Asbestos burden in lungs of mesothelioma patients with pleural plaques, lung fibrosis and/or ferruginous bodies at histology: a postmortem SEM-EDS study.

The causal attribution of asbestos-related diseases to past asbestos exposures is of crucial importance in clinical and legal contexts. Often this evaluation is made based on the history of exposure, but this method presents important limitations. To assess past asbestos exposure, pleural plaques (PP), lung fibrosis and histological evidence of ferruginous bodies (FB) can be used in combination with anamnestic data. However, such markers have never been associated with a threshold value of inhaled asbestos. With this study we attempted to shed light on the dose-response relationship of PP, lung fibrosis and FBs, investigating if their prevalence in exposed individuals who died from malignant mesothelioma (MM) is related to the concentration of asbestos in lungs assessed using scanning electron microscopy equipped with energy dispersive spectroscopy. Moreover, we estimated the values of asbestos concentration in lungs associated with PP, lung fibrosis and FB. Lung fibrosis showed a significant positive relationship with asbestos lung content, whereas PP and FB did not. We identified, for the first time, critical lung concentrations of asbestos related to the presence of PP, lung fibrosis and FB at histology (respectively, 19 800, 26 400 and 27 400 fibers per gram of dry weight), that were all well-below the background levels of asbestos identified in our laboratory. Such data suggest that PP, lung fibrosis and FB at histology should be used with caution in the causal attribution of MM to past asbestos exposures, while evaluation of amphibole lung content using analytical electron microscopy should be preferred.

A postmortem case control study of asbestos burden in lungs of malignant mesothelioma cases.

BACKGROUND: Asbestos lung content is regarded as the most reliable tool for causal attribution of malignant mesothelioma (MM) to previous asbestos exposures. However, there is a lack of studies on asbestos burden in lungs of MM patients in comparison with healthy individuals. This study aims to provide such a comparison, investigating, as well, differences in asbestos lung burden with sex and time trends. METHODS: Asbestos lung content has been assessed on formalin-fixed lung fragments using scanning electron microscopy coupled with energy dispersion spectroscopy (SEM-EDS) on individuals deceased from MM (cases) and healthy subjects without any lung disease who died from violent causes (controls) between 2005 and 2023. RESULTS: Asbestos and asbestos bodies (ABs) were found, respectively, in 73.7% and 43.2% of cases and in 28 and 22% of controls; in MM cases the most represented asbestos types were crocidolite and amosite, whereas in controls it was tremolite-actinolite asbestos. The concentration of both asbestos fibers and ABs was statistically significantly higher in MM cases compared to controls. The mean asbestos fibers width was also significantly higher in cases than controls. Males and females with MM showed similar asbestos and ABs concentrations, but females had higher concentrations of chrysotile, and significantly lower fibers width compared to males. Time trends show that MM lung asbestos concentrations decreased starting in 2011. DISCUSSION: The results suggest a correlation between asbestos burden in lungs and MM risk. The different concentration of chrysotile, as well as the different width of asbestos fibers in MM males and females might reflect a sex difference in response of the lung microenvironment to inhaled asbestos. Finally, this study provides the first pathological evidence of the effect of the ban of asbestos use, demonstrating a significant decrease of asbestos lung content after 2011.

Recurrence-free survival after total thyroidectomy and lobectomy in patients with papillary thyroid microcarcinoma.

