The role of CEA, CYFRA21-1 and NSE in monitoring tumor response to Nivolumab in advanced non-small cell lung cancer (NSCLC) patients.

BACKGROUND: CEA, CYFRA21-1 and NSE are tumor markers used for monitoring the response to chemotherapy in advanced adenocarcinoma, squamous cell carcinoma and small-cell lung cancer, respectively. Their role in cancer immunotherapy needs to be elucidated. METHODS: Patients with advanced non-small cell lung cancer (NSCLC) were treated with nivolumab 3 mg/kg every 2 weeks within the Italian Nivolumab Expanded Access Program. Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient's withdrawn from the study. All patients underwent a CT-scan after every 4 cycles of treatment and responses were classified according to RECIST 1.1. The biomarkers serum levels were measured with a chemiluminescent microparticle immunoassay for CEA and with an immuno radiometric assay for CYFRA21-1 and NSE. The markers values at baseline and after 4 cycles were used to analyze the relationship between their variation over baseline and the tumor response, evaluated as disease control rate (DCR: CR + PR + SD), and survival (PFS and OS). RESULTS: A total of 70 patients were evaluable for the analysis. Overall, a disease control was obtained in 24 patients (35.8%, 4 PR + 20 SD). After 4 cycles of nivolumab a CEA or CYFRA21-1 reduction ≥ 20% over the baseline was significantly associated with DCR (CEA, p = 0.021; CYFRA21-1, p < 0.001), PFS (CEA, p = 0.028; CYFRA21-1, p < 0.001) and OS (CEA, p = 0.026; CYFRA21-1, p = 0.019). Multivariate analysis confirmed the ability of CYFRA21-1 reduction ≥ 20% to predict DCR (p = 0.002) and PFS (p < 0.001). CONCLUSION: The reduction in serum level of CYFRA21-1 or CEA might be a reliable biomarker to predict immunotherapy efficacy in NSCLC patients. NSE was not significant for monitoring the efficacy of nivolumab.

Outcome of EGFR inhibitors treatment in advanced NSCLC patients, not enrolled in clinical trials.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become a treatment after first-line chemotherapy in patients with advanced NSCLC. We assessed the predictive and prognostic role of EGFR and Kras mutations in NSCLC patients treated with TKIs after progression, not included in clinical trials. Gefitinib 250 mg or Erlotinib 150 mg per os were administered to 70 patients. Radiological assessment was performed every six weeks. EGFR and Kras mutations were found in 21.4% and 24.3% of patients, respectively. At multivariate analysis, Kras mutation was positively associated with progression-free survival (PFS; HR=0.71, 95% CI: 0.53-0.96; p=0.027) and, less clearly, with response (OR=1.84, 95% CI: 0.98-3.45; p=0.057) and survival (HR=0.74, 95% CI:0.54-1.02; p=0.066). EGFR mutation influenced positively PFS (HR=0.69, 95% CI: 0.47-1.02; p=0.06), but not survival. In conclusion, in our unselected patients mutation of Kras correlated with a better outcome. The small number of patients may explain some discrepancies with data in literature.

New York Heart Association class and pulmonary artery pressure as prognostic factors of interstitial lung disease survival.

OBJECTIVE: The aim of this study was to evaluate New York Heart Association (NYHA) class and systolic pulmonary artery pressure (sPAP) as survival predictors in major interstitial lung diseases (ILD) including idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP) and hypersensitivity pneumonitis (HP) and in other ILD like granulomatosis with polyangiitis (GPA). PATIENTS AND METHODS: We analyzed survival, NYHA class, sPAP, and Octreoscan uptake index (UI) in 104 ILD patients (59 IPF, 19 NSIP, 10 HP and 16 GPA; median age 60.5 years) all referred to a single centre. RESULTS: Median survival was 68 months, with 1- and 2-year survival of 91% and 78%, respectively. Survival was lower among IPF and NSIP vs. HP and GPA patients (p=0.01). NYHA class 3-4 was more frequent among IPF (76.3%) vs. NSIP patients (31.6%; p<0.001). HP and GPA had NYHA class 1-2. NYHA class was negatively associated with survival (class 1=90.3 months vs. class 3=18.3 months and class 4=5.1 months; p=0.001). sPAP was >55 mmHg in 76.3% of patients with IPF and 35-55 mmHg in 63.2% of patients with NSIP. Patients with HP and GPA had sPAP < 55 mmHg. Among patients with IPF, NYHA and sPAP were negatively associated with survival (p<0.01) both showed a parallel trend. High-resolution computed tomography and survival were worse among IPF and NSIP vs. HP and GPA patients (p<0.001). Octreoscan UI was <10, 10-12, and >12 in IPF, NSIP, HP and GPA, respectively. Octreoscan UI was negatively associated with survival (p=0.002). CONCLUSIONS: NYHA class and sPAP are comparable ILD survival predictors. NYHA class is correlated with worse prognosis for IPF and NSIP vs. HP and GPA patients.

