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We conducted a study on 165 women with thyroid cancer and 214 hospital controls in order to investigate the role of reproductive and hormonal factors in the aetiology of thyroid cancer. Late age at menarche (Relative risk (RR) for menarche at greater than or equal to 14 vs less than or equal to 11 = 2.8), menstrual irregularity (RR = 1.7), late age at first birth (RR for first birth at greater than or equal to 28 vs less than or equal to 21 = 2.4) and at last birth (RR for last birth greater than or equal to 30 vs less than 30 = 2.2) significantly increased the risk of the development of thyroid cancer both in premenopausal and postmenopausal women. Parity was, in the present study rather inconsistently related to disease status whereas voluntary abortions and miscarriages were completely unrelated. A non significant increasing risk was observed with age at menopause older than 50, and with the use of oral contraceptives in premenopausal women. The mechanism of action of female hormones on the thyroid gland remains largely obscure, but the observation that age at first and, perhaps, subsequent pregnancies may be relevant points to an interplay of reproductive factors (and, possibly, their hormonal correlates) more complex than previously suggested.

The geographical patterns of cancer mortality have been studied in Friuli-Venezia Giulia Region (1.2 million inhabitants), the North-eastern part of Italy, with respect to certain characteristics (i.e., rural, mixed, urban) and the altitude of the commune where the deceased subjects lived permanently at the time of death. In males, significantly increased mortality rates in rural versus urban communes (after allowance for altitude) were found for cancer of the oral cavity and pharynx, oesophagus and stomach. Conversely, significantly decreased mortality rates emerged for cancer of the colo-rectum, liver, lung, bladder, kidney and Hodgkin's disease. In females, significantly increased mortality rates in rural as compared to urban communes were observed for stomach cancer while significantly decreased mortality rates emerged for cancer of the colo-rectum, gallbladder, lung, breast, ovary, bladder and brain. With respect to altitude, residence above 200 meters retained a significant association in males, after allowance for the degree of urbanization of the commune of residence, for cancer of the oral cavity and pharynx, stomach and larynx (positive) and cancer of the colorectum and brain (negative). Women in locations above 200 meters seemed significantly at risk for stomach cancer, but protected from cancer of the colo-rectum and kidney. These results may provide a useful summary guide for further aetiological investigations into the risk factors associated with the diseases and give practical indications for local strategies of cancer control.

The relation between meal frequency and the risk of colorectal cancer was investigated in a case-control study conducted in North Italy on 889 cases of colon cancer, 581 cases of rectal cancer, and 2475 controls admitted to hospital for acute, nonneoplastic, or digestive disorders. As compared to individuals who reported 2 or fewer meals per day, the multivariate colon cancer odds ratios were 1.7 [95% confidence interval (95% CI), 1.5-2.1] for 3, and 1.9 (95% CI, 1.1-3.3) for 4 meals or more. Corresponding rectal cancer odds ratios were 1.4 (95% CI, 1.1-1.7) for 3, and 1.9 (95% CI, 1.1-3.5) for 4 meals or more. The direct trends in risk of colorectal cancer with frequency of eating were not substantially modified by allowance for various dietary and nondietary potential confounding factors, including an approximate measure of total energy intake, and did not show significant effect modification across strata of age, sex, education, and other major risk covariates. A role of meal frequency in the etiology of colorectal cancer is biologically plausible, since when a meal is eaten, the gallbladder contracts and releases bile acids. Thus, eating patterns can influence the enterohepatic circulation and, consequently, the exposure time of intestinal mucosa to bile acids.

Background Scanty and inconsistent studies are available on the relation between dietary fiber intake and pancreatic cancer. A case–control study was carried out in northern Italy to further investigate the role of various types of dietary fibers in the etiology of pancreatic cancer. Patients and methods Cases were 326 patients with incident pancreatic cancer, excluding neuroendocrine tumors, admitted to major teaching and general hospitals during 1991–2008. Controls were 652 patients admitted for acute, nonneoplastic conditions to the same hospital network of cases. Information was elicited using a validated food frequency questionnaire. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for intake quintiles of different types of fiber after allowance for total energy intake and other potential confounding factors. Results Total fiber intake was inversely related to risk of pancreatic cancer (OR = 0.4 for highest versus lowest quintile of intake; 95% CI 0.2–0.7). An inverse association emerged between pancreatic cancer and both soluble (OR = 0.4; 95% CI 0.2–0.7) and total insoluble fiber (OR = 0.5; 95% CI 0.3–0.8), particularly cellulose (OR = 0.4; 95% CI 0.3–0.7) and lignin (OR = 0.5; 95% CI 0.3–0.9). Fruit fiber intake was inversely associated with pancreatic cancer (OR = 0.5; 95% CI 0.3–0.8), whereas grain fiber was not (OR = 1.2; 95% CI 0.7–2.0). Conclusions This study suggests that selected types of fiber and total fiber are inversely related to pancreatic cancer.

