colonoscopia é o melhor método de rastreamento, no entanto a adesão é inferior a 50%. A quantificação de DNA humano (hDNA) nas fezes pode ser um possível método não invasivo de rastreamento, que é consequência da elevada proliferação e esfoliação de células cancerosas. Objetivo - Quantificar o DNA humano nas fezes de pacientes com câncer colorretal ou pólipos Métodos - Cinquenta pacientes com câncer colorretal, 26 pólipos e 53 com colonoscopia normal foram incluídas. DNA total e humano foram analisados a partir de fezes congeladas. Resultados - Maior concentração de hDNA nas fezes foi observada em pacientes com câncer colorretal em comparação com controles e pólipos. Pacientes com tumores localizados no cólon esquerdo apresentaram concentrações mais elevadas de hDNA. Não houve diferença entre pólipos e controles. Um nível de corte de 0.87ng/mL de DNA humano foi determinado para pacientes com câncer colorretal pela curva ROC, com sensibilidade de 66% e especificidade de 86,8%. Para pólipos o nível de corte foi de 0,41, a sensibilidade foi de 41% e a especificidade de 77,4%. Conclusão - Maior concentração de hDNA foi encontrada em pacientes com câncer colorretal. A quantificação de hDNA das fezes pode ser um método de rastreio do câncer colorretal.

HUMAN DNA QUANTIFICATION IN THE STOOLS OF PATIENTS WITH COLORECTAL CANCER.

BACKGROUND: Colorectal cancer is one of the main cause of cancer in the world. Colonoscopy is the best screen method, however the compliance is less than 50%. Quantification of human DNA (hDNA) in the feces may be a possible screen non-invasive method that is a consequence of the high proliferation and exfoliation of cancer cells. OBJECTIVE: To quantify the human DNA in the stools of patients with colorectal cancer or polyps. METHODS: Fifty patients with CRC, 26 polyps and 53 with normal colonoscopy were included. Total and human DNA were analyzed from the frozen stools. RESULTS: An increased concentration of hDNA in the stools was observed in colorectal cancer patients compared to controls and polyps. Tumors localized in the left side of the colon had higher concentrations of hDNA. There were no difference between polyps and controls. A cut off of 0.87 ng/mL of human DNA was determined for colorectal cancer patients by the ROC curve, with a sensitivity of 66% and a specificity of 86.8%. For polyps the cut off was 0.41, the sensitivity was 41% and the specificity 77.4%. CONCLUSION: A higher concentration of hDNA had been found in colorectal cancer patients The quantification of hDNA from the stools can be a trial method for the diagnosis of colorectal cancer.

-765 g>c polymorphism of the cox-2 gene and gastric cancer risk in Brazilian population.

CONTEXT: Genomic alterations play important roles in gastric cancer carcinogenesis. Cyclooxygenases (COX) are important enzymes in the maintenance of mucosal integrity and in pathological processes, mainly in inflammation and cancer. The -765G>C COX-2 polymorphism has been implicated in gastric cancer risk. OBJECTIVES: To evaluate the COX-2 gene polymorphism as a predictor of gastric cancer risk. METHODS: One hundred gastric cancer patients and 150 controls were enrolled from a Brazilian centre. Personal data regarding related risk factors, including alcohol consumption and smoking behavior, were collected via questionnaire. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism. RESULTS: G/G, G/C and C/C genotypes frequencies was 42.7%, 50% and 7.3%, respectively in controls and 59.0%, 34.0% and 7.0% in gastric cancer. The frequency of the genotypes differed between the groups (P = 0.033). A higher risk of gastric cancer was associated with COX-2 -765G/G genotype (P = 0.048; OR:1.98, 95% CI = 1.01-3.90). Alcohol consumption and smoking in patients with -765G/G genotype also increased the risk of gastric cancer. CONCLUSIONS: The -765G/G genotype and the -765G allele had been associated with an increased risk for gastric cancer. The presence of smoking and alcohol consumption increased the risk for gastric cancer in subjects with -765G/G genotype compared with the control group. Polymorphism of COX-2 gene and gastric cancer risk.

