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Biomedical subjects

C Saieva

Publications and source records attributed to C Saieva.

At least 37 records · Page 2Linked to original sources

Instability at dinucleotide and trinucleotide repeats in breast cancer.

We analyzed 7 mono-, 6 di- and 2 trinucleotide repeat loci in a well characterized series of 69 breast cancer cases, treated in the period 1985-1986 and followed for 12 years. Tumor-associated allele contractions or expansions were observed only at di- and trinucleotide repeats, and were detected in 14/69 cases (20%), of which 7 (10%) showed instability at 2 or more loci (10%). No alterations were detected at mononucleotide repeats known to be unstable in gastrointestinal tumors with the microsatellite mutator phenotype. Disease-free survival at 5 years, overall survival at 12 years of follow-up, tumor stage, estrogen/progesteron receptor status, and expression of the Ki-67 proliferation marker were independent of microsatellite status.

Adult↗

Genetic and immunohistochemical analyses of p53 independently predict regional metastasis of gastric cancers.

Either p53 gene mutation or immunohistochemical detection of p53 protein has not been consistently shown to have prognostic significance in human cancers, including gastric carcinomas. One hypothesis to explain this inconsistency is that some p53 mutations and p53 protein accumulation are not indicative of tumor progression. To test this hypothesis, we categorized p53 status in 105 gastric carcinomas according to types of mutations, numerical scores of immunohistochemical staining (IHC), or combinations thereof. The p53 status was then correlated with metastasis to liver or peritoneum. Gastric cancers with no p53 mutations were significantly less likely to metastasize than tumors with mutations. Intermediate IHC scores were inversely associated with metastasis. A substantial number of gastric cancers (31 of 105) showed positive p53 immunostaining without detectable mutations (p53-/IHC+), which suggested an accumulation of wild-type p53 protein, and also a significantly lower risk for metastasis. After adjusting for depth of invasion and lymph node involvement, the p53-/IHC+ combination predicted low metastatic risk better than either p53- or IHC+ with intermediate scores. These findings suggest that an accumulation of wild-type p53 protein occurs in gastric cancer cells and represents a stress-response mechanism that lowers metastatic potential.

Adult↗

Dietary determinants of colorectal proliferation in the normal mucosa of subjects with previous colon adenomas.

Dietary determinants of colorectal mucosa proliferation were studied in 69 subjects previously operated for at least two sporadic colon adenomas. Information on recent dietary habits was collected by a validated food frequency questionnaire, and proliferation was measured by [3H]thymidine incorporation in colorectal biopsies by determining the labeling index (LI) and the percentage of LI in the upper part of the crypt, two parameters that are increased in subjects at high risk of colon cancer. The LI was significantly higher in women as compared with men (P = 0.01). Diet showed several associations with colorectal mucosa proliferation: (a) subjects in the highest tertile of fish consumption had a significantly lower LI (P = 0.0013) compared with those in the lower tertiles [5.20 +/- 1.87 versus 6.80 +/- 2.18 (mean +/- SD)]; (b) subjects with a low red meat consumption had lower proliferation in the upper part of the crypt [2.38 +/- 2.10, 5.30 +/- 4.62, and 5.89 +/- 4.82 in the low, middle, and high tertile of consumption, respectively (mean +/- SD); P = 0.0093]; (c) according to estimated nutrient intakes, the LI was lower in subjects reporting a high intake of starch (P = 0.006) and higher in subjects with a low intake of beta-carotene (P = 0.002). The results show that subjects reporting a diet rich in fish, starch, and beta-carotene and low in red meat had lower colorectal mucosa proliferation and a normal pattern of proliferation along the crypt. Given the correlation between colorectal proliferative activity and colon cancer risk, such a dietary pattern might be beneficial for subjects at high risk of colon cancer.

Adenomatous Polyps↗

Serum levels of ochratoxin A in healthy adults in Tuscany: correlation with individual characteristics and between repeat measurements.

