BACKGROUND: In order to determine the role of meat consumption and related nutrients in the etiology of prostate cancer we conducted a case-control study among Uruguayan men in the time period 1998-2007.
RESULTS: The study included 464 cases and 472 controls, frequency matched for age and residence. Both series were drawn from the four major public hospitals in Montevideo. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (95 % CI) of prostate cancer by quartiles of meat intake and related nutrients. The highest vs. the lowest quartile of intake of total meat (OR = 5.19, 95 % CI 3.46-7.81), red meat (OR = 4.64, 95 % CI 3.10-6.95), and processed meat (OR = 1.78, 95% CI 1.22-2.59) were associated with increased risk of prostate cancer. Meat nutrients were directly associated with the risk of prostate cancer (OR for cholesterol 5.61, 95 % CI 3.75-8.50). Moreover, both total meat and red meat displayed higher risks among obese patients.
CONCLUSIONS: This study suggests that total and red meat and meat nutrients may play a role in the etiology of prostate cancer in Uruguay.

Regarding 'mate' intake (infusion of Ilex paraguariensis herb, a staple beverage in temperate South American regions), most epidemiologic studies showed positive associations with risk of some cancers, (e.g. upper aerodigestive tract), but evidence on breast cancer (BC) risk is limited to a previous multi-site study, which reported a non significant odds ratio [OR]=0.85, 95% confidence interval [95% CI] 0.67-1.09, p for trend=0.31) for the highest quartile of intake. The present study was conducted in order to further assess associations of 'mate' intake with BC risk. We combined two databases of women belonging to public and private healthcare hospitals. The sample included 572 BC incident cases and 889 controls interviewed with a specific questionnaire featured by socio-demographic, reproductive and lifestyle variables, and a food frequency questionnaire of 64 items, also analyzing 'mate' intake (consumer status, daily intake, age at start, age at quit, duration of habit, intensity of intake). ORs and their 95%CI were calculated through unconditional logistic regression, adjusting for relevant potential confounders. The highest quartile of 'mate' intake was inversely associated with BC risk (OR=0.40, 95%CI 0.26-0.57, p for trend <0.001). Stratified analyses also displayed strong significant inverse associations for 'mate' in frequent tea drinkers (OR=0.22), high energy intake (OR=0.23), high body mass index (OR=0.29) and in postmenopausal women (OR=0.36), among other results. As conclusions, we found evidence of a significant inverse association for 'mate' intake and BC risk.

The aim of this study was to evaluate the demographic, clinical, and therapeutic characteristics and predictive factors of poor prognosis in patients with primary oral squamous cell carcinoma (OSCC) in Uruguay. Medical records of patients with the diagnosis of primary OSCC treated between 2000 and 2010 in Uruguayan public hospitals were selected. Data on demographic characteristics, risk factors, clinical features, treatment, and outcome were collected. Associations of independent variables with outcomes were assessed using Pearson chi-squared and Fisher's tests. Of 200 patients with OSCC, 79.4% were men (3.8:1 male:female ratio), with a mean age of 60.75 ± 11.26 years. Tobacco and alcohol consumption were reported by 85.3% and 63.5% of patients, respectively. The most commonly affected location was the tongue (42.5%), with lesions exhibiting ulcerous aspects in 87.9% of cases and pain at the time of diagnosis in 70.4% of cases. One hundred sixty-one (82.1%) patients had advanced-stage (III/IV) OSCC. Surgery was the most common treatment option, and the overall 5-year survival rate was 58.5%. Univariate analysis showed that the predictors of poor prognosis were clinical aspect, size, regional metastasis, clinical stage, and treatment. In Uruguay, OSCC is diagnosed late, which is associated with a low survival rate. Educational and preventive measures and investment to improve early diagnosis should be undertaken.

BACKGROUND: Uruguay exhibits one of the highest rates of breast cancer in Latin America, similar to those of developed nations, the reasons for which are not completely understood. In this study we investigated the effect that ancestral background has on breast cancer susceptibility among Uruguayan women.
METHODS: We carried out a case-control study of 328 (164 cases, 164 controls) women enrolled in public hospitals and private clinics across the country. We estimated ancestral proportions using a panel of nuclear and mitochondrial ancestry informative markers (AIMs) and tested their association with breast cancer risk.
RESULTS: Nuclear individual ancestry in cases was (mean ± SD) 9.8 ± 7.6% African, 13.2 ± 10.2% Native American and 77.1 ± 13.1% European, and in controls 9.1 ± 7.5% African, 14.7 ± 11.2% Native American and 76.2 ± 14.2% European. There was no evidence of a difference in nuclear or mitochondrial ancestry between cases and controls. However, European mitochondrial haplogroup H was associated with breast cancer (OR = 2.0; 95% CI 1.1, 3.5).
CONCLUSIONS: We have not found evidence that overall genetic ancestry differs between breast cancer patients and controls in Uruguay but we detected an association of the disease with a European mitochondrial lineage, which warrants further investigation.

