Genetic variation analysis in a follow‐up study of gastric cancer precursor lesions confirms the association of MUC2 variants with the evolution of the lesions and identifies a significant association with NFKB1 and CD14

Abstract

Gastric carcinogenesis proceeds through a series of gastric cancer precursor lesions (GCPLs) leading to gastric cancer (GC) development. Although Helicobacter pylori infection initiates this process, genetic factors also play a role. We previously reported that genetic variability in MUC2 is associated with the evolution of GCPLs. In order to replicate previous results in an independent sample series and to explore whether genetic variability in other candidate genes plays a role in the evolution of GCPL, genomic DNA from 559 patients with GCPLs, recruited from 9 Spanish hospitals and followed for a mean of 12 years, was genotyped for 141 SNPs in 29 genes. After follow-up, 45.5% of the lesions remained stable, 37% regressed and 17.5% progressed to a more severe lesion. Genetic association with the evolution of the lesions (progression or regression) was analyzed by multinomial and binomial logistic regression. After correction for multiple comparisons, the results obtained confirmed the inverse association between MUC2 variants and the regression of the lesions. A significant association was also observed between NFKB1 and CD14 variants and the evolution of the lesions; interestingly, this association was with both progression and regression in the same direction, which could reflect the dual role of inflammation in cancer. Stratified analyses according to H. pylori virulence factors indicated some significant and differential effects but none of them passed the FDR test. These results confirm that genetic variability in MUC2, NFKB1 and CD14 may have a role in the evolution of the GCPLs along time and in gastric carcinogenesis.

Whole-Genome Sequencing of Common Salivary Gland Carcinomas: Subtype-Restricted and Shared Genetic Alterations

“…We also highlighted a potential association between mutational signature of DNA repair-related pathways and the development of salivary cancers (60) DNA repair pathways in all three subtypes may suggest potential deficiencies of these pathways and induction of epithelial cells damage that are not well-protected by salivary mucins in the patients (61). Indeed, we found increased frequency of rare germline variations in 3 genes, MUC2 (62,63), MUC12, and FCGBP (42,43) in comparison to in the healthy population. These genes are linked to mucosal and salivary gland tissue homeostasis and defense against toxic and bacterial infection (42), suggesting that they play a role in the predisposition of certain individuals to SGC development.…”

Droplet Digital PCR Detects Low-Density Infection in a Significant Proportion of Helicobacter Pylori-Negative Gastric Biopsies of Dyspeptic Patients

“…In our case, to avoid false positive results, ddPCR positivity was determined on the amplification of 3 specific H. pylori genes, each of them in triplicate. In addition, we selected primers that showed a very high specificity in previous publications ( 23 , 35 ). Therefore, our study suggests that ddPCR may be a useful alternative for detecting H. pylori infection, especially for patients with very low-degree, “occult” infection.…”

Cross-sectional study of human coding- and non-coding RNAs in progressive stages of Helicobacter pylori infection

“…QT625-05, Bioline, UK). Details on VacAs , VacAm and cagA amplification are described in detail elsewhere 6 . For histopathological evaluation, sections were stained with haematoxylin-eosin (Fig.…”

“…Exclusion criteria were: patients who were not able to stop antisecretory drugs, those who had received antibiotics in the four weeks before the endoscopy and those with a history of prior treatment for H. pylori. Before the endoscopy, a 13 6 . For histopathological evaluation, sections were stained with haematoxylin-eosin ( Fig.…”