Breast cancer incidence trends in European women aged 20-39 years at diagnosis.

An increase in the incidence of breast cancer in women aged<40 years has been reported in recent years. Increased incidence could be partly explained by subtle detection biases, but the role of other risk factors cannot be ruled out. The purpose of the present study was to investigate the changes in temporal trends in breast cancer incidence in European women aged 20-39 years at diagnosis. Age specific breast cancer incidence rates for 17 European Cancer Registries were retrieved for the calendar period 1995-2006. Cancer registries data were pooled to reduce annual fluctuations present in single registries and increase incidence rates stability. Regression models were fitted to the data assuming that the number of cancer cases followed the Poisson distribution. Mean annual changes in the incidence rate (AIC) across the considered time window were calculated. The AIC estimated from all European registries was 1.032 (95% CI=1.019-1.045) and 1.014 (95% CI=1.010-1.018) in women aged 20-29 and 30-39 years old at diagnosis, respectively. The major change was detected among women aged 25-29 years at diagnosis: AIC=1.033 (95% CI=1.020-1.046). The upward trend was not affected when registries with high or low AIC were removed from the analysis (sensitivity analysis). Our findings support the presence of an increase in the incidence of breast cancer in European women in their 20s and 30s during the decade 1995-2006. The interpretation of the observed increase is not straightforward since a number of factors may have affected our results. The estimated annual increase in breast cancer incidence may result in a burden of the disease that is important in terms of public health and deserves further investigation of possible risk factors.

Cap-assisted endoscopic mucosal resection of large polyps involving the ileocecal valve.

Standard endoscopic mucosal resection (EMR) is limited with regard to lesions below or involving the ileocecal valve. We describe the treatment and outcomes when using cap-assisted EMR (EMR-C) to remove large laterally spreading tumors (LSTs) with ileal infiltration in seven patients (median age 74 years). Each LST (median size 40 mm) was successfully resected in one session (median procedure time 50 minutes). Intraprocedural and early bleeding occurred in two patients, and delayed hemorrhage in one. Circumferential resection of the ileum caused asymptomatic strictures in six patients, with regression during follow-up for five. We conclude that the novel EMR-C method is a potentially effective treatment for cecal LST involving the distal ileum. Serious complications such as perforation or symptomatic strictures of the ileocecal valve were not observed and any procedure-related bleeding was easily controlled.

Self-expanding plastic stent to palliate symptomatic tissue in/overgrowth after self-expanding metal stent placement for esophageal cancer.

Self-expanding metal stents (SEMS) are used to treat obstructive malignancies of the esophagus or esophagogastric junction; however, a potential complication is recurrent dysphagia because of tissue in/overgrowth. The placement of a second SEMS is one strategy to re-establish patency of the esophageal lumen. We evaluated the safety and efficacy of an alternative and likely less costly approach: placing a self-expanding plastic stent (SEPS) to manage relapsing dysphagia in patients previously treated with a partially covered SEMS. From December 2007 to January 2009, 13 patients previously treated with a SEMS for malignant dysphagia underwent treatment by inserting a SEPS to palliate relapsing dysphagia, as a result of tissue in/overgrowth. Stenosis was located in the upper esophagus in one patient, in the middle in four patients, and in the lower esophagus in eight patients. Clinical evaluation was performed at the time of stent placement, after 1 week, and then, monthly until death. The SEPS was successfully placed in a single treatment session for all patients. No preliminary dilation was required, and no further treatment was necessary for any patient. Before stenting, the median dysphagia score was 4 (range 3-4), and 1 week later the score was 0 for all patients. The resolution of dysphagia persisted until patient death (from tumor progression). The mean survival after the SEPS insertion was 4 months (range 3-8). This case series supports the use of a SEPS to palliate dysphagia from tissue in/overgrowth of a SEMS. Future clinical trials with larger patient samples are warranted.