In the period 1995-2004, a hospital-based case-control study on meat consumption and squamous cell carcinoma of the lung in men was conducted in Montevideo, Uruguay. The study included 300 cases and 600 controls, frequency matched on age and residence. The results showed that total meat [odds ratio (OR) = 1.72, 95% confidence interval (CI): 1.05-2.81, P value for trend = 0.03], red meat (OR = 1.82, 95% CI: 1.13-2.91, P value for trend = 0.01), beef consumption (OR = 2.22, 95% CI: 1.42-3.45, P value for trend = 0.0004), bacon (OR = 1.50, 95% CI: 1.00-2.24, P value for trend = 0.03), saucisson (OR = 1.69, 95% CI: 1.07-2.67, P value for trend = 0.01), and salted meat intake (OR = 2.70, 95% CI: 1.63-4.46, P value for trend = 0.0001) were positively associated with squamous cell lung cancer. These results are discussed and we suggest that meat consumption could be considered as a strong risk factor for squamous cell lung cancer.

BACKGROUND: The role of processed meat in the aetiology of squamous cell oesophageal cancer has been explored in detail.
METHODS: In the time period 1990-2005, a case-control study was conducted in Montevideo, Uruguay including 2,368 participants (876 cases of oesophageal cancer and 1,492 controls). Relative risks, approximated by the odds ratios, were estimated by multiple unconditional logistic regression.
RESULTS: Processed meat was positively associated with oesophageal cancer (upper quartile vs lower quartile OR 2.30, 95%CI 1.72-3.07), whereas salted meat intake was positively associated with squamous cell oesophageal cancer (OR 3.82, 95%CI 2.74-5.33). Finally other cured meats were positively associated with oesophageal cancer (OR 1.65, 95%CI 1.22- 2.22).
CONCLUSIONS: It could be concluded that processed meat consumption could be an important risk factor for the aetiology of squamous cell oesophageal cancer in Uruguay.

In the time period 1996-2004, all incident cases of bladder cancer were included in a case-control study in order to study the role of meat consumption and product animals in the etiology of urothelial cancer. The study included 225 cases and 1,510 hospitalized controls with non-neoplastic conditions, not related to smoking and alcohol drinking. Relative risks, approximated by the odds ratios, were calculated in order to clarify the effect of meat consumption in the etiology of urothelial cancer. Total meat consumption (OR 1.47, 95% CI 1.02-2.11), total processed meat (OR 1.57, 95% CI 1.08-2.27), frankfurters (hot dogs) (OR 2.03, 95% CI 1.28-3.21), ham (OR 1.79, 95% CI 1.21-2.67) and salted meat (OR 2.73, 95% CI 1.78-4.18) were positively associated with risk of bladder cancer. Animal products, like cheese, whole milk, and total eggs were also associated with bladder cancer risk (OR for eggs 4.05, 95% CI 2.68-6.12). In conclusion, total meat, processed meat, and eggs could play an important role in the etiology of bladder cancer in Uruguay.

BACKGROUND: Oesophageal cancer presents high incidence rates in the so-called Brazilian-Uruguayan belt.
MATERIALS AND METHODS: The present study included 1,170 participants (234 cases and 936 controls) which were analyzed by unconditional multiple logistic regression in order to examine risk of oesophageal squamous cell carcinoma (OESCC) associated with several food groups.
RESULTS: Boiled red meat (OR 2.59, 95%CI 1.69-3.97), lamb meat (OR 1.64, 95%CI 1.07-2.51), processed meat (OR 1.49, 95%CI 1.01-2.21), whole milk (OR 1.78, 1.19-1.68), fresh vegetables and fruits (OR 0.42, 95%CI 0.27-0.63), mate consumption (OR 2.04, 95%CI 1.32- 3.16), and black tea (OR 0.10, 95%CI 0.04-0.28) were significantly associated with risk of OESCC.
CONCLUSIONS: Hot beverages (mate) and hot foods (boiled meat) appear to be important determinants in the risk of OESCC, allowing the penetration of carcinogens in tobacco and alcohol into the oesophageal mucosa.