PURPOSE: The incidence of papillary thyroid microcarcinoma is increasing. We evaluated the recurrence-free survival following total thyroidectomy and lobectomy to identify the optimal surgical choice. METHODS: A meta-analysis was performed using the National Library of Medicine and the National Institutes of Health PubMed database to identify eligible studies. Summary 5- and 10-year RFS estimates after TT versus LT were calculated using random effects models. RESULTS: The literature search yielded 1117 studies (1990-2019). Nine studies met the inclusion criteria comprising 10,186 total thyroidectomy and 11,408 lobectomy patients. The 5-year recurrence-free survival was 98% [95% confidence interval (CI) 97-99%] after total thyroidectomy and 97% (95% CI 96-99%) after lobectomy, based on eight studies (9421 total thyroidectomy and 11,283 lobectomy patients); the 10-year recurrence-free survival was 95% (95% CI 92-98%) after total thyroidectomy and 92% (95% CI 86-96%) after lobectomy, based on eight studies (total thyroidectomy = 10,100, lobectomy = 11,389 patients). CONCLUSION: The present meta-analysis demonstrates excellent, long-term recurrence-free survival following both total thyroidectomy and lobectomy surgery in patients with papillary thyroid microcarcinoma. The analysis also suggests that patients undergoing total thyroidectomy trended toward a slightly better long-term 10-year recurrence-free survival in comparison to patients undergoing lobectomy, a finding of potential, clinical significance in the management decision-making process.

Associations between human papillomavirus and history of cancer among U.S. adults in the National Health and Nutrition Examination Survey (2003-2010).

BACKGROUND: Human papillomavirus (HPV) is an infectious agent that has been associated with human cancer. We have updated the U.S. population sero-prevalence using a large National Health and Nutrition Examination Survey (NHANES) sample of adults from 2003 to 2010, and have analysed the associations between HPV seropositivity and self-reported history of cancer. METHODS: Four cross-sectional cycles (2003-2004, 2005-2006, 2007-2008, and 2009-2010) were used, for a total of 12 759 participants who had both cancer history and HPV serum information. RESULTS: The sero-prevalences of HPV types 6, 11, 16, and 18 were 15.0%, 4.8%, 11.5%, and 4.1%, respectively. Females had significantly higher HPV prevalence than males (P<0.05) for all subtypes. Positive associations between HPV 16/18 seropositivity and lifetime history of any cancer (adjusted odds ratio-ORadj=1.68; 95% CI: 1.35, 2.01), history of any of eight selected cancers (ORadj=2.63; 95% CI: 1.78, 3.90), lung cancer (ORadj=5.14; 95% CI: 1.29, 20.44), and cervical cancer (ORadj=2.55; 95% CI: 1.63, 3.98) were observed. CONCLUSIONS: The finding of significant associations between HPV 16/18 seropositivity and lifetime history of cancer adds epidemiological evidence to the carcinogenicity potential of HPV 16 and 18 in other tissues. With increasing coverage of the HPV vaccine in the U.S., future NHANES data and sample collection may allow further detailed evaluation of the population impact of the HPV vaccination on cancer prevention.

Cleft lip and palate in family members of cancer survivors.

The presence of cleft lip with or without cleft palate (CL/P) in family members of cancer patients was investigated. An epidemiological questionnaire including family history of cancer and congenital oral cleft malformations was administered to 168 cancer survivors and a population-based sample of 170 healthy subjects. In the control group, 1.2% reported a family member with CL/P; among cancer survivors the figure was 4.2% (odds ratio: 3.7; 95% confidence interval: 0.75­17.8; p = .07). Among cancer survivors with a family member with CL/P, there was an apparent excess of testicular cancer and melanoma in comparison with the cancer survivors with no family history of CL/P. These preliminary results suggest a common etiologic background for cancer and CL/P.

Meta- and pooled analyses of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer: a HuGE-GSEC review.

Worldwide, over 1 million cases of colorectal cancer (CRC) were reported in 2002, with a 50% mortality rate, making CRC the second most common cancer in adults. Certain racial/ethnic populations continue to experience a disproportionate burden of CRC. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been associated with a lower risk of CRC. The authors performed both a meta-analysis (29 studies; 11,936 cases, 18,714 controls) and a pooled analysis (14 studies; 5,068 cases, 7,876 controls) of the C677T MTHFR polymorphism and CRC, with stratification by racial/ethnic population and behavioral risk factors. There were few studies on different racial/ethnic populations. The overall meta-analysis odds ratio for CRC for persons with the TT genotype was 0.83 (95% confidence interval (CI): 0.77, 0.90). An inverse association was observed in whites (odds ratio = 0.83, 95% CI: 0.74, 0.94) and Asians (odds ratio = 0.80, 95% CI: 0.67, 0.96) but not in Latinos or blacks. Similar results were observed for Asians, Latinos, and blacks in the pooled analysis. The inverse association between the MTHFR 677TT polymorphism and CRC was not significantly modified by smoking status or body mass index; however, it was present in regular alcohol users only. The MTHFR 677TT polymorphism seems to be associated with a reduced risk of CRC, but this may not hold true for all populations.

