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Biomedical subjects

Marco Vinceti

Publications and source records attributed to Marco Vinceti.

18 recordsLinked to original sources

The Childhood Cancer and Leukemia International Consortium (CLIC): Expanding global collaboration in pediatric cancer etiology research.

Childhood cancers are rare, but incidence has risen modestly in countries with robust registration, partly reflecting improved diagnosis. In high-income countries, cancer is the leading cause of disease-related death in children. Marked inequities in incidence, survival, and research capacity underscore the need for large-scale collaboration to identify environmental, genetic, and contextual determinants of risk. The Childhood Cancer and Leukemia International Consortium (CLIC) was established in 2007 to study the etiology of childhood leukemia and later expanded in 2019 to include other childhood cancers, principally solid tumors. CLIC pools harmonized, individual-level data from case-control and cohort studies, obtained through interviews, record linkage (insurance claims, registries), or geographic information systems, and integrates germline genomic data where available. Membership has grown from 13 studies in 9 countries to 57 studies in 21 countries; recruitment spans the early 1960s to the present and encompasses approximately 150,000 cases across all tumor types and 300,000 controls with clinical, demographic, and exposure data, centralized via harmonized data dictionaries at the Data Coordination Center, established in 2014 at the International Agency for Research on Cancer, and supported by a secure analysis platform. Pooled analyses across diverse populations have implicated parental age, prenatal vitamin or folic acid use, mode of delivery, fetal growth, selected congenital anomalies, occupational or household exposures (e.g., pesticides), paternal smoking, and markers of early-life immune modulation (e.g., breastfeeding, daycare attendance) in leukemia risk, informing carcinogen evaluation and prevention. The integration of genetic ancestry and germline susceptibility data is clarifying ancestry-related differences in leukemia biology and outcomes, while confirming risk loci with population-specific effects. CLIC is now adding polygenic risk scores and exposomic data to refine etiologic subtyping and identify modifiable pathways, while broadening representation from underserved regions through partnership-building and capacity-strengthening.

Humans↗

Case-control study of toenail cadmium and prostate cancer risk in Italy.

A role of cadmium exposure in prostate cancer etiology has been suggested by epidemiologic and laboratory studies, but conclusive evidence on this topic is still lacking. We investigated the relation between cadmium exposure, estimated by determining toenails cadmium levels, and prostate cancer risk in forty patients newly diagnosed with prostate cancer and fifty-eight hospital controls recruited in two provinces from southern and northern Italy. We found an excess cancer risk in subjects in the third and fourth (highest) quartiles of toenail cadmium concentration (odds ratio 1.3 and 4.7, respectively) compared with subjects in the bottom quartile. Results were basically unchanged when limiting the analysis to each province or entering toenail cadmium concentrations as continuous values in the regression model (P=0.004). Despite the limited statistical stability of the point estimates, these findings appear to support the hypothesis that cadmium exposure increases prostate cancer risk.

Adult↗

High risk of cutaneous melanoma amongst carriers of the intercellular adhesion molecule-1 R241 allele.

We examined the relation between cutaneous melanoma risk and the intercellular adhesion molecule-1 (ICAM-1) gene single nucleotide polymorphisms G241R and K469E, as well as the circulating soluble form of ICAM-1 determined in plasma, in the population of Modena Province, northern Italy. Individuals carrying at least one R241 allele, versus those carrying the wild-type GG genotype, had a relative risk of melanoma of 4.3 (P = 0.022), whereas the K469E polymorphism was unrelated to disease risk. Soluble ICAM-1 levels above 10 ng/ml directly and strongly correlated with melanoma risk. In this population, individuals carrying the R241 allele of the ICAM-1 gene appeared to show an enhanced susceptibility to cutaneous melanoma, possibly because of increased ICAM-1 expression.

Alleles↗

Acute-phase reactants and the risk of relapse/recurrence in polymyalgia rheumatica: a prospective followup study.

