Processed meat consumption and risk of cancer: a multisite case-control study in Uruguay.

BACKGROUND: The role of processed meat in the aetiology of several cancers was explored in detail. METHODS: In the time period 1996-2004, a multisite case-control study was conducted in Montevideo, Uruguay. The study included 6 060 participants (3 528 cases and 2 532 controls) corresponding to cancers of the oral cavity, pharynx, oesophagus, stomach, colon, rectum, larynx, lung, female breast, prostate, urinary bladder, and kidney (renal cell carcinoma only). RESULTS: The highest odds ratios (ORs) were positively associated with cancers of the colon, rectum, stomach, oesophagus, and lung. With the exception of renal cell carcinoma, the remaining cancer sites were significantly associated with elevated risks for processed meat consumption. Furthermore, mortadella, salami, hot dog, ham, and salted meat were strongly associated with risk of several cancer sites. CONCLUSION: It could be concluded that processed meat intake could be a powerful multiorgan carcinogen.

Education, tobacco smoking, alcohol consumption, and IL-2 and IL-6 gene polymorphisms in the survival of head and neck cancer

The association of education, tobacco smoking, alcohol consumption, and interleukin-2 (IL-2 +114 and -384) and -6 (IL-6 -174) DNA polymorphisms with head and neck squamous cell carcinoma (HNSCC) was investigated in a cohort study of 445 subjects. IL-2 and IL-6 genotypes were determined by real-time PCR. Cox regression was used to estimate hazard ratios (HR) and 95 percent confidence intervals (95 percentCI) of disease-specific survival according to anatomical sites of the head and neck. Mean age was 56 years and most patients were males (87.6 percent). Subjects with 5 or more years of schooling had better survival in larynx cancer. Smoking had no effect on HNSCC survival, but alcohol consumption had a statistically significant effect on larynx cancer. IL-2 gene +114 G/T (HR = 0.52; 95 percentCI = 0.15-1.81) and T/T (HR = 0.22; 95 percentCI = 0.02-3.19) genotypes were associated with better survival in hypopharynx cancer. IL-2 +114 G/T was a predictor of poor survival in oral cavity/oropharynx cancer and larynx cancer (HR = 1.32; 95 percentCI = 0.61-2.85). IL-2 -384 G/T was associated with better survival in oral cavity/oropharynx cancer (HR = 0.80; 95 percentCI = 0.45-1.42) and hypopharynx cancer (HR = 0.68; 95 percentCI = 0.21-2.20), but an inverse relationship was observed for larynx cancer. IL-6 -174 G/C was associated with better survival in hypopharynx cancer (HR = 0.68; 95 percentCI = 0.26-1.78) and larynx cancer (HR = 0.93; 95 percentCI = 0.42-2.07), and C/C reduced mortality in larynx cancer. In general, our results are similar to previous reports on the value of education, smoking, alcohol consumption, and IL-2 and IL-6 genetic polymorphisms for the prognosis of HNSCC, but the risks due to these variables are small and estimates imprecise.

Education, tobacco smoking, alcohol consumption, and IL-2 and IL-6 gene polymorphisms in the survival of head and neck cancer.