-765 g>c polymopphism of the cox-2 gene and gastric cancer risk in Brazilian populatoon / O polimorfismo -765 G>C do gene COX-2 e o risco de câncer gástrico na população Brasileira

Context Genomic alterations play important roles in gastric cancer carcinogenesis. Cyclooxygenases (COX) are important enzymes in the maintenance of mucosal integrity and in pathological processes, mainly in inflammation and cancer. The -765G>C COX-2 polymorphism has been implicated in gastric cancer risk. Objectives To evaluate the COX-2 gene polymorphism as a predictor of gastric cancer risk. Methods One hundred gastric cancer patients and 150 controls were enrolled from a Brazilian centre. Personal data regarding related risk factors, including alcohol consumption and smoking behavior, were collected via questionnaire. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism. Results G/G, G/C and C/C genotypes frequencies was 42.7%, 50% and 7.3%, respectively in controls and 59.0%, 34.0% and 7.0% in gastric cancer. The frequency of the genotypes differed between the groups (P = 0.033). A higher risk of gastric cancer was associated with COX-2 -765G/G genotype (P = 0.048; OR:1.98, 95% CI = 1.01-3.90). Alcohol consumption and smoking in patients with -765G/G genotype also increased the risk of gastric cancer. Conclusions The -765G/G genotype and the -765G allele had been associated with an increased risk for gastric cancer. The presence of smoking and alcohol consumption increased the risk for gastric cancer in subjects with -765G/G genotype compared with the control group. Polymorphism of COX-2 gene and gastric cancer risk. .

Contexto As alterações genômicas tem um papel importante na carcinogênese do câncer gástrico. As cicloxigenases (COX) são enzimas importantes na integridade da mucosa a nos processos patológicos, principalmente na inflamação e no câncer. O polimorfismo -765G>C COX- 2 pode se relacionar ao risco de câncer gástrico. Objetivos Avaliar o polimorfismo de COX-2 como um preditivo de risco de câncer gástrico. Métodos Cem pacientes com câncer gástrico e 150 controles foram estudados provenientes de um centro no Brasil. Foram coletados dados referentes ao consumo de álcool e fumo, considerados fatores de risco. O DNA foi extraído de sangue periférico e os genótipos foram analisados por PCR- RFLP. Resultados As frequências dos genótipos G/G, G/C e C/C foram 42,7%, 50% e 7,3%, respectivamente nos controles e 59,0%, 34,0% e 7,0% no câncer gástrico. A frequência dos genótipos diferiu entre os grupos (P = 0,033). O genótipo -765G/G COX-2 esteve associado a um maior risco de câncer gástrico (P = 0,048; OR:1,98, 95% CI = 1,01-3,90). O consumo de álcool e o fumo em pacientes com o genótipo -765G/G COX-2 também aumentou o risco de câncer gástrico. Conclusões O genótipo -765G/G e o alelo -765G foi associado a maior risco de câncer gástrico. O fumo e o etilismo aumentaram o risco de câncer gástrico em indivíduos com o genótipo -765G/G comparados com o grupo controle. .

Study of the polymorphisms of cyclooxygenase-2 (-765G>C) and 5-lipoxygenase (1708G>A) in patients with colorectal cancer.

Colorectal cancer (CRC) is the fourth most common cause of cancer-related mortality worldwide. Genetic alterations have been associated with an increased risk of cancer and greater tumor aggressiveness. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) genes are important in cell cycle regulation, tumor growth and prostaglandin synthesis. The aim of the present study was to investigate the association between polymorphisms in the COX-2 and 5-LOX genes and the risk of CRC. A case-control study was conducted in patients with CRC matched for gender and age to a control group. DNA was extracted from peripheral leukocytes, and the polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism and gene sequencing. A specific questionnaire was applied to evaluate smoking, excessive alcohol consumption, physical activity, non-steroidal anti-inflammatory drug use and meat, fiber and fat intake. A total of 185 patients with CRC and 146 controls were studied. The heterozygous GC genotype of the COX-2 gene polymorphism was the most common in the two groups (60.0% in CRC patients and 52.7% in controls). The CC genotype was associated with an increased risk of CRC (odds ratio, 3.63; 95% confidence interval, 1.31-10.1; P=0.013). The homozygous wild-type genotype of the 5-LOX gene polymorphism was detected in 72.4% of the CRC patients and in 71.2% of the control subjects. The homozygous mutant genotype (CC) of the COX-2 gene is an independent risk factor for CRC. No association was found between 5-LOX genotypes and CRC.