Cancer screening and cancer mortality in Nevis, West Indies: Pesquisaje de cáncer y mortalidad por cáncer en Nevis, West Indies

OBJECTIVE: Cancer screening is one approach that can reduce morbidity and mortality through early detection of precancers; however anxiety, fear, and lack of information are important barriers to universal cancer screening in the Caribbean. Nevis is a small island located in the Eastern Caribbean. We report available data on screening prevalence and cancer mortality for four common cancers: cervical, breast, colon and prostate. METHODS: Demographic information, screening utilization (when available) and cancer mortality statistics were obtained from the Charlestown Health Clinic and the annual reports from the Ministry of Health. Moreover, physicians and key stakeholders were interviewed to assess current guidelines for cancer screening as well as to indicate areas of need. RESULTS: Cervical cancer screening is underutilized in Nevis. Between 2001 and 2007, the overall prevalence of Pap testing fluctuated minutely (mean: 6.87%, range: 6.06 - 7.41%). Systematic screening for breast, colon, and prostate cancer is not routinely performed, thus utilization rates are not available. Cancer mortality varied slightly between 2002 and 2006; prostate cancer had the highest overall crude mortality rate (30.6 deaths/100 000 persons). Physician interviews revealed that adherence to US and European cancer screening guidelines are inappropriate for their population of patients. Breast and prostate cancers are frequently diagnosed in these geographic areas before the age when cancer screening is currently recommended. CONCLUSION: Cancer is perceived as an important health problem by physicians, key stakeholders and citizens, however cancer screening is underutilized in Nevis. Future research should focus on generating screening guidelines that are relevant for this population, as well as methods to promote screening.

OBJETIVO: El pesquisaje de cáncer es un método que puede reducir la morbilidad y la mortalidad mediante la detección precoz de precánceres. Sin embargo, la ansiedad, el miedo, y la falta de información son barreras importantes que se erigen frente al pesquisaje universal del cáncer en el Caribe. Nevis es una pequeña isla situada en el Caribe Oriental. Reportamos datos disponibles sobre la prevalencia del pesquisaje y la mortalidad por cáncer en relación con cuatro tipos de cánceres comunes: el cervical, y el de mamas, colon y próstata. MÉTODOS: La información demográfica, la utilización de pesquisaje (de hallarse disponible) y las estadísticas sobre la mortalidad por cáncer, se obtuvieron de la Clínica de la Salud de Charlestown, y los reportes anuales del Ministerio de Salud. Además, los médicos y las partes interesadas claves, fueron entrevistados a fin de evaluar las guías actuales para el pesquisaje del cáncer así como para indicar las áreas de necesidad. RESULTADOS: El pesquisaje del cáncer cervical es subutilizado en Nevis. Entre 2001 y 2007, la prevalencia general de la prueba citológica tuvo una fluctuación mínima (promedio: 6.87%, rango: 6.06 - 7.41%). El pesquisaje sistemático del cáncer de mamas, colon, y próstata no se realiza como rutina, y por consiguiente no existen tasas de utilización disponibles. La mortalidad por cáncer varió ligeramente entre 2002 y 2006. El cáncer de próstata tuvo la tasa de mortalidad cruda general más alta (30.6 muertes/100 000 personas). Las entrevistas médicas revelaron que las guías de pesquisaje en USA y Europa son inapropiadas para la población de pacientes. Los cánceres de mamas y próstata son diagnosticados con frecuencia en estas áreas geográficas antes de la edad en que se recomienda el pesquisaje actualmente. CONCLUSIÓN: El cáncer es percibido como un importante problema de salud por los médicos, las partes interesadas claves, y los ciudadanos. No obstante, el pesquisaje del cáncer es subutilizado en Nevis. Las investigaciones futuras deben centrarse en producir guías de pesquisaje que sean pertinentes para esta población, así como en métodos de promover el pesquisaje.

