Risk of cerebral vein thrombosis and oral contraceptives.
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Adolescent↗
Biomedical subjects
D Palli
Publications and source records attributed to D Palli.
Mutations at coding mononucleotide repeats in gastric cancer with the microsatellite mutator phenotype.
We analysed 50 gastric carcinomas (GCs) to verify whether mutations at coding repeats were associated with microsatellite instability (MSI). The tumors included: ten cases with no MSI, 14 cases with MSI = 1 locus, 13 cases with MSI = two loci and 13 cases with MSI > or = 3 loci. We investigated coding repeats within the TGF-beta RII, IGFIIR, BAX, hMSH6, hMSH3 and BRCA2 genes. The TGF-beta RII, IGFIIR, BAX, hMSH6 and hMSH3 repeats were altered in 11 (22%), five (10%), four (8%), 16 (32%) and five (10%) cases respectively. Mutations occurred only in MSI-positive (MSI+) tumors and correlated with increasing MSI levels. No alterations of the BRCA2 repeat were found. Mutations in genes other than hMSH6 were strongly associated to hMSH6 mutations, suggesting a key role of this gene. The non-coding BAT-26 and E-Cadherin 3' UTR poly(A)8/(T)15 repeats were analysed in 44 of the 50 cases. Novel tumor-associated alleles were observed only in MSI-positive GCs and were in most cases associated with mutations at coding repeats. Further investigations with BAT-40 confirmed that four cases manifested mononucleotide repeat alterations restricted to hMSH6 and one case to TGF-beta RII. A subset of tumors with MSI at two or more dinucleotide loci resulted negative for mutations at coding and non-coding mononucleotide repeats.
Aged↗
A dietary trial with a short-term low-sucrose diet in an Italian population: effects on colorectal mucosal proliferation.
Colorectal mucosal proliferation is supposed to predict colon cancer risk. We investigated whether a low-sucrose diet might reduce colorectal mucosal proliferation in a group of patients at higher risk of colorectal cancer after at least two colon adenoma resections. In a pilot phase, 14 patients [12 men and 2 women, 60.3 +/- 5 (SD) yr] were instructed to adopt a low-sucrose diet for one month. Colorectal biopsies were taken twice in the same patients, at the start and the end of the intervention period, and mucosal proliferation was measured by [3H]thymidine uptake in vitro and autoradiography. Although compliance of study participants to dietary modification was high, only a few agreed to two consecutive endoscopies; thus we carried out a randomized study, and 107 patients were assigned to a low-sucrose diet (50 treated patients: 31 men and 19 women, 59.7 +/- 7.5 yr) or instructed to continue their usual diet for one month (55 control patients: 32 men and 23 women, 59.6 +/- 7.7 yr). At the end of this period, colorectal biopsies were obtained. The results of the pilot phase and the randomized study showed that a low-sucrose diet for one-month did not affect proliferation or the distribution of proliferation activity along the crypt. The food-frequency questionnaires indicated that treated patients consumed significantly less sucrose (and fewer total calories) during the dietary modification. Urinary fructose, a measure of dietary sucrose intake, was also reduced at the end of the intervention period. In conclusion, we found no evidence that a low-sucrose diet for one month influences colorectal mucosal proliferation.
Adult↗
Implications of p53 mutation spectrum for cancer etiology in gastric cancers of various histologic types from a high-risk area of central Italy.