The association of education, tobacco smoking, alcohol consumption, and interleukin-2 (IL-2 +114 and -384) and -6 (IL-6 -174) DNA polymorphisms with head and neck squamous cell carcinoma (HNSCC) was investigated in a cohort study of 445 subjects. IL-2 and IL-6 genotypes were determined by real-time PCR. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) of disease-specific survival according to anatomical sites of the head and neck. Mean age was 56 years and most patients were males (87.6%). Subjects with 5 or more years of schooling had better survival in larynx cancer. Smoking had no effect on HNSCC survival, but alcohol consumption had a statistically significant effect on larynx cancer. IL-2 gene +114 G/T (HR = 0.52; 95%CI = 0.15-1.81) and T/T (HR = 0.22; 95%CI = 0.02-3.19) genotypes were associated with better survival in hypopharynx cancer. IL-2 +114 G/T was a predictor of poor survival in oral cavity/oropharynx cancer and larynx cancer (HR = 1.32; 95%CI = 0.61-2.85). IL-2 -384 G/T was associated with better survival in oral cavity/oropharynx cancer (HR = 0.80; 95%CI = 0.45-1.42) and hypopharynx cancer (HR = 0.68; 95%CI = 0.21-2.20), but an inverse relationship was observed for larynx cancer. IL-6 -174 G/C was associated with better survival in hypopharynx cancer (HR = 0.68; 95%CI = 0.26-1.78) and larynx cancer (HR = 0.93; 95%CI = 0.42-2.07), and C/C reduced mortality in larynx cancer. In general, our results are similar to previous reports on the value of education, smoking, alcohol consumption, and IL-2 and IL-6 genetic polymorphisms for the prognosis of HNSCC, but the risks due to these variables are small and estimates imprecise.

How much do smoking and alcohol consumption explain socioeconomic inequalities in head and neck cancer risk?

BACKGROUND: A higher burden of head and neck cancer has been reported to affect deprived populations. This study assessed the association between socioeconomic status and head and neck cancer, aiming to explore how this association is related to differences of tobacco and alcohol consumption across socioeconomic strata. METHODS: We conducted a case-control study in São Paulo, Brazil (1998-2006), including 1017 incident cases of oral, pharyngeal and laryngeal cancer, and 951 sex- and age-matched controls. Education and occupation were distal determinants in the hierarchical approach; cumulative exposure to tobacco and alcohol were proximal risk factors. Outcomes of the hierarchical model were compared with fully adjusted ORs. RESULTS: Individuals with lower education (OR 2.27; 95% CI 1.61 to 3.19) and those performing manual labour (OR 1.55; 95% CI 1.26 to 1.92) had a higher risk of disease. However, 54% of the association with lower education and 45% of the association with manual labour were explained by proximal lifestyle exposures, and socioeconomic status remained significantly associated with disease when adjusted for smoking and alcohol consumption. CONCLUSIONS: Socioeconomic differences in head and neck cancer are partially attributable to the distribution of tobacco smoking and alcohol consumption across socioeconomic strata. Additional mediating factors may explain the remaining variation of socioeconomic status on head and neck cancer.

Dietary folate intake and the risk of 11 types of cancer: a case-control study in Uruguay.

BACKGROUND: There is limited, but inconclusive, epidemiological evidence that high folate intake decreases the risk of colorectal and esophageal cancers. For other cancer sites, the evidence is even less consistent or extensive. MATERIALS AND METHODS: We conducted a case-control study of dietary folate intake and risk of 11 cancer sites in Uruguay between 1996 and 2004, including 3539 cancer cases and 2032 hospital controls. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of cancer associated with folate intake. RESULTS: In the multivariable model, there was a significant decrease in the risk of cancers of the oral cavity and pharynx (OR = 0.49, 95% CI 0.24-0.98), esophagus (OR = 0.29, 95% CI 0.14-0.60), upper aerodigestive tract (OR = 0.41, 95% CI 0.26-0.65), colorectum (OR = 0.42, 95% CI 0.23-0.76) and kidney (OR = 0.35, 95% CI 0.13-0.93) for the highest versus the lowest quartile of dietary folate intake. CONCLUSIONS: Our results not only confirm earlier findings of decreased risk of colorectal and esophageal cancers with a high dietary folate intake but also suggest decreased risk of several other cancers. However, we cannot exclude the possibility that residual confounding, multiple comparisons or other forms of bias could explain these results.

Drinking of maté and the risk of cancers of the upper aerodigestive tract in Latin America: a case-control study.