OBJECTIVE: To determine laboratory parameters that may be useful in identifying polymyalgia rheumatica (PMR) patients who require long-term corticosteroid therapy. METHODS: A prospective followup study of 94 consecutive untreated patients with PMR were assessed for relapse/recurrence for a mean of 39 months. This cohort represented all the patients diagnosed over a 4-year period in 2 Italian secondary referral centers. Patients were monitored for clinical signs and symptoms, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum interleukin-6 (IL-6). IL-6 levels were also measured in 43 controls matched to the patients for age and sex. RESULTS: The ESR was elevated in 91.5% of the patients prior to therapy initiation, as were CRP in 98.9% and serum IL-6 in 92.6%. Forty-seven (50.0%) patients had at least 1 relapse/recurrence during the followup period and 24 (25.5%) had at least 2. After 4 weeks of prednisone therapy, ESR was elevated in 13.2% patients, CRP in 41.9%, and serum IL-6 in 37.2%. IL-6 levels remained persistently elevated in 9.9% and CRP in 8.7% of patients during the first year of followup, whereas no patient had persistently elevated ESR. Persistently elevated CRP and IL-6 levels were significantly associated with an increased risk of relapse/recurrence. In particular, patients with persistently elevated levels of IL-6 during the first year of therapy had the highest relative risk. CONCLUSION: Despite the control of clinical symptoms, corticosteroids do not adequately control the inflammatory process in a subset of patients with PMR who have persistently elevated levels of CRP and IL-6 and who have a higher risk of relapsing.

Acute-Phase Proteins↗

Trace elements and melanoma.

Melanoma incidence has been steadily increasing in recent years in most western countries, thus suggesting a role of environmental risk factors. Among these determinants, it has been hypothesized that some trace elements of nutritional and toxicological interest may be implicated in the etiology of the disease. We examined patients with newly diagnosed melanoma of the skin and population controls from the Modena province northern Italy. Clinical and dietary data were collected through questionnaires, and toenails were sampled for trace element determination. Levels of cadmium, chromium, lead, selenium, zinc, copper and iron in toenails were measured by inductively coupled plasma optical emission spectrometry and by neutron activation analysis. Data obtained from 58 cases and 58 controls indicated higher levels of copper and lower concentrations of iron in melanoma patients, whilst no other differences were seen for the remaining elements. Patterns of correlations of zinc and copper with the estimated intake of some dietary factors were different between cases and controls. Results of the present study suggest that abnormal intake or metabolism of copper and of iron might be implicated in the etiology of melanoma, whilst they do not indicate an involvement of exposure to cadmium, chromium, lead, selenium and zinc in this disease.

Case-Control Studies↗

Environmental exposure to trace elements and risk of cutaneous melanoma.

PURPOSE: Our aim was to examine the risk of melanoma in association with exposure to trace elements of toxicological and nutritional interest. METHODS: We analyzed the concentrations of cadmium, lead, chromium, selenium, copper and zinc in toenails of 58 patients with newly diagnosed cutaneous melanoma as well as in 58 age- and sex-matched control subjects, randomly selected from the population of Modena province in northern Italy. RESULTS: Melanoma risk was substantially unrelated to toenail levels of cadmium, chromium, lead and selenium. Subjects with higher toenail copper levels showed an excess risk, both in the crude analysis and after adjusting for sun exposure and level of education, while in both analyses high iron concentrations were associated with a decreased risk of the disease. A weak direct association between zinc levels and melanoma risk also emerged in the multivariate analysis. CONCLUSIONS: Overall, these results do not suggest an involvement of heavy metals in melanoma etiology, while they do give some support to a possible role of zinc and, in particular, copper and iron exposure in influencing disease risk. However, these findings must be evaluated with caution due to the limited statistical stability of the point estimates.

Case-Control Studies↗

A population-based case-control study of diet and melanoma risk in northern Italy.

OBJECTIVE: We aimed at examining the association between dietary constituents and risk of cutaneous melanoma. DESIGN: In an area of northern Italy we recruited 59 newly diagnosed melanoma patients and 59 age- and sex-matched population controls, to whom we administered a validated semi-quantitative food-frequency questionnaire. RESULTS: We found an excess risk of melanoma in subjects with a higher energy-adjusted intake of total polyunsaturated fatty acids and, in particular, of linoleic acid (relative risk = 2.16 for intake in the highest tertile compared with the lowest tertile, P for linear trend = 0.061). Conversely, disease risk was inversely associated with the consumption of soluble carbohydrates (relative risk = 0.34 for intake in the upper vs. the lowest tertile adjusting for total energy intake, P for linear trend = 0.046). No other dietary factors, including alcohol, vitamins and trace elements, correlated with melanoma risk. The association of melanoma risk with linoleic acid and soluble carbohydrates intakes was further strengthened in multivariate analysis, and when analysis was limited to females. CONCLUSIONS: Overall, these results indicate that an excess energy-adjusted intake of linoleic acid and a lower consumption of soluble carbohydrates may increase melanoma risk.

Case-Control Studies↗

A retrospective cohort study of trihalomethane exposure through drinking water and cancer mortality in northern Italy.