Effect of vitamin levels on biomarkers of exposure and oxidative damage-the EXPAH study.

DNA adducts are markers of carcinogen exposure and of their biological effect; they have been shown to be related to mutagenesis, and therefore they could be a predictive biomarker of human cancer. The objective of this study was to assess if there is a relationship between vitamins A, C, and E, which are known to play a significant role as free radical scavengers and antioxidant agents, and biomarkers of genotoxicity and oxidative stress. Three hundred and fifty-six subjects from Czech Republic, Slovak Republic and Bulgaria, who completed a questionnaire on dietary information and had a measurement of plasma A, C, E vitamins, DNA adduct levels (benzo[a]pyrene (B[a]P) and bulky (DNA-Tot) DNA adducts) and oxidative damage (cyclic pyrimidopurinone N-1,N2 malondialdehyde-2 deoxyguanosine (M1dG) and 8-oxo-7,8-dihydro-2_deoxyguanosine (8-oxodG)) were analyzed. A significant inverse correlation was observed between plasma vitamin levels and both benzo[a]pyrene (B[a]P) and bulky DNA adducts. Vitamin A was also significantly inversely correlated with M1dG, a marker of oxidative damage. The associations were stronger in non-smokers than in smokers. Dietary intake of certain antioxidants such as vitamins is associated with reduced levels of markers of DNA damage (B[a]P and DNA-Tot) and oxidation (M1dG and 8-oxodG) measured in peripheral white blood cells. This could contribute to the protective role of such a dietary pattern on cancer risk. The protective effect of dietary vitamins is less evident in smokers.

Review and pooled analysis of studies on MTHFR C677T polymorphism and esophageal cancer.

Esophageal cancer has been associated with tobacco and alcohol consumption, gastric reflux, exposure to nitrosamines from food or other environmental sources, and diets lacking folate. Susceptibility to esophageal cancer may be modified by functional polymorphisms in genes along the folate metabolic pathway, such as methylenetetrahydrofolate reductase (MTHFR). The C677T polymorphism is the most common functional variant, leading to a reduction in enzyme activity. We report a pooled analysis of 5 studies on the association of MTHFR C677T polymorphism and esophageal cancer, including 725 cases and 1531 controls. A significant association between the MTHFR 677 TT genotype and esophageal cancer was observed (OR=2.63, 95% CI: 1.75-3.94), although there was significant heterogeneity between studies. A sensitivity analysis excluded one study; the association between TT genotype and esophageal cancer was still present, although of reduced magnitude (OR=1.57, 95% CI: 0.96-2.56). A significant interaction between smoking and TT genotype on esophageal cancer risk was observed, while no interaction was observed between alcohol consumption and genotype.

Cancer screening and cancer mortality in Nevis, West Indies.

OBJECTIVE: Cancer screening is one approach that can reduce morbidity and mortality through early detection of pre-cancers; however anxiety, fear, and lack of information are important barriers to universal cancer screening in the Caribbean. Nevis is a small island located in the Eastern Caribbean. We report available data on screening prevalence and cancer mortality for four common cancers: cervical, breast, colon and prostate. METHODS: Demographic information, screening utilization (when available) and cancer mortality statistics were obtained from the Charlestown Health Clinic and the annual reports from the Ministry of Health. Moreover physicians and key stakeholders were interviewed to assess current guidelines for cancer screening as well as to indicate areas of need. RESULTS: Cervical cancer screening is under-utilized in Nevis. Between 2001 and 2007, the overall prevalence of Pap testing fluctuated minutely (mean: 6.87%, range: 6.06-7.41%). Systematic screening for breast, colon, and prostate cancer is not routinely performed, thus utilization rates are not available. Cancer mortality varied slightly between 2002 and 2006; prostate cancer had the highest overall crude mortality rate (30.6 deaths/100,000 persons). Physician interviews revealed that adherence to US and European cancer screening guidelines are inappropriate for their population of patients. Breast and prostate cancers are frequently diagnosed in these geographic areas before the age when cancer screening is currently recommended. CONCLUSION: Cancer is perceived as an important health problem by physicians, key stakeholders and citizens, however cancer screening is under-utilized in Nevis. Future research should focus on generating screening guidelines that are relevant for this population, as well as methods to promote screening.