Aim of the study: We assessed the relation between metabolic syndrome (MetS) and its components and colorectal cancer. Methods: We analysed data from a multicentre case-control study conducted in Italy and Switzerland, including 1378 cases of colon cancer, 878 cases of rectal cancer and 4661 controls. All cases were incident and histologically confirmed. Controls were subjects admitted to the same hospitals as cases with acute non-malignant conditions. MetS was defined according to the International Diabetes Federation criteria. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated by multiple logistic regression models, including terms for major identified confounding factors for colorectal cancer. Results: With reference to each component of the MetS, the ORs of colorectal cancer in men were 1.27 (95% CI, 0.95-1.69) for diabetes, 1.24 (95% CI, 1.03-1.48) for hypertension, 1.14 (95% CI, 0.93-1.40) for hypercholesterolaemia and 1.26 (95% CI, 1.08-1.48) for overweight at age 30. The corresponding ORs in women were 1.20 (95% CI, 0.82-1.75), 0.87 (95% CI, 0.71-1.06), 0.83 (95% CI, 0.66-1.03) and 1.06 (95% CI, 0.86-1.30). Colorectal cancer risk was increased in men (OR = 1.86; 95% CI, 1.21-2.86), but not in women (OR = 1.13; 95% CI, 0.66-1.93), with MetS. The ORs were 2.09 (95% CI, 1.38-3.18) in men and 1.15 (95% CI, 0.68-1.94) in women with >= 3 components of the MetS, as compared to no component. Results were similar for colon and rectal cancers. Conclusion: This study supports a direct association between MetS and both colon and rectal cancers in men, but not in women. (C) 2010 Elsevier Ltd. All rights reserved.

Background: The issue of diet and laryngeal cancer has been rarely addressed considering the potential role of dietary patterns. Methods: We examined this association using data from a case-control study carried out between 1992 and 2000. Cases were 460 histologically confirmed incident laryngeal cancers hospitalized in two Italian areas. Controls were 1,088 subjects hospitalized for acute nonneoplastic diseases unrelated to tobacco or alcohol consumption. Dietary habits were investigated through a 78-item food frequency questionnaire. A posteriori dietary patterns were identified through principal component factor analysis carried out on a selected set of 28 major nutrients. The internal reproducibility, robustness, and reliability of the identified patterns were evaluated. Odds ratios (OR) of laryngeal cancer and 95% confidence intervals (95% CI) were estimated using unconditional multiple logistic regression models on quartiles of factor scores. Results: We identified five major dietary patterns named “animal products, ”“ starch-rich, ”“ vitamins and fiber, ”“ vegetable unsaturated fatty acids,” and “animal unsaturated fatty acids.” The vitamins and fiber dietary pattern was inversely associated with laryngeal cancer (OR, 0.35; 95% CI, 0.24-0.52 for the highest versus the lowest score quartile), whereas the animal products (OR, 2.34; 95% CI, 1.59-3.45) and the animal unsaturated fatty acids (OR, 2.07; 95% CI, 1.42-3.01) patterns were directly associated with it. There was no significant association between the vegetable unsaturated fatty acids and the starch-rich patterns and laryngeal cancer risk. Conclusion: These findings suggest that diets rich in animal products and animal fats are directly related, and those rich in fruit and vegetables inversely related, to laryngeal cancer risk. Cancer Epidemiol Biomarkers

Background: The role of selected micronutrients, vitamins and minerals in the aetiology of epithelial ovarian cancer was investigated using data from a case-control study conducted between 1992 and 1999 in five Italian areas. Patients and methods:Cases were 1031 patients with histologically confirmed incident epithelial ovarian cancer. Controls were 2411 subjects admitted for acute, non-neoplastic diseases to major hospitals in the same catchment areas. Dietary habits were elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed by quintiles of intake of nutrients. Results: Inverse associations emerged for vitamin E (OR = 0.6; 95% CI: 0.5-0.8), beta-carotene (OR = 0.8; 95% CI: 0.6-1.0), lutein/zeaxanthin (OR = 0.6; 95% CI: 0.5-0.8 for the highest vs. the lowest quintile of intake), and calcium intake (OR = 0.7; 95% CI: 0.6-1.0). When the combined effect of calcium and vitamin E was considered, the OR reached 0.4 (95% CI: 0.3-0.7) for subjects in the highest compared to those in the lowest intake tertile of both micronutrients. Results were consistent across strata of menopausal status, parity and family history of ovarian or breast cancer. Conclusions: The intake of selected micronutrients, which were positively correlated to a diet rich in vegetables and fruits, was inversely associated with ovarian cancer. RI Parpinel, Maria/B-1605-2012

