Occupational exposure to polychlorinated biphenyls and cancer risk.

Polychlorinated biphenyls (PCBs) are a class of chemicals characterized by a long-term persistence and diffusion in the environment, and by bioaccumulation through the food chain. The highest exposures occurred in occupational cohorts through inhalation or skin absorption in work environments. These cohorts can therefore provide important information on health risk from exposure to PCBs in the general population. To provide comprehensive evidence on cancer risk from PCB exposure, we have thus reviewed the epidemiological studies on workers occupationally exposed to PCBs. Overall, no excess for all cancer mortality was observed in the six studies providing information (573 cancer deaths versus 630.4 expected, corresponding to a standardized mortality ratio (SMR) of 91). Among neoplasms potentially related to PCB exposure, there were 12 deaths from liver cancer compared with 9.5 expected (SMR=126). No excess was found for cancers of the breast (40 observed versus 47.4 expected, SMR=84) and of the lymphatic and haematopoietic system (51 observed versus 53.2 expected, SMR=96). Therefore, studies on occupational exposure to PCBs do not show any excess in all cancer mortality, or in mortality for specific cancer sites of interest.     

The recent decline in gallbladder cancer mortality in Europe.

Mortality from gallbladder cancer has been traditionally high in Eastern Europe, and lower in northern countries. Trends in 18 European countries, including the European Union (EU) and selected Eastern European countries, have been updated using official death certification data abstracted from the WHO database over the period 1980-1999. In the EU, age-standardized rates declined by about 30% between the late 1980s and 1999 to reach 1.8/100 000 for women, and by about 10% to reach 1.4/100 000 for men. In the Czech Republic and Hungary, rates for women were over 6/100 000 until the early 1990s, and declined by about 25% thereafter. For males, gallbladder cancer mortality showed no consistent trend, with rates over 3/100 000. Thus, a high mortality area from gallbladder cancer is still evident for both sexes in Central and Eastern Europe. The trends in mortality from gallbladder cancer are probably influenced by changes in risk factor exposure, such as diet, nutrition or tobacco, but essentially reflect more widespread and earlier adoption of cholecystectomy in the EU, since gallstones are the major risk factor for gallbladder cancer. The data also indicate the scope for further improvement of the management of gallbladder disease in Eastern Europe.     

Cigarette tar yield and risk of upper digestive tract cancers: case-control studies from Italy and Switzerland.

BACKGROUND: Tobacco smoking is one of the main risk factors for oral, pharyngeal and oesophageal cancers in developed countries. Information on the role of the tar yield of cigarettes in upper digestive tract carcinogenesis is sparse and needs to be updated because the tar yield of cigarettes has steadily decreased over the last few decades. PATIENTS AND METHODS: We analysed two case-control studies, from Italy and Switzerland, conducted between 1992 and 1999, involving 749 cases of oral and pharyngeal cancer and 1770 controls, and 395 cases of squamous-cell oesophageal carcinoma and 1066 matched controls. Odds ratios (ORs) were estimated by unconditional multiple logistic regression models, including terms for age, sex, study centre, education and alcohol consumption. RESULTS: Based on the brand of cigarettes smoked for the longest time, the multivariate ORs for current smokers compared with never smokers were 6.1 for <20 mg and 9.8 for >or=20 mg tar for oral and pharyngeal neoplasms, and 4.8 and 5.4 for oesophageal cancer, respectively. For the cigarette brand smoked in the previous six months, the ORs for >or=10 mg compared with <10 mg were 1.9 for cancer of the oral cavity and pharynx and 1.8 for oesophageal cancer, after allowance for number of cigarettes and duration of smoking. CONCLUSIONS: The present study confirms the direct relationship between the tar yield of cigarettes and upper digestive tract neoplasms, and provides innovative information on lower tar cigarettes, which imply reduced risks compared with higher tar ones. However, significant excess risks were observed even in the lower tar category, thus giving unequivocal indications for stopping smoking as a priority for prevention of upper digestive tract neoplasms.     

Flavonoids and breast cancer risk in Italy.

