Medical Students Knowledge and Attitude Towards Direct-To-Consumer Genetic Tests

Aims: This study reports on the attitudes of 179 Italian Medical Students to direct-to-consumer genetic test and to participation in research practices. Methods: Data were collected using a self-completion online questionnaire sent to 380 medical students at the faculty of Medicine of the Università Cattolica del Sacro Cuore in Rome, Italy. Questions pertained issues related to awareness and attitudes towards genetic testing, reactions to hypothetical results, and views about contributing to scientific research. Results: The response rate was 47.1%. Less than 50% of students were aware of DTC genetic test. Seventy-four percent of the sample were interested in undergoing DTC genetic test, and the main reason was being aware on genetic predisposition to diseases. Among those who were not willing to undergo a genetic test, the main reason was the lack of confidence in the results. In the hypothetical situations of an increased disease risk after undergoing DTC genetic testing, respondents would take actions to reduce that risk, while in the opposite scenario they would feel unaffected because of the probabilistic nature of the test. Conclusions: We reported a good level of awareness about DTC genetic test and a high interest in undergoing DTC genetic test in our sample. Nevertheless, opinions and reactions are strongly dependent by the hypothetical good or bad result that the test could provide and by the context whereby a genetic test could be performed. Respondents seem to be exposed to the risk of psychological harms, and a strong regulation regarding their use is required

A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility

A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population

<p>Abstract</p> <p>Background</p> <p>The purpose of this study is to analyze the combined effects of selected <it>p</it>53 and <it>p</it>73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck (SCCHN) risk and progression in an Italian population.</p> <p>Methods</p> <p>Two hundred and eighty-three cases and 295 hospital controls were genotyped for <it>p</it>53 polymorphisms on exon 4 (Arg72Pro), intron 3 and 6, and <it>p</it>73 G4C14-to-A4T14. Their association with SCCHN was estimated using a logistic regression analysis, while a multinomial logistic regression approach was applied to calculate the effect of the selected polymorphisms on SCCHN different sites (oral cavity, oropharynx, hypopharynx and larynx). We performed an haplotype analysis of the <it>p</it>53 polymorphisms, and a gene-gene interaction analysis for the combined effects of <it>p</it>73 G4C14-to-A4T14 and <it>p</it>53 polymorphisms.</p> <p>Results</p> <p>We found a significant increased risk of SCCHN among individuals with combined <it>p</it>73 exon 2 G4A and <it>p</it>53 intron 3 variant alleles (OR = 2.22, 95% CI: 1.08–4.56), and a protective effect for those carrying the <it>p</it>53 exon 4-<it>p</it>53 intron 6 diplotype combination (OR = 0.67; 95% CI: 0.47–0.92). From the gene-environment interaction analysis we found that individuals aged < 45 years carrying <it>p</it>73 exon 2 G4A variant allele have a 12.85-increased risk of SCCHN (95% CI: 2.10–78.74) compared with persons of the same age with the homozygous wild type genotype. Improved survival rate was observed among <it>p</it>53 intron 6 variant allele carriers (Hazard Ratio = 0.51 (95% CI: 0.23–1.16).</p> <p>Conclusion</p> <p>Our study provides for the first time evidence that individuals carrying <it>p</it>53 exon 4 and <it>p</it>53 intron 6 variant alleles are significantly protected against SCCHN, and also shows that an additional risk is conferred by the combination of <it>p</it>73 exon 2 G4C14-to-A4T14 and <it>p</it>53 intron 3 variant allele. Larger studies are required to confirm these findings.</p

Collagen-specific T-cell repertoire in blood and synovial fluid varies with disease activity in early rheumatoid arthritis

Type II collagen is a DR4/DR1 restricted target of self-reactive T cells that sustain rheumatoid arthritis. The aim of the present study was to analyze the T-cell receptor repertoire at the onset of and at different phases in rheumatoid arthritis. We used the CDR3 BV-BJ spectratyping to study the response to human collagen peptide 261-273 in 12 patients with DR4+ rheumatoid arthritis (six at the onset of disease and six during the course of disease) and in five healthy DR4+ relatives. The collagen-specific T-cell repertoire is quite restricted at the onset of disease, involving approximately 10 rearrangements. Within the studied collagen-specific rearrangements, nearly 75% is shared among patients. Although the size of the repertoire used by control individuals is comparable to that of patients, it is characterized by different T-cell receptors. Part of the antigen-specific T-cell repertoire is spontaneously enriched in synovial fluid. The specific T-cell repertoire in the periphery was modulated by therapy and decreased with the remission of the disease. Failure of immunoscopy to detect this repertoire was not due to suppression of collagen-driven proliferation in vitro by CD4+ CD25+ T cells. Clinical relapse of the disease was associated with the appearance of the original collagen-specific T cells. The collagen-specific T-cell receptor repertoire in peripheral blood and synovial fluid is restricted to a limited number of rearrangements in rheumatoid arthritis. The majority of the repertoire is shared between patients with early rheumatoid arthritis and it is modulated by therapy