Examination of p53 mutation spectra may provide clues to molecular mechanisms involved in different histologic types of gastric cancer. A total of 105 gastric cancer cases classified according to the Laurén's system were selected from a high-risk area around Florence, Italy. Exons 5-8 of the p53 gene were examined for mutations by the polymerase chain reaction-single strand conformation polymorphism technique and DNA sequencing, using DNA from formalin-fixed paraffin-embedded tissues. Mutation frequency was similar in intestinal-type (12/28) and unclassified tumors (9/18), but was significantly lower in diffuse cancers (12/57, P < 0.05). A similar frequency of p53 mutations was observed among tumor stages in both intestinal-type and unclassified cancers, but in diffuse tumors mutations tended to be associated with invasion beyond the muscularis propria. When base changes were considered, G:C-->A:T transitions at CpG sites were the most common mutations for all the three tumor types with 6 of 11 (55%) in intestinal type, 8 of 12 (67%) in diffuse type, and 5 of 8 (63 %) in unclassified tumors. Frequent p53 mutations in both intestinal-type and unclassified tumors support the hypothesis that unclassified tumors represent variants of the intestinal type and suggest that unclassified tumors, like the intestinal type, may also associate with environmental exposures. The predominance of G:C-->A:T transitions at CpG sites, which are associated with methyltransferase-induced DNA methylation at carbon 5 of cytosine, in all three tumor types suggests that the status of DNA methylation may be the major determinant for p53 mutations and may be also equally important in gastric carcinogenesis regardless of histology.
Adult↗
Symptoms and Helicobacter pylori: any link? The Italian Helicobacter pylori Study Group.
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Dyspepsia↗
General and cancer specific mortality of a population based cohort of patients with inflammatory bowel disease: the Florence Study.
BACKGROUND: A population based epidemiological study identified all the patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) resident in the Florence area in the period 1978-1992. AIMS: To assess the mortality of unselected patients with inflammatory bowel disease (IBD) in a Mediterranean country. METHODS: Overall, 920 patients (689 UC and 231 CD) were followed until death or end of follow up (31 December 1996). Information on vital status was available for all except eight patients (0.9%); 70 deaths were identified (23 in patients with CD and 47 in patients with UC). Expected deaths were estimated on the basis of five year age group, gender, and calendar year national mortality rates. Standardised mortality ratios (SMR) and 95% confidence intervals were calculated. RESULTS: General mortality was significantly lower than expected in UC (SMR 0.6; 95% confidence interval 0.4 to 0.8), due to a reduced number of cardiovascular and, possibly, smoking related deaths. Cancers of the respiratory tract were significantly reduced in UC but tended to be increased in patients with CD. These latter patients had not only an increased cancer mortality but also a 40% increased risk of dying for all causes already evident in the first five year follow up period and persisting thereafter. In contrast, in patients with UC, SMRs were initially very low but tended to increase steadily over the follow up period. Gastrointestinal deaths were particularly increased in patients with CD, but only moderately in those with UC. Overall, there was some evidence of a twofold increased mortality for colorectal cancer, the risk being highest for rectal cancers in patients with UC. A non-significant excess of deaths due to haemolymphopoietic malignancies and suicides was also observed. CONCLUSIONS: This study, the first in a Mediterranean country, supports the existence of two divergent mortality patterns for patients with UC and CD, possibly explained by differences in smoking habits and by a greater severity of CD.
Aged↗
A capture-recapture estimate of inflammatory bowel disease prevalence: the Florence population-based study.
BACKGROUND: A recent population-based epidemiological study identified the patients with a diagnosis of ulcerative colitis or Crohn's disease resident in the metropolitan Florence area in the period 1978-1992 and defined their vital status on 31 December, 1992. AIMS: To estimate the completeness of Inflammatory Bowel Disease prevalent case ascertainment in the study area. SUBJECTS AND METHODS: In a Registry, specifically developed during the study, 767 patients fulfilled the criteria for the definition of prevalent cases as of 31 December, 1992. At the same time, we had access to an independent source of potential patients: the Regional Health Department kept a list of all Inflammatory Bowel Disease patients allowed free access to specific health care provided only to selected diagnostic categories. We then compared the two different sources and used a capture recapture analysis to estimate the number of cases missed by both sources. RESULTS: A total of 331 patients were reported by both sources, 436 were found only in the Registry while a large group of potential cases not present in our Registry was found only in the List. After careful confirmation of the diagnosis for each individual patient and contact with his/her physician, we identified an additional 102 cases that were included in the final population series of 869 prevalent cases. This capture-recapture analysis led to a revised estimate of 1,003 prevalent cases, suggesting that 134 patients had been missed by both sources, resulting in an Inflammatory Bowel Disease prevalence rate of 186 per 100,000. CONCLUSIONS: According to this method our previous study underestimated the true prevalence of 13.4% (95% confidence interval: 9.8-16.6%). On account of some degree of negative dependence between the two sources the loss was probably in the lower range of this interval. Completeness of case ascertainment should be evaluated and discussed in all studies designed to provide population-based estimates for health care planning.