A few epidemiologic studies have suggested that consumption of drinking water with high trihalomethane content increases the risk of cancer. We investigated the mortality of a cohort of 5144 residents in Guastalla, northern Italy, who were supplied tap water with high chloroform and trihalomethane content between 1965 and 1987. Using death rates of a nearby community as reference rates, the standardized mortality ratio from all cancers between 1987 and 1999 was slightly increased for both males (1.2, 95% confidence interval 1.1-1.4) and females (1.1, 95% confidence interval 1.0-1.3). This was mainly due to a higher mortality from stomach, liver, lung, prostate and bladder cancer in males and from stomach, pancreas, breast and ovarian cancer and lymphocytic leukemia in females. We also noted excess mortality from melanoma in both males and females. Overall, our findings were consistent with an association between trihalomethane exposure and increased cancer risk at some sites. However, the point estimates were statistically imprecise, due to the limited number of deaths for some site-specific cancers. In addition, we were unable to rule out the possibility of confounding due to smoking and other life-style factors with regard to some of the excess rates.

Adolescent↗

Italian family with two independent mutations: 3358T/A in BRCA1 and 8756delA in BRCA2 genes.

Hereditary breast/ovarian cancer is a well-characterized clinical entity, largely attributed to the inheritance of BRCA1 or BRCA2 mutations. Among general population, the mutation's frequency of these genes is very low; therefore, the identification of two independent mutations in the same family is a rare event. This study reports the presence of two mutations, one in the BRCA1 and the second in the BRCA2 gene in an Italian Caucasian kindred. This family is composed of more than 250 individuals, spanning through five generations, among which endogamy was a common phenomenon. Considering the tumor spectrum, this family is characterized by a high incidence of different types of cancer. In our study, we considered only three out of seven family units for BRCA1 and BRCA2 analysis. In one of the family units, we found independent mutations of both BRCA genes. The BRCA1 mutation on exon 11 (3358T-->A) was identified originally in the index case and subsequently in 18 members of this family, whereas the same mutation was not detected in a related family member with male breast cancer. The male breast cancer patient led to the identification, through mutational analysis, of a new BRCA2 mutation (8756delA). This BRCA2 mutation was also found in the male breast cancer patient's daughter. The discovery of the BRCA2 mutation allowed us to alert the patient's daughter who, otherwise, could be falsely reassured since she had a negative BRCA1 test.

Adult↗

Toenail selenium as biomarker: reproducibility over a one-year period and factors influencing reproducibility.

We assessed the reproducibility of selenium levels in toenails, comparing concentrations in two sets of specimens collected about a year apart, from 80 women (40 pre-menopausal and 40 post-menopausal) in the period October 1990 to February 1992. The women were participants in a prospective study on hormones and diet in relation to prediagnostic breast cancer (the ORDET study) conducted in northern Italy. Toenail selenium was determined by electrothermal atomic absorption spectrometry. The data were log-transformed as they were not normally distributed. To assess reproducibility Pearson correlation coefficients (r) for the two selenium determinations were calculated in pre- and post-menopausal women, according to smoking status and acetone treatment. A weighted kappa statistic (k) assessed inter-quintile agreement between the two sets of measures. Toenail selenium levels were highly reproducible (r = 0.57, p < 0.001), especially in pre-menopausal women (r = 0.66, p <0.001). Smoking lowered selenium levels (mean difference of 0.24 microg/g, p < 0.05 between smokers and non smokers) but did not significantly influence reproducibility. Acetone treatment to remove nail polish did not modify selenium levels but affected inter-quintile agreement, with moderate agreement (k = 0.58, p < 0.001) when acetone was used at both or neither samplings; and fair non significant agreement (k = 0.39, p = 0.06) when acetone was used at one sampling but not the other. As selenium levels in toenails are highly reproducible, notwithstanding variation in selenium levels in food and long-term changes in individuals' food choices, toenail selenium may be a useful biomarker of selenium exposure, particularly since toenail samples provide a measure of long-term exposure. However age, smoking status and acetone treatment are possible causes of misclassification.

Acetone↗

Is duplex ultrasonography useful for the diagnosis of giant-cell arteritis?.