Plasma miR-151-3p as a Candidate Diagnostic Biomarker for Head and Neck Cancer: A Cross-sectional Study within the INHANCE Consortium

Background: Identification of screening tests for the detection of head and neck cancer (HNC) at an early stage is an important strategy to improving prognosis. Our objective was to identify plasma circulating miRNAs for the diagnosis of HNC (oral and laryngeal subsites), within a multicenter International Head and Neck Cancer Epidemiology consortium. Methods: A high-throughput screening phase with 754 miRNAs was performed in plasma samples of 88 cases and 88 controls, followed by a validation phase of the differentially expressed miRNAs, identified in the screening, in samples of 396 cases and 396 controls. Comparison of the fold changes (FC) was carried out using the Wilcoxon rank-sum test and the Dunn multiple comparison test. Results: We identified miR-151-3p (FC = 1.73, P = 0.007) as differentially expressed miRNAs in the screening and validation phase. The miR-151-3p was the only overexpressed miRNA in validation sample of patients with HNC with early stage at diagnosis (FC = 1.81, P = 0.008) and it was confirmed upregulated both in smoker early-stage cases (FC = 3.52, P = 0.024) and in nonsmoker early-stage cases (FC = 1.60, P = 0.025) compared with controls. Conclusions: We identified miR-151-3p as an early marker of HNC. This miRNA was the only upregulated in patients at early stages of the disease, independently of the smoking status. Impact: The prognosis for HNC is still poor. The discovery of a new diagnostic biomarker could lead to an earlier tumor discovery and therefore to an improvement in patient prognosis

Glutathione s-transferase gene polymorphisms in italian patients with sudden sensorineural hearing loss.

HYPOTHESIS: To investigate the association between glutathione S-transferase (GST) gene polymorphisms and sudden sensorineural hearing loss (SSNHL) in a population of consecutive Italian patients. Assuming that reactive oxygen species formation may play a role in inner ear damage, we investigated whether profiles of GSTs antioxidant enzymes M1 and T1 genotypes may be associated with the risk of SSNHL. STUDY DESIGN: A prospective study in patients with SSNHL. PATIENTS AND METHODS: We investigated 80 Italian patients with SSNHL for the frequency of GSTT1 and GSTM1 polymorphisms. Genotype distribution of all factors found in patients were compared with those of 80 healthy control subjects of the same ethnic background using chi and odds-ratio analysis. Statistical significance was accepted at a level of p &lt; 0.05. RESULTS: In our series, the frequencies of GSTM1 and GSTT1 null genotypes did not differ from those of the control subjects. CONCLUSION: The few studies regarding genetic polymorphisms of GSTs in SSNHL are not conclusive. Further studies are needed to investigate the role of antioxidants including GSTs in SSNHL and to provide the lacking information to improve our knowledge in the field before implementing the use of genetic polymorphism in the SSNHL medicine daily practice

Plasma miR-151-3p as a candidate diagnostic biomarker for head and neck cancer: a cross-sectional study within the INHANCE consortium

Identification of screening tests for the detection of head and neck cancer at an early stage is an important strategy to improving prognosis. Our objective was to identify plasma circulating microRNAs for the diagnosis of head and neck cancer (oral and laryngeal subsites), within a multicenter International Head and Neck Cancer Epidemiology (INHANCE) consortium

CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms, smoking, consumption of alcohol and fruit and vegetables and risk of head and neck cancer