Ochratoxin A (OTA), a mycotoxin widely contaminating staple foods and beverages, has been classified as a "possible human carcinogen (Group 2B)" by the IARC. Serum levels of OTA were measured in a group of 138 healthy adults (age, 35-65 years) living in the area surrounding Florence (Tuscany, central Italy) and detected in all but four samples (97%). After the exclusion of one subject with a peak value of 57.2 ng/ml, OTA levels ranged between 0.12 and 2.84 ng/ml, with mean and median values of 0.56 and 0.48 ng/ml, respectively. OTA levels were significantly higher in men than in women (0.64 versus 0.50) and correlated positively with height. A strong association was found with the season in which blood samples were obtained, with summer values higher than autumn values. On the other hand, OTA levels tended to be negatively associated with blood pressure, either systolic or diastolic; no association was evident with age, weight, body mass index, and smoking history. The associations with height and season persisted in a multivariate regression analysis. A subgroup of subjects provided a repeat blood sample approximately 1 year later. The Spearman correlation coefficient between 68 pairs of original and repeat measurements was practically null (r = 0.05). Only two subjects (2.9%) had OTA levels of >1 ng/ml on both occasions. These results suggest that OTA contamination is widespread in foods consumed by this population, in agreement with previous reports from Italy and other countries. A strong seasonal variation, which possibly differs from year to year, was observed. OTA serum levels are a short-term biomarker with a high within-subject variability; therefore they have limited use at the individual level but can be used to characterize populations or subgroups of subjects. Additional analyses are needed to explore the dietary determinants of OTA levels in this population.

Adult↗

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↗

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↗

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↗

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↗

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↗

A population-based study of inflammatory bowel disease in Florence over 15 years (1978-92).

BACKGROUND: In the group of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) are considered to be more frequent in Western countries and in areas with a high socioeconomic development but relatively infrequent in southern Europe. Sporadic reports have indicated a lower incidence and a milder course of the disease in Mediterranean countries. Although conclusive data on this point are still lacking, recent reports suggest an increase in both incidence and prevalence rates. METHODS: The incidence of UC and CD during the period January 1978 to December 1992 and their prevalence on 31 December 1992 were estimated in the 15-year-old population of the metropolitan area of Florence. Clinical, demographic, and follow-up information was collected for all identified IBD patients. RESULTS: A total of 796 residents (345 females and 454 males) were newly diagnosed as having IBD during the study period. Of these 593 had UC and 203 CD. The age-standardized incidence rates, calculated for each of five 3-year consecutive periods, rose from 3.8 (in 1978-80) to 9.6 per 100,000 person-years (in 1990-92) for UC and from 1.9 (in 1978-80) to 3.4 (in 1990-92) for CD. Both trends were statistically significant. The prevalence estimated on 31 December 1992 was 121.0 and 40.0 per 100,000 inhabitants for UC and CD, respectively. CONCLUSIONS: Our results confirm that IBD incidence rates and prevalence in this area of central Italy are currently comparable with those reported in northern Europe. These data are necessary for planning adequate health care services for IBD patients.

Adolescent↗

Reproductive history and gastric cancer among post-menopausal women.

A total of 339 post-menopausal women with gastric cancer (GC) and 515 population controls were interviewed in a multicenter study in Italy for information on reproductive history, dietary habits and other socio-demographic variables. After adjusting for these factors, GC risk was significantly higher among women reporting menopause below age 45, while no effect was shown for age at menarche, parity, age at first livebirth, and number of abortions. When age at menopause was considered together with age at menarche for an index of fertility years, GC risk showed a significant inverse relation to duration of fertility. These results suggest a protective role for endocrine or other factors related to late age at menopause or to length of fertility. These findings may be relevant to explain the fact that rates of GC reported among females are lower than among males around the world, and suggest the need for further research into hormonal and other related risk factors.

Age Distribution↗