Dietary intake of vegetables, folate, and antioxidants and the risk of Barrett’s esophagus

Purpose

Diet is a potentially modifiable risk factor for Barrett’s esophagus (BE). We investigated the associations between intakes of fruits and vegetables and risk of BE.

Methods

We identified study subjects from 1,859 participants who underwent the endoscopy in a single VA Medical Center in the US between 2008 and 2011. Dietary intake in the previous year was elicited using a self-administered Block food frequency questionnaire (FFQ). Logistic regression model was used to estimate odds ratio (OR) and its 95 % confidence interval (CI) for BE.

Results

A total of 151 cases with definite BE and 777 controls completed the FFQ. When highest tertile of intake was compared with the lowest, the OR (95 % CI) was 0.46 (0.26–0.81) for dark green vegetables, 0.52 (0.30–0.90) for legumes, 0.50 (0.28–0.90) for total fiber, 0.45 (0.25–0.81) for isoflavones, 0.52 (0.30–0.67) for total folate, and 0.45 (0.26–0.79) for lutein, adjusting for multiple confounding factors including use of aspirin or proton pump inhibitor, gastro-esophageal reflux symptoms, and physical activity. The association for dark green vegetables was attenuated after adjustment for lutein, total fiber, and total folate (OR = 0.82; 95 % CI 0.30–2.22).

Conclusion

Higher intake of dark green vegetables was associated with a decreased risk of BE in a veteran population. Such an inverse association may be partially mediated by lutein, fiber, and folate. The novel findings on the association between intake of lutein, total folate, or isoflavones and risk of BE need further confirmation.     

Micro-RNAs,the Cornerstones of the Future of Radiobiology in Head and Neck Cancers?

Even though it is only the 6th most common malignancy at the modal level, head and neck cancers are distinguished by a considerable treatment failure rate, especially by locoregional recurrences, the intrinsic tumor radioresistance being one of the causes of this phenomenon. The efforts of radiobiological research of these cancers are oriented towards the identification of biomarkers associated with radioresistance and radiosensitivity in order to modulate the treatment so that the therapeutic benefit is maximum. Micro-RNAs (miRNAs, miRs), small single-stranded non-coding RNA molecules are currently being extensively evaluated as potential biomarkers in numerous diseases, including cancer. The evaluation of the potential of miRNAs to modulate or predict radiosensitivity or radioresistance, to anticipate the risk of recurrence and metastasis, and to differentiate different tumor subtypes is based on multiple mechanisms by which mRNAs control proliferation and apoptosis and interact with cell cycle phases or act as oncogenes with the potential to influence invasion promotion or tumor suppression. A refinement of radiosensitivity based on miRNAs with clinical and radiobiological application in head and neck cancers can lead to a personalization of radiotherapy. Thus, a miRNA signature can anticipate the risk of toxicity associated with chemoradiation, the possibility of obtaining locoregional control after treatment, and the recurrence and distant metastasis risk. The potential of miRNAs as an intrinsic predictor of sensitivity to chemotherapy may also guide the therapeutic decision toward choosing an escalation or de-escalation of concurrent or sequential systemic treatment. The choice of the irradiated dose, the fractional dose, the fractionation scheme, and the refining of the dose-volume constraints depending on the radiosensitivity of each tissue type estimated on a case-by-case basis by miRNAs profile are possible concepts for the future radiotherapy and radiobiology of head and neck cancers.     

Cancers of the lung,head and neck on the rise：perspectives on the genotoxicity of air pollution

Outdoor air pollution has been recently classified as a class I human carcinogen by the World Health Organization （WHO）. Cumulative evidence from across the globe shows that polluted air is associated with increased risk of lung, head and neck, and nasopharyngeal cancers--all of which affect the upper aerodigestive tract. Importantly, these cancers have been previously linked to smoking. In this article, we review epidemiologic and experimental evidence of the genotoxic and mutagenic effects of air pollution on DNA, purportedly a key mechanism for cancer development. The alarming increase in cancers of the upper aerodigestive tract in Asia suggests a need to focus government efforts and research on reducing air pollution, promoting clean energy, and investigating the carcinogenic effects of air pollution on humans.     

Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus-Differences in Etiology,Epidemiology and Prevention

In Germany,esophageal carcinoma is one of the ten most frequent causes of death.Normallythe disease is found in men over the age of 50.Although squamous cell carcinoma (SCC) of the esophagushas been more commonly diagnosed over the past 30 years,there is increasing incidence of esophagealadenocarcinoma (AC) in Western industrialized countries.For SCC the known etiological risk factorsare nicotine and alcohol abuse.For AC,they are moderate nicotine and alcohol consumption as well asgastro-esophageat reflux and obesity.     

