Unit of Molecular Epidemiology, National Cancer Research Institute, Genoa, Italy.

Exposure to asbestos fibers is a major risk factor for malignant pleural mesothelioma (MPM), lung cancer, and other non-neoplastic conditions, such as asbestosis and pleural plaques. However, in the last decade many studies have shown that polymorphism in the genes involved in xenobiotic and oxidative metabolism or in DNA repair processes may play an important role in the etiology and pathogenesis of these diseases. To evaluate the association between diseases linked to asbestos and genetic variability we performed a review of studies on this topic included in the PubMed database. One hundred fifty-nine citations were retrieved; 24 of them met the inclusion criteria and were evaluated in the review. The most commonly studied GSTM1 polymorphism showed for all asbestos-linked diseases an increased risk in association with the null genotype, possibly linked to its role in the conjugation of reactive oxygen species. Studies focused on GSTT1 null and SOD2 Ala16Val polymorphisms gave conflicting results, while promising results came from studies on alpha1-antitrypsin in asbestosis and MPO in lung cancer. Among genetic polymorphisms associated to the risk of MPM, the GSTM1 null genotype and two variant alleles of XRCC1 and XRCC3 showed increased risks in a subset of studies. Results for the NAT2 acetylator status, SOD2 polymorphism and EPHX activity were conflicting. Major limitations in the study design, including the small size of study groups, affected the reliability of these studies. Technical improvements such as the use of high-throughput techniques will help to identify molecular pathways regulated by candidate genes.

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Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.

The expression of mucin (MUC2) in prostate cancer has not been well studied previously and may be of prognostic and pathobiologic significance. It is, however, well known that MUC2 expression in mucinous pancreatic and breast cancer represents an indolent pathway since these tumors have a significantly better outcome than their conventional counterparts. Twenty-five cases each of Gleason pattern 3 and 4 mucinous adenocarcinoma of the prostate defined by greater than 25% mucinous component and nonmucinous adenocarcinoma of the prostate were obtained from the surgical pathology files of the Johns Hopkins Hospital and Emory University Hospital. Immunohistochemical stains were performed for MUC2 on all 50 cases. Mean patient age was 60 years (range 44-72 years). MUC2 was expressed in all 25 cases (100%) of mucinous adenocarcinoma of the prostate, irrespective of the Gleason pattern. The nonmucinous component of these cases was negative for MUC2. In contrast, MUC2 expression was significantly lower in nonmucinous adenocarcinoma of the prostate, detected in only 6/25 cases as a focal finding, while 19/25 (76%) of nonmucinous adenocarcinoma of the prostate were completely negative for MUC2 (P<0.01). In six cases that showed focal positivity, MUC2 was expressed in areas with Gleason pattern 3 cancer with extensive mucinous fibroplasia (one case) and prominent intraluminal mucin (five cases). Other areas of these tumors were negative for MUC2. Mucinous adenocarcinoma of the prostate shows diffuse expression of MUC2, a known tumor suppressor, which is not present in either normal prostate or the majority of conventional adenocarcinomas of this organ. This indicates that mucinous adenocarcinoma of the prostate is indeed of the ‘colloid type’ akin to those in other exocrine organs. It is highly conceivable that this de novo expression of MUC2 has a role, not only in the mucinous differentiation of these tumors and their colloid pattern, but also in their relatively indolent behavior that has been recently elucidated.Modern Pathology advance online publicaton, 16 May 2008; doi:10.1038/modpathol.2008.47.

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Department of Respiratory Cancer Medicine, Peking University Third Hospital, Haidian District, Beijing 100083, China.

OBJECTIVE: Previous studies have cancer demonstrated that exercise-induced asthma and bronchial hyperresponsiveness commonly occur in athletes. The present study investigates pulmonary function and cytokine levels in professional athletes to explore the impact of various sports on respiratory system cancer function and to evaluate the possible role of systemic anaphylaxis. METHODS: Lung function was measured at rest in professional athletes without a history of smoking. Athletes were recruited from 10 different sports including swimming, water ballet, shooting, volleyball, softball, football, kickboxing, fencing, judo, and track and field. Measurements included forced vital capacity (FVC), forced expiratory volume in one second (FEV(1)), vital capacity (VC), peak expiratory flow (PEF), maximal mid-expiratory flow curve (MMEF), and forced expiratory flow rate (FEF(25-75)%). In addition, the medical history of all athletes was recorded. Correlations between lung function measurements and the different sports, age, gender, height and weight were analyzed. In some athletes, serum was sampled to detect IL-4 and IL-10 concentrations. In these subjects, the correlation between pulmonary function and cytokine levels was analyzed. RESULTS: A total of 147 professional athletes and 30 healthy volunteers were enrolled in the study. Allergic rhinitis and asthma were detected only in swimmers with an incidence of 56.52% (13/23) and 8.70% (2/23), respectively. Lung function measures were significantly correlated with sport, age, gender, height, and weight. Ventilation functions (including FVC, FEV(1), FEV(1)/FVC, and MMV) in male athletes were superior to those in females, and the ventilation functions in swimmers were superior to those in others. However, the small airway functions (MMEF, FEF(50), FEF(75)) in swimmers and in track and field athletes were lower than predicted (swimmers: 72%, 70%, and 78%, respectively; track and field athletes: 79%, 75%, and 99%, respectively). Serum analyses for IL-4 and IL-10 revealed that IL-4 concentrations were higher in swimmers 69.34 +/- 22.4 pg/mL relative to non-swimmers (p = 0.000). By contrast IL-10 concentrations were lower in swimmers 34.94 +/- 9.71 pg/mL than that in the static group (44.69 +/- 16.32 pg/mL; p = 0.027). IL-4 levels were negatively correlated with FEV(1)%, FEF(25)%, FEF(50)%, and MMEF%. By contrast, IL-10 levels were not correlated with any of these measures. CONCLUSIONS: The lung function measurements were correlated with sport, age, gender, height, and weight in the various athletes. The lung capacity of swimmers was greater than that of other athletes. Small airway dysfunction was observed in some swimmers and endurance athletes. We observed an association between systemic anaphylaxis and small airway dysfunction after prolonged regular training, particularly following swimming and endurance training.