Adolescent↗
Gastric cancer, gastritis and plasma vitamin C: results from an international correlation and cross-sectional study. The Eurogast Study Group.
Low intake of foods rich in vitamin C is associated with an increased risk of gastric cancer, and geographic variation in average vitamin C intake, therefore, could explain some of the wide international variation in gastric cancer rates. This multicentre study investigated the relationships between plasma levels of vitamin C, as an indicator of vitamin C intake, and gastric cancer rates, markers of gastritis and other socio-demographic variables. Fasting plasma samples from about 1,400 individuals from 9 centres in 7 countries worldwide were assayed for total vitamin C using a fluorometric assay. There was no association between average plasma vitamin C levels and either gastric cancer mortality or incidence rates in the populations studied. Therefore, variation in fasting plasma vitamin C levels, as an indicator of consumption of vitamin C, does not appear to explain any of the wide geographic variation in gastric cancer rates. Furthermore, there was no association between plasma vitamin C levels and Helicobacter pylori infection, low serum levels of pepsinogen A (as a marker of severe chronic atrophic gastritis) or the presence of DNA adducts in blood leukocyte DNA. Multivariate models showed that fasting plasma vitamin C levels were associated positively with female sex, higher levels of education, never having smoked and increasing height and negatively with number of cigarettes smoked per day and increasing weight. This suggests not only that gender and tobacco smoking, in particular, are important predictors of plasma vitamin C levels but also that their effects are consistent throughout the developed world.
Adult↗
Microsatellite instability in gastric cancer is associated with tumor location and family history in a high-risk population from Tuscany.
We studied the presence of microsatellite instability (MSI) in a series of 108 gastric cancers (GCs) previously identified in an epidemiological study carried out in a high-risk area around Florence. To investigate associations between MSI and GC family history, 34 cases (31.5%) who had a GC-affected first-degree relative were included in the series. A family history positive for colorectal cancer was reported quite rarely (5.6%). The analysis of 6 microsatellite loci in DNA from paired normal tissue and tumor samples microdissected from paraffin-embedded specimens revealed varying degrees of instability: 56 cases (51.8%) did not show instability at any of the 6 loci; 19 (17.6%) showed instability at 1 locus; 16 (14.8%) showed instability at 2 loci; 11 (10.2%) showed instability at 3 loci; 4 (3.7%) showed instability at 4 loci; and 2 (1.9%) showed instability at 5 loci. The replication error-positive (RER+) phenotype, defined as the presence of MSI at 2 or more loci, had a frequency of 30.6% (33 of 108) and tended to be positively associated with female sex, intestinal histological type, advanced tumor stage, vascular invasion, positive GC family history, and blood group of A type. No correlation emerged between age at diagnosis and RER+ phenotype, whereas a significant association with the RER+ phenotype was shown by the antral location. A multivariate analysis adjusting for a selected group of potential confounding factors confirmed the strong association of the RER+ phenotype with the antral location (P = 0.001) and with a positive GC family history (P < 0.05). Survival analyses at 5 and 8 years showed no difference between RER+ and RER- patients, even when corrected for stage distribution. By the microdissection technique, we also used microsatellite allele patterns to investigate intratumoral heterogeneity and genetic relationships between tumors and adjacent dysplasia and/or intestinal metaplasia. Areas of metaplasia and dysplasia demonstrated MSI only in cases with MSI-positive tumors. In MSI-positive tumors, there was consistent evidence of intratumoral microsatellite allele heterogeneity, indicating the presence of genetically divergent tumor cell clones within the same neoplasm.