AIM: To assess whether the use of porcine models is useful for learning endoscopic submucosal dissection (ESD), thus contributing to its subsequent application in human patients.
METHODS: This study/learning process was carried out in 3 phases: Phase I: Ex vivo animal; Phase II: In vivo animal; Phase III: Humans. One endoscopist performed 30 gastric ESDs in porcine models, and later 5 gastric ESDs in 5 patients. The ESD was done following the method practiced at the National Cancer Center in Tokyo, Japan. Technical aspects, size, time and speed of ESD, as well as complications were registered. In patients, their clinical, endoscopic and histologic evolution was additionally added.
RESULTS: Thirty en bloc ESDs were carried out in animal models. The mean ± SD size of the pieces was of 28.4 ± 1.2 mm, and the time of ESD was 41.7 ± 2.4 min. The time of ESD in the first 15 procedures was 43.0 ± 3.0 min whereas in the next 15 procedures, the time was 40.3 ± 3.9 min, P = 0.588. The speed in the first 15 ESDs was 1.25 ± 0.11 cm(2)/min vs 2.12 ± 0.36 cm(2)/min in the remaining 15, P = 0.028. There were no complications. In patients, 5 lesions were resected en bloc. The size of the pieces was 25.2 ± 5.1 mm and the time was 85.0 ± 25.6 min. Endoscopic and histological controls did not show evidence of residual neoplastic tissue.
CONCLUSION: A sequential ESD training program of a unique endoscopist, based on the practice in porcine models, contributed to learning ESD for its subsequent application in humans, yielding good results in efficacy and safety.

CONTEXT: Several instruments have been developed to assess the symptom burden and fatigue produced by cancer and its treatment. However, little research has been conducted in Latin American Spanish-speaking patients.
OBJECTIVES: The aim of the study was to assess the psychometric properties of the Spanish versions of two commonly used patient-reported outcome measures, the Memorial Symptom Assessment Scale-Short Form (MSAS-SF), and the fatigue subscale of the Functional Assessment of Cancer Therapy-General (FACT-G), the FACIT-Fatigue.
METHODS: A classic psychometric approach was followed to assess the reliability and validity of the instruments. Responsiveness to change and effect sizes were calculated.
RESULTS: The translated version of the MSAS-SF proved to be comprehensible and easy to complete. Cronbach alpha reliability coefficients ranged from acceptable to excellent for the MSAS-SF subscale scores and the FACIT-Fatigue. There was evidence of convergent validity between the physical and the psychological subscales of the instruments. The MSAS-SF could discriminate among the known groups according to Eastern Cooperative Oncology performance status and level of anemia, and showed responsiveness to change of symptom burden at two times of treatment.
CONCLUSION: The study showed that both the MSAS-SF and the FACIT-Fatigue have good reliability and validity for use with patients with cancer in Uruguay. When used simultaneously, these instruments may provide a complete picture of the impact of cancer and its treatment on the patient's quality of life.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is characterized by intestinal polyposis, mucocutaneous pigmentation and an increased cancer risk, usually caused by mutations of the STK11 gene. This study collected epidemiological, clinical and genetic data from all Uruguayan PJS patients.
METHODS: Clinical data were obtained from public and private medical centers and updated annually. Sequencing of the STK11 gene in one member of each family was performed.
RESULTS AND DISCUSSION: 25 cases in 11 unrelated families were registered (15 males, 10 females). The average age of diagnosis and death was 18 and 41 years respectively. All patients had characteristic PJS pigmentation and gastrointestinal polyps. 72% required urgent surgery due to intestinal obstruction. 3 families had multiple cases of seizure disorder, representing 20% of cases. 28% developed cancer and two patients had more than one cancer. An STK11 mutation was found in 8 of the 9 families analyzed. A unique M136K missense mutation was noted in one family. Comparing annual live births and PJS birth records from 1970 to 2009 yielded an incidence of 1 in 155,000.
CONCLUSION: The Uruguayan Registry for Peutz-Jeghers patients showed a high chance of emergent surgery, epilepsy, cancer and shortened life expectancy. The M136K missense mutation is a newly reported STK 11 mutation.

