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.

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.

The safety profile of probiotic VSL#3®. A meta-analysis of safety data from double-blind, randomized, placebo-controlled clinical trials.

The article "The safety profile of probiotic VSL#3®. A meta-analysis of safety data from double-blind, randomized, placebo-controlled clinical trials", by V. Panetta, A. Bacchieri, S. Papetti, E. De Stefani, P. Navarra, published in Eur Rev Med Pharmacol Sci 2020; 24 (2): 963-973-DOI: 10.26355/eurrev_202001_20082-PMID: 32017005, has been retracted based on commentary received from a new set of reviewers.  The authors will be able to resubmit a new article addressing the reviewers' comments for the Journal's consideration. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20082.

The safety profile of probiotic VSL#3®. A meta-analysis of safety data from double-blind, randomized, placebo-controlled clinical trials.

OBJECTIVE: A high-concentration of a multi-strain probiotic mixture, VSL#3® is widely used 'whenever it is useful to promote the balance of intestinal flora'. As a food supplement, VSL#3® has been so far scarcely investigated on the aspect of safety. To fill this gap, in this paper, we analyzed the adverse events (AEs) recorded during the conduct of three (3) double-blind, randomized, placebo-controlled trials carried out to explore the efficacy of VSL#3® in various clinical settings. Data from a large open-label observational trial were also considered. MATERIALS AND METHODS: All trials included in the analysis were carried out according to good clinical practice (GCP) rules. AEs were classified by System Organ Class (SOC), Preferred Term (PT) and frequency. Differences vs. placebo control were considered as statistically significant if the p-value was < 0.05. RESULTS: A total of 120 patients were analyzed, 70 patients being included in the randomized controlled trials. In this population, 45 patients had at least one AE, 20 (64.5%) in the placebo group and 25 (64.1%) in the VSL#3® group. 29 patients had at least one related AE, 14 (45.2%) and 15 (38.5%) in the two treatment groups, respectively. Only one AE was assessed as serious, i.e., Foetal malformation, which occurred in the placebo group and was considered unrelated. No significant difference was found between VSL#3® and placebo for any of the SOC considered, with the exception of Injury, poisoning and procedural complications, which was in favor of VSL#3®. CONCLUSIONS: Based on GCP-quality data from clinical trials, we conclude that VSL#3® is a safe and well-tolerated agent.

Hot infusions and risk of colorectal cancer in Uruguay: a case-control study.

BACKGROUND/OBJECTIVES: The evidence of possible roles for the most common hot infusions intake (tea and coffee) in the risk of colorectal cancer (CRC) needs additional data. Regarding 'mate' intake (infusion of Ilex paraguariensis herb), a previous multi-site study reported lack of association for its highest intake on CRC risk. The present study was conducted to better understand the associations between the intake of this and other infusions and CRC risk. SUBJECTS/METHODS: Patients (611 CRC incident cases and 2394 controls, all belonging to public hospitals) were interviewed through a questionnaire, including socio-demographic, reproductive and lifestyle variables, and a food-frequency questionnaire of 64 items, analyzing tea, 'mate' and coffee intake (consumer status, daily intake, age at start and at quit). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated through unconditional logistic regression, adjusting for relevant potential confounders. RESULTS: Tea and coffee intake displayed significant and inverse associations with CRC risk, mainly among men (OR=0.54, 95% CI 0.38-0.76 for tea and OR=0.59, 95% CI 0.41-0.85 for coffee). Mate intake showed a significant inverse association among women (OR=0.50, 95% CI 0.33-0.77), with a marginal heterogeneity between sexes (P=0.07). Concerning age strata, tea intake displayed inverse associations in all ages, whereas 'mate' and coffee intake showed stronger inverse associations for age ⩾70, suggesting a gradient along time. CONCLUSIONS: We found evidence of different significant inverse associations for tea, 'mate' and coffee intake and CRC risk. To our knowledge, this is the first epidemiologic study reporting inverse results on 'mate' intake and CRC, which are explained by a stronger association among women.European Journal of Clinical Nutrition advance online publication, 23 August 2017; doi:10.1038/ejcn.2017.130.

Esophageal cancer in Uruguay: a case-control study.