Few epidemiologic studies have investigated the potential relation between flavonoids and breast cancer risk. We have applied recently published data on the composition of foods and beverages in terms of six principal classes of flavonoids (i.e., flavanones, flavan-3-ols, flavonols, flavones, anthocyanidines, and isoflavones) on dietary information collected in a large-case control study of breast cancer conducted in Italy between 1991 and 1994. The study included 2,569 women with incident, histologically confirmed breast cancer, and 2,588 hospital controls. Odds ratios (OR) and 95% confidence intervals were estimated by multiple logistic regression models. After allowance for major confounding factors and energy intake, a reduced risk of breast cancer was found for increasing intake of flavones (OR, 0.81, for the highest versus the lowest quintile; P-trend, 0.02), and flavonols (OR, 0.80; P-trend, 0.06). No significant association was found for other flavonoids, including flavanones (OR, 0.95), flavan-3-ols (OR, 0.86), anthocyanidins (OR, 1.09), as well as for isoflavones (OR, 1.05). The findings of this large study of an inverse association between flavones and breast cancer risk confirm the results of a Greek study.     

Dietary folate and risk of prostate cancer in Italy.

Folate status may affect cancer risk through its role in both methylation and nucleotide synthesis of DNA. A low dietary intake of folate has been linked to risk of several cancers, but epidemiologic studies with reference to prostate cancer are scanty. We therefore analyzed data from a case-control study of prostate cancer conducted between 1991 and 2002 in various areas of Italy. Cases were 1,294 patients with incident, histologically confirmed prostate cancer and controls were 1,451 patients admitted to the same network of hospitals of cases for acute, nonneoplastic conditions. All subjects were < 75 years old. Intake of folate and other nutrients was computed from a validated food frequency questionnaire. We adjusted for energy intake using the residual method, and calculated multivariate odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression. The OR of prostate cancer was 0.66 (95% CI, 0.51-0.85) for the highest versus the lowest quintile of folate intake. The relation between dietary folate and prostate cancer was consistent across strata of age, methionine, vitamin B6, and alcohol intake, and did not vary substantially according to Gleason score of prostate cancer. The combined OR for high-folate and low-alcohol intake versus low-folate and high-alcohol intake was 0.46 (95% CI, 0.29-0.75). Therefore, this study supports a favorable role of dietary folate on prostate cancer risk.     

Novel histone deacetylase inhibitors in the treatment of thyroid cancer.

Histone deacetylases (HDAC) and histone acetyltransferases exert opposing enzymatic activities that modulate the degree of acetylation of histones and other intracellular molecular targets, thereby regulating gene expression, cellular differentiation, and survival. HDAC inhibition results in accumulation of acetylated histones and induces differentiation and/or apoptosis in transformed cells. In this study, we characterized the effect of two HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and m-carboxycinnamic acid bis-hydroxamide, on thyroid carcinoma cell lines, including lines originating from anaplastic and medullary carcinomas. In these models, both SAHA and m-carboxycinnamic acid bis-hydroxamide induced growth arrest and caspase-mediated apoptosis and increased p21 protein levels, retinoblastoma hypophosphorylation, BH3-interacting domain death agonist cleavage, Bax up-regulation, down-regulation of Bcl-2, A1, and Bcl-x(L) expression, and cleavage of poly(ADP-ribose) polymerase and caspase-8, -9, -3, -7, and -2. Transfection of Bcl-2 cDNA partially suppressed SAHA-induced cell death. SAHA down-regulated the expression of the apoptosis inhibitors FLIP and cIAP-2 and sensitized tumor cells to cytotoxic chemotherapy and death receptor activation. Our studies provide insight into the tumor type-specific mechanisms of antitumor effects of HDAC inhibitors and a framework for future clinical applications of HDAC inhibitors in patients with thyroid cancer, including histologic subtypes (e.g., anaplastic and medullary thyroid carcinomas) for which limited, if any, therapeutic options are available.     

Does an apple a day keep the oncologist away?

BACKGROUND: Apples have commonly been described as a healthy food. To understand better their role on risk of cancer at several sites, we analyzed data from multicenter case-control studies conducted between 1991 and 2002 in Italy. PATIENTS AND METHODS: The studies included 598 patients with incident cancers of the oral cavity and pharynx, 304 of the oesophagus, 460 of the larynx, 1953 of the colorectum, 2569 of the breast, 1031 of the ovary and 1294 of the prostate. The comparison group included a total of 6629 patients admitted to the same network of hospitals as cases for acute, non-neoplastic diseases. Multivariate odds ratios (OR) were obtained with allowance for age, sex, study center, education, body mass index, tobacco smoking, alcohol drinking, total energy intake, vegetable consumption and physical activity. RESULTS: Compared with subjects reporting consumption of <1 apple/day, the ORs for > or =1 apple/day were 0.79 [95% confidence interval (CI) 0.62-1.00] for cancers of the oral cavity and pharynx, 0.75 (95% CI 0.54-1.03) for oesophagus, 0.80 (95% CI 0.71-0.90) for colorectum, 0.58 (95% CI 0.44-0.76) for larynx, 0.82 (95% CI 0.73-0.92) for breast, 0.85 (95% CI 0.72-1.00) for ovary and 0.91 (95% CI 0.77-1.07) for prostate. CONCLUSION: This investigation found a consistent inverse association between apples and risk of various cancers.     

