Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer

Background: genetics plays an important role in the susceptibility to sporadic colorectal cancer (CRC). In the last 10 years genome-wide association studies (GWAS) have identified over 40 independent low penetrance polymorphic variants. However, these loci only explain around 1‑4% of CRC heritability, highlighting the dire need of identifying novel risk loci. In this study, we focused our attention on the genetic variability of the TAS2R16 gene, encoding for one of the bitter taste receptors that selectively binds to salicin, a natural antipyretic that resembles aspirin. Given the importance of inflammation in CRC, we tested whether polymorphic variants in this gene could affect the risk of developing this neoplasia hypothesizing a role of TAS2R16 in modulating chronic inflammation within the gut. Methods: we performed an association study using 6 tagging SNPs, (rs860170, rs978739, rs1357949, rs1525489, rs6466849, rs10268496) that cover all TAS2R16 genetic variability. The study was carried out on 1902 CRC cases and 1532 control individuals from four European countries. Results: we did not find any statistically significant association between risk of developing CRC and selected SNPs. However, after stratification by histology (colon vs. rectum) we found that rs1525489 was associated with increased risk of rectal cancer with a (Ptrend of = 0.0071). Conclusions: our data suggest that polymorphisms within TAS2R16 gene do not have a strong influence on colon cancer susceptibility, but a possible role in rectal cancer should be further evaluated in larger cohorts

A cohort study to evaluate persistence of hepatitis B immunogenicity after administration of hexavalent vaccines

<p>Abstract</p> <p>Background</p> <p>In 2001, two hexavalent vaccines were licensed in Italy (Hexavac^®, Infanrix Hexa^®), and since 2002 were extensively used for primary immunization in the first year of life (at 3, 5, 11/12 months of age). In 2005, the market authorization of Hexavac^®was precautionary suspended by EMEA, because of doubts on long-term protection against hepatitis B virus. The objectives of this study were to evaluate the persistence of antibodies to anti-HBs, in children in the third year of life, and to investigate the response to a booster dose of hepatitis B vaccine.</p> <p>Methods</p> <p>Participant children were enrolled concomitantly with the offering of anti-polio booster dose, in the third year of life. Anti-HBs titers were determined on capillary blood samples. A booster dose of hepatitis B vaccine was administered to children with anti-HBs titers < 10 mIU/ml, with the monovalent precursor product of the previously received hexavalent vaccine. HBsAb titers were tested again one month after the booster.</p> <p>Results</p> <p>Sera from 113 children previously vaccinated with Hexavac^®, and from 124 vaccinated with Infanrix Hexa^®were tested for anti-HBs. Titers were ≥ 10 mIU/ml in 69% and 96% (p < 0,0001) respectively. The proportion of children with titers ≥ 100 mIU/ml did also significantly differ among groups (27% and 78%; p < 0,0001).</p> <p>Post-booster, 93% of children achieved titers ≥ 10 mIU/ml, with no significant difference by vaccine group.</p> <p>Discussion</p> <p>Fifteen months after third dose administration, a significant difference in anti-HBs titers was noted in the two vaccine groups considered. Monovalent hepatitis B vaccine administration in 3-year old children induced a proper booster response, confirming that immunologic memory persists in children with anti-HBs titers < 10 mIU/ml. However, long-term persistence of HBV protection after hexavalent vaccines administration should be further evaluated over time.</p

Association of the bitter taste receptor gene TAS2R38 (polymorphism RS713598) with sensory responsiveness, food preferences, biochemical parameters and body-composition markers. A cross-sectional study in Italy

This study examined the relationship between TAS2R38 gene polymorphism (RS713598), G/G, C/G or C/C genotype, and sensory responsiveness, food preferences, biochemical parameters and body composition in a cross-sectional study in 118 adults (24 men and 94 women). The frequencies of C/C, G/G and C/G were respectively 20.3%, 29.7% and 50.0%. As regards taste responsiveness, subjects with G-allele had a higher perception threshold than the C/C genotype for 6-n-propyl-2-thiouracil (PROP) (p < .05), and caffeine (p < .05). The G-alleles had higher preferences for beer (OR: 6.25; p < .05), but lower for butter (OR: 0.64; p < .05) and cured meat (OR: 0.55; p < .05). Biochemical parameters and body composition markers did not differ between genotypes. Subjects with RS713598 polymorphism had a higher bitter taste perception threshold and higher or lower preferences for selected nutrient/energy dense foods, such as beer, butter and cured meat

The strange case of a hematocele mistaken for a neoplastic scrotal mass

Hematoceles are usually associated with a history of scrotal trauma, are usually painful and rarely have an idiopathic origin. We describe the peculiar case of a hematocele mistaken for a testicular cance

The strange case of a hematocele mistaken for a neoplastic scrotal mass

Hematoceles are usually associated with a history of scrotal trauma, are usually painful and rarely have an idiopathic origin. We describe the peculiar case of a hematocele mistaken for a testicular cancer

Sarcopenia Predicts Disease Progression in Patients with T1 High-grade Non–muscle-invasive Bladder Cancer Treated with Adjuvant Intravesical Bacillus Calmette-Guérin: Implications for Decision-making?