DNA methylation as an epigenetic biomarker in colorectal cancer.

Sporadic colorectal cancer (CRC) is a consequence of the accumulation of genetic and epigenetic alterations that result in the transformation of normal colonic epithelial cells to adenocarcinomas. Studies have indicated that a common event in the tumorigenesis of CRC is the association of global hypomethylation with discrete hypermethylation at the promoter regions of specific genes that are involved in cell cycle regulation, DNA repair, apoptosis, angiogenesis, adhesion and invasion. The present study aimed to investigate the epigenetic changes (DNA methylation) in 24 candidate genes in CRC. A total of 10 candidate hypermethylated (HM) and unmethylated (UM) genes were identified that may be useful epigenetic markers for non-invasive CRC screening. The five genes that had the highest average UM percentages in the control group were MLH1 (71.7%), DKK2 (69.6%), CDKN2A (68.4%), APC (67.5%) and hsa-mir-342 (67.4%). RUNX3 (58.9%), PCDH10 (55.5%), SFRP5 (52.1%), IGF2 (50.4%) and Hnf1b (50.0%) were the five genes with the highest average HM percentages in the test group. In summary, the present preliminary study identified the methylation profiles of normal and cancerous colonic epithelial tissues, and provided the groundwork for future large-scale methylation studies.

N-Acetyltransferase 2 genetic polymorphisms and risk of colorectal cancer.

AIM: To investigate the possible association between meat intake, cigarette smoking and N-acetyltransferase 2 (NAT2) genetic polymorphisms on colorectal cancer (CRC) risk. METHODS: Patients with CRC were matched for gender and age to healthy controls. Meat intake and cigarette smoking were assessed using a specific frequency questionnaire. DNA was extracted from peripheral blood and the genotypes of the polymorphism were assessed by polymerase chain reaction-restriction fragment length polymorphism. Five NAT2 alleles were studied (WT, M1, M2, M3 and M4) using specific digestion enzymes. RESULTS: A total of 147 patients with colorectal cancer (76 women and 90 men with colon cancer) and 212 controls were studied. The mean age of the two groups was 62 years. More than half the subjects (59.8% in the case group and 51.9% in the control group) were NAT2 slow acetylators. The odds ratio for colorectal cancer was 1.38 (95% CI: 0.90-2.12) in slow acetylators. Although the number of women was small (n = 76 in the case group), the cancer risk was found to be lower in intermediate (W/Mx) acetylators [odds ratio (OR): 0.55, 95% confidence interval (95% CI): 0.29-1.02]. This difference was not observed in men (OR: 0.56, 95% CI: 0.16-2.00). Among NAT2 fast acetylators (W/W or W/Mx), meat consumption more than 3 times a week increased the risk of colorectal cancer (OR: 2.05, 95% CI: 1.01-4.16). In contrast, cigarette smoking increased the risk of CRC among slow acetylators (OR: 1.97, 95% CI: 1.02-3.79). CONCLUSION: The risk of CRC was higher among fast acetylators who reported a higher meat intake. Slow NAT2 acetylation was associated with an increased risk of CRC.

E-cadherin and metalloproteinase-1 and -7 polymorphisms in colorectal cancer.