[Evaluation of a series of serum mesothelin in patients with pleural malignant mesothelioma]. / Valutazione di dosaggi seriati di mesotelina sierica in pazienti affetti da mesotelioma maligno della pleura.

Pleural Malignant Mesothelioma (MM) is a highly aggressive neoplasm with a poor survival rate, hard diagnosis and treatment. The incidence of MM in Western Europe countries is expected to increase drammatically in the next 10-15 years. In spite of this drammatic scenario, at this time the only instruments for screening and early diagnosis are based on radiological tests with evident ethical and economical problems. For this reason, some authors are evaluating biological indicators with the significance of screening and early diagnosis markers. One of the most promising marker is serum mesothelin (SMRP). SMRP levels appeares to be significantly related to MM and its clinical (diagnostic/prognostic) usefulnes has been suggested. The purpose of this research is to show SMRP trend in relation both to the course of the disease and the response to therapies in some Epithelioid MM patients. The analysis of SMRP levels in these patients suggests that it may be a useful marker for monitoring the response to treatment. In fact, it was observed that SMRP increases in patients who did not respond to therapy, it tends to remain stable when therapies results into a clinical stabilization, while it decreases after surgical procedure and in case of clinical improvement.

[Serum mesothelin dosages in follow-up of previously exposed workers]. / Il dosaggio della mesotelina sierica nel follow-up dei lavoratori ex esposti ad amianto.

High dosages of Serum Mesothelin have been demonstrated to be significantly associated to Pleural Malignant Mesothelioma. We recently demonstrated that Serum Mesothelin may be clinically helpful both for diagnostic and prognostic purposes, with the best cut-off corresponding to 1 nM. We also discovered that high levels of Serum Mesothelin are significantly associated to Lung Cancer. The usefulness of this marker in secondary prevention has been suggested, though never demonstrated. We therefore started a long-term prospective cohort study including previously asbestos-exposed workers. These subjects periodically underwent both radiological tests and serum mesothelin dosages. As a mid-term goal of this longitudinal study we decided to check the variability of mesothelin dosages, comparing baseline and follow-up values, as well as the possible correlation with age, duration of exposure, smoking, any abnormality of respiratory functional tests (RFT) and/or radiological tests. At baseline, Mesothelin mean value was 0.66 +/- 0.4 (range 0.08-2.2 nM). Both age (p = 0.04) and abnormal thoracic TC (p = 0.04) were significantly correlated with increased serum mesothelin levels and increasing age. No association was found between baseline mesothelin levels and duration of asbestos exposure (p = 0.5), smoking habits (p = 0.2), abnormal RFT, DLCO (carbon monoxide diffusing capacity) or thoracic X-ray. No significant variation was observed between mesothelin values at baseline and at follow-up (p = 0.2).

Association between coffee or tea drinking and Barrett's esophagus or esophagitis: an Italian study.

BACKGROUND/OBJECTIVES: Only a few papers have treated of the relationship between Barrett's esophagus (BE) or erosive esophagitis (E) and coffee or tea intake. We evaluated the role of these beverages in BE and E occurrence. SUBJECTS/METHODS: Patients with BE (339), E (462) and controls (619) were recruited. Data on coffee and tea and other individual characteristics were collected using a structured questionnaire. RESULTS: BE risk was higher in former coffee drinkers, irrespective of levels of exposure (cup per day; ⩽1: OR=3.76, 95% CI 1.33-10.6; >1: OR=3.79, 95% CI 1.31-11.0; test for linear trend (TLT) P=0.006) and was higher with duration (>30 years: OR=4.18, 95% CI 1.43-12.3; TLT P=0.004) and for late quitters, respectively (⩽3 years from cessation: OR=5.95, 95% CI 2.19-16.2; TLT P<0.001). The risk of BE was also higher in subjects who started drinking coffee later (age >18 years: OR=6.10, 95% CI 2.15-17.3). No association was found in current drinkers, but for an increased risk of E in light drinkers (<1 cup per day OR =1.85, 95% CI 1.00-3.43).A discernible risk reduction of E (about 20%, not significant) and BE (about 30%, P<0.05) was observed in tea drinkers. CONCLUSIONS: Our data were suggestive of a reduced risk of BE and E with tea intake. An adverse effect of coffee was found among BE patients who had stopped drinking coffee. Coffee or tea intakes could be indicative of other lifestyle habits with protective or adverse impact on esophageal mucosa.

