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Biomedical subjects

R Filiberti

Publications and source records attributed to R Filiberti.

At least 19 recordsLinked to original sources

Meta- and pooled analysis of GSTT1 and lung cancer: a HuGE-GSEC review.

Lung cancer is the most common malignancy in the Western world, and the main risk factor is tobacco smoking. Polymorphisms in metabolic genes may modulate the risk associated with environmental factors. The glutathione S-transferase theta 1 gene (GSTT1) is a particularly attractive candidate for lung cancer susceptibility because of its involvement in the metabolism of polycyclic aromatic hydrocarbons found in tobacco smoke and of other chemicals, pesticides, and industrial solvents. The frequency of the GSTT1 null genotype is lower among Caucasians (10-20%) than among Asians (50-60%). The authors present a meta- and a pooled analysis of case-control, genotype-based studies that examined the association between GSTT1 and lung cancer (34 studies, 7,629 cases and 10,087 controls for the meta-analysis; 34 studies, 7,044 cases and 10,000 controls for the pooled analysis). No association was observed between GSTT1 deletion and lung cancer for Caucasians (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.87, 1.12); for Asians, a positive association was found (OR = 1.28, 95% CI: 1.10, 1.49). In the pooled analysis, the odds ratios were not significant for either Asians (OR = 0.97, 95% CI: 0.83, 1.13) or Caucasians (OR = 1.09, 95% CI: 0.99, 1.21). No significant interaction was observed between GSTT1 and smoking on lung cancer, whereas GSTT1 appeared to modulate occupational-related lung cancer.

Asian People↗

Study of pretreatment serum levels of HER-2/neu oncoprotein as a prognostic and predictive factor in patients with advanced nonsmall cell lung carcinoma.

BACKGROUND: HER-2/neu tissue overexpression is found in nearly 15% of patients with nonsmall cell lung carcinoma and is reported to affect prognosis adversely in surgical series. However, the prognostic role of serum HER-2/neu oncoprotein, particularly in patients with advanced lung carcinoma, remains unknown. This study was designed to assess the potential value of measuring serum levels of HER-2/neu oncoprotein in predicting response to treatment and survival in patients with locally advanced and metastatic nonsmall cell lung carcinoma. METHODS: Baseline serum HER-2/neu levels (fm/mL) were studied using an enzyme-linked immunosorbent assay method in 84 patients with newly diagnosed, advanced nonsmall cell lung carcinoma who underwent chemotherapy. RESULTS: The patients enrolled in the study included 76 males and 8 females, with a median age of 62 years (range, 36-73 years) and a median performance status of 1. Fifty patients (59.5%) had nonsquamous histology, and 34 patients (40.5%) had squamous cell carcinoma. Thirty-four patients (40.5%) had Stage III disease, and 50 patients (59.5%) had Stage IV disease. The mean baseline value of HER-2/neu in the whole series was 56.1 fm/mL (range, 13.0-103.8 fm/mL). HER2 immunohistochemistry on paraffin embedded tissue was performed in 18 patients. HER-2/neu tissue overexpression was found in only one patient, who also showed high serum levels (102 fm/mL). No correlation was observed between protein serum quantitation and gender, age, histology, stage, performance status, leukocyte count, or smoking. Nonresponding and responding patients exhibited similar oncoprotein levels (median, 57.6 fm/mL vs. 51.9 fm/mL, respectively). The overall survival rate was 42.5% at 1 year and 12% at 2 years, with a median survival duration of 10 months. At univariate analysis, high HER-2/neu serum levels were associated with an unfavorable survival outcome. Using a cut-off point for HER-2/neu of 73.0 fm/mL (corresponding to the 80th percentile of protein concentration), the survival of patients who had higher serum levels of HER-2/neu was significantly worse compared with patients who had lower serum levels (median, 7.1 months vs. 10.9 months; P = 0.004). Multivariate analysis confirmed the independent predictive value of serum HER-2/neu concentration as a negative prognostic factor (P = 0.02). CONCLUSIONS: High pretreatment levels of HER-2/neu oncoprotein are associated with an adverse prognostic impact on survival in patients with locally advanced or metastatic nonsmall cell lung carcinoma.