Background. The epidemiological evidence on the relation between dietary fiber intake and endometrial cancer is contradictory. Consequently, a case-control study was carried out to further investigate the role of dietary fiber intake in the etiology of endometrial cancer. Material and methods. Cases were 454 women with incident, histologically confirmed, endometrial cancer admitted to major teaching and general hospitals. Controls were 908 women admitted for acute, non-neoplastic conditions to the same hospital network. Information on diet was elicited using a validated food frequency questionnaire. Results. Odds ratios (OR) and 95% confidence intervals (CI) for quintiles of various types of fiber were estimated after allowance for total energy intake and other potential confounding factors. Lignin intake was significantly inversely related to endometrial cancer (OR=0.6 for the highest versus the lowest quintile of intake; 95%CI: 0.4-0.9) with a slightly significant linear trend in risk (p-value=0.04). Discussion. Data suggest the potential importance of lignin in the prevention of endometrial cancer at Italian consumption levels.

Background. The epidemiologic evidence on dietary vitamins E and C and prostate cancer is controversial. Therefore, a case-control study was carried out to investigate the role of dietary intake of vitamins E and C in the etiology of prostate cancer. Material and methods. Cases were 1 294 men with incident, histologically confirmed prostate cancer, admitted to the major teaching and general hospitals of five Italian areas between 1991 and 2002. Controls were 1 451 men admitted for acute, non-neoplastic conditions to the same hospitals. Information on dietary habits and nutrient intake was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) for increasing levels of vitamin intake were estimated after allowance for total energy intake and other confounding factors. Results. Vitamin E showed a significant inverse association with prostate cancer (OR = 0.78 for the highest versus the lowest tertile of intake, 95% CI: 0.58-0.96; p-value for trend = 0.02), whereas for vitamin C the inverse association was of borderline statistical significance (OR = 0.86; 95% CI: 0.65-1.08). Results were consistent in strata of age, body mass index, and family history of prostate cancer. Discussion. The present study shows an inverse association between dietary intake of vitamins E and prostate cancer incidence. This finding is likely to reflect the influence of diet itself since supplementation or food fortification with vitamins is rare in the Italian population.

The role of selected macronutrients, fatty acids and cholesterol in the etiology of renal cell carcinoma (RCC) was analyzed using data from a case-control study conducted in 4 Italian areas between 1992 and 2004. Cases were 767 patients with incident, histologically confirmed RCC, admitted to major teaching and general hospitals of the study areas. Controls were 1,534 subjects admitted for acute, nonneoplastic conditions to the same hospitals. Information on dietary habits and nutrient intake was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) for increasing levels of nutrient intake were estimated after allowance for total energy intake and other potential confounding factors. A direct association with RCC was found for starch intake (OR = 1.9 for highest versus lowest quintile of intake; 95% Cl: 1.4-2.6, p-value for trend = 0.001), while an inverse association was found for fats from vegetable sources (OR = 0.6; 95% CI: 0.5-0.8; p-value for trend = 0.002), unsaturated fatty acids (OR = 0.5; 95% Cl: 0.4-0.7; p-value for trend = 0.0002), and polyunsaturated fatty acids (OR = 0.5; 95% Cl: 0.40.7; p-value for trend = 0.001). Among polyunsaturated fatty acids, linoleic acid (OR = 0.5; 95% CI: 0.4-0.7; p-value for trend = 0.0001) and linolenic acid (OR = 0.7; 95% CI: 0.5-1.0; p-value for trend = 0.01) were inversely related to RCC. When 6 major macronutrients were included in the same model, the adverse effect of high intake of starch remained statistically significant, together with the protective effect of polyunsaturated fatty acids. Results were consistent in strata of age, body mass index, treated hypertension, energy intake, stage and family history of RCC. (C) 2008 Wiley-Liss, Inc.