Purpose As risk-modiWers of alcohol and tobacco eVects, metabolic genes polymorphisms were investigated as susceptibility candidates for squamous cell carcinoma of the head and neck (SCCHN). Methods A total of 210 cases and 245 hospital controls, age and gender matched, were genotyped for CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms. A measurement of the biological interaction among two risk factors was estimated by the attributable proportion (AP) due to interaction and its 95% conWdence interval (CI). Results SCCHN risk was associated with high-levels of alcohol intake [OR = 3.50 (95%CI: 1.93 6.35) and OR = 6.47 (95%CI: 2.92 14.35) for 19 30 g/day and &gt;30 g/day, respectively], cigarette smoking [OR = 3.47 (95%CI: 1.88 6.41) and OR = 7.65 (95%CI: 4.20 13.90) for 1 25 and &gt;25 packyears of smoking, respectively] and low-fruit and vegetables consumption (OR = 2.45; 95%CI: 1.53 3.92). No diVerences were observed for the genotypes or haplotypes distributions among cases and controls, and no biological interaction emerged from gene gene and gene environment interaction analyses. An attributable proportion (AP) due to biological interaction of 0.65 (95%CI: 0.40 0.90) was detected for heavy drinkers with a low intake of fruit and vegetables, and an AP of 0.40 (95%CI: 0.10 0.72) resulted forever smokers with low fruit and vegetables consumption. Conclusions Even in presence of high alcohol consumption or cigarette smoking, a high intake of fruit and vegetables might prevent the development of around one quarter of SCCHN cases. The lack of interaction between the studied polymorphisms and the environmental exposures suggests that chronic consumption of tobacco and alcohol overwhelm enzyme defences, irrespective of genotype

Polymorphisms in metabolic genes, their combination and interaction with tobacco smoke and alcohol consumption and risk of gastric cancer: a case-control study in an Italian population

Background: The distribution and the potential gene-gene and gene-environment interaction of selected metabolic genetic polymorphisms was investigated in relation to gastric cancer risk in an Italian population. Methods: One hundred and seven cases and 254 hospital controls, matched by age and gender, were genotyped for CYP1A1, CYP2E1, mEH, GSTM1, GSTT1, NAT2 and SULT1A1 polymorphisms. Haplotype analysis was performed for EPHX1 exons 3 and 4, as well as CYP2E1 RsaI (*5 alleles) and CYP2E1 DraI (*5A or *6 alleles). The effect modification by alcohol and cigarette smoking was tested with the heterogeneity test, while the attributable proportion (AP) was used to measure the biological interaction from the gene-gene interaction analysis. Results: Gastric cancer risk was found to be associated with the inheritance of GSTT1 null genotype (OR = 2.10, 95%CI: 1.27-3.44) and the SULT1A1 His/His genotype (OR = 2.46, 95%CI: 1.03-5.90). No differences were observed for the haplotype distributions among cases and controls. For the first time an increased risk was detected among individuals carrying the *6 variant allele of CYP2E1 if ever-drinkers (OR = 3.70; 95%CI: 1.45-9.37) with respect to never-drinkers (OR = 0.18; 95% CI: 0.22-1.46) (p value of heterogeneity among the two estimates = 0.001). Similarly, the effect of SULT1A1 variant genotype resulted restricted to ever-smokers, with an OR of 2.58 (95%CI: 1.27-5.25) for the carriers of His allele among smokers, and an OR of 0.86 (95%CI: 0.45-1.64) among never-smokers (p value of heterogeneity among the two estimates = 0.03). The gene-gene interaction analyses demonstrated that individuals with combined GSTT1 null and NAT2 slow acetylators had an additional increased risk of gastric cancer, with an OR of 3.00 (95%CI: 1.52-5.93) and an AP of 52%. Conclusion: GSTT1, SULT1A1 and NAT2 polymorphisms appear to modulate individual's susceptibility to gastric cancer in this Italian population, particularly when more than one unfavourable genotype is present, or when combined with cigarette smoke. The increased risk for the carriers of CYP2E1*5A or *6 alleles among drinkers need to be confirmed by larger prospective studies

Medical Students Knowledge and Attitude Towards Direct-To-Consumer Genetic Tests

Aims: This study reports on the attitudes of 179 Italian Medical Students to direct-to-consumer genetic test and to participation in research practices. Methods: Data were collected using a self-completion online questionnaire sent to 380 medical students at the faculty of Medicine of the Università Cattolica del Sacro Cuore in Rome, Italy. Questions pertained issues related to awareness and attitudes towards genetic testing, reactions to hypothetical results, and views about contributing to scientific research. Results: The response rate was 47.1%. Less than 50% of students were aware of DTC genetic test. Seventy-four percent of the sample were interested in undergoing DTC genetic test, and the main reason was being aware on genetic predisposition to diseases. Among those who were not willing to undergo a genetic test, the main reason was the lack of confidence in the results. In the hypothetical situations of an increased disease risk after undergoing DTC genetic testing, respondents would take actions to reduce that risk, while in the opposite scenario they would feel unaffected because of the probabilistic nature of the test. Conclusions: We reported a good level of awareness about DTC genetic test and a high interest in undergoing DTC genetic test in our sample. Nevertheless, opinions and reactions are strongly dependent by the hypothetical good or bad result that the test could provide and by the context whereby a genetic test could be performed. Respondents seem to be exposed to the risk of psychological harms, and a strong regulation regarding their use is required