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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
Author(s) -
Companioni Osmel,
Bonet Catalina,
García Nadia,
RamírezLázaro María José,
Lario Sergio,
Mendoza Jorge,
Adrados Mª Magdalena,
Poves Elvira,
Espinosa Laura,
PozoKreilinger José Juan,
Ortega Luís,
Bujanda Luis,
Cosme Angel,
Ferrández Angel,
Muñoz Guillermo,
Cuatrecasas Miriam,
Elizalde Ignasi,
Andreu Victoria,
Paules Mª José,
Madrigal Beatriz,
Barrio Jesús,
Berdasco María,
Calvet Xavier,
SanzAnquela José Miguel,
Gisbert Javier P.,
González Carlos A.,
Sala Núria
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31839
Subject(s) - genetic association , biology , single nucleotide polymorphism , carcinogenesis , cancer , genetic variation , genome wide association study , genetics , candidate gene , genotype , gene
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.