Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Residential exposure to magnetic fields from transformer stations and risk of childhood leukemia.

BACKGROUND: Several studies have documented an increased risk of leukemia among children exposed to magnetic fields from high-voltage power lines, with some evidence of dose-response relation. However, findings in some studies have been inconsistent, and data on the effects of different sources of exposure are lacking. In this study, we evaluated the relation of childhood leukemia risk to exposure to magnetic fields from transformer stations. METHODS: We conducted a population-based case-control study in a pediatric population of two Northern Italian provinces of Modena and Reggio Emilia. We included 182 registry-identified childhood leukemia cases diagnosed during 1998-2019 and 726 population controls matched on sex, year of birth, and province of residence. We assessed exposure by calculating distance from childhood residence to the nearest transformer station within a geographical information system, computing disease odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, adjusting for potential confounders. We evaluated exposure using two buffers (15 m and 25 m radius) and assessed two case groups: leukemia (all subtypes) and acute lymphoblastic leukemia (ALL). RESULTS: Residing within 15 m of a transformer station (vs. ≥15 m) was not appreciably associated with risk of leukemia (all subtypes) or ALL. We found similar results using a less stringent exposure buffer (25 m). Among children aged ≥5 years, the adjusted ORs were 1.3 (95% CI 0.1-12.8) for leukemia and 1.3 (95% CI 0.1-12.4) for ALL using the 15 m buffer, while they were 1.7 (95% CI 0.4-7.0) for leukemia and 0.6 (95% CI 0.1-4.8) for ALL using the 25 m buffer. CONCLUSIONS: While we found no overall association between residential proximity to transformer stations and childhood leukemia, there was some evidence for elevated risk of childhood leukemia among children aged ≥5 years. Precision was limited by the low numbers of exposed children.

Residential proximity to petrol stations and risk of childhood leukemia.

Petrol stations emit benzene and other contaminants that have been associated with an increased risk of childhood leukemia. We carried out a population-based case-control study in two provinces in Northern Italy. We enrolled 182 cases of childhood leukemia diagnosed during 1998-2019 and 726 age- and sex-matched population controls. We geocoded the addresses of child residences and 790 petrol stations located in the study area. We estimated leukemia risk according to distance from petrol stations within a 1000 m buffer and amount of supplied fuel within a buffer of 250 m from the child's residence. We used conditional logistic regression models to approximate risk ratios (RRs) and 95% confidence intervals (CIs) for associations of interest, adjusted for potential confounders. We also modeled non-linear associations using restricted cubic splines. In secondary analyses, we restricted to acute lymphoblastic leukemia (ALL) cases and stratifed by age (<5 and ≥5 years). Compared with children who lived≥1000 m from a petrol station, the RR was 2.2 (95% CI 0.5-9.4) for children living<50 m from nearest petrol station. Associations were stronger for the ALL subtype (RR=2.9, 95% CI 0.6-13.4) and among older children (age≥5 years: RR=4.4, 95% CI 0.6-34.1; age<5 years: RR=1.6, 95% CI 0.1-19.4). Risk of leukemia was also greater (RR=1.6, 95% CI 0.7-3.3) among the most exposed participants when assigning exposure categories based on petrol stations located within 250 m of the child's residence and total amount of gasoline delivered by the stations. Overall, residence within close proximity to a petrol station, especially one with more intense refueling activity, was associated with an increased risk of childhood leukemia, though associations were imprecise.

Particulate matter exposure from motorized traffic and risk of conversion from mild cognitive impairment to dementia: An Italian prospective cohort study.