Purpose: Cytokines such as IL-10 and IL-18 seem to be involved in the inflammatory response of undifferentiated carcinoma of nasopharyngeal type (UCNT). The aim of this study was to evaluate the correlation between functional single nucleotide polymorphisms (SNPs) in the promoter region of IL-10 and IL-18 genes and the virological and clinical characteristics in a large case series of Caucasian patients suffering from UCNT, a tumor regularly associated with the Epstein Barr Virus (EBV). Methods: Eighty-nine patients with histologically confirmed UCNT and 130 healthy donors were included in our study. DNA was examined for the polymorphisms of IL-10 gene at positions –1082, −819, −592 by direct sequencing and IL-18 gene at position −607 and −137 by allele –specific PCR. EBV DNA serum viremia was evaluated by QC-PCR. Results: The distributions of the IL-10 and IL-18 genetic variants were not different between UCNT patients and healthy controls. The frequency of IL-10 –1082G allele, which is associated with high IL-10 expression, showed a nearly statistically significant increase in UCNT patients EBV DNA-negative as compared to healthy controls (OR=3.3 95% CI: 1.2–9.8). Subjects with C/C or C/G combined IL-18 genotypes showed an increased risk of being with Stages III-IV (OR=2.1 95% CI: 1.2–6.6). Conclusion: This study was performed to improve the definition of the pathogenetic factors implicated in UCNT by addressing the correlation between cytokine polymorphisms and clinical parameters. This is the first study investigating the possible role of the IL-18 and IL-10 polymorphisms in the development and outcome of UCNT. In our genetic analysis there is no evidence for involvement of IL-10 promoter polymorphisms alone in the genetic predisposition to this tumor. On the other hand, IL18 genetic variants may represent a genetic risk factor for tumor aggressiveness.

Background: The role of selected macronutrients, fatty acids and cholesterol in the etiology of prostate cancer was analyzed using data from a case-control study carried out in five Italian areas between 1991 and 2002. Patients and methods: Cases were 1294 men with incident, histologically confirmed prostate cancer, and admitted to the major teaching and general hospitals of study areas. Controls were 1451 men admitted for acute, non-neoplastic conditions to the same hospital network. Information on dietary habits was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for increasing levels of nutrient intake. Results: A direct association with prostate cancer was found for starch intake (OR = 1.4 in the highest versus the lowest quintile of intake; 95% CI: 1.1-1.8), whereas an inverse association emerged for polyunsaturated fatty acids (OR = 0.8; 95% CI: 0.6-1.0). Among polyunsaturated fatty acids, linolenic acid (OR = 0.7; 95% CI: 0.6-0.9) and linoleic acid (OR = 0.8; 95% CI: 0.6-1.0) were inversely related to prostate cancer. When the six major macronutrients were included in the same model, the adverse effect of high intake of starch and monounsaturated fatty acids was statistically significant together with the protective effect of polyunsaturated fatty acids. Results were consistent in separate strata of age, body mass index and family history of prostate cancer. Conclusions: Starch and monounsaturated fatty acids were directly associated with prostate cancer risk and polyunsaturated fatty acids were inversely associated.

In order to obtain prognostic clinicopathological information, 49 cases of pure ductal carcinoma in situ of the breast (DCIS), were evaluated for the immunohistochemical expression of potential predictor markers including c-erbB-2 oncogene product, p53 protein, oestrogen (ER) and progesterone (PR) receptors, oestrogen-regulated proteins pS2 and cathepsin-D (cath-D), CD44 protein and 67-kDa laminin receptor (MLuC5). Immunohistochemical findings were compared with conventional pathological parameters, clinical findings, and the clinical outcome of the patients. When markers were matched to each other, statistical analyses provided a significant positive correlation between c-erbB-2 overexpression and p53 positivity (P < 0.01) and between ER and PR (P < 0.01), ER, PR and pS2 (P < 0.01), pS2 and MLuC5 (P < 0.05). Significant negative correlations between c-erbB-2 overexpression and ER (P < 0.05), PR (P < 0.01) and pS2 (P < 0.01) positivity was also observed. Data on the relationship between marker status and pathological findings revealed a significant positive trend between c-erbB-2, p53, and increased grade values (P < 0.05) and opposite results with SR receptor expression (P < 0.01). c-erbB-2 overexpression was further significantly associated with comedotype carcinoma (P < 0.05) and distribution of disease in confluent neoplastic ducts (P < 0.01). Although no statistically significant correlation among biological markers expression, clinical findings and outcome was demonstrated, overall this study indicates that tumour cells from a subset of DCIS, which includes comedotype carcinoma, express significantly unfavourable prognostic factors. Copyright (C) 1996 Elsevier Science Ltd