Adult↗

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.

Adenocarcinoma↗

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.

Antigens, Neoplasm↗

Analysis of erythrocyte glycophorin-A variants by flow cytometry in lung disease patients detects the effect of tobacco smoke.

The glycophoryn A (GPA) assay evaluates somatic in vivo mutations. It is considered a cumulative biodosimeter for genotoxic exposures and is under evaluation in cancer risk assessment. GPA, a polymorphic membrane protein of the erythrocytes, determines the MN blood groups. The NO and NN variant frequencies (VF) may be detected in MN subjects (about 50% of the population) by flow cytometry using two differently labelled antibodies. We explored if GPA NO and NN VF might be relevant to the assessment of individual lung cancer risk and susceptibility, in a small population with a high prevalence of heavy tobacco smokers: 8 lung cancer patients and 16 subjects with non-malignant lung diseases associated with increased risk of lung cancer. There was a wide interindividual variability and complete overlap between non-neoplastic and neoplastic patients. A significant positive correlation was seen with smoking duration in NO VF (p = 0.04, age-adjusted). Current smokers (n = 12) displayed higher NO values than never (n = 1) or ex-smokers (n = 11), 36.3 +/- 18.2 and 21.0 +/- 13.2, respectively (p < 0.01). No association was shown with occupational exposure. The present exploratory study suggests that assessment of individual lung cancer risk and susceptibility by the GPA assay does not seem to be feasible. The assay appears to provide a biomarker of longterm exposure to tobacco smoke.

Aged↗

Endoscopic Nd:YAG laser therapy for villous adenomas of the right colon.

BACKGROUND: Endoscopic laser therapy is considered an acceptable treatment of benign colorectal adenomas. The aim of our study was to evaluate the efficacy of Nd:YAG laser to ablate right-sided colonic sessile adenomas. METHODS: Between January 1990 and February 1996, 56 patients underwent laser therapy because of high operative risk or refusal of surgery. Lesions were located as follows: cecum (23), ascending, (15), and hepatic flexure (18). Six patients (10.7%) had multiple polyps in the ascending colon. Histologic examination showed a tubulovillous pattern in 20 (35.7%) and a villous pattern in 36 (64.3%). Low-grade dysplasia was detected in 44 patients (78. 5%) and high-grade dysplasia in 12 (21.4%). RESULTS: The number of laser sessions ranged between 1 and 6 (median 3) and complete ablation, histologically confirmed, was achieved in 49 cases (87.5%). Seven patients (12.5%) underwent surgery: 2 for incomplete tumor destruction, 3 because of invasive carcinoma on repeated biopsies. Two patients (3.6%) had complications (one perforation of the cecum and one hemorrhage). Follow-up ranged from 6 to 60 months and no recurrences were observed. CONCLUSION: Laser therapy is an effective method for the destruction of sessile adenomas of the right colon in selected patients.

Adenoma, Villous↗

Physical activity and risk of cancers of the colon and rectum: an Italian case-control study.

We investigated the relationships between risk of colon and rectal cancers and physical activity in both sexes at different ages by a case-control study conducted between 1991 and 1996 in six Italian centres. Cases were 1225 patients (688 men, 537 women) below the age of 75 with colon cancer and the controls included 4154 patients (2073 men, 2081 women) admitted to hospital for acute, non-neoplastic conditions. We also analysed 722 cases of rectal cancer. Compared with the lowest level of occupational physical activity at 30-39 years old the odds ratios (OR) for the highest level were 0.64 (95% confidence interval, CI 0.44-0.93) in men and 0.49 (95% CI 0.33-0.72) in women. The inverse association in both sexes was similar at 15-19 and 50-59 years old. No association was found in either sex for leisure-time physical activity. For both sexes the inverse relationship between occupational physical activity at 30-39 years old and colon cancer risk was not significantly heterogeneous across strata of selected covariates, and for ascending, transverse, descending and sigmoid colon. Rectal cancer risk was not associated with any measure of physical activity (OR = 1.32 for men and 0.88 for women for the highest level of occupational physical activity at 30-39 years old compared with the lowest). This study confirms that occupational physical activity is protective against colon, but not against rectal cancer.