BACKGROUND: Maté tea is a nonalcoholic infusion widely consumed in southern South America, and may increase risk of esophageal squamous cell carcinoma (ESCC) and other cancers due to polycyclic aromatic hydrocarbons (PAH) and/or thermal injury.
METHODS: We pooled two case-control studies: a 1988 to 2005 Uruguay study and a 1986 to 1992 multinational study in Argentina, Brazil, Paraguay, and Uruguay, including 1,400 cases and 3,229 controls. We computed ORs and fitted a linear excess OR (EOR) model for cumulative maté consumption in liters/day-year (LPDY).
RESULTS: The adjusted OR for ESCC with 95% confidence interval (CI) by ever compared with never use of maté was 1.60 (1.2-2.2). ORs increased linearly with LPDY (test of nonlinearity; P = 0.69). The estimate of slope (EOR/LPDY) was 0.009 (0.005-0.014) and did not vary with daily intake, indicating maté intensity did not influence the strength of association. EOR/LPDY estimates for consumption at warm, hot, and very hot beverage temperatures were 0.004 (-0.002-0.013), 0.007 (0.003-0.013), and 0.016 (0.009-0.027), respectively, and differed significantly (P < 0.01). EOR/LPDY estimates were increased in younger (<65) individuals and never alcohol drinkers, but these evaluations were post hoc, and were homogeneous by sex.
CONCLUSIONS: ORs for ESCC increased linearly with cumulative maté consumption and were unrelated to intensity, so greater daily consumption for shorter duration or lesser daily consumption for longer duration resulted in comparable ORs. The strength of association increased with higher maté temperatures.
IMPACT: Increased understanding of cancer risks with maté consumption enhances the understanding of the public health consequences given its purported health benefits.

BACKGROUND: Melanocytic nevi are frequently found on acral volar skin. Differentiation between nevi and melanoma is essential and sometimes difficult, although dermoscopy has enabled a more specific diagnosis of pigmented lesions. Dermoscopic patterns of lesions on acral volar skin have mostly been described in European and Asian populations. The Latin American population is heterogeneous, and particularly so in the case of Uruguayans, who largely descend from 3 distinct populations.
OBJECTIVE: To describe dermoscopic patterns of acral melanocytic nevi and evaluate their applicability in a Latin American population in Uruguay.
PATIENTS AND METHODS: This was an observational, descriptive, cross-sectional study conducted by 2 dermatologists from 4 dermatology clinics in Uruguay. Uruguayan patients older than 18 years with acral melanocytic nevi were included. Digital dermoscopic images were captured and jointly analyzed by 2 investigators.
RESULTS: A total of 158 acral volar nevi in 80 patients were analyzed. The most-prevalent pattern was the parallel furrow pattern (51.3% of nevi), followed by the latticelike pattern (13.3%), the homogeneous pattern (12.7%), the globular pattern (9.5%), the fibrillar pattern (7%), the globulostreaklike pattern (3.8%), and the nontypical pattern (2.5%). The reticular and transition patterns were not observed in our population.
CONCLUSIONS: The parallel furrow pattern, followed by the latticelike and homogeneous patterns, was the most-prevalent pattern in acral melanocytic nevi in the Uruguayan population. The fibrillar pattern was found exclusively on the soles. No new dermoscopic patterns were observed. The patterns described in Asian and European literature apply to our population.

PURPOSE: Biological markers are crucial factors in order to differentiate female breast cancers and to determine the right therapy. This study aims at evaluating whether testing for biomarkers for female breast cancer has similar frequency and characteristics across and within countries.
METHODS: Population-based cancer registries of the Association for cancer registration and epidemiology in Romance language countries (GRELL) were asked to complete a questionnaire on biomarkers testing. The data collected referred to invasive female breast cancer cases diagnosed between 2004 and 2009. The investigation focused on 1) the overexpression and amplification of the human epidermal growth factor receptor 2 oncogene (HER2); 2) the expression of oestrogen (ER) and progesterone (PgR) receptors; and 3) the proliferation index (PI). Weighted percentages, the heterogeneity among and within countries, and the correlation between responses and calendar years were evaluated. The study was based on 19,644 breast cancers.
RESULTS: Overall, 85.9% of the cases were tested for HER2, 91.8% for both ER and PgR, and 74.1% for proliferative markers. For HER2 and ER-PgR, the frequency of testing increased from 2004 to 2009. Testing varied among countries (HER2 from 82.0% to 95.9%, ER-PgR from 89.3% to 98.9%, PI from 10% to 92%) and also within the same country (e.g. HER2 in Italy from 51% to 99%) as well as within single cancer registries. The most relevant differences were in the scores for positive/negative/not clearly defined HER2 (e.g. HER2 was defined positive if IHC 3+ in 21/33 registries), and in the cut-off of positive cells for ER/PgR (from >0% to >30%) and PI positivity (from >0% to >20%).
CONCLUSIONS: Biological markers are widely tested in the Romance language countries; however, the parameters defining their positivity may vary, raising concerns about homogeneity in breast cancer classification and treatment.