PURPOSE: E-cadherin (CDH1) and metalloproteinase (MMP) polymorphisms could play a crucial role in cancer invasion. Our aim was to investigate the influence of the -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 polymorphisms on the frequency and progression of colorectal cancer (CRC). EXPERIMENTAL DESIGN: A total of 130 patients with CRC and 130 noncancer controls were studied. The -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Patients with the 1G allele and a family history of CRC showed a six times higher risk of developing CRC (OR: 6.45, 95% CI: 2.02-20.6, p=0.001). The A/A CDH1 genotype was associated with a higher risk of metastatic disease (OR: 3.43, 95% CI: 1.27-9.27, p=0.023). A higher marginal risk of metastatic disease was observed for MMP-1 genotypes 1G/1G and 1G/2G (OR: 2.97, 95% CI: 0.93-9.47, p=0.098). CONCLUSIONS: The -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 single nucleotide polymorphisms did not modify the risk of CRC development. Patients with the 1G/1G or 1G/2G genotype and a family history of CRC presented a higher risk of CRC. The AA CDH1 and 1G/1G and 1G/2G MMP-1 genotypes might be associated with advanced metastatic disease, but are not markers of lymphatic metastasis.

[Weight, educational achievement, basic sanitation, alcoholism, smoking and eating habit in patients with gastric cancer]. / Variação de peso, grau de escolaridade, saneamento básico, etilismo, tabagismo e hábito alimentar pregresso em pacientes com cancêr de estômago.

BACKGROUND: About 35% of the cancer patients are involved in factors coming from the diet and others like alcohol, smoking, sunlight, chemical agents and infections caused by virus. The stomach cancer is the second cause of cancer in the world with 9.9 % of all diagnosis and about 12.1 % of death cases. AIMS: Evaluate the body weight, educational achievement, basic sanitation, smoking, alcoholism and eating habit among patients with gastric cancer and a control group. METHODS: Seventy patients with gastric cancer were paired with 70 subjects without cancer. Data on the weight and height, educational attainment, basic sanitation, smoking, alcoholism and eating habits of the patients were collected from the clinical records and from interviews. RESULTS: Forty two patients were men, the mean age were 60 years old. The actual weight and body mass index of the patients were smaller when compared to the controls. Within the group of patients with gastric cancer, 21 never attended school, and for those who attended, 55% did not finish the elementary school. Among the patient group, 32.9% of them lived in housing with basic sanitation and 37.1% with electricity, against 68.6% of the controls, and 58.6% of the patients lived in rural area, against only 7.1% of the controls. Among the test group, 65.7% of the patients were smokers, whereas in the control group, 44.3% were smokers. In addition, there was also difference in the duration of smoking habit. Alcoholism was also more frequent in the cancer group (44% vs 19%). Food rich in salt, condiments, nitrates, saturated fat, complex carbohydrates, refined sugar and fried salted food had been more used by gastric cancer patients. CONCLUSION: The patients with gastric cancer presented with: less weight, low quality of life as indicated by lower or no access to basic sanitation, electricity and schooling, lived predominantly in rural area, high incidence of alcohol intake and higher intake of high fat foods and industrialized foods.

Variação de peso, grau de escolaridade, saneamento básico, etilismo, tabagismo e hábito alimentar pregresso em pacientes com cancêr de estômago / Weight, educational achievement, basic sanitation, alcoholism, smoking and eating habit in patients with gastric cancer

RACIONAL: Cerca de 35 por cento dos casos de câncer estão envolvidos com fatores advindos da dieta e de outros como o álcool, o fumo, a luz solar, agentes químicos e infecções por vírus. O câncer de estômago é o segundo tipo de câncer mais diagnosticado no mundo, sendo responsável por cerca de 9,9 por cento de todos os diagnósticos e cerca de 12,1 por cento das mortes. OBJETIVOS: Comparar o peso corpóreo atual e habitual, grau de escolaridade, saneamento básico, tabagismo, etilismo e freqüência pregressa de consumo de alimentos entre pacientes com câncer de estômago e população controle. MÉTODO: Setenta pacientes com câncer gástrico foram pareados a outros 70 indivíduos sem diagnóstico de neoplasia. Foram coletados peso, altura, informações sobre grau de escolaridade, saneamento básico, tabagismo e etilismo e preenchido um questionário de freqüência alimentar pregressa. RESULTADOS: Dos 75 pacientes elegíveis para o estudo, 42 eram homens, com média de idade de 59,5 anos. O grupo de pacientes com câncer apresentou menor peso e índice de massa corporal atual do que o grupo controle. Em relação ao grau de escolaridade, verificou-se que, no grupo de pacientes com câncer, 21 indivíduos nunca ingressaram na escola e dos que estudaram, cerca de 55 por cento não conseguiram concluir o primeiro grau. Nesse grupo, 32,9 por cento dos indivíduos tiveram acesso ao saneamento básico e 37,1 por cento à eletricidade no passado; no grupo controle, esse percentual foi de 68,6 por cento para cada uma das variáveis. No grupo caso, 58,6 por cento dos pacientes moraram na zona rural, enquanto no grupo controle apenas 7,1 por cento. No grupo caso, 65.7 por cento eram fumantes versus 44.3 por cento, no grupo controle. Observou-se também que os pacientes com câncer fumaram por período maior. O alcoolismo também foi mais freqüente entre os pacientes com câncer (45 por cento versus 19 por cento). Verificou-se que, entre os pacientes com câncer, houve maior consumo...