Binding capacity of ER-α ligands and SERMs: comparison of the human, dog and cat

The estrogen molecule is the major risk factor related to mammary gland tumors, with estrogen receptor alpha (ER- α) as the important target stimulating growth. Therefore one alternative approach to treatment of breast cancer is to use selective estrogen receptor modulator (SERM), hormonal therapy. In this study, the structures of ER- α in humans, dogs and cats were predicted using the amino acid sequencing data bank and corrected for general protein structures, receptor sites and docking by adding 2,344 ligands with 15 SERMs into the database and calculating estimated inhibition constants (Ki). Thereby, ranking of best ligands of SERMs in humans, dogs and cats could be achieved. The results show that the shapes of ER- α differ between species but the major pocket sites are the same. Bazedoxifene, a new SERM proved to be the best estrogen antagonist and ER- α inhibitor in all species (human, dog, cat) with the lowest Ki. The other good ligands for dogs and cats are Neohesperidin, Dihydrochalcone, and Schreiber2. The differences in these protein structures may explain why there are only a few SERMs or other ligands which can be used as anti-cancer drugs.     

New developments in the lymphocyte micronucleus assay—the effect of diet,genotype and the importance of nucleoplasmic bridges

The cytokinesis-block micronucleus(CBMN)assay is an established method for studying chromosome breakage and loss in human cells both in vitro and in vivo. However, its use in the study of genomic stability could be improved by a better understanding of the impact of (a) micronutrients (b) genetic background and (c) of other associated important nuclear events indicative of chromosome rearrangement (ie nucleoplasmic     

Alcohol and tobacco, and the risk of cancers of the upper aerodigestive tract in Latin America: a case�Ccontrol study

Background

Cancers of the upper aerodigestive tract (UADT; including oral cavity, pharynx, larynx and oesophagus) have high incidence rates all over the world, and they are especially frequent in some parts of Latin America. However, the data on the role of the major risk factors in these areas are still limited.

Methods

We have evaluated the role of alcohol and tobacco consumption, based on 2,252 upper aerodigestive squamous-cell carcinoma cases and 1,707 controls from seven centres in Brazil, Argentina, and Cuba.

Results

We show that alcohol drinkers have a risk of UADT cancers that is up to five times higher than that of never-drinkers. A very strong effect of aperitifs and spirits as compared to other alcohol types was observed, with the ORs reaching 12.76 (CI 5.37?C30.32) for oesophagus. Tobacco smokers were up to six times more likely to develop aerodigestive cancers than never-smokers, with the ORs reaching 11.14 (7.72?C16.08) among current smokers for hypopharynx and larynx cancer. There was a trend for a decrease in risk after quitting alcohol drinking or tobacco smoking for all sites. The interactive effect of alcohol and tobacco was more than multiplicative. In this study, 65% of all UADT cases were attributable to a combined effect of alcohol and tobacco use.

Conclusions

In this largest study on UADT cancer in Latin America, we have shown for the first time that a prevailing majority of UADT cancer cases is due to a combined effect of alcohol and tobacco use and could be prevented by quitting the use of either of these two agents.     

Paget’s disease of the breast: the experience of the European institute of oncology and review of the literature

Background Paget’s disease of the breast is an uncommon presentation of breast malignancy, accounting for 1–3% of all the breast tumors and presents in different histopathologic patterns: in association with an underlying invasive or non invasive carcinoma, or without any underlying neoplasia. In the literature, different methods are used for the treatment. Mastectomy with or without axillary dissection has been considered as the standard treatment procedure for many years. Several studies have already shown that breast conservation with radiation therapy is an oncologically safe option. Regarding the axillary approach, several studies have documented the presence of positive sentinel lymph node even in Paget’s disease alone. The objective of this study was to retrospectively analyze outcome of patients affected by Paget’s breast disease and to define our institutional experience. Patients and methods Between May 1996 and February 2003, 114 patients with confirmed Paget’s disease of the breast were retrieved and underwent surgery at the European Institute of Oncology of Milan, Italy. The median age of the patients was 54 years at the time of the diagnosis. In our study, the histopathological examination of the operated specimen revealed one hundred seven patients with Paget’s disease associated with an underlying invasive or non invasive carcinoma, and seven patients without underlying carcinoma. Patients underwent either conservative breast surgery or mastectomy, with or without sentinel lymph node biopsy and/or axillary surgery. Each patient was evaluated after surgery at a multidisciplinary meeting to selecting systemic therapy. Results Seven patients had “pure” Paget’s disease of the breast and one hundred seven had the disease associated with an underlying carcinoma. As surgical techniques 71 mastectomies and 43 breast conserving surgeries have been performed. Complete axillary dissection was done in patients with clinically positive lymph node and/or sentinel lymph node biopsy positive. Sentinel lymph node biopsy was performed in nineteen patients with invasive component and five were positive and underwent axillary dissection. Eleven sentinel lymph node biopsies were done in patients with non invasive component and none of them was positive. Adjuvant systemic therapies were based on the final tumor, node and metastasis stage: thirty patients received adjuvant chemotherapy alone, fourteen received endocrine treatment alone, twenty-six patients were evaluated to receive both chemo and endocrine therapy. The median duration of follow up was 73 months and was updated in the last 6 months. Five patients developed local recurrence, one had regional recurrence, another two had loco-regional recurrences and fourteen had distant metastasis as a first event. Malignancy-related deaths were censored in the statistical analyses cancer for and due to another tumor in eleven patients. Additionally, deaths were not related to malignancy totally in thirteen patients. Conclusions Screening examination and imaging techniques are fundamental. Breast conserving surgery combined with breast irradiation for patients with invasive and non invasive breast carcinoma has become the treatment of first choice. All surgical conservative approaches should include the complete nipple–areolar complex and margins of resected specimen free of tumor. Thanks to the evolution of the conservative approach, good cosmetic result can be obtained. To be informed about the axillary lymph node status and to avoid the patient to have a second surgical approach, sentinel lymph node biopsy should be performed.     