Prevalence of cancer-associated viral infections in healthy afro-Caribbean populations: a review of the literature.

Cancer is one of the five leading causes of death in the Caribbean. Viral infections have been associated with cancer development and propagation, but the prevalence of such infections in the Caribbean is unknown. This review of the published literature shows that in 161,196 subjects from 14 Caribbean Islands, the adjusted prevalence of HHV8 infection is 4.5%, HTLV-1: 1.0%, HPV: 57.5%, HCV: 0.4%, HBV: 9.4%, and EBV: 92.2%. With the exception of HCV, the prevalence was significantly higher in the Caribbean than in the United States. These findings may significantly contribute to the high incidence of cancer observed in the Caribbean.

Predictors of moderate and severe injuries in Italian major leagues soccer teams: results from a cohort study.

AIM: The possible consequences of injury in soccer players could be a relevant public health issue, due the large diffusion of this sport around the world. We have evaluated the predictive value of both personal and professional characteristics on the occurrence of injuries and their severity in a prospective cohort study. METHODS: A cohort of 1 041 professional soccer players from the two Italian major Leagues was assembled during the season 2003-2004: 743 out of 785 subjects available the day of the interview (94.6%) answered an epidemiological questionnaire. A validation study was performed to assess if participating subjects were representative of the whole cohort. The risk of injuries and their severity according to several variables were assessed. RESULTS: A total of 157 subjects suffered 177 injuries during the season 2002-2003. Differences exist between injured and non-injured players according to both the number of matches played during the season and the League. A trend in risk of injury with anthropometric measures was observed, although not significant. The type of tissue and the type of injury were significantly associated with the duration of the stop. CONCLUSION: Anthropometric measures and career history (such as type of League and number of played matches) could require further attention, since they seem to be predictive of injury occurrence in soccer players.

Distinct distribution of HPV types among cancer-free Afro-Caribbean women from Tobago.

Human papillomavirus (HPV), a sexually transmitted virus causes cervical carcinomas, and is associated with approximately 36% of oropharyngeal tumours where HPV16 is the predominant genotype. The cervical cancer incidence rate in Trinidad and Tobago is about two times higher than the worldwide rate. We have for the first time determined the prevalence and type distribution of cervical HPV infections among cancer-free Afro-Caribbean women from Tobago, and compared it with the HPV subtypes observed in their oral cavity. Thirty-five per cent of the women were cervical HPV positive. The most common high-risk type detected in the cervix was HPV45 rather than HPV16 and 18. The prevalence of HPV infection in the oral mucosa was 6.6%. The distribution of HPV genotypes in healthy Tobagonian women is different from that reported in studies conducted in European and North American populations. This may have important implications for vaccine introduction in this and other Afro-Caribbean countries.

Association of A313 G polymorphism (GSTP1*B) in the glutathione-S-transferase P1 gene with sporadic Parkinson's disease.