BACKGROUND: Evidence of a dark halo on ultrasonography has been considered a specific sign of giant-cell arteritis and may replace temporal artery biopsy for the diagnosis of giant-cell arteritis in patients with typical clinical manifestations. OBJECTIVE: To assess the usefulness of temporal artery duplex ultrasonography and to compare this mode of ultrasonography with physical examination of temporal arteries for the diagnosis of giant-cell arteritis in patients with suspected giant-cell arteritis or polymyalgia rheumatica. DESIGN: Diagnostic test study. SETTING: Several divisions of Reggio Emilia Hospital, Reggio Emilia, Italy. PATIENTS: 86 consecutive patients with a suspected diagnosis of giant-cell arteritis or polymyalgia rheumatica identified over a 22-month period. MEASUREMENTS: The temporal arteries were examined in all 86 patients. Duplex ultrasonography of the temporal arteries was then performed by two ultrasonographers who were unaware of the clinical diagnosis. Before corticosteroid therapy was started, temporal artery biopsies were performed in all patients at the site targeted by the ultrasonographer. RESULTS: A hypoechoic halo around the lumen of the temporal arteries had a sensitivity of only 40% (95% CI, 16% to 68%) and a specificity of 79% (CI, 68% to 88%) for the diagnosis of biopsy-proven giant-cell arteritis. The negative likelihood ratio was 0.8 (CI, 0.5 to 1.2), and the positive likelihood ratio was 1.9 (CI, 0.9 to 4.1). When the thickness of the halo was at least 1 mm, specificity increased to 93% (CI, 84% to 98%) and the positive likelihood ratio increased to 5.7 (CI, 2.0 to 16.2); however, sensitivity remained low at 40% (CI, 16% to 68%). On physical examination, temporal artery abnormalities had a higher sensitivity of 67% (CI, 38% to 88%), a higher specificity of 99% (CI, 92% to 100%), and a higher positive likelihood ratio of 47.3 (CI, 6.5 to 342.4) than did ultrasonographic findings. None of the patients with giant-cell arteritis had a normal temporal artery inspection and a hypoechoic halo on ultrasonography. CONCLUSION: Evidence on ultrasonography of a halo around temporal arteries, either any halo or a halo 1 mm or greater in thickness, only modestly increased the probability of biopsy-proven giant-cell arteritis but did not improve the diagnostic accuracy of a careful physical examination.

Aged↗

Risk of second cancer in patients with hairy cell leukemia: long-term follow-up.

PURPOSE: The purpose of the present study was to assess the risk of second cancers in patients with hairy cell leukemia (HCL). PATIENTS AND METHODS: We investigated the incidence of additional cancers in those patients registered in the nationwide registry of the Italian Cooperative Group for the Study of HCL, asking the cooperating centers for additional information on initial and subsequent therapies and on time and type of second malignancies, if they developed. Here we report the final results of this survey, consisting of 54 cases of second malignancies (excluding nine cases of epithelial skin cancer) which developed in 54 patients of 1,022 with adequate follow-up. RESULTS: The cumulative risk of development of a second cancer was 5%, 10%, and 14% at 5, 10, and 15 years, respectively. The incidence of second malignancies was not significantly higher than the expected rate (standardized incidence ratio [SIR], 1.01; 95% confidence interval [CI], 0.74 to 1.33; P = 1.0). However, the SIR of non-Hodgkin's lymphoma in the entire cohort was 5.3 (95% CI, 1.9 to 11.5). Second malignancies occurred in eight (4.7%) of 386 patients who never received interferon (IFN), nine (5.9%) of 495 patients treated with IFN at the time of diagnosis, and seven (6.9%) of 102 patients who received IFN as second-line therapy. These differences were not statistically significant. Analysis of the separate calendar periods did not reveal any particular trends with respect to variations in SIR. CONCLUSION: The present study does not support the suspicion that patients with HCL are at increased risk of additional second malignancies, although the incidence of lymphoid neoplasms was significantly higher than expected. In addition, our data indicate that IFN therapy did not exert an oncogenic effect in such patients.

Adult↗

Environmental exposure to trace elements and risk of amyotrophic lateral sclerosis: a population-based case-control study.

We analyzed the association between the environmental exposure to trace elements and the risk of sporadic amyotrophic lateral sclerosis (ALS) in a population-based case-control study in the Emilia-Romagna region in northern Italy. We evaluated exposure to selected trace elements by measuring toenail concentrations of the same by means of inductively coupled plasma optical spectrometry and instrumental neutron activation analysis. The final number enrolled in the study was 22 patients and 40 controls. Disease progression, assessed through a clinical score, was generally unassociated with toenail trace element levels, with the exception of an inverse relation with zinc and selenium content and a direct correlation with copper concentration. In logistic regression analysis, we found no evidence of an association between ALS risk and toenail content of cadmium, lead, copper, zinc, manganese, selenium, chromium, cobalt, iron, and aluminum. This investigation does not suggest a major role in sporadic ALS etiology of environmental exposure to these trace elements, though results for zinc, selenium, and copper should be evaluated with caution due to the potential limitations of toenails as biomarkers of chronic exposure in patients.

Amyotrophic Lateral Sclerosis↗

Selenite inhibition of Coxsackie virus B5 replication: implications on the etiology of Keshan disease.