Cancers of the upper aerodigestive tract (UADT: oral cavity, oropharynx, hypopharynx, larynx, esophagus) have high incidence rates all over the world and they are especially frequent in some parts of Latin America. In this study, we have evaluated the role of the consumption of maté, a hot herb-based beverage, based on 1168 UADT squamous-cell carcinoma cases and 1,026 frequency-matched controls enrolled from four centers in Brazil and Argentina. The effect of maté drinking on the risk of head-and-neck cancers was borderline significant. A significant effect was observed only for cancer of the esophagus (OR 3.81 (95% CI 1.75-8.30)). While duration of maté drinking was associated with the risk of all UADT cancers, the association with cumulative maté consumption was restricted to esophageal cancer (p-value of linear trend 0.006). The analyses of temperature at which maté was drunk were not conclusive. The increased risk associated with maté drinking was more evident in never-smokers and never-alcohol drinkers than in other individuals. Our study strengthens the evidence of an association between maté drinking and esophageal cancer; the hypothesis of an association with other UADT cancers remains to be clarified.

TP53 and EGFR mutations in combination with lifestyle risk factors in tumours of the upper aerodigestive tract from South America.

Cancers of the upper aerodigestive tract [(UADT): oral cavity, pharynx, larynx and oesophagus] have high incidence rates in some parts of South America. Alterations in the TP53 gene are common in these cancers. In our study, we have estimated the prevalence and patterns of TP53 mutations (exons 4-10) in 236 UADT tumours from South America in relation to lifestyle risk factors, such as tobacco smoking and alcohol drinking. Moreover, we have conducted a pilot study of EGFR mutations (exons 18-21) in 45 tumours from the same population. TP53 mutation prevalence was high: 59% of tumours were found to carry mutant TP53. We found an association between TP53 mutations and tobacco smoking and alcohol drinking. The mutation rate increased from 38% in never-smokers to 66% in current smokers (P-value for trend = 0.09). G:C>T:A transversions were found only in smokers (15%). Alcohol drinkers carried more G:C>A:T transitions (P = 0.08). Non-exposed individuals were more probable to carry G:C>A:T transitions at CpG sites (P = 0.01 for never-smokers and P < 0.001 for never-drinkers). EGFR mutations were found in 4% of cases. Inactivation of TP53 by mutations is a crucial molecular event in the UADT carcinogenesis and it is closely related to exposure to lifestyle risk factors. EGFR mutations do not appear to be a common event in UADT carcinogenesis in this population.

Food groups and risk of squamous cell carcinoma of the oesophagus: a case-control study in Uruguay.

In the time period January 1998-December 2000, a case-control study on squamous cell cancer of the oesophagus was conducted in Montevideo, Uruguay. The main objective of the study was to estimate the odds ratios (ORs) associated with main food groups. For this purpose, 166 patients afflicted with squamous cell oesophageal cancer and 664 hospitalised controls were frequency matched on age and sex. Both series of patients were administered with a structured questionnaire. Aside from queries related with tobacco smoking, alcohol drinking and maté drinking, patients were interviewed with a food-frequency questionnaire (FFQ) on 64 items, representative of the usual Uruguayan diet. Red meat, salted meat and boiled meat displayed strong direct associations (OR for red meat 2.4, 95% CI 1.4-4.2). On the other hand, fish and total white meat showed moderate protective effect (OR for total white meat 0.5, 95% CI 0.3-0.9). Total fruit intake displayed a strong inverse association (OR 0.2, 95% CI 0.1-0.4), whereas total vegetable consumption presented a weak inverse association (OR for total vegetable intake 0.7, 95% CI 0.4-1.2). These results suggest that vegetables, mainly cooked vegetables, are rich in thermolabile protective substances. On the other hand, boiled (stewed) meat, which is ingested at high temperature could be, like maté, a risk factor for squamous cell cancer of the oesophagus.

Plant foods and differences between colon and rectal cancers.