OBJECTIVE: The aim of this study was to investigate the association between nutrient-based dietary patterns and squamous cell cancers of the head and neck.
METHODS: We used a case-control study which included 548 cases and 548 controls. From these participants, we derived 23 nutrients and they were then submitted to a factorability analysis in order to conduct a principal component factor analysis.
RESULTS: We were able to identify four nutrient-derived patterns. The first pattern (meat-based pattern) was positively associated with squamous cell cancer of the head and neck (OR 2.85, 95 % CI 1.81-4.15), whereas the third pattern (fruit-based) was strongly protective (OR 0.43, 95 % CI 0.27-0.63). The other nutrient patterns were also significantly associated with head and neck squamous cell carcinoma with minor ORs.
CONCLUSION: Both patterns suggest that red meat and fruits are major factors in the etiology of head and neck squamous cell cancer, replicating previous studies in the field.

In the time period 1996-2004, we conducted a case-control study in Montevideo, Uruguay with the objective of exploring the role of foods and alcoholic beverages in the etiology of cancers of the upper aerodigestive tract (UADT). In brief, 563 male cases and 1099 male controls were frequency matched on age and residence using random sampling. All the participants were drawn from the 4 major public hospitals in Montevideo. We used exploratory factor analysis among controls. Through Scree plot test, the model retained 4 factors, which were labeled as prudent, starchy plants, Western, and drinker. These dietary patterns explained 34.8% of the total variance. Whereas the prudent pattern was inversely associated with UADT cancer [odds ratios (OR) for the upper tertile vs. the lowest one 0.52, 95% confidence intervals 0.32-0.76, P value for trend = 0.0005), the remaining patterns were significantly and positively associated with UADT cancers. We conclude that these patterns were similar among the oral and laryngeal cancers, both in the direction of the ORs and in the magnitude of the associations, suggesting that these cancer sites share the effect of dietary patterns in the etiology of cancer of the upper aerodigestive tract.

OBJECTIVES: Persistent infection with specific genotypes of human papillomaviruses (HPVs) is the main cause of invasive cervical cancer (ICC). Only a few of the various HPV types account for most of the cases worldwide, and geographical differences in their distribution are evident. Data from locally prevalent genotypes are essential in view of introduction of HPV type-specific prophylactic vaccines.
METHODS: In this work, we have investigated HPV type distribution in samples of ICC cases that occurred in Uruguayan women. DNA extracted from ICC treated in Centro Hospitalario Pereira Rossell of Montevideo between 1999 and 2007 were analyzed. Search and typing were performed by polymerase chain reaction using generic GP5+/GP6+ primers and specific primers for HPV types 16, 18, 33, and 45. Positive GP5+/GP6+ samples, which were negative for all 4 high-risk HPV-specific types screened were further analyzed by sequencing.
RESULTS: Human papillomavirus DNA sequences were found in 163 (92.6%) of 176 cases. The most prevalent genotypes were HPV16 (67.6%) and HPV18 (8.5%) followed by HPV45 (6.8%) and HPV33 (3.4%), as single or mixed infection. Other less frequent genotypes were HPV31, HPV35, HPV39, HPV51, HPV52, HPV58, HPV66, and HPV73. The viral type could not be determined (HPV X) in 1 case (0.6%) of the HPV DNA-positive cervical cancers and double infections were found in 1.7% of the cases. The higher percentage of most aggressive HPV (16/18/45) genotypes was detected in cases diagnosed at younger than 60 years old, whereas these genotypes were less frequent in older patients.
CONCLUSION: We conclude that HPV types 16, 18, and 45 have a very high prevalence in ICC of Uruguayan women. Results provide evidence that 16 of 18 infections are more aggressive, but most cancers could be vaccine preventable.

Thanks to modern treatment with all-trans retinoic acid and chemotherapy, acute promyelocytic leukemia (APL) is now the most curable type of leukemia. However, this progress has not yielded equivalent benefit in developing countries. The International Consortium on Acute Promyelocytic Leukemia (IC-APL) was established to create a network of institutions in developing countries that would exchange experience and data and receive support from well-established US and European cooperative groups. The IC-APL formulated expeditious diagnostic, treatment, and supportive guidelines that were adapted to local circumstances. APL was chosen as a model disease because of the potential impact on improved diagnosis and treatment. The project included 4 national coordinators and reference laboratories, common clinical record forms, 5 subcommittees, and laboratory and data management training programs. In addition, participating institutions held regular virtual and face-to-face meetings. Complete hematological remission was achieved in 153/180 (85%) patients and 27 (15%) died during induction. After a median follow-up of 28 months, the 2-year cumulative incidence of relapse, overall survival (OS), and disease-free survival (DFS) were 4.5%, 80%, and 91%, respectively. The establishment of the IC-APL network resulted in a decrease of almost 50% in early mortality and an improvement in OS of almost 30% compared with historical controls, resulting in OS and DFS similar to those reported in developed countries.