BACKGROUND: About 35 percent of the cancer patients are involved in factors coming from the diet and others like alcohol, smoking, sunlight, chemical agents and infections caused by virus. The stomach cancer is the second cause of cancer in the world with 9.9 percent of all diagnosis and about 12.1 percent of death cases. AIMS: Evaluate the body weight, educational achievement, basic sanitation, smoking, alcoholism and eating habit among patients with gastric cancer and a control group. METHODS: Seventy patients with gastric cancer were paired with 70 subjects without cancer. Data on the weight and height, educational attainment, basic sanitation, smoking, alcoholism and eating habits of the patients were collected from the clinical records and from interviews. RESULTS: Forty two patients were men, the mean age were 60 years old. The actual weight and body mass index of the patients were smaller when compared to the controls. Within the group of patients with gastric cancer, 21 never attended school, and for those who attended, 55 percent did not finish the elementary school. Among the patient group, 32.9 percent of them lived in housing with basic sanitation and 37.1 percent with electricity, against 68.6 percent of the controls, and 58.6 percent of the patients lived in rural area, against only 7.1 percent of the controls. Among the test group, 65.7 percent of the patients were smokers, whereas in the control group, 44.3 percent were smokers. In addition, there was also difference in the duration of smoking habit. Alcoholism was also more frequent in the cancer group (44 percent vs 19 percent). Food rich in salt, condiments, nitrates, saturated fat, complex carbohydrates, refined sugar and fried salted food had been more used by gastric cancer patients. CONCLUSION: The patients with gastric cancer presented with: less weight, low quality of life as indicated by lower or no access to basic sanitation, electricity and schooling, lived...

Cyclin D1 A870G polymorphism in Brazilian colorectal cancer patients.

INTRODUCTION: Cyclin D1 (CCND1) is a regulatory protein involved in the cell cycle. A common G to A polymorphism in the CCND1 gene is implicated on the splicing of the CCND1 transcript, and this protein may be associated to a deregulated cell proliferation. AIM: Correlate the polymorphism A870G of CCND1 to the risk of colorectal cancer (CRC), to environmental risk factors and clinical aspects in Brazilian patients. PATIENTS AND METHODS: One hundred twenty-three Brazilian patients with colorectal cancer were matched by age and sex to 120 healthy individuals. PCR-RFLP was performed to investigate the A870G CCND1 genotype. RESULTS: Between the cases 70 were men, the mean age was 62.6 years, 74.78% were stage II or III, and 91% were well or moderately differentiated. The patients were followed for a mean time of 37.22 months. The frequency of ethanol and fat intake was similar among the groups. Patients with a family history of CRC had a higher frequency of CRC compared with the controls (OR 4.16, CI 1.89-9.16). There was no difference in the frequency of the alleles A (43.8% versus 43.9%) and G (56.3% versus 56.1%) in the groups. In analysis of both control and cancer group, the influence of sex, smoking, alcohol, fiber, or meat intake did not differ significantly according to CCND1 genotype. The genotype AA or AG was associated with an increased risk of CRC (OR 3.63 CI 1.25-10.5) in patients with a family history of cancer. We did not find any association among the genotypes and localization of the tumor or prognosis. Although a difference on age onset of the tumor and genotype was not observed, patients with GG genotype had a mean 8 years lower than the others. This genotype was also associated to an increase risk of metastatic disease (OR 3.47, CI 1.38-8.68, p = 0.024). CONCLUSION: We did not find a correlation among the polymorphism of CCND1 A870G and colorectal cancer risk or between this polymorphism and lifestyle habits, diet, or follow-up. GG genotype patients had an increased risk of advanced disease and between the young patients, this genotype was associated to a lower mean age. On the other hand, the genotype AA or AG had been involved to a higher risk of CRC in patients with family history of CRC.