Age Factors↗
Body mass index and post-menopausal breast cancer: an age-specific analysis.
The relationship between body mass index (BMI, Quetelet's index, kg m(-2)) and post-menopausal breast cancer risk was considered in age-specific strata on the basis of a pooled analysis of three Italian case-control studies, including a total of 3108 post-menopausal breast cancer patients aged 50 years or over and 2664 control subjects. Overall, there was a moderate, but significant, association between BMI and post-menopausal breast cancer: the odds ratios (ORs) were around 1.3 for the three intermediate quintiles compared with the lowest one, and 1.4 for the highest one. The association was moderate among women aged 50-59 years and 60-69 years, with ORs around 1.3 for the highest BMI quintiles, but stronger among elderly women, with ORs of 1.6 for the fourth and 2.1 for the fifth quintile. An 8-unit increase in BMI involved an OR of 1.18 at age 50-59 years, of 1.14 at age 60-69 years and of 1.59 above age 70 years. This pattern of risk is similar to that observed for post-menopausal hormone replacement treatment and is consistent with a duration-risk relationship in the exposure to high oestrogen levels and with a greater differential in oestrogen levels in overweight elderly women. In terms of population attributable risk, 19.6% of all post-menopausal breast cancer patients and 27.1% of those in women above age 70 years were attributable to overweight and obesity in this population. This has, therefore, major preventive implications as to reduce breast cancer risk late in life, it is essentially important to control weight gain in elderly women.
Age Factors↗
A serologic survey of Helicobacter pylori infection in 3281 Italian patients endoscoped for upper gastrointestinal symptoms. The Italian Helicobacter Pylori Study Group.
AIM: To assess the seroprevalence of Helicobacter pylori infection in a large series of patients with upper gastrointestinal symptoms referred for their first upper gastrointestinal endoscopy, and to evaluate any association with disease. METHODS: A large survey of 3281 dyspeptic patients undergoing their first endoscopic examination was undertaken, involving 93 centres in Italy. A blood sample was taken from each participant, for measuring IgG antibodies against H. pylori using a commercially available kit, and two biopsies of the antral gastric mucosa were obtained for evaluating a Giemsa-stained specimen. RESULTS: Endoscopic macroscopic diagnoses included normal mucosa (25.3%), gustroduodenitis (51.6%), gastric and duodenal ulcers (3.7 and 14.9%, respectively) and other conditions, including gastric cancer (0.8%). Overall, the seroprevalence result was 71.3% with a strong positive association with increasing age and male sex and a negative one with educational level. According to endoscopic diagnoses, the association with H. pylori seropositivity was highest for duodenal and gastric ulcer (multivariate odds ratio: 6.1 and 2.2) and lowest for carcinoma. The comparison between the results of serology and the single Giemsa-stained specimen showed good reliability of H. pylori IgG, particularly in a subgroup (n = 2056) for which the interpretation was performed by a single dedicated pathologist: sensitivity and specificity were 92 and 78%, respectively. CONCLUSION: Commercial IgG serology is a reliable tool for the assessment of H. pylori infection in large-scale multicentre surveys. A very high seroprevalence among dyspeptic patients was confirmed, particularly in the presence of peptic disease. Factors associated with the infection were very similar to those usually reported in the general population, but male patients showed a significantly higher prevalence.
Adolescent↗
Prospective screening of dyspeptic patients by Helicobacter pylori serology: a safe policy? The Italian Helicobacter pylori Study Group.