Age and comorbidities deeply impact on clinical outcome of patients with myelodysplastic syndromes.

BACKGROUND: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders, with very different prognosis in given individuals; age and comorbidities are emerging as relevant patient-related factors influencing clinical outcome in MDS. Our aim was to evaluate the impact of age, comorbidities and disease severity (IPSS and IPSS-R prognostic scores) in a "real-life" series of MDS patients. METHODS: 318 patients with available assessment of comorbidities at diagnosis and consecutively registered into the Registro Ligure delle Mielodisplasie were analyzed. Comorbidities were evaluated according to HCT-CI and MDS-CI comorbidity indexes. Overall survival (OS) and the probability of death among patients who did not develop acute myeloid leukemia (NLD cumulative incidence) were analyzed. RESULTS: Comorbidities were seen in 177 (55.7%) patients. An older age (>75 y) had a significant negative impact on OS (p=0.008). HCT-CI was not associated with OS. MDS-CI was of prognostic significance (p=0.001), but the association was limited to pts with IPSS or IPSS-R "lower-risk". In multivariate analysis, MDS-CI remained an independent factor associated with OS and with an increased risk of NLD both when controlling for IPSS (p=0.019 and p=0.001, respectively) and for IPSS-R (p=0.048 and p=0.002, respectively). CONCLUSIONS: Evaluation of age and comorbidities according to a tailored tool such is MDS-CI helps to predict survival in patients with MDS and should be incorporated to current prognostic scores.

Reproducibility of an Italian food frequency questionnaire for cancer studies: results for specific food items.

To evaluate the reproducibility of a quantitative food frequency questionnaire (FFQ) used in a case-control study on cancer of the breast, ovary and digestive tract, we compared the result of a 98-item questionnaire administered twice at an interval of 3-10 months (median = 5.4 months) to 452 volunteers (144 males and 308 females, median age = 50 years) from three Italian provinces (Pordenone, Genoa and Forlí). Spearman correlation coefficients (r) for intake frequency of 87 dietary items ranged from 0.35 ("chicken or turkey, boiled") to 0.84 ("wine"). Most coefficients were between 0.60 and 0.80, only two being below 0.40 and five equal or above 0.80 (mean r = 0.59). The concordance of the two measurements tended to be somewhat better for alcoholic and non-alcoholic beverages, bread, cereals and first courses, fruits and summary questions at the end of each section of the questionnaire than for side dishes, sweets and desserts. Also, the reproducibility of 11 subjective questions, such as those concerning the amount of fat in seasoning and the intake of garlic or salt, seemed to be high. Age, sex, educational level of the volunteers and interval between the two FFQ did not have a large or systematic impact on the concordance of the two measurements. In conclusion, the present study has shown a good level of reproducibility of our questionnaire and has provided a few important hints on ways of improving the description of various food items.

The influence of reproductive and hormonal factors on the risk of colon and rectal cancer in women.

A case-control study was conducted between 1992 and 1996 in six Italian areas. It included 537 women with colon cancer, 291 women with rectal cancer and 2081 control women in hospital for acute conditions, unrelated to hormonal or gynaecological diseases. A higher age at menopause was associated with increased colon cancer risk (odds ratio (OR) for > or = 53 years compared with < 50 years = 1.39, 95% confidence interval (CI) 1.04-1.87). Among parous women, a significant trend of decreasing colon cancer risk with increasing number of births was seen for colon (OR for > or = 4 births compared with 1 birth = 0.62, 95% CI 0.42-0.90), but not for rectal cancer. Nulliparous women, however, were at lower risk than women with a single birth, and age at first birth was directly associated with risk. While oral contraceptive use showed no significant influence, ever users of hormone replacement therapy had a reduced risk of rectal cancer (OR = 0.56, 95% CI 0.31-1.01). Thus, the association of colorectal cancer with reproductive and menstrual factors is neither strong nor consistent.