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.

In order to thoroughly analyze risk factors of breast cancer (BC) in premenopausal Uruguayan women, a case-control study was carried out at the Pereira Rossell Women's Hospital, Montevideo, where 253 incident BC cases and 497 frequency-matched healthy controls were interviewed on menstrual and reproductive story, were administered a short food frequency questionnaire and undertook a series of body measurements necessary to calculate body composition and somatotype. Odds ratio (OR) coefficients were taken as estimates of relative risk derived from unconditional logistic regression. Among the classical risk factors, only the family history of BC in first degree relatives was significantly associated with risk of premenopausal BC (OR=2.20, 95% CI 1.33-3.62). Interestingly, this risk factor was found to be stronger in women of ages >40 (OR=4.05, 95% CI 2.10-7.81), late menarche (OR= 2.39, 95% CI 1.18-4.85), early age for their first delivery (OR=3.02, 95% CI 1.26-7.22), short time between menarche and first delivery (OR=3.22, 95% CI 1.29-8.07), and with high parity (OR=4.10, 95% CI 1.79-9.36), although heterogeneity was detected only for age and parity. High consumption of red meat was positively associated with the disease risk (OR=2.20, 95% CI 1.35-3.60), in the same way as fried foods (OR=1.79, 95% CI 1.12-2.84). Conversely, a high intake of plant foods displayed a protective effect (OR=0.41, 95% CI 0.26-0.65). Except for hypertension (OR=1.55, 95% CI 1.03-2.35), none of the analyzed components of metabolic syndrome were associated to BC risk. Particular increases of risk for premenopausal BC were found for family history in first degree relatives in certain subsets derived from the menstrual-reproductive history. Preventive strategies could broaden their scope if new studies confirm the present results, in view of the limited prevention measures that premenopausal BC currently has.

BACKGROUND: In the period 1990 to 2001, a case-control study on oral cancer and maté consumption was conducted at the Cancer Institute of Uruguay.
METHODS: The study included 696 newly diagnosed cases with squamous cell carcinoma and 696 controls afflicted with nonneoplastic conditions not related to tobacco smoking and alcohol drinking. The participants were matched on age and residence and the study was restricted to men.
RESULTS: In order to control confounding for tobacco and alcohol, we fitted 2 models. According to model 1, the odds ratio (OR) for maté consumption was 1.15 (95% confidence interval [CI], 0.76-1.73), whereas the results for model 2 showed an OR of 3.47 (95% CI, 1.60-7.52).
CONCLUSIONS: The inclusion of a term for the interaction between maté and smoking (or drinking) was rewarding and the ORs were even higher than those observed with the crude estimates.

Maté, a tea-like infusion of Ilex paraguariensis, is suspected to be a risk factor for esophageal squamous cell carcinoma; however, no meta-analysis on the subject has been performed to date. A meta-analysis of studies reporting the consumption of maté in patients with esophageal squamous cell carcinoma was conducted to provide a quantitative estimate of the risk of esophageal squamous cell carcinoma associated with maté consumption. A search was conducted through MEDLINE, PubMed, EMBASE, and Current Contents Connect to April 5, 2012. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using a random effects model for the risk of esophageal squamous cell carcinoma associated with exposure to maté (ever- vs. never-drinkers), as well as for the dose-dependent risk of esophageal squamous cell carcinoma associated with different levels of maté consumption (highest vs. lowest intake). Nine studies, with 1565 esophageal squamous cell carcinoma cases, met our inclusion criteria. Esophageal squamous cell carcinoma was associated with exposure to maté drink, with an OR of 2.57 and a 95% CI of 1.66-3.98. There was an increased risk of esophageal squamous cell carcinoma associated with a higher consumption of maté versus low consumption (OR 2.76, 95% CI 1.33-5.73 vs. OR 1.84, 95% CI 1.12-3.00). Heterogeneity was observed in the ever versus never and the high-consumption analyses but not in the low-consumption analysis. Publication bias was present. Maté consumption was associated with an increased risk of esophageal squamous cell carcinoma.