Background: Skeletal muscle loss (sarcopenia) has been linked to cancer cachexia and can predict survival in several tumors, including advanced genitourinary malignancies. Objective: To investigate the predictive and prognostic role of sarcopenia in patients with T1 high grade (HG) non-muscle invasive bladder cancer (NMIBC) treated with adjuvant intravesical Bacillus Calmette-Guerin (BCG). Design, setting, and participants: Oncological outcomes were evaluated for 185 patients with T1 HG NMIBC treated with BCG at two European referral centers. Sarcopenia, identified from computed tomography scans performed within 2 mo after surgery, was defined as a skeletal muscle index of <39 cm2/m2 for women and <55 cm2/m2 for men. Outcome measurements and statistical analysis: The main endpoint was the association between sarcopenia and disease recurrence and progression. Kaplan-Meier curves and multivariable Cox models were built, and the clinical value of any association was assessed using Harrell’s C index and decision curve analysis (DCA). Results and limitations: Sarcopenia was present in 130 patients (70%). On multivariable Cox regression analyses that accounted for the effect of standard clinicopathological prognosticators, sarcopenia was independently associated with disease progression (hazard ratio 3.41; p = 0.02). Addition of sarcopenia to a standard model for prediction of disease progression improved the discrimination of the model from 62% to 70%. DCA revealed superior net benefits for the proposed model in comparison to the strategies of treating all or no patients with radical cystectomy, and in comparison to the existing predictive model. Limitations are inherent to the retrospective design. Conclusions: We demonstrated the prognostic role of sarcopenia in T1 HG NMIBC. Pending external validation, this tool could be easily incorporated into existing nomograms for prediction of disease progression to improve clinical decision-making and patient counseling. Patient summary: We looked at the role of loss of skeletal muscle (sarcopenia) as a factor in predicting prognosis for stage T1 high-grade non–muscle-invasive bladder cancer. We found that sarcopenia is a ready-to-use, cost-free marker that could be used to guide treatment and follow-up in this disease, although the results need to be confirmed in other studies

Opioid response in paediatric cancer patients and the Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene: an Italian study on 87 cancer children and a systematic review

Abstract Background Genetic polymorphisms in genes involved in pain modulation have been reported to be associated to opioid efficacy and safety in different clinical settings. Methods The association between COMT Val158Met polymorphism (rs4680) and the inter-individual differences in the response to opioid analgesic therapy was investigated in a cohort of 87 Italian paediatric patients receiving opioids for cancer pain (STOP Pain study). Furthermore, a systematic review of the association between opioid response in cancer patients and the COMT polymorphism was performed in accordance with the Cochrane Handbook and the Prisma Statement. Results In the 87 paediatric patients, pain intensity (total time needed to reach the lowest possible level) was significantly higher for G/G than A/G and A/A carriers (p-value = 0.042). In the 60 patients treated only with morphine, the mean of total dose to reach the same pain intensity was significantly higher for G/G than A/G and A/A carriers (p-value = 0.010). Systematic review identified five studies on adults, reporting that opioid dose (mg after 24 h of treatment from the first pain measurement) was higher for G/G compared to A/G and A/A carriers. Conclusions Present research suggests that the A allele in COMT polymorphism could be a marker of opioid sensitivity in paediatric cancer patients (STOP Pain), as well as in adults (Systematic Review), indicating that the polymorphism impact could be not age-dependent in the cancer pain context. Trial registration Registration number: CRD42017057831

Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer

Background: genetics plays an important role in the susceptibility to sporadic colorectal cancer (CRC). In the last 10 years genome-wide association studies (GWAS) have identified over 40 independent low penetrance polymorphic variants. However, these loci only explain around 1‑4% of CRC heritability, highlighting the dire need of identifying novel risk loci. In this study, we focused our attention on the genetic variability of the TAS2R16 gene, encoding for one of the bitter taste receptors that selectively binds to salicin, a natural antipyretic that resembles aspirin. Given the importance of inflammation in CRC, we tested whether polymorphic variants in this gene could affect the risk of developing this neoplasia hypothesizing a role of TAS2R16 in modulating chronic inflammation within the gut. Methods: we performed an association study using 6 tagging SNPs, (rs860170, rs978739, rs1357949, rs1525489, rs6466849, rs10268496) that cover all TAS2R16 genetic variability. The study was carried out on 1902 CRC cases and 1532 control individuals from four European countries. Results: we did not find any statistically significant association between risk of developing CRC and selected SNPs. However, after stratification by histology (colon vs. rectum) we found that rs1525489 was associated with increased risk of rectal cancer with a (Ptrend of = 0.0071). Conclusions: our data suggest that polymorphisms within TAS2R16 gene do not have a strong influence on colon cancer susceptibility, but a possible role in rectal cancer should be further evaluated in larger cohorts