Reproducibility of an Italian food frequency questionnaire for cancer studies. Results for specific nutrients.

The reproducibility of measures of the intake of total energy and 27 selected nutrients from a quantitative food frequency questionnaire (FFQ) used in a case-control study on cancer of the breast, ovary, and digestive tract was evaluated. The results of two FFQ administrations at an interval of 3 to 10 months (median = 5.4 months) to 452 volunteers (144 males and 308 females; median age = 50 years) from three Italian provinces (Pordenone, Genoa, and Forì) were compared. Pearson correlation coefficients (r) between crude nutrient intake (unadjusted for energy) ranged from 0.50 for vegetable fat to 0.80 for alcohol, with most values falling between 0.60 and 0.70 (median r = 0.67). Adjustment of nutrient intakes for total energy slightly decreased most coefficients (median r = 0.60). The agreement between the two measurements did not differ substantially by sex, age, education, and interval between interviews. The contribution of specific FFQ components (i.e., frequency-only questions, open questions, portion size, and fat intake pattern) was also assessed separately with respect to the performance and reproducibility of nutrient measures, yielding, in general, very similar results. The seven questions concerning individual fat intake pattern, which were used to modulate the composition of various recipes, led, however, to a significant increase in mean daily intake of vegetable fat, oleic acid, and vitamin E, but a reduction of estimated daily intake of linoleic acid and polyunsaturated fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic value of CYFRA 21-1 tumor marker and CEA in pleural effusion due to mesothelioma.

STUDY OBJECTIVE: The aim of our study was to assess the clinical value of CYFRA 21-1 tumor marker and carcinoembryonic antigen (CEA) as diagnostic tools that are complementary to cytology in the diagnosis of malignant mesotheliomas. PATIENTS: We measured CEA and CYFRA 21-1 in the pleural effusions (PEs) and serum of 106 patients (benign lung disease, 34 patients; bronchogenic and metastatic carcinoma, 40 patients; mesothelioma, 32 patients). METHODS: CEA and CYFRA 21--1 levels were determined by means of two commercial enzyme immunoassays. RESULTS: The cutoff levels of CYFRA 21--1 and CEA in malignant PEs, selected on the basis of the best diagnostic efficacy, were 41.9 ng/mL and 5.0 ng/mL, respectively. In all neoplastic PEs, CYFRA 21--1 and CEA sensitivity was 78% and 30.6%, respectively, with a specificity of 80% and 91%, respectively. The sensitivity of CYFRA 21--1 and CEA in patients with mesothelioma was 87.5% and 3.1%, respectively. The results of the CYFRA 21--1 assay were positive in 17 of 19 cases of mesothelioma (89.5%) with a negative or uncertain cytology. The association of the tumor marker assay and the cytology allowed a correct diagnosis in 30 of 32 cases of mesothelioma (93.7%). CONCLUSION: This study suggests that CYFRA 21--1 would provide a useful parameter for the differential diagnosis between benign and malignant PE from mesothelioma when the result of cytology is negative or uncertain and the clinical context does not allow a more aggressive approach. Moreover, the association of CYFRA 21--1 with CEA could provide details for a differential diagnosis between mesotheliomas and carcinomas. In fact, an elevated CYFRA 21--1 level with a low CEA level is highly suggestive of mesothelioma, whereas high levels of CEA alone or high levels of both the markers suggest a diagnosis of malignant PE, excluding mesothelioma.

Socioeconomic status, migration and the risk of breast cancer in Italy.

BACKGROUND: High socioeconomic status and migration to a higher risk area have been linked to increased breast cancer risk. To evaluate the occurrence of breast cancer in women of different social class and residential history, we conducted a multicentre case-control study in Italy. METHODS: A total of 2569 cases of incident breast cancer were ascertained in northern, central and southern Italy. The controls were 2588 women admitted for a wide spectrum of acute conditions to the same hospitals where cases had been hospitalized. The effect of socioeconomic variables was evaluated with multiple logistic regression after stratification and adjustment for age, origin, centre, and selected reproductive and dietary factors. RESULTS: Compared to housewives, managers and professionals had a 1.7-fold increased risk, whereas the relative risk was 0.7 and 0.6 respectively in helpers and manual workers. The risk of breast cancer also increased with increasing social level of the husbands's occupation and subjects's number of years of schooling. Women who originated in central and southern Italy, and migrated to northern Italy after age 24, but not those who migrated at a younger age, had a relative risk of 0.6 and 0.7 respectively, compared to lifelong residents in northern Italy. CONCLUSIONS: Our findings show that correlates of sociocultural level and place of origin exert an influence on breast cancer risk which is not accounted for completely by known risk factors (i.e. reproductive and menstrual characteristics and recent dietary habits). Such influence may thus occur early in life.