Esophageal cancer has constituted a major public health problem in Uruguay, with age-adjusted death rates of 14.5 X 10(5) for males and of 3.8 X 10(5) for females. A case-control study was undertaken to ascertain the possible association of the local custom of drinking infusions of Ilex paraguariensis ("maté") with cancer of the esophagus, after controlling for well-known risk factors, such as alcohol and tobacco consumption. Two hundred twenty-six patients with esophageal cancer and 469 controls (control:case = 2.1) were interviewed at the time of admission or consultation at the Oncology Institute of Montevideo from 1979 through 1984. Males showed elevated risks of esophageal cancer associated with heavy tobacco [relative risk (RR) = 10.8] and alcohol (RR = 10.3) exposures. Among females, the independent effects of tobacco and alcohol were nonsignificant. Maté consumption had an independent effect in both males and females, with odds ratios of 6.5 and 34.6, respectively, for heavy users. Moreover, a well-defined dose response was evident in both sexes.

Mate drinking, alcohol, tobacco, diet, and esophageal cancer in Uruguay.

A case-control study was conducted in Uruguay to investigate the role of mate drinking, alcohol, tobacco, and certain dietary factors in the etiology of esophageal cancer. The study included 261 patients with squamous cell carcinoma of the esophagus and 522 hospital controls matched by sex and age. A strong association with a clear dose-response relationship was observed with the amount of mate drunk daily and duration of the habit. The relative risk for those drinking over 2.5 liters of mate per day was 12.2 (95% confidence interval, 3.8-39.6) after adjusting for the effects of age, area of residence, alcohol, and tobacco. Strong associations were also observed with tobacco smoking and alcohol drinking which appear to act in a multiplicative way. The relative risk for those who smoke and drink heavily compared to that of light smokers and drinkers was 22.6. The risk associated with black tobacco was about three times higher than that associated with blond tobacco. A clear protective effect was found for the consumption of fruits and vegetables but a dose-response relationship was present only for fruits. Finally, an increased risk was also found for those eating barbecued meat daily.

Salted meat consumption as a risk factor for cancer of the oral cavity and pharynx: a case-control study from Uruguay.

A hospital-based, case-control study of oropharyngeal cancer was conducted in the Oncology Institute, Montevideo, Uruguay, during 1988-1992, in which 246 new cases and 253 controls were interviewed. The study was restricted to males. As in most previous studies, tobacco smoking and alcohol drinking were the major risk factors. Past and current salted meat consumption was associated with increased risks of oropharyngeal cancer after controlling for the effects of tobacco and alcohol; current consumption was associated with a significant increase in risk (odds ratio, 2.3; 95% confidence interval, 1.1-5.2). Current heavy consumption of salted meat was associated with a significant 4.7% increased risk of oropharyngeal cancer after adjusting for tobacco smoking and alcohol drinking. These findings suggest that current consumption of salted meat is more relevant to the etiology of this set of neoplasms than past consumption. Furthermore, the joint effect of pack-years of cigarette smoking, alcohol drinking, and ever consumption of salted meat was associated with a high risk of oral and pharyngeal cancer (odds ratio, 10.0; 95% confidence interval, 4.7-21.3) using the referent category of moderate smokers, moderate drinkers, and never users of salted meat.

Dietary nitrosodimethylamine and the risk of lung cancer: a case-control study from Uruguay.

Evidence from animal studies indicates that various N-nitroso compounds are carcinogenic. We investigated whether consumption of nitrosodimethylamine (NDMA) and foods and beverages containing NDMA are carcinogenic for the lung. In a hospital-based case-control study in Uruguay, dietary intake of NDMA and its food sources was measured in 320 cases of lung cancer and 320 controls afflicted with diseases not related with tobacco use and diet. After adjusting for tobacco smoking and total energy intake, NDMA displayed a significant dose-response pattern, with a 3-fold increase in risk for the higher category of intake. The risks were slightly more elevated for adenocarcinoma of the lung. Also, salted meat consumption and beer intake were associated with an increased risk of lung cancer.

Meat intake, heterocyclic amines, and risk of breast cancer: a case-control study in Uruguay.

To study the effects of meat intake, including heterocyclic amine exposure, on the risk of breast cancer, we conducted a hospital-based case-control study involving 352 patients with breast cancer and 382 controls. A strong effect of red meat, total meat, beef, fried meat, and heterocyclic amine exposure was found, after controlling for potential confounders. The odds ratio for the highest quartile of 2-amino-3-methylimidazo [4,5-f]quinoline exposure was 3.34 (95% confidence interval 1.85-6.02). According to these results, meat intake and chemicals formed during the cooking process appear to be strong risk factors in human breast carcinogenesis.

Alpha-linolenic acid and risk of prostate cancer: a case-control study in Uruguay.