A case-control study on plant food intake and its role in the risk of colon and rectal cancers was carried out in Montevideo, Uruguay. Four hundred and eighty-four (484) cases of colorectal cancer and 1452 controls were frequency matched on age, sex, residence and urban/rural status. Among cases, 260 patients had colon cancer whereas 224 had rectal tumours. Controls had non-neoplastic conditions. Both cases and controls were interviewed in the four major hospitals in Montevideo shortly after admittance for diagnosis or treatment. The questionnaire included a section on frequency of foods, which included 64 items, in particular, queries on 18 vegetables, 10 fruits and 6 cereal dishes were included. Thus, the amount of plant foods consumed was complete and included the main plant foods in the Uruguayan diet. The analysis showed that rectal cancer displayed inverse associations with total plant foods, total vegetables, cooked vegetables, potatoes and legumes. When data were stratified by tumour site and sex, only men showed a protective effect of plant foods (odds ratio (OR) of rectal cancer for men 0.4, 95% confidence interval (CI) 0.2-0.7). In contrast, women with rectal carcinoma were not associated with plant food intake. It can be concluded that plant foods are protective factors for men afflicted with colorectal cancer but that plant food intake is not associated with risk in women. This is, at least in part, due to the high risk associated with bread intake in this gender.

Foods and risk of bladder cancer: a case-control study in Uruguay.

A case-control study on 144 cases of transitional cell bladder carcinoma and 576 hospitalized controls was conducted in Montevideo, Uruguay. Barbecued meat, salted meat and fried eggs were associated with significant increased risks of bladder cancer (odds ratio (OR) for high intake of salted meat 4.04, 95% confidence interval (CI) 2.24-7.27). On the other hand, all fruits, cooked vegetables, potatoes and cheese were associated with inverse associations (OR for high consumption of potatoes 0.38, 95% CI 0.23-0.64). The associations with salted and barbecued meat suggest that the way of preserving or cooking meat play a role in bladder carcinogenesis. More precisely, N-nitroso compounds and heterocyclic amines could be involved in this process.

Plant foods and risk of gastric cancer: a case-control study in Uruguay.

The association between plant foods intake and gastric cancer risk was investigated in a Uruguayan study on environmental factors and cancer. The study included 160 newly diagnosed and histologically verified cases of gastric carcinoma and 320 hospitalized controls. These controls were frequency-matched to the cases on age, sex, residence and urban/rural status. Total vegetable intake was associated with a reduction in risk (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.38-1.08), which was markedly attenuated after adjustment for total fruit intake. The only group of vegetables that persisted as significantly protective after controlling for total energy and total fruit consumption were allium vegetables (OR 0.56, 95% CI 0.34-0.92). On the other hand, total fruit consumption displayed a strong inverse association after controlling for total vegetable intake (OR 0.35, 95% CI 0.21-0.59). Neither tubers nor pulses were associated with gastric cancer risk. Finally, total plant foods were strongly associated with a reduced risk of stomach cancer (OR 0.31, 95% CI 0.18-0.54). It is suggested that vitamins (vitamin C and carotenoids) and bioactive substances (diallyl sulfide) could be involved in the mechanisms of action of plant foods.

Meat, fat and risk of laryngeal cancer: a case-control study in Uruguay.

The effect of meat and fat in laryngeal carcinogenesis was examined in a case-control study carried out in Uruguay in the time period 1998-1999. One-hundred and forty patients with squamous cell laryngeal carcinoma and 420 hospitalized patients, afflicted with conditions not related with tobacco smoking, alcohol drinking or recent dietary changes comprised the cases and controls in this study. All patients were interviewed face-to-face in the hospitals with a detailed questionnaire which included queries on 64 food items. Red and total meat intakes were associated with strong increases in risk of laryngeal cancer (odds ratio [OR] for high total meat intake 3.32, 95% confidence interval [C.I.] 1.23-8.95). This effect disappeared after controlling for total fat intake. On the other hand, total fat intake displayed a strong association with risk of laryngeal cancer when red meat was included in the same model (OR for high fat intake 7.05, 95% C.I. 2.51-19.8). Total fat intake combines its effect multiplicatively with tobacco smoking.

