Association of Helicobacter pylori with oral potentially malignant disorders and oral squamous cell carcinoma—a systematic review and meta-analysis

Objective

To assess any potential association between Helicobacter pylori and oral squamous cell carcinoma/oral potentially malignant disorders.

Materials and methods

Data mining was done using PubMed, Cochrane Library, and SCOPUS databases. The search included articles published up to May 2019. Newcastle-Ottawa scale was used to score the quality of the included articles. Data including the type of study, the sample population, the type of oral lesion, and the resulting statistical data were extracted.

Results

Out of 131 screened articles, only 15 articles fulfilled the eligibility criteria. Among the 15 studies, 9 focused on oral squamous cell carcinoma and 6 focused on oral potentially malignant disorders. Eight out of the 9 oral squamous cell carcinoma studies were included in the meta-analysis. Forest plot was generated using the odds ratio and confidence intervals calculated for each of the included studies. Due to the lack of sufficient studies, the meta-analysis was not performed for oral potentially malignant disorders.

Conclusion

Due to the contradictory results of the included studies, it was not possible to make any conclusive statement on the potential association of H. pylori with oral squamous cell carcinoma. The variations in the methodology, especially the differences in the sensitivity/specificity of the diagnostic modalities could be the cause for differential results.

Clinical relevance

Although the association of H. pylori with oral squamous cell carcinoma could not be confirmed, it is vital to reduce the excess oral microbial load, especially in patients exhibiting oral mucosal changes with no history of associated risk factors.

     

Analysis of exome sequence in 604 trios for recessive genotypes in schizophrenia

Genetic associations involving both rare and common alleles have been reported for schizophrenia but there have been no systematic scans for rare recessive genotypes using fully phased trio data. Here, we use exome sequencing in 604 schizophrenia proband–parent trios to investigate the role of recessive (homozygous or compound heterozygous) nonsynonymous genotypes in the disorder. The burden of recessive genotypes was not significantly increased in probands at either a genome-wide level or in any individual gene after adjustment for multiple testing. At a system level, probands had an excess of nonsynonymous compound heterozygous genotypes (minor allele frequency, MAF ⩽1%) in voltage-gated sodium channels (VGSCs; eight in probands and none in parents, P=1.5 × 10⁻⁴). Previous findings of multiple de novo loss-of-function mutations in this gene family, particularly SCN2A, in autism and intellectual disability provide biological and genetic plausibility for this finding. Pointing further to the involvement of VGSCs in schizophrenia, we found that these genes were enriched for nonsynonymous mutations (MAF ⩽0.1%) in cases genotyped using an exome array, (5585 schizophrenia cases and 8103 controls), and that in the trios data, synaptic proteins interacting with VGSCs were also enriched for both compound heterozygosity (P=0.018) and de novo mutations (P=0.04). However, we were unable to replicate the specific association with compound heterozygosity at VGSCs in an independent sample of Taiwanese schizophrenia trios (N=614). We conclude that recessive genotypes do not appear to make a substantial contribution to schizophrenia at a genome-wide level. Although multiple lines of evidence, including several from this study, suggest that rare mutations in VGSCs contribute to the disorder, in the absence of replication of the original findings regarding compound heterozygosity, this conclusion requires evaluation in a larger sample of trios.     

Interplay between RAS and opioids: Opening the Pandora of complexities

Angiotensin and endogenous opioids are important bioactive neuropeptides, which are widely distributed in the brain and peripheral regions to produce diverse biological and neurobiological activities. An endogenous opioid system includes proopiomelanocortin-derived enkephalin, dynorphin and endorphin that act on their specific receptors such as delta (δ), kappa (κ) and mu (μ) receptors. Research evidence demonstrates significant positive as well as negative interactions between renin angiotensin system (RAS) and endogenous opioids in the brain and periphery. The diverse actions of Ang II are possibly mediated indirectly through endogenous opioids, while opioids are also shown to activate RAS components suggesting the up-regulation of each system in concern with each other. On the contrary, there are reports suggesting a negative correlation between RAS and opioid system. Research evidence also supports the notion that Ang II acts as anti-opioid peptide to decrease the actions of opioids. Moreover, opioids-induced decline in angiotensin release and functioning has also been reported. Co-administration of ACE inhibitors with opioids exhibits significant interactions possibly due to decreased metabolism of opioids leading to potentiation of their actions. The present review describes the complexities of positive and negative interactions between RAS and opioids along with possible mechanisms responsible for these interactions.     

Tetralogy of Fallot with restrictive ventricular septal defect by accessory tricuspid leaflet tissue

In tetralogy of Fallot septal defect is usually large because of malalignment of outlet septum, restrictive defect has been reported rarely. We present a case of tetralogy of Fallot with accessory tricuspid leaflet tissue restricting ventricular septal defect. The report includes echocardiographic and catheter images of this rare presentation of tetralogy of Fallot.