IMRT for breast. a planning study.

BACKGROUND AND PURPOSE: To evaluate the performance of ten different treatment-planning systems when intensity modulated (IMRT) plans are designed for breast treatments that include the irradiation of the internal mammary chain. PATIENTS AND METHODS: A dataset of five patients (CT images and volumes of interest) was distributed to design IMRT plans on the ten systems. To minimise biases, the same geometry and clinical planning aims were imposed on the individual plans. Results were analysed in terms of dose distributions and dose volume histograms. RESULTS AND CONCLUSIONS: For target coverage, the volume receiving more than 95% of the prescribed dose ranged from 77% (OTP) to 91% (Eclipse and Pinnacle), the volume receiving more than 107% ranged from 3.3% (Hyperion) to 23.2% (OTP). The mean dose to ipsilateral lung ranged from 13 Gy (Eclipse) to 18 Gy (OTP). The volume of the contralateral breast receiving more than 10 Gy ranged from 3% (Pinnacle) to 26% (Precise). The volume of heart receiving more than 20 Gy ranged from 7% (Eclipse) to 47% (Precise), the maximum significant dose to heart ranged from approximately 27 Gy (XiO) to approximately 49 Gy (Precise). The maximum significant dose to healthy tissue ranged from approximately 51 Gy (Eclipse) to approximately 62 Gy (OTP). It was also possible to show that the treatment geometry proposed here enables to minimise contralateral breast irradiation while keeping minimal ipsilateral lung (or heart) involvement and satisfactory target coverage.     

Lung cancer mortality in European women: recent trends and perspectives

Background: Lung cancer mortality in men has been decliningsince the late 1980s in most European countries. In women, althoughrates are still appreciably lower than those for men, steadyupward trends have been observed in most countries. To quantifythe current and future lung cancer epidemic in European women,trends in lung cancer mortality in women over the last fourdecades were analyzed, with specific focus on the young. Patients and methods: Age-standardized (world standard) lungcancer mortality rates per 100 000 women—at all ages,and truncated 35–64 and 20–44 years—were derivedfrom the WHO for the European Union (EU) as a whole and for33 separate European countries. Joinpoint regression analysiswas used to identify points where a significant change in trendsoccurred. Results: In the EU overall, female lung cancer mortality ratesrose by 23.8% between 1980–1981 and 1990–1991 (from7.8 to 9.6/100 000), and by 16.1% thereafter, to reach the valueof 11.2/100 000 in 2000–2001. Increases were smaller inthe last decade in several countries. Only in England and Wales,Latvia, Lithuania, Russia and Ukraine did female lung cancermortality show a decrease over the last decade. In several Europeancountries, a decline in lung cancer mortality in young women(20–44 years) was observed over the last decade. Conclusions: Although female lung cancer mortality is stillincreasing in most European countries, the more favorable trendsin young women over recent calendar years suggest that if effectiveinterventions to control tobacco smoking in women are implemented,the lung cancer epidemic in European women will not reach thelevels observed in the USA. Key words: Europe, lung cancer, mortality, trends, women     

High affinity for the rat brain sodium channel of newly discovered hydroxybenzoate saxitoxin analogues from the dinoflagellate Gymnodinium catenatum.

The paralytic shellfish poison family has been recently extended by the discovery of several analogues possessing a hydoxybenzoate moiety instead of the carbamoyl group one finds in saxitoxin, the parent molecule of this toxin family. We have investigated the potency of these new analogues on a representative isoform of the pharmacological target of these toxins, the voltage gated sodium channel. These toxins were found to have K1's in the low nanomolar range, only slightly less potent than saxitoxin. The hydroxybenzoate group may increase the lipophilicity of these toxins and improve their ability to pass through epithelia and therefore its uptake and elimination in both intoxication victims and animals that bioaccumulate paralytic shellfish toxins.