BACKGROUND: Based on epidemiologic and laboratory studies, exposure to air pollutants has been linked to many adverse health effects including a higher risk of dementia. In this study, we aimed to evaluate the effect of long-term exposure to outdoor air pollution on risk of conversion to dementia in a cohort of subjects with mild cognitive impairment (MCI). METHODS: We recruited 53 Italian subjects newly-diagnosed with MCI. Within a geographical information system, we assessed recent outdoor air pollutant exposure, by modeling air levels of particulate matter with equivalent aerodynamic diameter ≤10 µm (PM10) from motorized traffic at participants' residence. We investigated the relation of PM10 concentrations to subsequent conversion from MCI to any type of dementia. Using a Cox-proportional hazards model combined with a restricted cubic spline model, we computed the hazard ratio (HR) of dementia with its 95% confidence interval (CI) according to increasing PM10 exposure, adjusting for sex, age, and educational attainment. RESULTS: During a median follow up of 47.3 months, 34 participants developed dementia, in 26 cases diagnosed as Alzheimer's dementia. In non-linear restricted spline regression analysis, mean and maximum annual PM10 levels positively correlated with cerebrospinal fluid total and phosphorylated tau proteins concentrations, while they were inversely associated with ß-amyloid. Concerning the risk of dementia, we found a positive association starting from above 10 µg/m3 for mean PM10 levels and above 35 µg/m3 for maximum PM10 levels. Specific estimates for Alzheimer's dementia were substantially similar. Adding other potential confounders to the multivariable model or removing early cases of dementia onset during the follow-up had little effect on the estimates. CONCLUSIONS: Our findings suggest that exposure to outdoor air pollutants, PM10 in particular, may non-linearly increase conversion from MCI to dementia above a certain ambient air concentration.

Residential exposure to magnetic fields from high-voltage power lines and risk of childhood leukemia.

BACKGROUND: Several studies have suggested an excess risk of leukemia among children living close to high-voltage power lines and exposed to magnetic fields. However, not all studies have yielded consistent results, and many studies may have been susceptible to confounding and exposure misclassification. METHODS: We conducted a case-control study to investigate the risk of leukemia associated with magnetic field exposure from high-voltage power lines. Eligible participants were children aged 0-15 years residing in the Northern Italian provinces of Modena and Reggio Emilia. We included all 182 registry-identified childhood leukemia cases diagnosed in 1998-2019, and 726 age-, sex- and province-matched population controls. We assessed exposure by calculating distance from house to nearest power line and magnetic field intensity modelling at the subjects' residence. We used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders (distance from nearest petrol station and fuel supply within the 1000 m-buffer, traffic-related particulate and benzene concentrations, presence of indoor transformers, percentage of urban area and arable crops). RESULTS: In multivariable analyses, the OR comparing children living <100 m from high-voltage power-lines with children living ≥400 m from power-lines was 2.0 (95% CI 0.8-5.0). Results did not differ substantially by age at disease diagnosis, disease subtype, or when exposure was based on modeled magnetic field intensity, though estimates were imprecise. Spline regression analysis showed an excess risk for both overall leukemia and acute lymphoblastic leukemia among children with residential distances <100 m from power lines, with a monotonic inverse association below this cutpoint. CONCLUSIONS: In this Italian population, close proximity to high-voltage power lines was associated with an excess risk of childhood leukemia.

Amyotrophic lateral sclerosis incidence following exposure to inorganic selenium in drinking water: A long-term follow-up.

Some studies have reported an association between overexposure to selenium and risk of amyotrophic lateral sclerosis (ALS), a rare degenerative disease of motor neurons. From 1986 through 2015, we followed a cohort in Northern Italy that had been inadvertently consuming tap water with unusually high concentrations of inorganic hexavalent selenium from 1974 to 1985. We had previously documented an excess incidence of ALS in this cohort during 1986-1994. Here, we report extended follow-up of the cohort for an additional 21 years, encompassing 50,100 person-years of the exposed cohort and 2,233,963 person-years of the unexposed municipal cohort. We identified 7 and 112 incident ALS cases in the exposed and unexposed cohorts, respectively, yielding crude incidence rates of 14 and 5 cases per 100,000 person-years. A Poisson regression analysis, adjusting for age, sex and calendar year, produced an overall incidence rate ratio (IRR) for ALS of 2.8 (95% confidence interval (CI) 1.3, 6), with a substantially stronger IRR in 1986-1994 (8.2, 95% CI 2.7, 24.7) than in 1995-2015 (1.5, 95% CI 0.5, 4.7), and among women (5.1, 95% CI 1.8, 14.3) than men (1.7, 95% CI 0.5, 5.4). Overall, these results indicate an association between high exposure to inorganic selenium, a recognized neurotoxicant, and ALS incidence, with declining rates after cessation of exposure and stronger effects among women.