Keshan disease is a cardiomyopathy of unknown origin reported in some areas of China. Because of epidemiologic features, this disease was ascribed to an infectious agent, likely a Coxsackie virus, but it has also been thought to depend on selenium deficiency, mainly because selenite is effective in its prophylaxis. We examined the hypothesis that pharmacological activity of selenite on Coxsackie virus growth was associated with prevention of Keshan disease. We studied the antiviral effects of three selenium compounds on Coxsackie virus B5 replication: five microM selenite reduced viral replication, whilst 10 microM selenate and selenomethionine did not exhibit any antiviral activity. The inhibitory activity of selenite on viral replication was due to its toxicity following its interaction with thiols, as that activity could be blocked by dithiothreitol, a sulfhydryl-protecting agent known to reverse several toxic effect of selenite. Zinc, another inhibitor of selenite toxicity, also counteracted the antiviral effect of selenite. The selenium compounds showed only limited activity against herpes simplex 1 virus and IHD strain of vaccinia virus. A direct inhibitory effect of selenite on Coxsackie virus replication might explain the efficacy demonstrated by this compound in the prophylaxis of Keshan disease.

Animals↗

Changes in breast cancer incidence and stage distribution in Modena, Italy: the effect of a mammographic screening program.

OBJECTIVE: Assessing changes in breast cancer (BC) incidence and stage distribution in the District of Modena, Italy, during the period 1992-1998, and their relationship to a mammographic screening program launched in 1995. METHODS: Demographic, clinical, and pathological data of all BC cases reported to the population-based Modena Cancer Registry between 1992 and 1998 were collected and linked to the screening database. RESULTS: A total of 3429 women were diagnosed with BC in the District of Modena between 1992 and 1998. In this period the incidence rate increased by 15.7% (from 134.3 in 1992 to 155.4 per 100,000 in 1998). The increase began in 1995 and exclusively included women aged 50-69; the incidence rose by 30.4%. Moreover, the rise was confined to early tumors, with more than half (54%) of all cases reported in 1998 diagnosed as stage 0 or I disease, compared with 42% in 1992. Screen-detected tumors were significantly smaller (13.2 mm) than other tumors diagnosed in women aged 50-69 (18.5 mm), with 46% of screen-detected tumors smaller than 10 mm. Overall, a decline in the average tumor diameter was shown (from 20.2 mm in 1992-1994 to 18 mm in 1996-1998). CONCLUSIONS: Our data confirm that mammographic screening leads to an increase in the incidence of early-stage BC cancers.

Aged↗

Erythrocyte zinc, copper, and copper/zinc superoxide dismutase and risk of sporadic amyotrophic lateral sclerosis: a population-based case-control study.

We investigated through a population-based case-control study the hypothesis that disturbances in the chemistry of copper and zinc and in activity of the antioxidant enzyme copper/zinc superoxide-dismutase (SOD1) are involved in the etiopathogenesis of sporadic amyotrophic lateral sclerosis (ALS). We recruited 20 patients with sporadic ALS and 22 population controls from three northern Italian provinces, and we analyzed zinc and copper content and SOD1 activity in erythrocytes. These variables were unrelated to disease progression as evaluated through a disability score; zinc concentrations inversely correlated with copper in referents but not in patients. SOD1 activity was lower and erythrocyte zinc and copper levels were slightly higher in patients than in referents. Comparing the second to the bottom tertile of erythrocyte SOD1 activity, relative risk of ALS was 0.4 (95% confidence interval 0.1-2.0); the risk further decreased to 0.1 (95% confidence interval 0-0.9) for comparison of highest to lowest tertile (P for trend 0.027). Copper and zinc levels were not associated with disease risk. Our findings indicate that a lower SOD1 activity is associated with ALS, but we cannot be sure whether this association is a marker of causal action or is secondary to a confounder, or to disease onset itself.

Amyotrophic Lateral Sclerosis↗

[Low back pain risk in nurses and its prevention].

We present the results of a study on the prevalence of low back pain (LBP) in a group of hospital nursing personnel. In 180 subjects (89% women) a questionnaire on LBP was collected. The prevalence of LBP episodes during the last 12 months was 63,9%; no difference was observed according to the working area (medicine, surgery, emergency). The proportion of subjects with LBP tended to increase according to the previous duration of work, but not with age. The prevalence of LBP was significantly lower in nursing personnel working according the team nursing model, that is less repetitive, and involves less work load, compared to the functional nursing model. Furthermore, LBP prevalence was lower among nurses that received an adequate formation on the prevention of occupational LBP. The results of the study confirm the relevance of LBP in nursing personnel, but suggest also that an adequate preventive programme can significantly reduce the risk.

Adult↗