Meat consumption and risk of stomach cancer in Uruguay: a case-control study.

We previously reported an association between meat intake and stomach cancer in Uruguay: in that analysis, we did not control for total energy intake. To better study the relationship between intake of meat and meat constituents and gastric cancer, we conducted a further case-control study including 123 cases and 282 controls who were enrolled between September 1997 and August 1999. Total meat intake (highest tertile) was associated with an odds ratio (OR) of 4.6 [95% confidence interval (CI) = 2.3-9.0]. After adjustment for total energy intake and intake of proteins and total fat by the residuals method, the OR was 1.7 (95% CI = 0.7-4.0). The energy-adjusted OR for high intake of processed meat was 1.9 (95% CI = 1.1-3.5). Intake of fried, barbecued, and salted meat and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine was not associated with risk of gastric cancer. The energy-adjusted OR of high intake of nitrosodimethylamine was 1.5 (95% CI = 0.9-2.8). These results suggest that, in a country with elevated meat consumption, total energy intake and intake of proteins and fat are powerful confounders in the relationship between meat intake and gastric cancer risk. However, a modest independent effect of meat, in particular of processed meat, is suggested.

Dietary carotenoids and risk of gastric cancer: a case-control study in Uruguay.

In the period 1997-1999, 120 incident and histologically verified cases of stomach cancer were frequency matched on age, sex, residence and urban/rural status with 360 controls in order to study the role of diet in gastric cancer in Uruguay. Our attention was focused on the role of carotenoids in gastric carcinogenesis, after controlling for major confounders. According to the results, vitamin A, alpha-carotene and lycopene were associated with strong inverse relationships with stomach cancer (OR of stomach cancer for high alpha-carotene intake 0.34, 95% CI 0.17-0.65). Joint exposure to high intakes of alpha-carotene and vitamin C intakes were associated with a strong reduction in risk (OR 0.11, 95% CI 0.03-0.36). It was also suggested that high lycopene intake explained most of the reduction in risk of gastric cancer associated with vegetable intake, whereas no such effect was observed for fruit intake.

Lung cancer risk in nonsmokers and GSTM1 and GSTT1 genetic polymorphism.

Glutathione S-transferase (GST) polymorphism may contribute to the individual variability in detoxifying lung carcinogens. This effect might be particularly relevant at low-level exposure to environmental carcinogens, such as in nonsmokers exposed to environmental tobacco smoke (ETS). We conducted a case-control study among 122 nonsmoking lung cancer cases and 121 nonsmoking controls from eight countries. Information on environmental exposures was obtained through a personal interview. The presence of GSTM1 and GSTT1 genes was determined using multiplex PCR. GSTM1-positive samples were then analyzed for *1A and *1B polymorphism using an allele-specific amplification-PCR method. GSTM1*2 (null) individuals had an odds ratio (OR) of lung cancer of 1.5 [95% confidence interval (CI), 0.9-2.7]; the risk associated with this genotype was higher for cases with squamous and small cell carcinomas (OR, 2.3; 95% CI, 0.9-6.1) than for cases with adenocarcinomas. It was also elevated in individuals with long-term exposure to indoor wood combustion (OR, 3.1; 95% CI, 0.9-9.9), in subjects who mainly lived in a rural setting (OR, 3.6; 95% CI, 1.0-13), and in cases exposed to occupational carcinogens (OR, 10.7; 96% CI, 0.4-260) but not in subjects exposed to ETS. GSTT1*2 subjects did not show a risk of lung cancer. Our study suggests that the effect of GSTM1 polymorphism in nonsmokers is similar to that found in smokers. It does not seem to interact with ETS exposure, although we cannot exclude that it does in association with exposure to other specific environmental carcinogens.