Proximity to overhead power lines and childhood leukaemia: an international pooled analysis.

BACKGROUND: Although studies have consistently found an association between childhood leukaemia risk and magnetic fields, the associations between childhood leukaemia and distance to overhead power lines have been inconsistent. We pooled data from multiple studies to assess the association with distance and evaluate whether it is due to magnetic fields or other factors associated with distance from lines. METHODS: We present a pooled analysis combining individual-level data (29,049 cases and 68,231 controls) from 11 record-based studies. RESULTS: There was no material association between childhood leukaemia and distance to nearest overhead power line of any voltage. Among children living < 50 m from 200 + kV power lines, the adjusted odds ratio for childhood leukaemia was 1.33 (95% CI: 0.92-1.93). The odds ratio was higher among children diagnosed before age 5 years. There was no association with calculated magnetic fields. Odds ratios remained unchanged with adjustment for potential confounders. CONCLUSIONS: In this first comprehensive pooled analysis of childhood leukaemia and distance to power lines, we found a small and imprecise risk for residences < 50 m of 200 + kV lines that was not explained by high magnetic fields. Reasons for the increased risk, found in this and many other studies, remains to be elucidated.

Adverse pregnancy outcomes in women with changing patterns of exposure to the emissions of a municipal waste incinerator.

Municipal solid waste incinerators emissions contain pollutants that, despite their low concentration, might adversely affect reproductive health. In the present study, we examined rates of miscarriage and birth defects among women who resided or were employed in the vicinity of a municipal solid waste incinerator plant from 2003 to 2013. In 2009, a progressive shutdown of the old incineration lines and operation of a new line caused considerably higher atmospheric release of polycyclic aromatic hydrocarbons, particularly of dioxins, due to these irregular operating conditions, technological renovation, and increased capacity. We used dioxin emission levels, based on a dispersion model, to define exposure status of the residing population to air pollutants emitted by the waste incinerator. In women who resided in areas characterized by higher emission exposures compared with a referent area, the relative risk (RR) of miscarriage was 1.04 (95% confidence interval (CI) 0.80-1.32) based on 62 cases overall, with little evidence of a dose-response relation. RRs were similarly null for both 2003-2008 and 2010-2013 periods (RR 1.12 (95% CI 0.80-1.53) and 0.98 (95% CI 0.63-1.48), respectively). Concerning birth defects in the offspring of women residing in the exposed area, no evidence of increased risk emerged, since the prevalence ratio at birth was 0.64 (95% CI 0.29-1.26), with comparable results in the 2003-2008 and 2010-2013 period. Corresponding analyses carried out in municipal residents who worked in the exposed area confirmed these findings. We also did not detect abnormally high rates of miscarriage and birth defects in the exposed cohorts in the single year 2009. Overall, these results do not suggest an effect of exposure to the emissions of the municipal solid waste incinerator we investigated on two indicators of reproductive health. However, the limited statistical stability of the estimates and the absence of individual-based information on some potential confounders suggest caution in the interpretation of study findings.

Glycaemic index, glycaemic load and risk of cutaneous melanoma in a population-based, case-control study.

Glycaemic index (GI) and glycaemic load (GL) are indicators of dietary carbohydrate quantity and quality and have been associated with increased risk of certain cancers and type 2 diabetes. Insulin resistance has been associated with increased melanoma risk. However, GI and GL have not been investigated for melanoma. We present the first study to examine the possible association of GI and GL with melanoma risk. We carried out a population-based, case-control study involving 380 incident cases of cutaneous melanoma and 719 age- and sex-matched controls in a northern Italian region. Dietary GI and GL were computed for each subject using data from a self-administered, semi-quantitative food frequency questionnaire. We computed the odds ratio (OR) for melanoma according to quintiles of distribution of GL and GL among controls. A direct association between melanoma risk and GL emerged in females (OR 2·38; 95 % CI 1·25, 4·52 for the highest v. the lowest quintile of GL score, P for trend 0·070) but not in males. The association in females persisted in the multivariable analysis after adjusting for several potential confounders. There was no evidence of an association between GI and melanoma risk. GL might be associated with melanoma risk in females.