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Authors’ Affiliations: Laboratory of Molecular Neuro-oncology, Departments of Research and Surgery, University Hospitals, Basel, Switzerland.

PURPOSE: High-grade gliomas are difficult to treat due to their location behind the blood-brain barrier and to inherent radioresistance and chemoresistance. EXPERIMENTAL DESIGN: Because tumorigenesis is considered a multistep process of accumulating mutations affecting distinct signaling pathways, combinations of compounds, which inhibit nonoverlapping pathways, are being explored to improve treatment of gliomas. Histone deacetylase inhibitors (HDI) have proven antitumor activity by blocking cell proliferation, promoting differentiation, and inducing tumor cell apoptosis. RESULTS: In this report, we show that the HDIs trichostatin A, sodium butyrate, and low nanomolar doses of LAQ824 combined with the glycolysis inhibitor 2-deoxy-d-glucose induce strong apoptosis in cancer cell lines of brain, breast, and cervix in a p53-independent manner. HDIs up-regulate p21, which is blocked by concomitant administration of 2-deoxy-d-glucose. CONCLUSIONS: We propose simultaneous blockade of histone deacetylation and glycolysis as a novel therapeutic strategy for several major cancers.

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Affiliations of authors: Department of Surgery, University of cancer Michigan, Ann Arbor, MI (AMM, AJH, JDB); Michigan Surgical Collaborative for Outcomes Research and Evaluation, University of Michigan, Ann Arbor, MI (AMM, JDB); Department of Family Medicine, University of Washington, Seattle, WA (BM, LMB); Department of cancer Surgery, Oregon Health and Science University, Portland, OR (KGB).

Background Black patients with rectal cancer are considerably less likely than white patients to receive adjuvant therapy. We examined the hypothesis that the lower treatment rate for blacks is due to cancer underreferral to cancer medical and radiation cancer oncologists. Methods We used 1992-1999 Surveillance, Epidemiology, and End Results-Medicare data to identify elderly (>/=66 years of age) patients who had been hospitalized for resection of stage II or III rectal cancer (n = 2716). We used chi(2) tests to examine associations between race and 1) consultation with an cancer oncologist and 2) receipt of adjuvant therapy. We then used logistic regression to analyze the influence of sociodemographic and clinical characteristics (age at diagnosis, sex, marital status, median income and education in area of residence, comorbidity, and cancer stage) on black-white differences in the receipt of adjuvant therapy. All statistical tests were two-sided. Results There was no statistically significant difference between the 134 black patients and the 2582 white cancer patients in the frequency of consultation with a medical oncologist (73.1% for blacks vs 74.9% for whites, difference = 1.8%, 95% confidence interval [CI] = >5.9% to 9.5%, P = .64) or radiation oncologist (56.7% vs 64.8%, difference = 8.1%, 95% CI = >0.5% to 16.7%, P = .06), but blacks were less likely than whites to consult with both a medical oncologist and a radiation oncologist (49.2% vs 58.8%, difference = 9.6%, 95% CI = 0.9% to 18.2%, P = .03). Among patients who saw an cancer oncologist, black patients were less likely than white patients to receive cancer chemotherapy (54.1% vs 70.2%, difference = 16.1%, 95% CI = 6.0% to 26.2%, P = .006), radiation therapy (73.7% vs 83.4%, difference = 9.7%, 95% CI = 0.4% to 19.8%, P = .06), or both (60.6% vs 76.9%, difference = 16.3%, 95% CI = 4.3% to 28.3%, P = .008). Patient and provider characteristics had minimal influence on the racial disparity in the use of adjuvant therapy. Conclusion Racial differences in oncologist consultation rates do not explain disparities in the use of adjuvant cancer treatment for rectal cancer. A better understanding of patient preferences, patient-provider interactions, and potential influences on provider decision making is necessary to develop strategies to increase the use of adjuvant treatment for rectal cancer among black patients.

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