[Role of the genetic polymorphism of p53 (codon 72) gene in colorectal cancer]. / Estudo do polimorfismo genético no gene p53 (códon 72) em câncer colorretal.

BACKGROUND: Polymorphisms are genetic variations that can occur in sequences of codons, leading to defective proteins. p53 is the most commonly gene affected in human cancer. The polymorphism of this gene occurs by a substitution of a base in codon 72 and may increase the risk of cancer. AIM: To investigate the possible association between p53 arginine/72 proline polymorphism and susceptibility to colorectal cancer. PATIENTS AND METHODS: This polymorphism was studied by polymerization chain reaction using specific primers in 100 patients with colorectal cancer paired by sex and age to 100 patients without cancer. Alcohol and tobacco used by all the patients and clinical aspects as stage, grade of differentiation and recurrence in the case group was compared with the genotype analyzed. RESULTS: The frequency of homozygosis for arginine was 56% in the cancer group and 58% in the control group. No significant difference was observed among both groups. This genotype was more frequent in colorectal cancer patients stage IV than in stage I (80% versus 14%). There was no significant difference between genotypes and alcohol, tobacco, grade of differentiation or recurrence. CONCLUSION: Homozygosity for arginine was the most prevalent genotype in both groups. The frequency of codon 72 proline/arginine p53 gene polymorphism was not correlated with a higher risk of colorectal cancer. Arginine/arginine genotype was more prevalent in advanced cancer patients (stage IV).

Estudo do polimorfismo genético no gene p53 (códon 72) em câncer colorretal / Role of the genetic polymorphism of p53 (codon 72) gene in colorectal cancer

RACIONAL: Polimorfismos genéticos são variações genéticas que podem ocorrer em seqüências codificadoras e não-codificadoras, levando a alterações qualitativas e/ou quantitativas das proteínas em questão. O p53 é o gene mais comumente alterado no câncer humano. O polimorfismo desse gene no códon 72 ocorre por substituição de uma base e tem sido associado a maior risco de câncer. OBJETIVO: Determinar a possível associação entre o polimorfismo no códon 72 (72 arginina/prolina) do gene p53 e câncer colorretal. CASUíSTICA E MÉTODOS: Foram avaliados em 100 pacientes com câncer colorretal e em 100 indivíduos sem câncer, pareados quanto ao sexo idade, o hábito de fumar, o etilismo e no grupo caso o estádio, o grau de diferenciação e a evolução da doença. O genótipo (72 arginina/prolina) foi determinado por PCR, utilizando-se primers (seqüências de nucleotídeos) específicos. RESULTADOS: O genótipo homozigoto arginina/arginina foi prevalente em 56 por cento no grupo controle e em 58 por cento no grupo caso. Não se observou diferença entre os dois grupos. No estádio IV este genótipo foi mais freqüente quando comparado ao estádio I (80 por cento versus 14 por cento). Não se observou diferença entre as variações do genótipo e fumo, álcool, evolução clínica ou grau de diferenciação. CONCLUSAO: A prevalência do genótipo arginina/arginina foi a mais freqüente nos dois grupos. Não foi encontrada correlação entre maior risco de câncer e o polimorfismo no códon 72 prolina/arginina do gene p53. Apesar do pequeno número de doentes com câncer em estádio avançado (IV), estes tiveram maior prevalência do genótipo arginina/arginina.