Pesticides, polychlorinated biphenyls and polycyclic aromatic hydrocarbons in cerebrospinal fluid of amyotrophic lateral sclerosis patients: a case-control study.

Neurotoxic chemicals including several pesticides have been suggested to play a role in the etiology of amyotrophic lateral sclerosis (ALS). We investigated the relation between organochlorine pesticides and their metabolites (OCPs), polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) in the etiology of sporadic ALS, determining for the first time their levels in cerebrospinal fluid as indicator of antecedent exposure. We recruited 38 ALS patients and 38 controls referred to an Italian clinical center for ALS care, who underwent a lumbar puncture for diagnostic purposes between 1994-2013, and had 1mL of cerebrospinal fluid available for the determination of OCPs, PCBs and PAHs. Many chemicals were undetectable in both case and control CSF samples, and we found little evidence of any increased disease risk according to higher levels of exposure. Among males >60 years, we found a slight but statistically very unstable increased ALS risk with higher levels of the congener PCB 28 and the OCP metabolite p,p'-DDE. Overall, these results do not suggest an involvement of the neurotoxic chemicals investigated in this study in disease etiology, although small numbers limited the precision of our results.

Pesticide exposure assessed through agricultural crop proximity and risk of amyotrophic lateral sclerosis.

BACKGROUND: Epidemiologic studies have raised the possibility that some pesticide compounds induce the neurodegenerative disease amyotrophic lateral sclerosis (ALS), though the available evidence is not entirely consistent. METHODS: We conducted a population-based case-control study in two Italian populations to assess the extent to which residence in the vicinity of agricultural crops associated with the application of neurotoxic pesticides is a risk factor for ALS, using crop acreage in proximity to the residence as an index of exposure. RESULTS: Based on 703 cases and 2737 controls, we computed an ALS odds ratio of 0.92 (95% confidence interval 0.78-1.09) for those in proximity to agricultural land. Results were not substantially different when using alternative exposure categories or when analyzing specific crop types, with the exception of a higher risk related to exposure to citrus orchards and olive groves in Southern Italy, though based on few exposed subjects (N = 89 and 8, respectively). There was little evidence of any dose-response relation between crop proximity and ALS risk, and using long-term residence instead of current residence did not substantially change our estimates. CONCLUSIONS: Though our index of exposure is indirect and subject to considerable misclassification, our results offer little support for the hypothesis that neurotoxic pesticide exposure increases ALS risk.

Long-term mortality patterns in a residential cohort exposed to inorganic selenium in drinking water.

Selenium (Se) is a metalloid of considerable nutritional and toxicological importance in humans. To date, limited epidemiologic evidence exists about the health effects of exposure to this trace element in drinking water. We investigated the relationship between Se levels in water and mortality in the municipality of Reggio Emilia, Italy, where high levels of Se were previously observed in drinking water. From 1974 to 1985, 2065 residents consumed drinking water with Se levels close to the European standard of 10µg/l, in its inorganic hexavalent form (selenate). Follow-up was conducted for the years 1986-2012 in Reggio Emilia and a lesser exposed comparison group of around 100,000 municipal residents, with comparable socio-demographic characteristics. Overall mortality from all causes, cardiovascular disease and cancer showed little evidence of differences. However, excess rate ratios were seen for some site specific cancers such as neoplasms of buccal cavity and pharynx, urinary tract, lymphohematopoietic tissue, melanoma, and two neurodegenerative diseases, Parkinson's disease and amyotrophic lateral sclerosis. Excess mortality in the exposed cohort for specific outcomes was concentrated in the first period of follow-up (1986-1997), and waned starting 10 years after the high exposure ended. We also found lower mortality from breast cancer in females during the first period of follow-up. When we extended the analysis to include residents who had been consuming the high-selenium drinking water for a shorter period, mortality rate ratios were also increased, but to a lesser extent. Overall, we found that the mortality patterns related to long-term exposure to inorganic hexavalent selenium through drinking water were elevated for several site-specific cancers and neurodegenerative disease.