OBJECTIVE: The role of foods and beverages has been studied in detail in order to establish probable risk factors for prostate cancer.
METHODS: Data were derived from 326 cases with incident and microscopically confirmed adenocarcinomas of the prostate and 652 controls. Odds ratios and 95 % confidence intervals of prostate cancer were estimated by unconditional multiple logistic regression.
RESULTS: We identified the following food items as risk factors: lamb meat, salted meat, whole milk, total eggs, and maté consumption. The highest OR was associated with total eggs (OR, 2.43; 95 % CI, 1.70-3.48), followed by salted meat (OR, 2.65; 95 % CI, 1.36-3.76), maté consumption (OR, 1.96; 95 % CI, 1.17-3.31), and whole milk (OR, 2.01; 95 % CI, 1.26-2.51).
CONCLUSIONS: The final model, fitted by stepwise forward method, included total eggs, salted meat, whole milk, and maté consumption, whereas fruits were protective.

OBJECTIVES: Several clinical trials conducted in Europe and US reported favorable outcomes of patients with APL treated with the combination of all trans retinoic acid (ATRA) and anthracyclines. Nevertheless, the results observed in developing countries with the same regimen was poorer, mainly due to high early mortality mainly due bleeding. The International Consortium on Acute Promyelocytic Leukemia (IC-APL) is an initiative of the International Members Committee of the ASH and the project aims to reduce this gap through the establishment of international network, which was launched in Brazil, Mexico and Uruguay.
METHODS: The IC-APL treatment protocol is similar to the PETHEMA 2005, but changing idarubicin to daunorubicin. All patients with a suspected diagnosis of APL were immediately started on ATRA, while bone marrow samples were shipped to a national central lab where genetic verification of the diagnosis was performed. The immunofluorescence using an anti-PML antibody allowed a rapid confirmation of the diagnosis and, the importance of supportive measures was reinforced.
RESULTS: The interim analysis of 97 patients enrolled in the IC-APL protocol showed that complete remission (CR) rate was 83% and the 2-year overall survival and disease-free survival were 80% and 90%, respectively. Of note, the early mortality rate was reduced to 7.5%.
DISCUSSION: The results of IC-APL demonstrate the impact of educational programs and networking on the improvement of the leukemia treatment outcome in developing countries.

In order to explore the role of nutrients and bioactive related substances in colorectal cancer, we conducted a case-control in Uruguay, which is the country with the highest production of beef in the world. Six hundred and eleven (611) cases afflicted with colorectal cancer and 1,362 controls drawn from the same hospitals in the same time period were analyzed through unconditional multiple logistic regression. This base population was submitted to a principal components factor analysis and three factors were retained. They were labeled as the meat-based, plant-based, and carbohydrates patterns. They were rotated using orthogonal varimax method. The highest risk was positively associated with the meat-based pattern (OR for the highest quartile versus the lowest one 1.63, 95 % CI 1.22-2.18, P value for trend = 0.001), whereas the plant-based pattern was strongly protective (OR 0.60, 95 % CI 0.45-0.81, P value for trend <0.0001. The carbohydrates pattern was only positively associated with colon cancer risk (OR 1.46, 95 % CI 1.02-2.09). The meat-based pattern was rich in saturated fat, animal protein, cholesterol, and phosphorus, nutrients originated in red meat. Since herocyclic amines are formed in the well-done red meat through the action of amino acids and creatine, it is suggestive that this pattern could be an important etiologic agent for colorectal cancer.

Obese postmenopausal women increase their risk of developing breast cancer (BC), in particular if they display an android-type pattern of adiposity, which is also associated to increased risks of diabetes mellitus, hypertension and cardiovascular disease. In order to explore the associations among anthropometry (body mass index, body composition, somatotype), some specific items of medical history (diabetes, hypertension, dislypidemias, hyperuricemia) and the risk of BC in Uruguayan women, a case-control study was carried out between 2004-2009 at our Oncology Unit. 912 women of ages between 23-69 years (367 new BC cases and 545 non hospitalized, age-matched controls with a normal mammography) were interviewed. Twenty body measurements were taken in order to calculate body composition and somatotype. Patients were queried on socio-demographics, reproductive history, family history of cancer, a brief food frequency questionnaire and on personal history of diabetes, dislypidemias, hyperuricemia, hypertension and gallbladder stones. Uni- and multivariate analyses were done, generating odds ratios (ORs) as an expression of relative risks. A personal history of diabetes was positively associated to BC risk (OR=1.64, 95% CI 1.00-2.69), being higher among postmenopausal women (OR=1.92, 95% CI 1.04-3.52). The risks of BC for diabetes in postmenopausal women with overweight combined with dislypidemia (OR=9.33, 95% CI 2.10-41.5) and high fat/muscle ratio (OR=7.81, 95% CI 2.01-30.3) were significantly high. As a conclusion, a personal history of diabetes and overweight was strongly associated to BC. The studied sample had a subset of high-risk of BC featured by postmenopausal overweight and diabetic women, who also had a personal history of hypertension and/or dyslipidemia. The present results could contribute to define new high risk groups and individuals for primary as well as for secondary prevention, since this pattern linked to the metabolic syndrome is usually not considered for BC prevention.