Genetic predisposition, environmental toxins and aging contribute to Parkinson's disease (PD) multifactorial etiology. Weak environmental neurotoxic factors may accumulate over time increasing the disease risk in genetically predisposed subjects. Polymorphic genes encoding drug-metabolizing-enzymes (DMEs) are considered to account for PD susceptibility by determining individual toxic response variability. In this work, the allelic distributions and genotype associations of three major brain-expressed DMEs were characterized, in sporadic PD cases and controls. No significant association was found between CYP2D6 genotype and PD, but subjects with extensive metabolizer (EM) CYP2D6 phenotype, and the variant GSTP1*B genotype were at significantly higher PD risk than the corresponding poor or intermediary metabolizers (CYP2D6 poor metabolizer phenotype+intermediary metabolizers). A significant association was observed between the GSTP1*B allele and zygosity with PD (GSTP1*A/*B- 51.58%/34.37%, odds ratio (OR) = 2.29; 95% confidence interval (95% CI) = 1.25-4.18; *B/*B- 6.32%/1.05%, OR = 10.67; 95% CI = 1.19-94.79). This association was particularly strong in the elder patients group (> or =69 year) who showed double PD risk for GSTP1*B heterozygous, whilst GSTP1*B/*B homozygous were exclusively found amongst patients. An interaction between GSTM1 and GSTP1 was observed in this late onset PD group. The present results suggest that native GSTP1 encoding the fully active transferase variant should play a relevant role in dopaminergic neuroprotection.

11q13 amplification status and human papillomavirus in relation to p16 expression defines two distinct etiologies of head and neck tumours.

Two distinct etiologies of head and neck squamous cell carcinoma (HNSCC) have been proposed, DNA damage owing to tobacco and alcohol exposure and human papillomavirus (HPV) oncogene-mediated transformation. Common genetic alterations in HNSCC include TP53 mutations, 11q13 amplification (amp) and CDKN2A/p16 mutations or promoter methlyation. However, in HPV+ HNSCC it is frequent to observe wild-type TP53 and expression of p16. The relationship of this unusual pattern with 11q13 amp has not been tested. In a retrospective study on 125 HNSCC patients, only 17% (five out of 30) of HPV+ vs 44% (39 out of 89) of HPV - tumours expressed 11q13 amp (adjusted odds ratio (OR)=0.2, 95% confidence interval (CI)=0.1-0.6). A subpopulation of tumours (n=69) were classified according to the three molecular markers, TP53, p16 and 11q13 amp. In addition to wild-type TP53, and p16 expression, HPV+ tumours were more likely not to be amplified at 11q13 (OR=6.5, 95% CI=1.8-23.9). As HPV+ HNSCC lack the genetic alterations which are common in other tumours, we hypothesise that HPV infection may represent an early event in the HNSCC carcinogenic process, thus suggesting a distinct molecular pathway.

Meta- and pooled analysis of GSTT1 and lung cancer: a HuGE-GSEC review.

Lung cancer is the most common malignancy in the Western world, and the main risk factor is tobacco smoking. Polymorphisms in metabolic genes may modulate the risk associated with environmental factors. The glutathione S-transferase theta 1 gene (GSTT1) is a particularly attractive candidate for lung cancer susceptibility because of its involvement in the metabolism of polycyclic aromatic hydrocarbons found in tobacco smoke and of other chemicals, pesticides, and industrial solvents. The frequency of the GSTT1 null genotype is lower among Caucasians (10-20%) than among Asians (50-60%). The authors present a meta- and a pooled analysis of case-control, genotype-based studies that examined the association between GSTT1 and lung cancer (34 studies, 7,629 cases and 10,087 controls for the meta-analysis; 34 studies, 7,044 cases and 10,000 controls for the pooled analysis). No association was observed between GSTT1 deletion and lung cancer for Caucasians (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.87, 1.12); for Asians, a positive association was found (OR = 1.28, 95% CI: 1.10, 1.49). In the pooled analysis, the odds ratios were not significant for either Asians (OR = 0.97, 95% CI: 0.83, 1.13) or Caucasians (OR = 1.09, 95% CI: 0.99, 1.21). No significant interaction was observed between GSTT1 and smoking on lung cancer, whereas GSTT1 appeared to modulate occupational-related lung cancer.

Role of simian virus 40 in cancer incidence in solid organ transplant patients.