Determinants of serum cadmium levels in a Northern Italy community: A cross-sectional study.

INTRODUCTION: Cadmium (Cd) is a heavy metal and a serious environmental hazard to humans. Some uncertainties still exist about major sources of Cd exposure in non-occupationally exposed subjects in addition to cigarette smoking, such as diet and outdoor air pollution. We sought to determine the influence of these sources on a biomarker of exposure, serum Cd concentration. METHODS: We recruited 51 randomly selected residents from an Italian urban community, from whom we obtained detailed information about dietary habits and smoking habits, and a blood sample for serum Cd determination. We also assessed outdoor air Cd exposure, by modeling outdoor air levels of particulate matter ≤10µm (PM10) from motorized traffic at geocoded subjects' residence. RESULTS: In crude analysis, regression beta coefficients for dietary Cd, smoking and PM10 on serum Cd levels were 0.03 (95% CI -0.83 to 0.88), 6.96 (95% CI -0.02 to 13.95) and 0.62 (95% CI -0.19 to 1.43), respectively. In the adjusted analysis, regression beta coefficients were -0.34 (95% CI -1-40 to 0.71), 5.81 (95% CI -1.43 to 13.04) and 0.47 (95% CI -0.35 to 1.29), respectively. CONCLUSION: Cigarette smoking was the most important factor influencing serum Cd in our non-occupationally exposed population, as expected, while dietary Cd was not associated with this biomarker. Outdoor air pollution, as assessed through exposure to particulate matter generated by motorized traffic, was an additional source of Cd exposure.

Diet Quality and Risk of Melanoma in an Italian Population.

BACKGROUND: Some results from laboratory and epidemiologic studies suggest that diet may influence the risk of melanoma, but convincing evidence for a role of single nutrients or food items is lacking. Diet quality, which considers the combined effect of multiple food items, may be superior for examining this relation. OBJECTIVE: We sought to assess whether diet quality, evaluated with the use of 4 different dietary indexes, is associated with melanoma risk. METHODS: In this population-based case-control study, we analyzed the relation between 4 diet quality indexes, the Healthy Eating Index 2010 (HEI-2010), Dietary Approaches to Stop Hypertension (DASH) index, Greek Mediterranean Index (GMI), and Italian Mediterranean Index (IMI), and melanoma risk in a northern Italian community, with the use of data from 380 cases and 719 matched controls who completed a semiquantitative food frequency questionnaire. RESULTS: In the overall sample, we found an inverse association between disease risk and the HEI-2010 and DASH index, but not the Mediterranean indexes, adjusting for potential confounders (skin phototype, body mass index, energy intake, sunburn history, skin sun reaction, and education). However, in sex stratified analyses, the association appeared only in women (P-trend: 0.10 and 0.04 for the HEI-2010 and DASH index, respectively). The inverse relations were stronger in women younger than age 50 y than in older women, for whom the GMI and IMI scores also showed an inverse association with disease risk (P-trend: 0.05 and 0.02, respectively). CONCLUSIONS: These results suggest that diet quality may play a role in cutaneous melanoma etiology among women.

A review and meta-analysis of outdoor air pollution and risk of childhood leukemia.