In view of the persisting uncertainty concerning possible mechanisms by which high vegetable and fruit intake decreases cancer risk, foods with divergent values for potentially important micronutrients are a priority for investigation. Tomatoes are low in beta-carotene, but high in lycopene, an active antioxidative agent. In order to assess the effect of tomatoes on risk of cancers of the digestive tract, data were analyzed from an integrated series of case-control studies conducted between 1985 and 1991 in northern Italy, where tomato intake is high but, also, heterogeneous. The overall dataset included the following histologically confirmed cancer cases: oral cavity and pharynx, 314; esophagus, 85; stomach, 723; colon, 955; and rectum, 629; and a total of 2,879 controls admitted to hospital for acute non-neoplastic or non-digestive conditions, unrelated to long-term dietary modifications. Multivariate odds ratios (OR) and 95% confidence interval (CI) for subsequent quartiles of intake of raw tomatoes were derived, after allowance for age, sex, study center, education, smoking and drinking level, and tertile of total caloric intake. There was a consistent pattern of protection for all sites (OR in the upper quartile ranging between 0.4 and 0.7), most notable for gastrointestinal neoplasms. All trends in risk were highly significant. The beneficial effect of raw tomatoes in this population may be partly due to the fact that they constitute perhaps the most specific feature of the Mediterranean diet. However, if it is true that tomatoes protect against digestive-tract cancers, this is of interest from both a scientific and a public health viewpoint. (C) 1994 Wiley-Liss, Inc.

In order to explore the potential differences in the effect of alcohol in men and women we took advantage of a case-control study of upper aerodigestive tract tumors conducted between 1986 and 1991 in Northern Italy. Five hundred forty-six incident cases of cancer of the oral cavity and pharynx (of whom 81 were women), 410 of cancer of the esophagus (of whom 67 were women), and 388 with cancer of the larynx, (of whom 19 were women) were interviewed. The control group included 2263 inpatients (of whom 557 were women) with acute conditions unrelated to alcohol and tobacco consumption. Among alcohol drinkers, similar odds ratios were detected in men and women. In the highest, well comparable intake category (i.e., greater-than-or-equal-to 42 drinks/week in women and 42-55 drinks/week in men), odds ratios were 4.5 and 3.8 for cancer of the oral cavity and pharynx, 3.0 and 4.7 for cancer of the esophagus, and 2.6 and 2.0 for cancer of the larynx in women and men, respectively, as compared to light drinkers. However, for all cancer sites a reduced risk was found among abstaining women but not in abstaining men, when compared with light-to-moderate drinkers. The present study, therefore, does not support the hypothesis that women may be substantially more vulnerable than men to alcohol carcinogenesis, at least at the level of the upper aerodigestive tract. It highlights, however, the importance of the choice of the reference category (i.e., abstainers versus the combination of abstainers and light drinkers) in the comparison of risk estimates across population groups who greatly differ with respect to drinking patterns and other correlates of alcohol consumption.

Six patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma receiving chemotherapy (CT) with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus granulocyte colony-stimulating factor were sequentially monitored to study the effects of these treatments on their immunologic status (CD4 and CD8 cell counts) and on HIV plasma viremia. We show that mean CD4 cell counts declined significantly after the third cycle of CT (187 +/- 117/microliters before CT versus 92.4 +/- 60/microliters; p = 0.04) and remained significantly reduced 4 months after completion of CT. Modifications of CD8 cell counts were not statistically significant. The effects of CT on plasma viremia, as measured by a competitive polymerase chain reaction technique, were delayed until the fourth cycle, when an increase of viral load ranging from 0.6 to 2 logs (p = 0.027) was observed. After this point, viremia returned to baseline levels, with the exception of two patients who later developed opportunistic infections and one who underwent disease progression. These results suggest that, contrary to CD4 cell counts, plasma viremia could be a faithful surrogate marker for monitoring of HIV disease progression in patients undergoing CT.

A hospital-based case-control study of upper aerodigestive tract tumors was conducted between June 1986 and June 1989 in Northern Italy. One hundred fifty-seven male cases of oral cavity cancer, 134 of pharyngeal cancer, 162 of laryngeal cancer, and 288 of esophageal cancer, and 1272 male inpatients with acute conditions unrelated to tobacco and alcohol were interviewed. Odds ratios for current smokers of cigarettes were 11.1 for oral cavity, 12.9 for pharynx, 4.6 for larynx, and 3.8 for esophagus. For all 4 sites, the risk increased with increasing number of cigarettes and duration of smoking habits and, with the exception of esophageal cancer, decreased with increasing age at the start of and years since quitting smoking. Smokers of pipes and cigars showed a more elevated risk of cancer of the oral cavity and esophagus than did cigarette smokers. Significantly increased risks emerged also in heavy drinkers (odds ratio greater than 60 versus greater than or equal to 19 drinks/week = 3.4, 3.6, 2.1, and 6.0 for oral cavity, pharynx, larynx, and esophagus, respectively), deriving predominantly from wine consumption.