Transplant recipients have an increased risk of developing cancer in comparison with the general population. We present here data on cancer development in transplanted subjects who received organs from donors whose DNA was previously examined for the genomic insertion of Simian Virus 40 (SV40). Active follow-up of 387 recipients of solid organs donated by 134 donors, not clinically affected by cancer, was performed through the National Transplant Center (NTC). The average length of follow-up after transplant was 671+/-219 days (range 0-1085 days). Out of 134 proposed donors, 120 were utilised for organ donation. Of these, 12 (10%) were classified as positive for SV40 genomic insertion. None of the 41 recipients of organs from SV40 positive donors developed a tumour during the follow-up. In all, 11 recipients of organs given by SV40 negative donors developed a tumour (cancer incidence: 0.015 per year). In conclusion, cancer rates observed in our study are comparable to what reported by the literature in transplanted patients. Recipients of solid organs from SV40 positive donors do not have an increased risk of cancer after transplant. The role of SV40 in carcinogenesis in transplanted patients may be minimal.

MTHFR C677T polymorphism, GSTM1 deletion and male infertility: a possible suggestion of a gene-gene interaction?

Methylenetetrahydrofolate reductase (MTHFR) is a gene involved in the process of DNA synthesis and methylation. The MTHFR C677T polymorphism has been associated with male infertility. A prospective study was conducted on men seeking care at the infertility clinic in Milano to determine if the MTHFR C677T polymorphism is associated with infertility, and if such an association is modified by a common deletion of one of the glutathione transferases, GSTM1. One year after enrolment, 46 subjects reported having had a child, while 59 were still childless. Subjects carrying the MTHFR C677T homozygous variant polymorphism were at increased risk of being infertile after 1-year follow-up (OR 3.7, 95% CI?=?1.4-10.4); carriers of the homozygous variant MTHFR genotype and of a functional copy of GSTM1 appear to have a significantly higher risk of infertility (n=11; OR?=?22.0 95% CI?=?3.8-127.9) than subjects who carry the wild-type genotype for both genes. Such risk becomes non-significant when the GSTM1 deletion is also present (n=5; OR?=?1.1 95% CI?=?0.2-5.1). A possible explanation of this unexpected result could lie in the known involvement of glutathione transferases in the metabolic pathways of both methylation and transulfuration. The interaction found deserves confirmation and replication in a larger population, since it may be relevant to several chronic diseases such as cardiovascular diseases and cancer.

Meta-analysis of cancer incidence in children born after assisted reproductive technologies.

A meta-analysis was performed on 11 cohort studies of Assisted Reproductive Technologies (ART) and subsequent childhood cancer, published up to February 2005, which reported comparable, nonoverlapping data, and then restricted to eight studies which presented a similar research design. The overall Standardised Incidence Ratio was 1.33 (95% CI 0.62-2.85), and 0.77 (95% CI 0.41-1.42) when the analysis was restricted to eight studies. No evidence of publication bias was observed for the overall analysis. The data are consistent with a lack of increase in risk of childhood cancer, though the amount of data on ART and cancer is still limited; larger multicentric studies as well as a pooled analysis on the available data are warranted.

Human exposure to dioxins through diet in Italy.

We have measured the content of polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans (together defined as "dioxins") in 269 samples of food of animal origin collected through the regional veterinary services, covering the national territory. Quantification of the dioxins was accomplished by isotope dilution method, and toxic equivalents (TEQ) were calculated. The average daily food intake was obtained from two main sources: national data collected by the National Institute of Nutrition, and data from an ongoing cohort study on diet and cancer including 40,000 Italian subjects. The mean value of dioxins measured in food of animal origin was 0.144 +/- 0.266 pg-TEQ/g (range: 0.003-1.655 pg-TEQ/g). Fish was the item with the highest content. The estimated intake of dioxins with main food items of animal origin is presented. The major contribution to dioxins intake with food comes from cow milk and fish consumption. These results are in agreement with what observed in studies conducted in other countries, such as Germany, Finland, Japan, Spain, and are below the limits set by the European legislation.