Leukemia is the most frequent malignant disease affecting children. To date, the etiology of childhood leukemia remains largely unknown. Few risk factors (genetic susceptibility, infections, ionizing radiation, etc.) have been clearly identified, but they appear to explain only a small proportion of cases. Considerably more uncertain is the role of other environmental risk factors, such as indoor and outdoor air pollution. We sought to summarize and quantify the association between traffic-related air pollution and risk of childhood leukemia, and further examined results according to method of exposure assessment, study quality, leukemia subtype, time period, and continent where studies took place. After a literature search yielded 6 ecologic and 20 case-control studies, we scored the studies based on the Newcastle-Ottawa Scale. The studies assessed residential exposure to pollutants from motorized traffic by computing traffic density in the neighboring roads or vicinity to petrol stations, or by using measured or modeled nitrogen dioxide and benzene outdoor air levels. Because heterogeneity across studies was observed, random-effects summary odds ratios (OR) and 95% confidence intervals (CI) were reported. Whenever possible we additionally conducted stratified analyses comparing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Limiting the analysis to high-quality studies (Newcastle-Ottawa Scale ≥ 7), those using traffic density as the exposure assessment metric showed an increase in childhood leukemia risk in the highest exposure category (OR = 1.07, 95% CI 0.93-1.24). However, we observed evidence of publication bias. Results for NO2 exposure and benzene showed an OR of 1.21 (95% CI 0.97-1.52) and 1.64 (95% CI 0.91-2.95) respectively. When stratifying by leukemia type, the results based upon NO2 were 1.21 (95% CI 1.04-1.41) for ALL and 1.06 (95% CI 0.51-2.21) for AML; based upon benzene were 1.09 (95% CI 0.67-1.77) for ALL and 2.28 (95% CI 1.09-4.75) for AML. Estimates were generally higher for exposures in the postnatal period compared to the prenatal period, and for European studies compared to North American studies. Overall, our results support a link between ambient exposure to traffic pollution and childhood leukemia risk, particularly due to benzene.

Increased incidence of childhood leukemia in urban areas: a population-based case-control study.

OBJECTIVE: We carried out a population-based case-control study to assess the possibility of an excess risk of childhood leukemia in urban areas, independently from road traffic pollution. METHODS: Study subjects were the 111 cases of childhood leukemia diagnosed from 1998 to 2011 among residents of two provinces of the northern Italian Emilia-Romagna region, and 444 controls matched by age and sex. Through mapping of the region carried out by remote sensing, we examined the percentage of urban or rural area in the 100-meter circular buffer around each child's house. We also modeled annual average exposure to benzene and PM10 from vehicular traffic at each residence. RESULTS: In a multivariate model adjusting for benzene and PM10, the odds ratio of leukemia associated with residence in a highly urbanized area and residential area (≥95% land use of this type near the child's home) was 1.4 (95% confidence intervals 0.8-2.4) and 1.3 (0.8-2.2), respectively. An increased risk was also found in association with the proximity to «dumps, scrap yards, and building sites¼. No association emerged with residence in rural areas or near industrial plants. CONCLUSIONS: These results indicate that children living in urban areas experience an excess leukemia risk, independently from exposure to pollutants from vehicles.

Risk of birth defects associated with maternal pregestational diabetes.

Maternal diabetes preceding pregnancy may increase the risk of birth defects in the offspring, but not all studies confirm this association, which has shown considerable variation over time, and the effect of having type 1 versus type 2 diabetes is unclear. We conducted a population-based cohort study in the Northern Italy Emilia-Romagna region linking administrative databases with a Birth Defects Registry. From hospital discharge records we identified all diabetic pregnancies during 1997-2010, and a population of non-diabetic parturients matched for age, residence, year and delivery hospital. We collected available information on education, smoking and drug prescriptions, from which we inferred the type of diabetes. We found 62 malformed infants out of 2,269 births among diabetic women, and 162 out of 10,648 births among non-diabetic women. The age-standardized prevalence ratio (PR) of malformation associated with maternal pregestational diabetes was 1.79 (95 % confidence interval 1.34-2.39), a value that varied little by age. Type of diabetes strongly influenced the PR, with higher values related to type 2 diabetic women. Most major subgroups of anomalies had PRs above 1, including cardiovascular, genitourinary, musculoskeletal, and chromosomal abnormalities. There was an unusually high PR for the rare defect 'extra-ribs', but it was based on only two cases. This study indicates that maternal pregestational type 2 diabetes is associated with a higher prevalence of specific birth defects in offspring, whereas for type 1 diabetic mothers, particularly in recent years, the association was unremarkable.