High-risk subjects for vitamin deficiency.

Chronic deficiency of various vitamins can influence the occurrence of some chronic degenerative diseases such as cancer, cardiovascular pathology, cataract, arthritis, disorders of the nervous system and photosensitivity. Similarly, vitamin intake can influence various disorders in infants and elderly people, in burns and in subjects following unbalanced diets or undergoing strenuous physical exercise. Among vitamins, beta-carotene, vitamin E and vitamin C have received most attention, particularly in the prevention of oxidative damage from free radicals. It is supposed that each vitamin plays a different role in the pathogenesis of various diseases, depending on the type of damage relevant to a specific disease. Results from different studies are still far from conclusive and the effects on longevity are not well defined. In industrialized countries, vitamin deficiencies seem to be related only to specific and clearly identifiable groups in the population: therefore, at the moment, it seems more advisable to target vitamin supplementation at risk groups.

Regional and national variation in lung cancer mortality in Italy and Czechoslovakia.

In developed countries lung cancer mortality has been shown to be related to lifestyle, occupational and environmental aspects, diet, and other factors which may vary widely from one region to another. To investigate inter-area differences in lung cancer mortality and cigarette smoking a descriptive study has been carried out in three areas of Italy and two republics of Czechoslovakia. The highest death rates from lung cancer were found in the Czech Republic and Northern Italy, for both sexes. Analysis of age-specific rates by birth cohort, comparing all five areas, showed the greatest differences in trends between Slovakia and Northern Italy in men, and between the Czech Republic and Southern Italy in women. The lowest rates were observed in Southern Italy throughout the period under study, particularly among women. Making allowance for the latency period between the onset of exposure and the development of the disease, data on the occurrence of lung cancer could be interpreted looking at previous smoking habits. An imperfect overlap between the trend of cigarette smoking and the corresponding lung cancer mortality pattern was present in Northern and Southern Italy, a finding suggesting that even non-smoking-related factors could have played a significant role in lung cancer aetiology.

Carditis, intestinal metaplasia and adenocarcinoma of oesophagogastric junction.

Barrett's oesophagus is a precancerous condition in which the normal squamous epithelium is replaced by intestinal metaplasia (IM). IM can then progress through increasingly severe dysplasia to oesophageal adenocarcinoma (EAC). In the gastric cardia the normal gastric mucosa, when inflamed (carditis), can be replaced by IM and can then progress to gastric adenocarcinoma (GAC). The same histopathological sequence can take place on either side of the oesophagogastric junction. Since the location of that junction can be uncertain this can result in confused diagnosis between EAC and GAC. In this review, the diagnostic criteria, incidence and risk factors for Barrett's oesophagus and carditis are discussed, together with the factors determining the risk of progression to adenocarcinoma of the oesophagus or cardia. The risk factors include familial/genetic, environmental and dietary characteristics. Finally, these risk factors are discussed within the context of cancer prevention.

Vitamins and cancer chemoprevention.

Chemoprevention is in an area of cancer research with perhaps the greatest potential for reducing cancer mortality. Several agents, and in particular antioxidant vitamins, appear to be effective against early rather than later steps of the premalignant process at different sites. Particular attention must be paid to possible side effects and safety of the agents and to optimal doses in long-term administration regimens. The results of numerous trials on the preventive role of vitamins (e.g. beta-carotene, retinols, retinoids, alpha-tocopherol, ascorbic acid, folic acid) are contradictory and far from conclusive. Multiple primary and secondary intervention trials currently under way should assess in the coming years the role of some vitamins in the prevention of various cancers (oral cavity, pharynx, oesophagus, colon, lung, breast, skin, cervix, bladder).