Adult↗

Macronutrient intake and risk of colorectal cancer in Italy.

To provide further insight on the relationship between macronutrients and colorectal cancer, overall and by specific subsite(s), we carried out between 1992 and 1996 in 6 Italian areas a case-control study on 1,953 individuals of both sexes with incident colorectal cancer (age range 19-74) and 4,154 controls (age range 19-74) in hospital with acute, non-neoplastic diseases. A validated food-frequency questionnaire was used, including questions on 78 foods or recipes and on individual fat-intake pattern. The risk of cancer of the colon and rectum increased with total energy intake (odds ratio in highest vs. lowest quintile 1.43 and 1.50, respectively). The risk also rose significantly with an increase of starch intake, whereas it moderately decreased with an increase of protein intake. Monounsaturated fat intake appeared uninfluential, while saturated fat intake showed a modest direct association with rectal cancer. Polyunsaturated fat intake was inversely associated with colon cancer risk, particularly with the right colon.

Adult↗

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.

Adult↗

Family history of cancer and risk of colorectal cancer in Italy.

Subjects with a family history of colorectal cancer (CRC) are at increased risk of CRC, but quantification of the risk in different populations, the possible differences in risk according to localization of the cancer and the association of family history of other cancers with CRC risk are still open issues. We have therefore analysed data from a multicentric case-control study conducted in six Italian areas between 1992 and 1996 of 1225 incident cases of colon cancer, 728 cases of rectal cancer and 4154 controls admitted for acute conditions to the same network of hospitals as the cases. Unconditional logistic regression models including terms for gender, age, study centre, years of education and number of siblings were used to estimate the odds ratios (ORs) of CRC according to various aspects of history of CRC and other cancers in first-degree relatives. The OR for family history of CRC was 3.2 (95% confidence interval, CI, 2.5-4.1) for colon cancer and 2.2 (95% CI 1.6-3.1) for rectal cancer. Colon cancer was significantly associated with a family history of stomach (OR 1.4), bone (OR 2.1) and kidney (OR 2.3) cancers, while rectal cancer was significantly associated with a family history of lymphomas (OR 2.8). There was a 30% higher risk of colon and rectal cancer in subjects with a family history of any cancer, excluding intestine. The ORs for family history of CRC were 5.2 for colon and 6.3 for rectum when the proband's age was below 45 years. The ORs were similar when the affected relative was a parent or a sibling and in different strata of age of relative(s). For subjects with two or more first-degree relatives with CRC, the risk was 6.9 for the right colon, 5.8 for the transverse and descending colon, 3.8 for the sigma, 3.2 for the rectosigmoid junction and 1.9 for the rectum. This study confirms that a family history of CRC in first-degree relatives increases the risk of both colon and rectal cancer, the association being stronger at younger ages and for right colon.

Adult↗

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.

Adult↗

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).

Animals↗

Vitamin requirements: present recommendations and future prospects.

Dietary recommendations evolved from instructions directed at prevention of starvation diseases to the level of intake of essential nutrients that are adequate to meet the known nutrient needs of practically all healthy persons. Vitamin requirements have been modified various times over the years and there are still differences in recommended intakes in different countries. A debate on optimal vitamin intake is ongoing, based on the concepts of deficiency, sufficiency and hypothetical identification of a range within which a further biological advantage can be expected. In establishing appropriate criteria for food and nutrient intakes, additional studies are warranted on the physiological interactions between nutrients and non-nutrients and on many other factors such as genetic determinants and lifestyle which could interfere with disease prevention.

Adult↗

Intake of selected micronutrients and the risk of breast cancer.