In the time period of 1994-1998, a case-control study on diet and prostate cancer was carried out in Uruguay to examine the risk associated with fat intake. Two hundred and seventeen (217) incident cases afflicted with advanced prostate cancer were frequency-matched with 431 controls on age, residence, and urban/rural status. The analysis was carried out using unconditional multiple logistic regression. Alpha-linolenic acid was associated with a strong positive association (fourth quartile of intake odds ratio, 3.91; 95% confidence interval, 1.50-10.1) after controlling for total calorie intake and for the other types of fat. The effect was similar when alpha-linolenic acid was analyzed by its sources of origin (odds ratio for vegetable linolenic acid, 2.03; 95% confidence interval, 1.01-4.07). Including this report, five of six studies that have examined the relationship between alpha-linolenic acid and prostate cancer yielded a positive association, which was significant in four studies. Thus, there appears to be evidence of a role of alpha-linolenic acid in prostate carcinogenesis.

The effect of alcohol on the risk of lung cancer in Uruguay.

A hospital-based case-control study of the association between alcohol drinking and lung cancer was carried out in Uruguay between January 1988 and December 1990. The sample included 327 men with lung cancer and 350 male controls. Personal interviews were conducted in the Institute of Oncology by trained personnel using a structured questionnaire. The results showed a significant positive association between beer intake and the risk of lung cancer. The odds ratio for beer drinkers in the highest quartile was 3.4 (95% confidence limits, 1.3-6.6) after adjustment for tobacco. The association between beer and lung cancer was consistent for all the cell types, analyzed separately. A moderate effect for total alcohol consumption was also observed, with a relative risk of 2.2 for those subjects in the highest quartile.

Mate drinking and risk of lung cancer in males: a case-control study from Uruguay.

During the period from January 1988 to December 1994, a case-control study that included 497 cases of lung cancer and 497 controls was carried out at the Instituto de Oncologia, Montevideo, Uruguay, to evaluate the relationship between the drinking of mate (a local tea prepared with infusions of the herb Ilex paraguariensis) and the risk of lung cancer in men. Mate drinking has been associated with risk of most upper-aerodigestive tract cancers. After adjusting for major covariates, including pack-years of cigarette smoking, the amount of mate was associated with a 1.6-fold increase in risk for heavy drinkers, compared with light drinkers, with a significant dose-response pattern. When the analysis was performed by cell type, small cell lung cancer showed a significant increase in relative risk for mate amount (odds ratio, 2.9; 95% confidence interval, 1.3-6.2) and mate duration (odds ratio, 3.6; 95% confidence interval, 1.3-9.9). On the other hand, pulmonary adenocarcinoma was not associated with mate drinking. Possible reasons for these results are discussed, and areas for future research are suggested.

Black (air-cured) and blond (flue-cured) tobacco and cancer risk. III: Oesophageal cancer.

Relative risks of oesophageal cancer for smoking were higher in communities smoking mainly black tobacco, when compared with results from populations comprising mainly users of blond tobacco. Also, hand-rolled cigarette smoking, which could be considered as a proxy indicator of black tobacco smoking, was also associated with higher risk of oesophageal cancer, in comparison with the use of commercial (manufactured) cigarettes. Finally, the use of pipes and cigars showed odds ratios of higher magnitude than those associated with cigarettes. This indirect evidence of a higher risk of oesophageal cancer due to the use of black products was confirmed in three recent hospital-based case-control studies. These investigations were able to compare the effect of both types of tobacco; relative risks for black tobacco were two to three times higher than risks associated with blond tobacco smoking, after controlling for major potential confounders. Laboratory evidence suggests that swallowing tobacco condensates could be a major risk factor for oesophageal cancer. Also, the higher content of tobacco-specific N-nitroso compounds in black tobacco, including organospecific substances, could explain its higher carcinogenic effect on the oesophageal mucosa.

Tobacco, alcohol, diet and risk of non-Hodgkin's lymphoma: a case-control study in Uruguay.

To test whether high meat intake is associated with the development of non-Hodgkin lymphoma (NHL) in the Uruguayan population, a case-control study was performed at the Instituto Nacional de Oncologia, Montevideo, Uruguay. After controlling for age, sex, residence, education, urban/rural status and the habit of drinking the beverage 'mate', red meat intake was associated with an increased risk of NHL of 2.5. This finding was similar in both sexes separately. Odds ratios (OR) for the highest tertile of barbecued meat was 1.7 among men, whereas salted meat was associated with an increased risk of NHL (OR 4.9, 95% CI 1.4-17.7). The effect of processed and salted meat among women was of much less magnitude and the OR's were non-significant. Also, cumulative exposure to 'mate' drinking displayed an OR of 2.4 (95% CI 1.0-5.6). Smokers of black tobacco and hand-rolled cigarettes were associated with an increased risk of 3.5 (95% 1.1-10.9), whereas beer drinkers showed an increased OR of 5.5 (95% 1.1-26.7) in men. It could be concluded that red or salted meat intake, smoking of black tobacco, and beer and 'mate' drinking are risk factors for NHL in the Uruguayan population.