BACKGROUND AND STUDY AIMS: Endoscopic screening of all dyspeptic patients is not cost-effective, nor is it feasible in many health-care delivery systems. To select the most appropriate candidates, various preendoscopic screening strategies have been proposed, some of which include Helicobacter pylori serology and patient age. We assessed the value of these two criteria in preendoscopic screening of a large series of dyspeptic patients, and compared the results obtained in a referral hospital (university center with an extensive H. pylori research program) with those in nonreferral hospital (participating centers that did not have such a program). PATIENTS AND METHODS: Blood samples for determination of anti-H. pylori IgG antibody were collected from patients with uninvestigated dyspepsia undergoing endoscopy at one referral hospital and in 93 nonreferral hospitals throughout Italy. For IgG antibody assay, an in-house enzyme-linked immunosorbent assay (ELISA) technique was used in the referral hospital, while a commercial kit was used in the nonreferral hospitals. RESULTS: A total of 1638 patients were evaluated at the referral hospital (845 men and 793 women, mean age 46.1 years, range 18-89), and 3281 at the nonreferral hospitals (1718 men and 1563 women, mean age 48.8, range 18-96), respectively. If endoscopy had not been performed in patients who were seronegative for H. pylori and younger than 45 years, 19% versus 17.5% of the tests would have been avoided in the referral and nonreferral hospitals, respectively, while six of 304 ulcers (2%) and no cancers would have been missed versus 35 of 557 ulcers (6.3%) and two of 557 cancers (0.3%). CONCLUSIONS: A screening strategy based on age and H. pylori serology is a valid means of selecting dyspeptic patients for endoscopy; however, the policy needs further refinement for use in nonreferral hospitals.
Adolescent↗
Population-based studies of IBD incidence in Italy and capture-recapture methods.
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Epidemiologic Methods↗
Relative validity and reproducibility of a food frequency dietary questionnaire for use in the Italian EPIC centres.
A pilot questionnaire was developed for the EPIC centres of northern Italy, and validated in the feasibility part of the cohort project. The questionnaire was self-administered and of the food frequency type with portion size estimated by means of pictures. It was structured by courses within a meal characteristic of Italian dietary habits. Dietary intake estimated by the questionnaire was compared to the corresponding estimates obtained from 8-14 24-hour recall interviews administered over a 1-year period. The reference method was validated by means of urinary nitrogen in 4-6 repeated 24-hour urine collections. One hundred and ninety-seven volunteers (47 men and 150 women) were enrolled and completed the study lasting 1 year. They filled out two questionnaires at the beginning and at the end of the study, and had a 24-hour recall interview once a month. Twenty-four-hour urine samples were collected at regular intervals. Usual intake of energy, the major nutrients and some vitamins were estimated for the questionnaires and the reference method by means of food composition tables compiled for this study. The agreement between the questionnaire and the 24-hour recalls was only good for alcohol consumption: Pearson's correlation was 0.73 and 0.77 in men and women respectively. Otherwise the relative validity of the questionnaire ranged between 0.28 for fat to 0.52 for carbohydrates in men and 0.25 and 0.50 in women for the same nutrients. The validity of the two interview methods in estimating protein intake, compared to mean urinary nitrogen was 0.24 (M) and 0.18 (W) for the questionnaire and 0.63 (M) and 0.48 (W) for 24-hour recalls. The main causes of low performance of the questionnaire were identified to be the estimated intake of dressing and cooking fats, vegetables and meat. Remedies were devised and introduced in the final version of the questionnaire currently in use in the EPIC project.
Cohort Studies↗
Gastric cancer and Helicobacter pylori: a critical evaluation of the epidemiological evidence.