Friend or foe? The current epidemiologic evidence on selenium and human cancer risk.

Scientific opinion on the relationship between selenium and the risk of cancer has undergone radical change over the years, with selenium first viewed as a possible carcinogen in the 1940s then as a possible cancer preventive agent in the 1960s-2000s. More recently, randomized controlled trials have found no effect on cancer risk but suggest possible low-dose dermatologic and endocrine toxicity, and animal studies indicate both carcinogenic and cancer-preventive effects. A growing body of evidence from human and laboratory studies indicates dramatically different biological effects of the various inorganic and organic chemical forms of selenium, which may explain apparent inconsistencies across studies. These chemical form-specific effects also have important implications for exposure and health risk assessment. Overall, available epidemiologic evidence suggests no cancer preventive effect of increased selenium intake in healthy individuals and possible increased risk of other diseases and disorders.

Association between dietary vitamin C and risk of cutaneous melanoma in a population of Northern Italy.

Cutaneous melanoma incidence has been increasing during the last few years, and diet has been suggested as one of the lifestyle factors responsible for this increase. Since antioxidant nutrients such as ascorbic acid might prevent skin carcinogenesis, we investigated the risk of cutaneous melanoma related to vitamin C intake in a population-based case-control study in Northern Italy based on 380 melanoma patients and 719 matched controls, to whom we administered a semiquantitative food-frequency questionnaire. After adjusting for potential confounders, odds ratio of melanoma were 0.86 (95 % confidence interval 0.65 - 1.15) and 0.59 (95 % confidence interval 0.37 - 0.94) in the intermediate and highest categories of vitamin C dietary intake respectively, compared with the bottom one. The association between vitamin C and decreased risk persisted after adjustment for some potential confounders. In age- and gender-stratified analyses, this association was seen in young females (< 60 years old), and was found to be enhanced in subjects with phototypes II and III. These results suggest a possible protective activity of vitamin C intake against cutaneous melanoma in specific subgroups of this population of Northern Italy.

Human serum albumin-bound selenium (Se-HSA) in serum and its correlation with other selenium species.

INTRODUCTION: Selenium (Se) is a trace element with different toxicological and nutritional properties according to its chemical forms. Among the wide range of selenium species, human serum albumin-bound selenium (Se-HSA) has still uncertain composition in terms of organic or inorganic selenium species. This study aimed at investigating the relation between Se-HSA levels with total selenium and the specific organic and inorganic selenium species. METHODS: We determined levels of total selenium and selenium species in serum of participants enrolled in two populations of the Emilia-Romagna region, in Northern Italy. Anion exchange chromatography coupled with inductively coupled plasma dynamic reaction cell mass spectrometry was used as quantification method. Correlations between Se-HSA and the other selenium compounds were analyzed using linear regression and restricted cubic spline regression models, adjusted for potential confounders. RESULTS: The first cohort comprised 50 participants (men/women: 26/24) with median (interquartile range, IQR) age 50 (55-62) years, while the second was composed of 104 participants (M/W: 50/54), median (IQR) age 48 (44-53) years. Median (IQR) levels of total selenium were 118.5 (109-136) µg/L and 116.5 (106-128) µg/L, respectively, while Se-HSA was 25.5 µg/L (16.2-51.5) and 1.1 (0.03-3.1) µg/L, respectively. In both populations, Se-HSA was positively associated with inorganic selenium species. Conversely, Se-HSA was inversely associated with organic selenium, especially with selenoprotein P-bound-Se (Se-SELENOP) and less strongly with selenomethionine-bound-Se (Se-Met), while the relation was null or even positive with other organic species. Evaluation of non-linear trends showed a substantially positive association with inorganic selenium, particularly selenite, until a concentration of 30 µg/L, above which a plateau was reached. The association with Se-SELENOP was inverse and strong until 100 µg/L, while it was almost null at higher levels. CONCLUSIONS: Our findings seem to indicate that Se-HSA incorporates more selenium when circulating levels of inorganic compounds are higher, thus supporting its mainly inorganic nature, particularly at high circulating levels of selenite.