Tomatoes, tomato-rich foods, lycopene and cancer of the upper aerodigestive tract: a case-control in Uruguay.

In order to study the relationship between tomatoes, tomato products, lycopene and cancers of the upper aerodigestive tract (UADC; oral cavity, pharynx, larynx, esophagus) a case-control study was carried out in Uruguay, in the time period 1996-98. Two-hundred and thirty eight cases and 491 hospitalized controls were frequency matched on age, sex, residence and urban/rural status. Both series were submitted to a detailed questionnaire, including tobacco smoking, alcohol drinking and queries on 64 food items. These data were analyzed by unconditional logistic regression, after adjusting by total energy intake. Tomato intake was associated with a reduction in risk of 0.30 (95% confidence interval [CI], 0.18-0.51), whereas tomato sauce-rich foods displayed a protective effect of 0.57 (95% CI, 0.33-0.96 for the highest quartile of intake). The food group composed of raw tomato and tomato-rich foods showed a strong inverse association with UADC (odds ratio [OR], 0.23; 95% CI, 0.13-0.39 for the highest quartile of intake). Lycopene was also strongly associated with a reduced risk of 0.22 (95% CI, 0.13-0.37). Adjustment of tomato intake for several phytochemicals explained almost completely its protective effect, which disappears in this model. Finally, the joint effect of lycopene and total phytosterols was associated with a significant reduction in risk (OR, 0.11; 95% CI, 0.05-0.23).

Plant foods and risk of laryngeal cancer: A case-control study in Uruguay.

In order to examine the relationships between plant foods, defined as the grouping of vegetables, fruits, tubers and legumes, with the risk of developing laryngeal cancer, a case-control study was conducted in Uruguay between 1998-1999. The study included 148 cases with histologically verified squamous cell carcinoma of the larynx, which were frequency matched on age, residence and urban/rural status with 444 hospitalized controls, afflicted by non-neoplastic conditions. Both series of patients were face-to-face interviewed in the hospitals shortly after admittance using a detailed questionnaire. This questionnaire included 62 queries on food items, representative of the usual diet of the Uruguayan population. Food items and food groups were adjusted for tobacco smoking, alcohol drinking and total energy intake. High consumption of plant foods was associated with an OR of 0.42 (95% CI 0.21-0.84). Among subgroups of plant foods, fruits and raw vegetables were associated with a strong reduction in risk (OR for the highest quartile of raw vegetables 0.29, 95% CI 0.15-0.56). Also, legumes were associated with a protective effect (OR 0.62, 95% CI 0.33-1.19). Among individual food items, tomatoes and oranges were associated with the stronger protective effects (OR for tomato intake 0.32, 95% CI 0. 17-0.58). The joint effect of heavy smoking and the low intake of vegetables and fruits displayed an increased risk of 19.2 (95% CI 5. 7-64.9).

Occupational exposures and lung cancer in Buenos Aires, Argentina.

The main objective of this study was to analyze the risks associated with occupational exposures in an industrializing country where lung cancer is the primary neoplastic cause of death in men. A full occupational history was collected through interviewing 199 men with lung cancer and 393 control subjects. Exposure to arsenic, asbestos, chromium, dust, nickel, and polynuclear aromatic hydrocarbons was assessed by means of a job-exposure matrix. Elevated odds ratios were observed for employment in the alcoholic beverages industry (5.2; 95% confidence interval [CI], 1.1 to 23.1), sawmills and wood mills (4.8; 95% CI, 1.2 to 19.0), water transport (3.3; 95% CI, 1.1 to 12.1), and chemicals/plastics manufacturers (1.9; 95% CI, 1.1 to 3.3). A small, non-significant increased risk was observed after long-term exposure to arsenic and chromium, with a dose-response for chromium. Although some of the present results may result from chance, most are consistent with those of previous investigations in other countries.