The role of meat in squamous cell carcinoma of the esophagus (ESCC) has been considered conflictive. For this reason, we decided to conduct a case-control study on meat consumption and ESCC. Data included 234 newly diagnosed and microscopically examined ESCC and 2,020 controls with conditions not related to tobacco smoking nor alcohol drinking and without changes in their diets. We studied total meat, red meat, beef, lamb, processed meat, poultry, fish, total white meat, liver, fried meat, barbecued meat, boiled meat, heterocyclic amines, nitrosodimethylamine, and benzo[a]pyrene in relation with the risk of ESCC. Red meat, lamb, and boiled meat were directly associated with the risk of ESCC, whereas total white meat, poultry, fish, and liver were mainly protective against this malignancy.

In order to determine to the effect of benzo[a]pyrene (BaP) on breast cancer risk we conducted a case-control study in the time period 1996-2004. The study included 1,098 participants (460 cases and 638 controls). All the patients were drawn from the four major hospitals in Montevideo, Uruguay. Statistical analysis was performed using unconditional multiple logistic regression and the models included age, residence, urban/rural status, education, monthly income, body mass index, menopausal status, age at menarche, parity, smoking index, alcohol drinking, mate consumption, total energy, total vegetables and fruits, and BaP intake. The highest vs. the lowest quartile of BaP intake (OR 2.0, 95% CI 1.2-3.3) was significantly associated with breast cancer risk. Alcohol drinking was also directly associated with breast cancer risk (OR 1.63, 95% CI 1.19-2.23) and the joint effect of BaP and alcohol drinking showed an elevated risk of the disease (OR 3.32, 95% CI 2.17-5.06). The present study suggests that elevated consumption of BaP could play an important role in the etiology of breast cancer. This effect is enhanced by the intake of alcohol.

In the time period 1990-2004 we conducted a multisite case-control study in order to examine the relationship of mate consumption and risk of 13 cancer sites in Montevideo, Uruguay. The study included 13,201 participants (8,875 cases and 4,326 controls) drawn from the four major public hospitals in the city of Montevideo. Newly diagnosed and microscopically confirmed cases of cancers of the mouth, pharynx, esophagus, stomach, colon, rectum, larynx, lung, female breast, cervix uteri, prostate, bladder and kidney were included in the study. Controls were drawn from the same hospitals and in the same time period and were afflicted by non-neoplastic conditions not related with tobacco smoking or alcohol drinking and without recent changes in their diets. Odds ratios for mate consumption was directly associated with cancers of the upper aerodigestive tract (UADT), esophagus, stomach, larynx, lung, cervix uteri, prostate, bladder, and kidney. In conclusion these results suggest that chemicals, like benzo[a]pyrene, could be responsible of the carcinogenic effect of mate in the above mentioned cancer sites.

In total, 17 pediatric patients with hematologic malignancies (n=14) and Fanconi anemia (FA) (n=3) underwent haploidentical SCT with T-cell depletion. The patients were conditioned with reduced-intensity regimens, and CYA was used for GVHD prophylaxis. Successful engraftment occurred in 16 patients (94%). One patient failed to achieve a primary engraftment. Another patient rejected the first SCT after 10 weeks and had a successful second transplant. Of all engrafted patients, only one developed severe acute GVHD. Ten patients were alive at a median follow-up of 18 months (range, 5-62 months). The 5-years' OS was 53.8%. The three patients with FA are currently well with full-donor chimerism at 16, 6 and 5 months post transplant, respectively. The OS of 14 patients with high-risk hematologic malignancies was 47.6%. Three patients died as a result of post transplant leukemia relapse. CMV infection, GVHD and organ injury were other causes of mortality. Haploidentical SCT was found to be an alternative feasible treatment in Uruguay for patients who need allogenic transplantation but lack an HLA-identical family donor. It should be considered as an early option in FA patients before transformation or significant exposure to blood products.