Despite a dramatic reduction in incidence and mortality, gastric cancer (GC) still was recently reported to be the second most common neoplastic cause of death worldwide. GC treatment has not been improved substantially, and large-scale early diagnosis programs have not proved feasible outside Japan. On the other hand, even if diet has been shown to play a relevant role in the etiology of GC, primary prevention programs based on dietary modifications are difficult to implement, and results of human chemoprevention trials, although encouraging, have not been confirmed. Overall, the observed reduction in GC risk can reasonably be considered to be the result of a spontaneous trend, somehow related to the wide-spread improvements in socioeconomic conditions. Domestic refrigeration, an increased availability of fresh fruit and vegetables, and a reduced use of salt are considered to be the most relevant factors in explaining the decreasing temporal trend and the geographical patterns of GC. Recently, evidence of an association between Helicobacter pylori infection and GC has been provided by epidemiological studies, particularly three studies specifically designed as nested case-control studies in which blood samples were collected well before diagnosis was made. The results of these studies, however, have been confirmed only in part. A strong direct association is not yet widely accepted, and no specific carcinogenic compound or mechanism has been identified. Relevant aspects of GC and H. pylori epidemiology actually do not fit perfectly in a causal hypothesis (i.e., the geographical and gender distribution, the paradoxical association with duodenal ulcer) though, on the other hand, several other factors certainly play a role in the complex multifactorial process leading, over several decades, to GC. Studies focused on H. pylori eradication and its effects on lesions that predispose to GC (atrophic gastritis and metaplasia), however, represent a priority for research, in view of the potential preventive applications. This issue remains controversial, and it is possible that progression of these lesions might occur after eradication.
Helicobacter Infections↗
Update on Helicobacter pylori research. Malignancies.
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Animals↗
Diet, Helicobacter pylori, and p53 mutations in gastric cancer: a molecular epidemiology study in Italy.
A series of 105 gastric cancer (GC) cases with paraffin-embedded specimens interviewed in a previous population-based case-control study conducted in a high-risk area around Florence, Italy, was examined for the presence of p53 mutations. Overall, 33 of 105 cases had a mutation (p53+) identified by single-strand conformational polymorphism and confirmed by sequencing (Y-H. Shiao et al., submitted for publication). p53+ cases had a more traditional dietary pattern (i.e., corn meal mush, meat soup, and other homemade dishes) and reported less frequent consumption of raw vegetables (particularly lettuce and raw carrots). A positive association with a high nitrite intake and a negative association with raw vegetables and diffuse type histology persisted in a multivariate analysis. In addition, p53+ cases tended to be located in the upper portion of the stomach and to be associated with advanced age and blood group A. No relation was found between the presence of p53 mutations and histologically defined Helicobacter pylori infection, smoking history, family history of gastric cancer, education, and social class. Of the 33 p53+ cases, 19 had G:C-->A:T transitions at CpG sites. These tumors tended to occur in females and in association with H. pylori infection but not other risk factors. The remaining 14 cases with a p53 mutation had mainly transversions but also two deletions and two transitions at non-CpG sites. These tumors showed a strong positive association with a traditional dietary pattern and with the estimated intake of selected nutrients (nitrite, protein, and fat, particularly from animal sources). The findings of this case-case analysis suggest that p53 mutations at non-CpG sites are related to exposure to alkylating compounds from diet, whereas p53 mutations at CpG sites might be related to H. pylori infection.
Aged↗
Reproducibility of histological diagnosis of breast lesions: results of a panel in Italy.
Sixteen pathologists independently examined and classified a series of 81 breast lesions selected from the files of several Italian Pathology Departments in the context of a national task force on breast cancer (FONCAM). A four category classification system was used for analysis; according to the majority diagnosis (MD), simply defined as the most frequently reported in the panel, the series included 37 benign lesions without atypia (45.7%), nine atypical hyperplasias (11.1%), 18 in situ (22.2%) and 17 invasive carcinomas (21.0%). Concordance, estimated for all possible pair-wise comparisons between pathologists, was good (mean kappa value: 0.59). A comparison between the diagnoses of each pathologist and the panel majority diagnosis was also made. Overall, a global kappa value of 0.72 was found (range 0.57-0.85), with category-specific values being excellent for invasive carcinoma (0.89) and benign lesions without atypia (0.77), relatively good for in situ carcinoma (0.69) but poor for atypical hyperplasia (0.38). These results confirm that quality assurance procedures are particularly indicated for large screening programmes for breast cancer, and suggest that for atypical lesions strict diagnostic criteria should be adopted.
Breast Neoplasms↗