Observations on the effect of abolishing analgesic abuse and reducing smoking on cancers of the kidney and bladder in New South Wales, Australia, 1972–1995

Objectives: We have assessed the effect on the rates of cancers of the kidney and bladder of measures undertaken by the government in 1979–1983 to limit smoking and analgesic abuse in New South Wales (NSW). Sale of phenacetin-containing analgesics, previously available without restriction and regularly taken by 11–13% of women and 4–9% of men in NSW, was prohibited from 1979. The prevalence of current smokers among adult Australian men had fallen from 72% in 1945 to 43% in 1980 and to 28% in 1992. In women the corresponding figures were 26%, 31% and 24%.Methods: Incidence and mortality data from the New South Wales Central Cancer Registry for the period 1972 to 1995 were analyzed, by sex and age, for trends over time. Relative survival was calculated for cases diagnosed in the period 1980–94 and followed until the end of 1996.Results: Significant trends evident from these data were: throughout the period of review a rising incidence of, and to a lesser extent mortality from, renal parenchymal cancer for which relative survival has steadily improved; falling mortality from bladder cancer throughout the period of review, but more rapid after 1985; a reversal of the earlier increasing incidence of, and mortality from, cancer of the renal pelvis; and relative survival for bladder and renal pelvic cancers which was worse in women than men. Changes in registration practice in 1985 and 1993 introduced artifacts into the trends in incidence of bladder cancer.Conclusions: Improvements in the trends of incidence and mortality of cancers of the renal pelvis and bladder in the mid-1980s are interpreted, in the light of registration and clinical practice, to indicate a beneficial effect of regulations which virtually abolished analgesic abuse and, less certainly, a contribution from measures restricting smoking, in New South Wales. However, renal parenchymal cancer continues to increase, although there has been some apparent benefit of earlier detection.     

Microarray and histopathological analysis of tumours: the future and the past?

The excitement surrounding the development of DNA microarray analysis and proteomics has raised questions about the role of these techniques in clinical practice and patient management. But how did the traditional methods of cancer diagnosis and prognosis develop, and how can high-throughput techniques contribute?     

Effect of gastrectomy on the pharmacokinetics of tegafur,uracil, and 5-fluorouracil after oral administration of a 1∶4 tegafur and uracil combination

The effects of gastrectomy on the pharmacokinetics of UFT, a combined oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 14, were examined in 26 patients with macroscopic State I gastric cancer. In all, 200 mg UFT (in terms of tegafur) was given to 17 patients who underwent partial gastrectomy (9 cases of Billroth I reconstruction, 8 cases of Billroth II reconstruction) and to 9 patients who underwent total gastrectomy with modified Roux-en-Y reconstruction. Before the operation, the area under the curve (AUC) for tegafur, uracil, and 5-fluorouracil (5-FU) was 79.28±26.88, 4.41±1.78, and 0.51±0.20 g h ml^–1, respectively. Partial (Billroth I and II) and total gastrectomy did not alter the AUC of tegafur, and partial gastrectomy using the Billroth I and II methods decreased the AUCs of uracil and 5-FU during the first 2 weeks postoperation. However, plasma levels of uracil and 5-FU reverted to preoperative values at 3 months postsurgery. Our findings show that when UFT is prescribed for patients treated in the early postoperative period following partial gastrectomy for cancer, dose increases and the timing of administration should be given close attention.     

Epidemiology of leukaemia and lymphoma in children and young adults from the north of England, 1990–2002

AimWe aimed to describe and contrast the epidemiology of haematological malignancies among 0–14 and 15–24-year-olds in northern England from 1990 to 2002 and compare clinical trial entry by age group.Patients and methodsIncidence rates were examined by age, sex and period of diagnosis and differences were tested using Poisson regression. Differences and trends in survival were assessed using Cox regression.Results1680 subjects were included comprising 948 leukaemias and 732 lymphomas. Incidence rates for acute lymphoblastic leukaemia were significantly higher for 0–14 compared to 15–24-year-olds, whilst Hodgkin lymphoma showed the reverse. No significant changes in incidence were observed. 60% of leukaemia patients aged 15–24 years entered trials compared to 92% of 0–14-year-olds. Survival rates were significantly lower and improved less markedly over time for 15–24 compared to 0–14-year-olds, particularly for leukaemia.ConclusionsTrial accrual rates need to be improved amongst 15–24-year-olds and a more structured follow-up approach adopted for this unique population.