To investigate the relation between selected micronutrients and breast cancer risk, we conducted a case-control study of breast cancer between June 1991 and April 1994 in 6 Italian areas. The study included 2569 women admitted to the major teaching and general hospitals of the study areas with histologically confirmed incident breast cancer and 2588 control women with no history of cancer, who were admitted to hospitals in the same catchment areas for acute, non-neoplastic, nongynecological conditions unrelated to hormonal or digestive tract diseases or to long-term modifications of the diet. Dietary habits, including alcoholic beverage consumption, were investigated using a validated food frequency questionnaire, including 78 foods or food groups, several types of alcoholic beverages, some "fat intake pattern" questions and some open sections for foods consumed frequently by the subject and not reported in the questionnaire. To control for potential confounding factors, several multiple logistic regression models were used. When major correlates, energy intake and the mutual confounding effect of the various micronutrients were taken into account, beta-carotene, vitamin E and calcium showed a significant inverse association with breast cancer risk. The estimated odds ratios of the 5th quintile compared to the lowest one were 0.84 for beta-carotene, 0.75 for vitamin E and 0.81 for calcium. No significant association emerged for retinol, vitamin C, thiamin, riboflavin, iron and potassium. Our results suggest that a diet rich in several micronutrients, particularly beta-carotene, vitamin E and calcium, may be protective against breast cancer.

Adult↗

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.

Breast Neoplasms↗

Cigarette smoking and the risk of breast cancer.

The relation between cigarette smoking and breast cancer risk was investigated in a multicentric case-control study conducted in Italy on 2,569 women with incident, histologically confirmed breast cancer and 2,588 control women admitted to hospital for acute, non-neoplastic, non-hormonal, non-gynaecological or smoking-related conditions. Compared with women who had never smoked, current smokers had a multivariate odds ratio (OR) of 0.84 [95% confidence interval (CI) 0.7-1.0] and former smokers an OR of 1.14 (5% CI 0.9-1.4), while the OR for ever vs never smokers was 0.93 (95% CI 0.8-1.1). The ORs were 1.02 for < 5 cigarettes per day, 0.99 for 5-14 cigarettes per day, 0.78 for 15-24 cigarettes per day and 1.18 for > or = 25 cigarettes per day. No consistent pattern of risk was observed according to duration of smoking, age at starting and time since starting smoking. Compared with never smokers, former smokers had ORs of 1.45 for < 3 years since stopping smoking, 1.79 for 3-6 years, 1.16 for 7-15 years and 0.74 for > or = 16 years. No heterogeneity emerged across strata of selected covariates. Thus, this study, one of the largest conducted in Europe to date, does not support the presence of any association of practical importance between cigarette smoking and breast cancer risk.

Adult↗

Oral contraceptives and breast cancer: a cooperative Italian study.

The relationship between oral contraceptives (OC) and breast-cancer risk was analysed using data from a case-control study conducted between June 1991 and February 1994 in 6 Italian centres on 1,991 patients below age 65 with histologically confirmed incident breast cancer and 1,899 controls admitted to hospital for a wide range of acute, non-neoplastic, non-hormone-related diseases. "Ever OC use" was reported by 18% of cases versus 14% of controls, corresponding to a multivariate odds ratio (OR) of 1.1 (95%) confidence interval, Cl 0.9 to 1.4). The ORs were 1.3 for use lasting < 1 year, 1.1 for 1 to 4 years, 0.9 for 5 to 8 years, and 1.2 for over 8 years. With reference to age at first use, there was some indication that the OR was elevated in women who had started use before age 30, but not in those starting at a later age. With reference to time since last OC use, the OR was above unity for women who had stopped for less than 10 years (1.6 for 1 to 4 years; 1.7 for 5 to 9 years), but the OR declined to unity for women who had stopped OC use for 10 years or longer. The OR for women who had stopped OC use for less than 10 years was consistently elevated across strata of selected covariates, and was directly related to the duration of use (OR 1.3 for < 5 years, 1.7, for > or = 5 years). In contrast, the OR was 0.6, for use lasting > or = 5 years in women who had stopped for 10 years or more. The elevated OR for women who had recently stopped OC use, together with the absence of association (or the suggestion of some protection) for those who had stopped for 10 years or more is consistent with the pattern of breast-cancer risk observed after a full-term pregnancy, and provides important reassurance on a public health level on the long-term impact of OCs on breast carcinogenesis.

Adult↗