Phytosterols and risk of lung cancer: a case-control study in Uruguay.

Plant sterols are substances present in vegetable oils, corn and some fruits. According to previous studies, phytosterols are protective in colon carcinogenesis. This case-control study was carried out in order to establish a possible protective role of plant sterols in lung carcinogenesis. The study was performed in Montevideo, Uruguay, during 1993-1996, and included 463 cases with lung cancer and 465 hospitalized controls. Total plant sterol intake was associated with a reduction in risk of 50% when contrasting the upper exposure quartile with the lower, after controlling for major confounders, including tobacco smoking and total energy intake. This protective effect was specially evident in adenocarcinoma of the lung (OR 0.29, 95% CI 0.14-0.63). Therefore, plant sterol intake appears to be an important variable in lung carcinogenesis. Further studies are needed in order to replicate the present findings.

Smoking of hand-rolled cigarettes as a risk factor for small cell lung cancer in men: a case-control study from Uruguay.

During the time period January 1989-December 1992, a case-control study involving 476 cases of lung cancer and 561 controls was carried out at the Instituto Nacional de Oncología, Montevideo, Uruguay, in order to analyze the patterns of risk of the different cell types of lung cancer, associated with smoking manufactured and hand-rolled cigarettes. Lifelong smokers of hand-rolled cigarettes displayed a non-significant 30% increased risk, compared with smokers of commercial cigarettes, for all types of lung cancer combined. The analysis for cell-type disclosed a fourfold increase in the risk of small cell lung carcinoma associated with lifelong smoking of hand-rolled products. The possibilities of a chance finding and of misclassification of the disease appears to be an unlikely explanation of this strong and rather specific association.

Consumption of tea and coffee and the risk of lung cancer in cigarette-smoking men: a case-control study in Uruguay.

This study investigated the effect of drinking tea or coffee on the lung cancer risk of male cigarette smokers in a case-control in Uruguay. Four hundred and twenty-seven lung cancer cases were frequency matched on age and residence with 428 hospitalized controls suffering from conditions unrelated to tobacco smoking and diet. Whereas coffee drinking had no effect on the lung cancer risk of the cigarette-smoking men in this study, black tea consumption decreased this risk. Heavy drinkers of tea (two or more cups of tea per day) were associated with a reduced risk of 0.34 (95% CI 0.14-0.84). This protective effect was more evident among Kreyberg I tumors (squamous cell and small cell) and among light smokers. Possible sources of bias and mechanisms of action are discussed.

Meat consumption and risk of lung cancer; a case-control study from Uruguay.

A case-control study was conducted at the Instituto Nacional de Oncologia, Uruguay, in order to investigate the relationship between meat consumption and lung cancer risk. The study included 256 cases of lung cancer and 284 controls, frequency matched with the cases on age, residence and urban/rural condition. A significant increase in risk of lung cancer associated with red meat, beef and fried meat was observed. The increase in risk was more evident in squamous cell lung cancer. This association remained after controlling for total energy and saturated fat intake, suggesting a possible role of heterocyclic amines in lung carcinogenesis.

Dairy foods and risk of breast cancer: a case-control study in Montevideo, Uruguay.

In order to investigate possible associations of milk and dairy products and the risk of breast cancer (BC) in Montevideo, the authors performed a case-control study in the period 1999-2001. A total of 333 women were interviewed with a specific questionnaire; 111 of them had been diagnosed with BC and 222 were frequency-matched healthy women, with a recent normal mammography (BIRADS 1). The questionnaire included a detailed 120-item food-frequency section, as well as questions related to socio-demographic, reproductive, familial, medical and lifestyle variables. There was particular emphasis on types of milk and dairy products. After controlling for age, years of urban status, education, body mass index, age at menarche, menopausal status, family history of BC, number of childbirths, total energy and total fruits, a multivariate analysis found that high intakes of whole milk, chocolate milk and Gruyère cheese were associated with significant increased risk of BC, whereas ricotta cheese and skim yoghurt were associated with significant decreased risks. Low-fat and fermented products combined appear to be the most protective dairy foods. The results suggest that separate analyses for types of milk and cheese, as well as for dairy products in general should be performed in the future.